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Mito Pereira tells a wonderful story about a moment when he realized he might have a future as a top-level golfer.
Between the ages of 3 and 15, the Chilean had played golf with strong support from his parents. He competed in junior tournaments and was looking like a teenager whose obvious next step would be to move to a U.S. college to hone his game.
Suddenly, he quit. He simply didn’t want to play the game any more. Pereira didn’t pick up a golf club for two years, until a fateful day when he was 17.
“A friend said, ‘You want to go and play golf?’ Two years without touching a club… and I shot 4 under. I thought, ‘OK, maybe I need to get back to it!’”
Pereira has no regrets about taking that break, which allowed him to play other sports and do plenty of growing up. But ever since returning to the game, his focus and progress have been impressive.
Now, as a member of LIV Golf team Torque GC, he is part of a strong Latino element of the League. As he moves into his thirties, he believes he has plenty of successful golf years in him yet.
Korn Ferry triple triumph triggers instant rise to PGA Tour
Mito Pereira was born in Santiago in 1995 and it was in his homeland that he started to win following that unorthodox two-year break. As an amateur, he won the Abierto Las Brisas de Chicureo on the Chilean pro tour in 2013.
He moved to Texas Tech in 2014 but never really settled and, after a year playing college golf for the Red Raiders – and reaching No. 5 on the world amateur rankings – he turned pro in 2015.
More wins followed on the Chilean Tour and the PGA Tour Latinoamerica and, in the 2020-21 season, he recorded three victories on the Korn Ferry Tour.
That earned Pereira an instant promotion to the PGA Tour, where he found the transition smooth – he started making cuts and recording strong finishes straight away.
Mito Pereira’s comes close at the PGA Championship
Mito Pereira proudly represented Chile at the Olympic Games in Tokyo in 2021 and finished in a tie for third place, only to miss out on the bronze medal after a seven-man playoff.
The following year – at only his second major tournament – he was close to a sensational win at the PGA Championship at Southern Hills.
Three sub-70 rounds carried him to a three-shot lead going into the final day and he battled bravely throughout a long Oklahoma afternoon.
Pereira eventually finished one shot out of a playoff where Justin Thomas claimed victory.
As he said in the immediate aftermath of the event: “I’m just happy with how the week turned out. I’m hoping to take this to learn for the future.”
Since then he has finished tied for 43rd at the 2023 Masters, and tied for 18th at the PGA Championship that same year.
Pereira enjoys ‘amazing’ year after signing with LIV Golf
Mito Pereira joined the LIV Golf ranks at the start of 2023 and immediately found himself among friends. As a member of Torque GC, his captain is fellow Chilean Joaquin Niemann, while the other members are Ecuador’s Sebastian Munoz and Carlos Ortiz of Mexico.
“It’s a really good team, four friends,” said Pereira. “We push ourselves hard… it’s really nice to be in a team like this.”
Torque GC won the team prize at four tournaments in 2023, and were third on the overall season standings. Pereira contributed six top-10 finishes, including second at The Greenbrier, and said: “The first year has been amazing.”
He described his move to LIV Golf as “one of the best decisions I’ve made in my life.”
On the golf course, Mito Pereira brings a measured, methodical approach to the game.
Away from the course, Pereira also has his life in good order. His wife is his childhood sweetheart, Antonia Prida. He said in 2022: “I started dating Antonia when I was away from playing, so I know she doesn’t just like me because of golf. It’s just because I’m handsome!”
The couple married in December 2021, and celebrated their union with family and friends the following month and welcomed a baby boy in 2024.
The Pereira family lives in Jupiter, Florida, a popular base for pro golfers.
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Bringing Total Raised to US$4M to Advance AI-Driven Preventive Health
Today we are excited to announce that Mito Health has raised an additional $2.2 million in seed funding
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Your belief in our vision is a driving force in our work
We are equally excited to welcome renowned longevity researcher Professor Brian Kennedy to our scientific advisory committee
He brings over 40 years of experience studying the biological processes of aging and developing clocks like LinAge
a blood-based formula for assessing biological age
Longevity science is advancing at an unprecedented pace
and our scientific advisory committee will help us translate new breakthroughs and technology into personalized
Since our launch in San Francisco last summer
we’ve expanded to all 50 states working with labs including LabCorp and BioReference
has helped customers detect early signs of disease and achieve peak health
We have also partnered with companies like BodySpec (DEXA scans) and Prenuvo (preventative MRIs) to give our customers deeper insights into their health
These results are possible because Mito Health builds the most in-depth profile of each customer’s health — combining blood biomarkers
With AI-assisted medical analysis connecting the dots between personal data and the latest research
Mito Health is able to pick up issues earlier and give better insights
our vision of providing “an AI doctor in your pocket” grows ever closer to reality
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and gave me a clear plan for what to do.”
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I especially love the dashboard for tracking my biomarkers over time and seeing long-term trends.”
New York Times Bestselling author of Hooked
Our fresh funding will allow us to invest in expanding our US operations in the coming months and years
We look forward to being able to serve more clients
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Mito Health recently partnered with Bryan Johnson’s Don’t Die Summit in New York City in February
I was thrilled to have met so many passionate clients who are now living healthier lives thanks to our product
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our platform empowers individuals to proactively manage their health and optimize their healthspan
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Coxsey sent her first V14 way back in July 2014 when she made the first female ascent of New Base Line in Magic Wood, Switzerland. She went on a bouldering tear in 2024. In late February, she made the first ascent of Fotofobia Sit V14 in La Pedriza, Spain. She also sent Pin y Pon V13 while on her Spanish trip. Two months later she repeated Fat Lip V13 at Raven Tor and became the first woman to send V14 on British soil with her ascent of Ned Feehally’s The Boss.
In June 2024, she repeated Hazel Grace V14 (8B+) in Gotthard Pass, Switzerland. The line was established by Giuliano Cameroni in August 2017 at a grade of V15, which settled at V14 with subsequent ascents. The aesthetic boulder trends leftward across a seam to an arete topout in a beautiful alpine setting. She recently made the second ascent of the stout lowball Lupin V13 at Stanton in the Woods, U.K.
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Volume 12 - 2024 | https://doi.org/10.3389/fcell.2024.1460061
This article is part of the Research TopicSurvival Strategies: Cellular Responses to Stress and DamageView all 9 articles
Mitochondrial quality control is finely tuned by mitophagy
the selective degradation of mitochondria through autophagy
Removal of damaged mitochondria is essential to preserve cellular bioenergetics and prevent detrimental events such as sustained mitoROS production
pro-apoptotic cytochrome c release or mtDNA leakage
The array of tools available to study mitophagy is very limited but in constant development
we developed a method to assess mitophagy flux using MitoTracker Deep Red in combination with lysosomal inhibitors
using the novel tandem-fluorescence reporter mito-QC (mCherry-GFP-FIS1101−152) that allows to differentiate between healthy mitochondria (mCherry+GFP+) and mitolysosomes (mCherry+GFP−)
we have developed a robust and quantitative method to assess mitophagy by flow cytometry
This approach has been validated in ARPE-19 cells using PINK1/Parkin-dependent (CCCP) and PINK1/Parkin-independent (DFP) positive controls and complementary techniques
we show that the mito-QC reporter can be multiplexed
especially if using spectral flow cytometry
to simultaneously study other cellular parameters such as viability or ROS production
we evaluated and characterized two prospective mitophagy inducers and further dissected their mechanism of action
we developed a protocol to measure mitophagy levels in the retina ex vivo
This novel methodology will propel mitophagy research forward and accelerate the discovery of novel mitophagy modulators
all pathways lead to mitochondria being engulfed into an autophagosome
which will later fuse with a lysosome to ensure degradation of its cargo
however this procedure is time- and resource-consuming
we describe a medium-throughput protocol to assess simultaneously mitophagy and mitochondrial mass by flow cytometry in vitro and in ex vivo retinal cultures and highlight the possibility of performing more complex assays and targeted screens by multiplexing with additional fluorescent probes
we present an optimized traditional and spectral flow cytometry protocol that provides sensitive simultaneous readouts of mitophagy and mitochondrial mass using tandem fluorescent reporters like mito-QC
This assay can be performed in vitro or using organotypic ex vivo culture and may be multiplexed to analyze other parameters such as reactive oxygen species (ROS) production or viability
ARPE-19 cells (Dunn et al., 1996) stably expressing the mito-QC reporter were generated by retroviral transfection in the laboratory of Dr. Ian G. Ganley as previously described (Montava-Garriga et al., 2020) and maintained in DMEM: F-12 medium (Gibco
21765037) supplemented with 15% FBS (Merck
and 1 U/mL Pen/Strep antibiotics (Gibco
15140122) in a humidified incubator at 37°C
To ensure stable expression of the reporter
selection was performed by adding 800 ug/mL Hygromycin B (Gibco
For flow cytometry or immunofluorescence experiments
5-6 × 104 cells per well were seeded in a 24-well plate the day before the experiment and left to adhere overnight
3 × 105 cells were seeded in a 6-well plate and left to adhere overnight
Treatments were added for the indicated timepoints at the following concentrations: 25 μM CCCP (Carbonyl cyanide m-chlorophenyl hydrazone; 25 mM stock in DMSO; Merck
1 mM DFP (Deferiprone; 125 mM stock in sterile H2O; Merck
10 μM Fisetin (10 mM stock in EtOH; Merck
50 μM Phenanthroline (50 mM stock in DMSO; Merck
20 mM SI (Sodium iodate; 333 mM fresh stock in DMEM; Merck
750 μM H2O2 (30% stock in DMEM; Fluka
Medium containing floating dead cells was collected in a standard plastic flow cytometry tube
Cells were washed with 500 μL of sterile PBS 1X to remove FBS residue and PBS was also collected
150 μL of 0.05% Trypsin (Gibco
11500636) was added per well and cells were incubated for 5′ in an incubator at 37°C and 5% CO2
Verify that cells have detached from the bottom of the well using a brightfield microscope
500 μL of FBS-containing complete medium were added to each well to inactivate Trypsin
Cells were collected in the flow cytometry tube and pelleted by centrifugation at 1,000 g for 5′
Supernatant was discarded and 100–200 μL of complete medium was added to each tube
cells were incubated with 1 nM MitoTracker Deep Red (Invitrogen
1 μM MitoSOX Red (Invitrogen
for 30′ min or 1:2,000 ViaDye Red (Cytek
CellROX Deep Red 5 μM (Invitrogen
C10433) for 15′ at 37°C and 5% CO2
Samples were resuspended by gentle shaking and
50 μL of 5X DAPI (4′,6-diamidino-2-phenylindole; Merck
reaching a final concentration of 1 μg/mL
there are far red-emitting nuclear dyes available such as TO-PRO-3 (Thermo Fisher
Tubes were kept in ice until flow cytometry analysis
C57BL/6J mice expressing the mito-QC reporter ubiquitously were generated and provided by Dr. Ian G. Ganley (McWilliams et al., 2018). Organotypic ex vivo retina culture was performed as previously described (Gomez-Sintes et al., 2017)
mice were sacrificed by cervical dislocation and both eyes were enucleated using curved forceps
a circular incision was made along the limbus and both cornea and lens were removed using fine forceps
The optic nerve was sectioned and the neuroretina was isolated by gently pulling from the RPE/choroid-containing eyecup
Retinas were cultured in flotation in a 24-well plate and maintained in DMEM supplemented with 1 μM Insulin (Merck
100 U/mL penicillin and 0.1 mg/mL streptomycin
Treatments were added for the indicated timepoints at the following concentrations: 25 μM CCCP (25 mM stock in DMSO)
1 mM DFP (125 mM stock in sterile H2O)
medium containing floating dead cells was collected in a standard plastic flow cytometry tube
Whole retinas were washed with 500 μL of sterile PBS 1X to remove medium residue and PBS was also collected
300 μL of 5 mg/mL Trypsin in HBSS (Gibco
14170-088) was added per well and retinas were incubated for 5–10′ in an incubator at 37°C and 5% CO2
900 μL of 10% FBS in HBSS were added to each well to inactivate Trypsin and retinas were dissociated by gentle pipetting using a p1000 tip (10–20 times)
Single cell suspension was collected in the flow cytometry tube and pelleted by centrifugation at 1,000 g for 5′
Supernatant was discarded and 200 μL of complete medium was added to each tube
Samples were resuspended by gentle shaking and 50 μL of 5X DAPI was added to each tube
Using a CytoFLEX S V4-B2-Y4-R3 Flow Cytometer (Beckman Coulter), at least 10,000 events were acquired using mCherry-PI (610/20), FITC-GFP (525/40), PB450-DAPI (450/45) and APC (660/10) emission filters. Gating of the viable cell population was performed as shown in Supplementary Figures S1, S3
Control cells were used to set the threshold of mitophagyhigh population defined by a mCherry/GFP ratio of ∼5%
FITC-GFP MFI and APC MFI were exported for downstream analysis performed using CytExpert v1.2 (Beckman Coulter)
Using a Cytek Aurora equipped with five lasers (Cytek Biosciences), at least 10,000 events were acquired. Similarly, control cells were used to set the threshold of mitophagyhigh population defined by a mCherry/GFP ratio of ∼5%. Wild-type, control cells and unstained cells were used to set the gates and spectra for every probe (Supplementary Figure S5)
Analysis was performed using SpectroFlo (Cytek Biosciences) for raw data unmixing and downstream analysis was performed using Flowjo v10.10 (BD Biosciences)
treated as indicated and fixed using 3.7% PFA containing 175 mM HEPES (Gibco
Cells were incubated with 1 µg/mL DAPI in PBS pH 7.0 for 15 min
washed 3 times with PBS pH 7.0 and mounted using or ProLong Diamond (Thermo Fisher
Images were captured with a 0.5-µm z-step using a Leica TCS SP8 confocal microscope equipped with a × 63 immersion objective
Membranes were developed using Pierce ECL Western Blotting substrate (Thermo Fisher
10308449) and x-ray film (AGFA) using a CURIX 60 Processor (AGFA)
Data shown in figures represents the mean ± s.e.m
of at least three independent experiments with biological replicates
Differences between groups were assessed using Student’s t-test (two groups)
one-way or two-way ANOVA (more than two groups) with appropriate post hoc tests
A P-value under 0.05 was considered statistically significant and exact
Raw data management was done in Microsoft Excel and statistical analyses were performed using GraphPad Prism 10.0 software
The ARPE-19 cell line originated from the retinal pigment epithelium of a healthy adult donor, and underwent spontaneous immortalization (Dunn et al., 1996). ARPE-19 cells stably expressing the mito-QC reporter were used for all experiments (Montava-Garriga et al., 2020) and mitophagy levels were defined as the population of cells with an increased mCherry/GFP ratio (Supplementary Figure S1)
indicating that mito-QC can also be measured using this novel technology
In addition, we also analyzed mitophagy in organotypic ex vivo retina culture from mito-QC mice (Figure 2A; Supplementary Figure S3). Replicating our findings in vitro, CCCP was able to induce mitophagy after 6 h of treatment but DFP was not (Figures 2B, C)
The mito-QC reporter can therefore be used as a medium-throughput readout to assess mitophagy and mitochondrial mass in vitro and ex vivo
indicating that their activity is PINK1/Parkin-independent
Phenanthroline and Fisetin are potent mitophagy inducers
(A) ARPE-19 mito-QC cells were treated with 10 μM Fisetin (Fis) or 50 μM Phenanthroline (Phen) for the indicated timepoints
quantification of % of mitophagyhigh population is shown
(B) Quantification of mitochondrial mass (GFP MFI)
(C) Immunobloting against proteins involved in receptor-mediated mitophagy (HIF-1α
(D) Immunoblotting against proteins involved in PINK1/Parkin-dependent mitophagy (phospho-UbiquitinSer65
All data are expressed as the mean ± s.e.m
P values were calculated using two-way ANOVA with Dunnett’s post hoc test
differentially modulates mitophagy and stimulates ROS production
ARPE-19 mito-QC cells were treated with 20 mM sodium iodate (SI) or 750 μM H2O2 for 24 h
(A) Simultaneous measurement of viability by nuclear exclusion assay using DAPI in SI-treated cells
Viable population does not incorporate the dye and are identified as DAPI−
(B) Quantification of % of mitophagyhigh population in SI-treated cells
(C) Quantification of mitochondrial mass (GFP MFI) in SI-treated cells
(D) Simultaneous measurement of reactive oxygen species (ROS) using CellROX Deep Red dye in SI-treated cells
(E) Simultaneous measurement of viability using ViaDye Red in H2O2-treated cells
Viable population does not incorporate the dye and are identified as ViaDye−
(F) Quantification of % of mitophagyhigh population in H2O2-treated cells
(G) Quantification of mitochondrial mass (GFP MFI) in H2O2-treated cells
(H) Simultaneous measurement of mitochondrial ROS using MitoSOX Red dye in H2O2-treated cells
P values were calculated using one-way ANOVA with Dunnet’s post hoc test
Spectral unmixing overcomes partial spectrum overlap and allows for simultaneous measurement of mito-QC and probes with similar fluorescence profiles
Both compounds showed no signs of cytotoxicity in vitro and warrant further exploration in diseases involving impaired mitophagy
Boosting mitophagy could therefore be a novel potential therapeutic strategy in the prevention and/or treatment of AMD
therefore represents an update to previously used methodology
cost and resources when compared to traditional microscopy analysis
Herein we provide a standardized protocol for mito-QC analysis using traditional and spectral flow cytometry
multiplexing with an array of intracellular probes and insight on mitophagy regulation using two inducers and models of oxidative stress
mito-QC reporter analysis by flow cytometry is a reliable and semi-high throughput method to measure mitophagy in vitro and ex vivo
The raw data supporting the conclusions of this article will be made available by the authors
Ethical approval was not required for the studies on humans in accordance with the local legislation and institutional requirements because only commercially available established cell lines were used
The animal study was approved by Margarita Salas Center for Biological Research Bioethics Comitee and Comunidad de Madrid (PROEX 154.3/21)
The study was conducted in accordance with the local legislation and institutional requirements
The author(s) declare that financial support was received for the research
Research in the PB lab is supported by grants 310030_215271 Swiss National Science Foundation (SNSF) and PID2021-126864NB I00 from MCIN
JJ-L holds a FPI fellowship from MCIN (PRE2019-088222)
CJ-G is supported by the University of Fribourg
We thank Ian Ganley for generating and providing the mito-QC reporter mice and mito-QC ARPE-19 cell lines; the animal facility (Angélica Horrillo
María Tijero) at the CIB Margarita Salas; the flow cytometry facility at the CIB Margarita Salas and University of Fribourg (Patricia Yagüe and Sarah Cattin
respectively); Beatriz Villarejo-Zori for advice on ex vivo experiments and all members of the Autophagy Lab for thoughtful discussions and support
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations
Any product that may be evaluated in this article
or claim that may be made by its manufacturer
is not guaranteed or endorsed by the publisher
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2024.1460061/full#supplementary-material
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; BNIP3L/NIX
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like; CCCP
Carbonyl cyanide m-chlorophenyl hydrazone; DFP
Loss of iron triggers PINK1/Parkin-independent mitophagy
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Phenanthroline impairs βAPP processing and expression
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Received: 05 July 2024; Accepted: 02 September 2024;Published: 11 September 2024
Copyright © 2024 Jiménez-Loygorri, Jiménez-García, Viedma-Poyatos and Boya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use
distribution or reproduction in other forums is permitted
provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited
in accordance with accepted academic practice
distribution or reproduction is permitted which does not comply with these terms
*Correspondence: Patricia Boya, cGF0cmljaWEuYm95YUB1bmlmci5jaA==
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In the rapidly growing wellness technology market, where design, user experience, and functionality converge, Scott Chaverri's story stands out. As the founder of Mito Red Light
a US-based company specializing in red light therapy devices
his journey showcases how a personal quest for healing led to the creation of a thriving business
His experience is not just one of innovation but also a testament to the importance of perseverance
and intellectual property protection in bringing revolutionary wellness products to market
Scott Chaverri’s journey began with his personal struggle as a young adult
only to discover the root of his problems: blue light exposure after sunset
This light bulb moment revealed that artificial lighting was disrupting his sleep
Turning to red light therapy - a treatment gaining recognition for its benefits to sleep
and overall well-being - Scott began to experience transformative results
With just a few minutes of red light therapy daily
and a significant improvement in his overall mood
Scott faced a challenge: red light devices were prohibitively expensive
making them inaccessible to the broader public
and beautifully designed red light therapy devices for everyone
bootstrapping the business while maintaining a corporate job
The company’s mission: to empower people to live healthier lives by combating the harmful effects of “junk light” - excessive exposure to artificial blue light that disrupts the body's natural rhythms
the energy powerhouses of the body’s cells
affordable red light and near-infrared therapy devices
Mito Red Light has grown into a company with 11 employees
The company’s success story stems from its dedication to creating not only effective products but also aesthetically pleasing designs that fit seamlessly into customers’ homes
The science behind Mito Red Light’s mission is rooted in the concept of photobiomodulation—using light to stimulate cellular function
Scott’s rationale is clear: humans evolved to spend much of their time outdoors
exposed to natural sunlight and its beneficial wavelengths
the vast majority of people spend most of their time indoors
According to the Environmental Protection Agency
the average American spends about 93% of their life indoors
leading to a deficiency in natural sunlight
Mito Red Light’s devices are designed to help users supplement their exposure to these beneficial wavelengths
offering a range of potential health benefits
which ranges from about 620 to 750 nanometers
penetrates the skin and tissues to stimulate cellular processes and promote healing
This wavelength is absorbed by mitochondria
boosting cellular function and regeneration
While research on red light therapy is still developing
it has garnered increasing interest from health professionals for its potential to address various physical and mental conditions
Mito Red Light’s customers have reported benefits such as improved sleep
and even enhanced hair growth from regular use of their red light therapy devices
“Red light therapy offers a way to address modern issues caused by our indoor lifestyle while promoting cellular health and overall well-being.”
While Mito Red Light’s success is grounded in science
Scott quickly learned that design plays an equally vital role
he approached product development from a purely functional standpoint
after releasing a black version of one of the company’s LED panels
he discovered the importance of aesthetics when customers overwhelmingly preferred the white version
leading to the discontinuation of the black model
His marketing team is now working closely with designers to ensure that each product meets high standards of both performance and design
prototypes will also be tested among their clients for design and visual appeal
This approach will involve gathering feedback to refine the products
ensuring that they are not only effective but also align with customers' preferences and home environments
exemplifies this balance of form and function
it demonstrates how thoughtful design enhances the user experience
“Our products are often displayed in our customers' homes
so making them as beautiful as they are functional is essential.”
Mito Red Light’s commitment to quality goes beyond aesthetics
Each product is designed to be durable and resistant to wear
with no planned obsolescence - ensuring that customers can use their devices for years without needing replacements
“Continuous improvement drives our innovation,” explains Scott
“We aim to offer long-term value to our customers
not just with performance but also with reliability and design.”
Scott recognized the importance of protecting the company's intellectual property portfolio
design protection became a particular focus
Safeguarding their unique designs from imitation was seen as crucial for maintaining a competitive edge and preserving their value
Mito Red Light aimed to ensure its creations stand out in a crowded market and that its investments in creativity and research are shielded from competitive threats
To effectively manage design protection, Scott consulted his attorney, Steven Jay Miller, the founder of IPath, who recommended The Hague System for the International Registration of Industrial Designs
Administered by the World Intellectual Property Organization
the Hague System offers a streamlined process for securing design rights in over 90 countries
It provides a cost-effective way to protect creations globally
avoiding the financial burden of defending designs in multiple jurisdictions while ensuring they are safeguarded against exploitation
Mito Red Light holds four active Hague registrations covering eight designs
underscoring their commitment to comprehensive design protection
This approach fosters innovation by providing a secure environment for the company to invest time and resources into developing new ideas without the fear of imitation
It also ensures they can reap the rewards of their innovations
Such protection not only benefits Mito Red Light directly but also enhances their competitive edge
driving the development of unique and improved solutions
this contributes to better products for consumers and reinforces their position as a leader in design innovation
“I can’t overemphasize the importance of internationally registering their product designs to my clients
Obtaining an International Design Registration allows them to file for protection globally in jurisdictions where their products will be manufactured or marketed by filing a single application
A recorded design registration places infringers on notice
WIPO’s standardized registration procedures save tremendous amounts of attorney time and clients’ money.”
WIPO’s Hague System provides a unique international mechanism for securing and managing design rights simultaneously in multiple countries or regions through one application
If you are interested in sharing your own Designs in Action story, illustrating how you’ve leveraged the Hague System to secure international design protection, we would love to hear from you! Contact Hague
21 November 2024 – The United Mitochondrial Disease Foundation’s (UMDF) venture philanthropy arm
a Netherlands-based clinical stage biopharmaceutical company discovering and developing therapies targeting primary mitochondrial disease (PMD)
Khondrion is currently preparing to initiate a Phase III study investigating the potential of its lead proprietary drug candidate
to treat adult patients with PMD due to the m.3243A>G mutation
the most common genetic defect causing multi-systemic PMD
which has an estimated prevalence of 4.4:100,000 impacting hundreds of thousands of patients worldwide
showing strong patient benefits from sonlicromanol in multiple outcome measures of global health
"We believe sonlicromanol holds incredible potential for treating primary mitochondrial disease which impacts hundreds of thousands of people worldwide," said Dr
UMDF's Interim Managing Director and Science and Alliance Officer
The diseases associated with this mutation are devastating and remarkably progressive
The approval of this therapy would meet an urgent and unmet therapeutic need.”
Jan Smeitink: “Patients with primary mitochondrial disease currently have no treatment options available to them
we see the great potential sonlicromanol may have on these patients
particularly on their most burdensome symptoms of chronic fatigue and muscle weakness
With the support and investment by the UMDF via The Mito Fund
we look forward to further progressing our clinical work on sonlicromanol at pace in our upcoming Phase III trial in adult patients with PMD.”
Like all investments made by The Mito Fund
the Khondrion consideration went through a rigorous review process by UMDF’s Venture Philanthropy Investment Committee
an advisory group consisting of world-class experts in the areas of mitochondrial disease
After receiving the committee’s recommendation
the investment was then approved by UMDF’s full Board of Trustees
there were several really attractive elements to the investment
sonlicromanol represents an innovative treatment for an underserved population
which shortens the runway to approval,” said Dr
“UMDF looks forward to partnering with Khondrion in advancing this investigational therapeutic in a patient-centric manner.”
The Mito Fund is UMDF’s most ambitious effort to date to ramp up the development of mitochondrial disease treatments and cures
The fund’s venture philanthropy model is designed not only to financially support the development of the next generation of mitochondrial disease treatments
but also to leverage UMDF’s experience and network to accelerate the development process and lower the risk associated with entry into the field for a wide range of investors and researchers
This is the second official investment for The Mito Fund
the fund announced an investment in Pierrepont Therapeutics
which is working on a preclinical proprietary intracellular enzyme replacement therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
Companies exploring the mitochondrial science space are encouraged to start a conversation about investment opportunities at www.themitofund.org
The United Mitochondrial Disease Foundation (UMDF) has built a global network of patients
and industry partners dedicated to fighting mitochondrial disease
UMDF is committed to a mission of funding the best science no matter where it is found in the world while at the same time providing critical education
and support-focused programs and services to patient families
Khondrion is a clinical stage biopharmaceutical company developing therapies for patients with primary mitochondrial disease (PMD)
brain-penetrant redox-modulator with anti-inflammatory properties
that targets key metabolic and inflammatory pathways underlying PMD
potentially disease-modifying drug candidates for mitochondrial disease in development
sonlicromanol has been tested in three clinical trials in patients with m.3243A>G PMD
as well as in the first wave of a 6-month Phase 2 study in children with genetically confirmed PMD and who suffer from motor symptoms
Sonlicromanol has been granted orphan drug designations for the treatment of MELAS syndrome (mitochondrial encephalopathy
Leigh disease and patients with maternally inherited diabetes and deafness (MIDD) in Europe
and for all inherited mitochondrial respiratory chain disorders in the US
It has also been granted a rare pediatric disease designation in the US for the treatment of MELAS
ICR Healthcare David Daley, Kris Lam, Tom DanielEmail: khondrion@icrhealthcare.com
UMDF / The Mito FundAndy Dearth, Director of Marketing & CommunicationsEmail: Andy.dearth@umdf.org
Metrics details
Targeting mitochondrial metabolism represents a novel approach in the discovery and development of anti-tumor drugs
Celastrol (Cel) is a naturally-derived small molecule from Tripterygium wilfordii with significant anticancer activities
we investigated the anti-tumor mechanisms involving mitochondrial metabolic reprogramming regulated by Cel in breast cancer (BRCA)
We showed that Cel potently inhibited the proliferation of triple-negative breast cancer cells (MDA-MB-231) and ER+ breast cancer cells (MCF-7) with IC50 values of 2.15 μM and 2.29 μM
for three times after tumor formation) significantly suppressed the tumor growth in syngeneic allograft and CDX breast cancer mouse models
Using activity-based protein profiling (ABPP) technology
we identified mitochondrial isocitrate dehydrogenases (including IDH2 and IDH3A
collectively referred to as mito-IDHs) as direct targets of Cel
We demonstrated that Cel significantly inhibited mito-IDHs mediated mitochondrial metabolism to induce the accumulation of metabolites α-ketoglutaric acid
and that Cel enhanced the interaction between DPYSL2 with IDH3A while promoting the accumulation of DPYSL2 within mitochondria of BRCA cells resulting in inactivation of JAK/STAT pathway and ultimately induced ferroptosis and apoptosis in cancer cells
this study elucidates a pharmacological mechanism by which Cel exerts its tumor-inhibiting effects through modulation of mitochondrial metabolism
it provides compelling evidence supporting Cel as a promising candidate for development as a small-molecule inhibitor targeting mitochondrial metabolism
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Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy
Targeting mitochondria metabolism for cancer therapy
Publisher Correction: In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer
IDH3alpha regulates one-carbon metabolism in glioblastoma
Effect of IDH3a on glucose uptake in lung adenocarcinoma: A pilot study based on [18F]FDG
promotes hepatocellular carcinoma migration and invasion through regulation of MTA1
Wild-type IDH2 is a therapeutic target for triple-negative breast cancer
Aberrant IDH3alpha expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis
Celastrol in cancer therapy: recent developments
Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum
Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1
Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis
Small-molecule MHC-II inducers promote immune detection and anti-cancer immunity via editing cancer metabolism
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data
clusterProfiler: an R package for comparing biological themes among gene clusters
Inhibition of Ca2+ release-activated Ca2+ channel (CRAC) by curcumin and caffeic acid phenethyl ester (CAPE) via electrophilic addition to a cysteine residue of Orai1
DYNLT1 promotes mitochondrial metabolism to fuel breast cancer development by inhibiting ubiquitination degradation of VDAC1
Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species
Exploring novel strategies to improve anti-tumour efficiency: The potential for targeting reactive oxygen species
CRMP2 is a therapeutic target that suppresses the aggressiveness of breast cancer cells by stabilizing RECK
DPYSL2 interacts with JAK1 to mediate breast cancer cell migration
Mitochondrial metabolism as a target for cancer therapy
Dihydropyrimidinase like 2 promotes bladder cancer progression via pyruvate kinase M2-induced aerobic glycolysis and epithelial-mesenchymal transition
Identification of multiple organ metastasis-associated hub mRNA/miRNA signatures in non-small cell lung cancer
Dihydropyrimidinase-like 2 can serve as a novel therapeutic target and prognostic biomarker in acute myeloid leukemia
Protein-protein interaction prediction with deep learning: a comprehensive review
JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation
Interaction between MUC1 and STAT1 drives IFITM1 overexpression in aromatase inhibitor-resistant breast cancer cells and mediates estrogen-induced apoptosis
Celastrol as an emerging anticancer agent: current status
IFNgamma enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma
IFNgamma-mediated repression of system xc(-) drives vulnerability to induced ferroptosis in hepatocellular carcinoma cells
Molecular mechanisms of anti-cancer bioactivities of seaweed polysaccharides
Chinese herbal medicines for prostate cancer therapy: From experimental research to clinical practice
Download references
China Academy of Chinese Medical Sciences for assistance with the generation of confocal microscopy data
The schematic diagram was drawn by Figdraw
This work was supported by National Natural Science Foundation of China (82404657
U24A20798); the Natural Science Foundation of Shenzhen for Basic Research (JCYJ20240813104209012) and Guangdong Provincial Enterprise Joint Fund for Basic and Applied Research Foundation (2024A1515220163); Guangdong Basic and Applied Basic Research Foundation (2023A1515110710); the National Key Research and Development Program of China (2020YFA0908000
2022YFC2303603); the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (CI2023D003
CI2023E005TS09); the Shenzhen Medical Research Funds (B2302051); the Establishment of Sino-Austria “Belt and Road” Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research (2020YFE0205100); the CACMS Innovation Fund (CI2023E002
ZG2024001-05); the Fundamental Research Funds for the Central Public Welfare Research Institutes (ZZ13-ZD-07
These authors contributed equally: Qiao-li Shi
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs
Guangdong Provincial Clinical Research Center for Geriatrics
Shenzhen Clinical Research Center for Geriatrics
Southern University of Science and Technology
Dongguan Maternal and Child Health Care Hospital
Postdoctoral Innovation Practice Base of Southern Medical University
National Clinical Research Center for Chinese Medicine Cardiology
China Academy of Traditional Chinese Medicine
Innovative Vaccine and Immunotherapy Research Center
The Second Affiliated Hospital Zhejiang University School of Medicine
All authors contributed to data acquisition and analysis
SJQ performed bioinformatics analysis of the clinical data
and JZZ performed the mice experiment and LC-MS/MS assay
LH and QLS wrote the original draft of the paper
The authors declare no competing interests
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law
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DOI: https://doi.org/10.1038/s41401-025-01548-0
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Mito Pereira led the PGA Championship at Southern Hills going into the final round
Pereira showed no cracks in his golf armor through 54 holes
It didn’t work out on that Sunday with a 5-over 75 that included a double bogey on the 18th hole
dropping the Chilean from a one-shot lead to missing out on the playoff with Zalatoris and Justin Thomas by a shot
Pereira cashed in by accepting a position with LIV in 2023 and playing for Torque
which includes fellow countryman Joaquin Niemann
Sebastian Munoz of Colombia and Carlos Ortiz of Mexico
Mito Pereira and captain Joaquín Niemann of Torque GC attend a press conference during the practice round before the start of LIV Golf Mexico City at Club de Golf Chapultepec on Wednesday
Pereira sees himself in the "drop zone," or in a position to lose his playing status at the end of the season if he doesn’t find his game
The 30-year-old finished eighth in the LIV Golf League rankings in his first year
including a runner-up finish at The Greenbrier
posting only one top-10 and barely keeping playing privileges
Pereira has not registered a round under par
recording 36-over par in the nine-round period
and has earned only 0.6 points toward keeping his card this season
Niemann currently leads the rankings with 124.66 points
“You can never work too much,” Pereira said before the LIV Mexico City event
so you'll have plenty of opportunities
so don't take just one bad week or one bad tournament to ruin you
You've just got to keep working and try to visualize your success.”
about the league not being more like the PGA Tour
but one issue that is only LIV’s is the teams' ability to drop players and get someone else to replace that player
After seeing Pereira’s play in 2024
Mito Pereira (CHI) chips onto the 18th green during Sunday’s Final Round of the PGA Championship 2022 at Southern Hills
Niemann is instead stuck with his fellow countryman
Pereira would be sent down or put on waivers; these are not options for any LIV team
it needs to be nimble and able to make roster changes whenever necessary
This is one of the significant flaws of LIV Golf
You can’t claim to be a team sport and not act like one
Element Electronics, one of the largest TV assemblers in America, announced that Element TVs are newly available for the RV market from MITO Corporation
With MITO’s extensive distribution network
the partnership expands the brand’s reach to even more customers
offering smart TVs for on-the-go entertainment at an exceptional value
Element said it is committed to delivering high-quality
Element has been the only major TV company to assemble in the U.S.
all products come with a two-year limited warranty with product registration
“We’re excited to partner with MITO Corporation to bring Element TVs to the RV market,” said Vlad Kazhdan
“Our commitment to assembling TVs in America underscores our dedication to quality and supporting American jobs
We look forward to working with MITO to bring Element to the expanding RV and outdoor market
offering customers entertainment for family adventures and travel experiences.”
appliances and more all designed for simplicity and affordability
Element has solutions for all types of recreational vehicles
MITO Corporation currently has the Element 32” HD Smart Xumo TV
Element 40” FHD Smart Xumo TV and the Element 50” 4K Smart Xumo TV in stock and available to order
the new project that brings Turin closer to Milan
strengthening the ties between the two cities during the Fair
Promoted by Unione Industriali Torino and the Torino Chamber of Commerce
MiTo Design Connections aims to foster relationships between companies and offer reception and hospitality services to exhibitors and professional visitors
This is a unique opportunity for everyone taking part in Milan design week
with the opportunity to stay in Turin and discover its artistic
The high-speed train makes it possible to reach Milan Rho Fiera by train from Turin Porta Susa station in just 35-40 minutes
MiTo Design Connections offers a selection of hotel facilities to ensure a comfortable stay for participants
Turin is also an ideal destination to experience design in a new perspective
offering opportunities for organizing corporate events in exceptional locations.
Conceived by architects Laura Bongiovanni and Elena Ferrero
the project is supported by Salone del Mobile.Milano
the Tourism and Culture Group of the Turin Industrial Union
with the contribution of the Turin Chamber of Commerce and the patronage of the Piedmont Region
Find out more and have a unique experience between Turin and Milan during one of the most important events in international design
Among the products presented at the last Salone del Mobile.Milano
many companies stood out for their increasingly integrated approach to managing resources
Calia Italia’s is a family history closely bound up with the values of its region
The leading international furnishing and design industry event will be back at Fiera Milano Rho from 21st to 26th April next year
LoadingHole-in-one! Mito Pereira makes ace in Hong KongTorque GC's Mito Pereira makes an unreal ace at the LIV Golf Hong Kong 2025.
The Miami Dade College softball program is in the midst of a resurgent season
the Lady Sharks are showing some bite with a 26-10 record
The biggest contributor has been freshman Caroline Mito
who leads the team in batting average (.470)
the shortstop prefers to remain hyper focused on her team’s turnaround
and I’m very happy with our performance,” Mito said
“Our team is strong and we have a lot of potential to keep winning.”
That laser focus on the game has always been there for the Brazilian-born Mito
She picked up the sport in her homeland when she was seven
“My decision to start playing was influenced by my grandparents,” she said
to help with concessions during tournaments.”
Mito played softball for two years before shifting to baseball for six years while she played for her hometown team in Londrina
Mito won a bevy of accolades for her batting and fielding and back-to-back championships in 2018 and 2019
“She’s been playing some really good softball,” De Agüero said
and just likes to come out and play ball.”
which includes four other Brazilian players
have noticed her on-field and off-field contributions
“Caroline is known for her incredible skills on the softball field
and it’s very clear that she’s always had a natural talent for the game,” said Lady Sharks outfielder Mayah Bostic
“It’s not just her performance during games that make Caroline stand out
it’s also her dedication to practice and genuine kindness she shows to her teammates.”
including six games with at least three hits
15 during an 8-2 win versus Chipola College
Mito collected four hits (including a double and triple)
a stolen base and scored two runs that day
“This sport teaches me so much,” Mito said
“It’s a team sport; it requires you to have good relationships and unity because that reflects on your performance on the field.”
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is an architecture major in The Honors College at Kendall Campus
who graduated from Florida Christian School in 2023
will serve as a sports writer for The Reporter during the 2024-2025 school year
Copyright © 2025 The Reporter: The Student Newspaper at Miami Dade College
Bandai Namco Entertainment America added the third DLC to its Sword Art Online: Fractured Daydream game on April 24
The game adds Sachi from the Hollow Fragment Arc as a support and Philia from the Aincrad Arc as a rogue
The company also announced the fourth DLC for the game
"Worlds Beyond IV: Symphony of a Dazzling Dawn," which will launch on September 30 with Mito and Kat Knight Alice as playable characters
2 holders can play as these characters now
The game features co-op raids for up to 20 players
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The chief executive of StrongRoom AI has denied confessing to “willful fraud” in a board meeting with two of the collapsed start-up’s biggest investors last month
The pharmacy software developer is in the midst of a complicated dispute with its biggest investor, Sydney-headquartered venture capital firm EVP, which is attempting to claw back more than $10 million it invested earlier this year. EVP has accused StrongRoom of misrepresenting its financial position by claiming government grants
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a leader in innovative nutrient delivery systems
proudly announces the launch of its new Mito Cocktail Patch
designed to support mitochondrial function for individuals with Autism Spectrum Disorder (ASD)
this groundbreaking patch offers a convenient
effective solution to deliver essential nutrients that play a vital role in mitochondrial health
Addressing the Link Between Mitochondrial Dysfunction and Autism
Emerging research highlights the connection between mitochondrial dysfunction and ASD
Studies show that mitochondrial issues are common in individuals with ASD
PatchMD’s Mito Cocktail Patch is formulated to deliver nutrients known to support mitochondrial function
Science-Backed Ingredients for Mitochondrial Support
The Mito Cocktail Patch features a powerful combination of key ingredients
This advanced formula is designed to provide targeted nutritional support without the need for pills or powders
offering an easy-to-use transdermal solution that bypasses the digestive system for optimal absorption
“Our goal at PatchMD is to create products that make a real difference in people’s lives,” said Earl Hailey
we’re addressing a critical need for individuals with ASD who may struggle with mitochondrial dysfunction
By providing these vital nutrients in a patch form
we’re ensuring better absorption and easier compliance.”
Learn More About Mitochondrial Dysfunction in ASD
To understand the connection between mitochondrial dysfunction and ASD
The Mito Cocktail Patch will be available for purchase starting April 1st
PatchMD specializes in cutting-edge transdermal patch technology
offering a wide range of vitamin and nutrient solutions
With a focus on bypassing the digestive system
PatchMD products provide maximum absorption and convenience for individuals of all ages and health backgrounds
Mito Material Solutions (Indianapolis
U.S.) a specialty chemical company featuring a verified functional graphene additive, is currently engaged in two initiatives focused on bringing graphene’s technical properties to energy storage applications — specifically electric vehicle (EV) batteries
While the company says these particular projects will not involve composite materials
Mito is interested in composites partners going forward
Graphene’s properties — mechanical strength and flexibility
chemical stability and capacitance contribution — make it a useful addition for battery technologies
U.S.) are collaborating to create a multifunctional adhesive for EV batteries using advanced 2D materials
product while taking into account market dynamics
including pricing and regulatory requirements
Mito is also participating in the 2024 cohort of ChargeUp by NENY
a technology ecosystem in upstate New York supporting R&D
technology translation and workforce development to advance the domestic battery and energy storage industry. ChargeUp is an accelerator dedicated to supporting battery and energy storage startups and is designed to propel domestic battery industry innovation
This program exemplifies how targeted support and strategic collaboration can catalyze profound advancements in battery and energy storage technologies
“The two projects enable Mito to pave the way for wider adaptation of these energy storage platforms
we are developing multifunctional solutions that offer better performance
higher safety and lighter weight in battery packaging
faster charging and better low-temperature performance for battery cells,” notes Mahdi Ghazizadeh
“The AD project focuses on safety concerns and reducing vehicle weight and ChargeUp is addressing inconveniences that come with use of batteries and EV hampering their expansion
Together these efforts will enhance energy storage technologies using graphene’s potential and demonstrating Mito’s commitment to sustainability and innovation.”
Mito Material Solutions (Indianapolis
One of the biggest opportunities for composites in BEVs is battery enclosures — covers and trays that hold and protect the frames and battery cells within an EV
switching to composite battery enclosures can also enable a host of other benefits such as more complex geometries
greater durability and — with specific formulations — improved flame resistance/fire containment
Read “Composites end markets: Automotive (2024),” for more info.
Volume 10 - 2022 | https://doi.org/10.3389/fenrg.2022.941606
This article is part of the Research TopicPerspectives for Marine Energy in the Mediterranean Area Volume IIView all 10 articles
Availability of detailed short-term forecasts of the ocean main characteristics (circulation and waves) is essential for a correct management of the human activities insisting on coastal areas
These activities include the extraction of renewable energy
and will play an important role in the context of future blue growth
The present work describes the implementation of a new ocean operational system
that provides daily 5 days forecasts of the Mediterranean Sea circulation
Distinctive features of this system are the inclusion of the main effects of the tidal forcing
both local and propagating from the Atlantic
The horizontal resolution is of 1/48° (about 2 km) in most of the computational domain
and is smoothly increased (down to few hundred meters) in key passages
such as the Gibraltar Strait and the Turkish Straits
to correctly resolve the complex local dynamics
Initial and boundary conditions for MITO are taken from the reference European operation model of Copernicus
which covers the Mediterranean Sea with a uniform resolution of 1/24°
A thorough validation of the new system is performed
whose results are compared with in situ and remote observational data (sea surface temperature
temperature and salinity profiles by floats
available through the Copernicus portal) using the same large-scale metrics applied in the validation of the Copernicus operational model
MITO results are generally found in very good agreement with the observations
despite the fact that the model does not make explicit use of data assimilation
We also give examples of the capability of the model to correctly describe complex local mesoscale dynamics
and point out aspects that need to be improved
which will be addressed in a future upgrade of the operational implementation
and in a few coastal sites in the Aegean Sea
Another font of potential interest relies on the exploitation of salinity gradients due to river discharges
but the technologies in this field have not yet reached a mature stage
It can be easily understood that activities aimed at harvesting energy from these fonts do require a detailed knowledge of the marine environment
both in terms of circulation and sea state (waves)
Multidecadal simulations of the past climate
are necessary to assess the resources and their variability
and consequently to choose the best technological solutions
the optimization and management of the devices being deployed requires the availability of detailed and reliable short-term forecasts
which contains the Proceedings of the 9th EuroGOOS Conference (EuroGOOS is the European branch of GOOS
the intergovernmental Global Ocean Observing System)
devoted to “Advances in operational oceanography: expanding Europe’s ocean observing and forecasting capacity”
Current operational ocean forecasts are mainly “deterministic”; they are based on a single high-resolution simulation that starts from the “best” possible initial condition
an initial three-dimensional sea state that is as close as possible to the available observations
by constraining the numerical models with new observational data that have become available
through sophisticated numerical techniques of data assimilation analogous to those initially developed in the atmospheric context
Models for the ocean forecast and reanalysis are being constantly improved, building on the advances in the numerical modelling techniques, on the developments in the field of high-performance computing, and on the growing amount of observations, both in-situ and from satellite. At European level, most of these observations are collected by the Copernicus Marine Environment Monitoring Service (CMEMS; https://marine.copernicus.eu/it)
the marine component of the Copernicus Programme of the European Union
which makes these data freely available to the interested research community
The CMEMS repository also contains state of the art modelling products for the European seas
which can be used as reference in the development of new products
and for the nesting with regional models of higher spatial resolution
together with those that are the subject of the present paper
have been carried out at ENEA (the National Agency for New Technologies
Energy and Sustainable Economic Development)
in the context of a long-term agreement with the Italian Ministry of Economic Development (MISE) that has promoted research activities in the energy sector
nonlinear effects of the tides on the dynamics were present in several regions of the Mediterranean Sea
This means that tidal effects cannot be linearly superposed a posteriori; they need to be included in forecasting models at basin scale to have a correct description of the dynamics
to provide the correct boundary conditions to higher resolution regional models
We shall assess the performance of MITO by comparing the results of the forecasts of the year 2020 with in situ and remote experimental observations (sea surface temperature, altimeter data, temperature and salinity profiles by floats, tide-gauge measurements) available through CMEMS. The comparison will make use of the same large-scale metrics applied in the validation of the reference Mediterranean operational model of CMEMS (NEMO; Clementi et al., 2021)
The current version of the model produce forecasts at 1/24° of horizontal resolution with 141 vertical levels and includes current-wave interactions
The main features of the model and of its operational implementation are described in MITO system: Main model features and operational details Section
whereas Sections 3-6 are concerned with the system validation and the analysis of some interesting aspects of the 2020 Mediterranean circulation
Sea surface temperature Section focuses on the sea surface temperature
and Hydrological profiles Section on the hydrological properties
Circulation Section examines the large-scale surface circulation patterns produced by the system
and gives some examples of the model capability of capturing small-scale mesoscale features
and Conclusion Section presents the conclusions
indicating aspects that should be examined to further improve the skill of the system
K1) have been prescribed inside the computational domain
The model is initialized and forced at the Atlantic boundary by temperature and salinity data from the NEMO-CMEMS model (details are given in MITO system: Main model features and operational details Section of Palma et al., 2020)
also objective analysis of the SST is used to correct the surface heat fluxes]
We found that this is sufficient to keep the forecasts close to the observations
although future developments envisage the implementation of assimilation procedures
The whole operational chain is repeated every week
The operational forecasting system produces every day hourly datasets of currents (3D)
and hydrological variables (temperature—T - and salinity—S; 3D)
a format widely used in the ocean modelling community
The validation makes use of the first day of each forecast
The following data from CMEMS are used to assess the skill of the system:
• Sea Surface Temperature (SST) measured from satellite; product SST_MED_SST_L4_NRT_OBSERVATIONS_010_004, which is provided on a regular grid at 1/16°, and represents the reconstruction of the daily SST based on the data measured at 0:00 UTC using various types of sensors (Buongiorno Nardelli et al., 2013);
• Vertical profiles of temperature and salinity obtained from Argo floaters (product INSITU_MED_NRT_OBSERVATIONS_013_035; data provided by the European Research Infrastracture Consortium);
• Absolute Dynamic Topography (ADT) measured from satellite altimeters, and corresponding geostrophic reconstructions of the circulation [product SEALEVEL_EUR_PHY_L4_MY_008_068; data processed by SSALTO/DUACS and distributed by AVISO+ (https://www.aviso.altimetry.fr) with support from CNES (Centre national d'études spatiales; France)];
• Sea level data from coastal tide-gauge stations (product INSITU_MED_NRT_OBSERVATIONS_013_035);
• Turbidity data from satellite (product OCEANCOLOUR_MED_OPTICS_L3_REP_ OBSERVATIONS_009_095)
The comparison between the model forecasts and the observations has been done for the whole 2020, for the eight regions shown in Figure 2, which are considered as dynamically coherent. The operational system has been validated via the same method adopted for the CMEMS forecasting system (Clementi et al., 2021)
which makes use of the bias between the predicted and observed values
and of the corresponding root-mean-square deviation (RMSD)
as the main statistical metrics to assess the reliability of the relevant predicted variables
Regions on which statistical analyses for the SST
SSH and the hydrological variables have been carried out
The comparison between modeled and observed daily series of SST (values taken at 00 UTC for both) for the eight regions is shown in Figure 3
There is generally a good agreement between model data and observations
even though in some regions the model SST underestimates the observed one in the second half of the year
FIGURE 3. Comparison between time series of SST from MITO (black) and from satellite measurements (red), in the eight regions defined in Figure 2
Note that the MITO data are those from the first day of each forecast
The corresponding bias and RMSD values are reported in Table 1
The best agreement is found in the Aegean Sea (7) and the Levantine basin (8)
Discrepancies can be attributable to deficiencies either in the data (L4 data making use of climatologic values to fill missing data) or in the forecasts
as a consequence of the approximations implied by the use of vertical mixing parameterizations and bulk formulas
Bias and RMSD of the SST [°C]–(MITO vs
The SST diurnal Cycle for Mediterranean Basin Gulf of Lion and the Southern Tyrrhenian sea
The vertical profiles of temperature and salinity produced by the model have been compared with Argo profiles The number of available profiles for 2020 is 2,993. These profiles are quite regularly distributed over the period from March to December; their spatial distribution is displayed in Figure 5
the corresponding modelled one was extracted at the nearest grid point and output time
Spatial distribution of the Argo profiles available in 2020 (period March-December)
The average bias and RSMD for temperature and salinity are reported in Table 2
for nine reference layers in the first 2000 m of the water column
In the first 30 m model temperatures are lower than those observed
consistently with the results obtained for SST (Section 2.2)
the bias is slightly higher and changes sign
Model salinity is generally lower than the observations in the surface layers
Bias (MITO-observation) and RMSD for temperature (in °C) and salinity (psu)
The monthly biases computed for temperature (A) and salinity (B) are shown in Table 3
The temperature bias exhibits moderate seasonal variability; it is higher in spring and summer and quite low in December and March
The corresponding values for salinity do not indicate significant variations along the year
Bias (MITO-observation) for temperature (A) and salinity (B): monthly variability
The nine reference layers considered are indicated in the first column
The annual averages of the surface circulation (30 m of depth) for the western and eastern basins are shown in Figure 6 (upper panels)
and compared with the average geostrophic flow reconstruction by AVISO (lower panels)
It can be seen that the model reproduces all the well-known circulation features of the western basin
the cyclone-anticyclone dipole in the north Tyrrhenian
the anticyclonic region in the south of the Ionian
and the cyclonic gyre of the south Adriatic
The model features are in very good agreement with those present in the average geostrophic flow
Currents tend to be stronger in the model circulation
because the model resolution is much higher than that of the altimeter maps
and we can consequently resolve mesoscale dynamics that are not well captured in the latter
the model includes ageostrophic dynamics induced by nonlinear advection and wind-driven dynamics that are missing in the altimetric reconstruction
There are also local details not resolved in the average geostrophic reconstruction
that originates in the Messina Strait (the very narrow passage between the eastern tip of Sicily and the western tip of Calabria
in the southern Italy) and borders the eastern coast of Sicily
Average 2020 circulation in the western and central Mediterranean
MITO circulation at 30 m of depth in the left panels; geostrophic reconstruction from altimeter data (AVISO) in the right panels
Results for the eastern Mediterranean are also very good
Here we recognize the Ionian current that enters the Levantine and flows cyclonically along the coasts of the basin
forming large meanders including mesoscale structures
The model also reproduces well the cyclonic region represented by the gyre of Rhodes and the anticyclonic gyres such as Mersha Mathrut
for the years 2018 (A) 2019 (B) and 2020 (C)
with the corresponding geostrophic circulations superimposed
The anticyclonic cell still present in the northern Ionian in 2018 is rapidly destroyed
An example of the effects of high resolution is given in Figure 8
where we compare the average circulation of July 2020 in the Gulf of Lion
produced by MITO (b) with the July average of the ADT in the area
with the corresponding geostrophic circulation superimposed (a)
Average July surface circulation in the area of the Gulf of Lion: (A) ADT (colors)
with a geostrophic reconstruction of the circulation superimposed (AVISO
satellite data); (B) MITO currents at 10 m; (C) map of K490 (coefficient of light extinction at 490 nm) measured from satellite
The model surface circulation is very similar to that derived from ADT data
The main feature in both fields is a westward coastal current
with a wide cyclonic circulation on the offshore side
This current is part of the wide cyclonic cell present in the northern portion of the western Mediterranean (Ligurian-Provençal basin)
The model field has more details in the inner portion of the gulf
Indications of the presence of these small-scale structures can be found in the turbidity map (K490; data from the CMEMS portal) of July 18th
The image shows the presence of two coastal plumes in the inner part of the gulf
The westernmost plume bifurcates while heading towards south
with a branch that veers towards the coast
exactly in the region in which is the boundary of a small coastal anticyclone present in the model map
This small structure could not be resolved in the altimeter maps
the small eastern branch may be consistent with the presence of the anticyclonic pole of the dipole previously noted
which corresponds to the outflow of the Rhone river
but then gets trapped by the westward current; the main branch veers towards south-west
bordering the wide cyclonic circulation present both in the ADT and model maps
this example indicates that the model is indeed capable of capturing mesoscale structures with sizes of few tens of kilometers
for experimental observations of the dynamics in the area)
the map of temperature shows the presence of a cold tongue that appears to originate in the southeastern corner of the Tyrrhenian Sea
Another interesting feature revealed by the temperature map is the presence of a wave-train that propagates towards south-east in the Ionian Sea
MITO maps of circulation and temperature at 25 m of depth
in a wide region around the Messina Strait
The maps are taken from the website (climaweb.casaccia.enea.it/mito) where daily forecast data from the operational system are made available for visualization purposes
The sea surface elevation predicted by the model was compared with the AVISO altimetric data
which integrates data from all the available altimeters on board of different satellites
to yield ADT maps covering the Mediterranean Sea and part of the Atlantic and of the North Sea
at a uniform spatial resolution of 1/8° (about 14 km)
We have compared the weekly series of modelled elevation anomalies (with respect to the annual mean) to the corresponding series of mean ADT anomalies
because spectral analysis of the ADT time series shows no significant component with periods below 7–10 days
A quantitative measure of the agreement between the observed and modelled elevation is provided by the map of the pointwise time correlation between the two time series, which is displayed in the top panel of Figure 10
In the lower panel of the same figure is the map of the 2020 ADT error obtained from AVISO data
The figure shows that the correlation is high (about 0.6 or more) in most of the basin
located along the paths of the main currents systems (Algerian Current
This indicates that significant high frequency mesoscale variability associated with these currents is not fully captured by the altimeter observations
It should also be noted that some regions of low correlation correspond to regions with higher values of the ADT error
We finally note that another possible reason for low correlation is that the model does not include the steric component
the agreement with the observations can be considered as satisfactory
(A) SSH time correlation map between MITO and AVISO data
(B) AVISO error map for 2020 (units are in cm)
Table 4 shows regional averages (over the eight regions defined in Figure 2) of the RMSD and of the time correlation
since lower values of the RMSD and higher values of the correlation are found in the eastern basin
The RMSD values are just a little higher than the typical values for the Copernicus operational model
where the comparison between observed and simulated values was made along the satellite tracks
RMSD between the free surface of MITO and AVISO data (SSH anomaly)
The predicted sea level heights were compared with the tide gauge measurements available for 2020 (55 stations, see left top panel of Figure 11)
The 2020 observations are concentrated in the western Mediterranean and all along the Italian coasts
Comparisons were made using the model grid point closest to the station
Left top panel: tidal stations for which elevation data are available for the year 2020 (not always with continuous coverage)
The other panels show histograms of the correlation coefficients between model and observed data
for the four seasons (right) and January sea surface elevation time series at four stations (San Benedetto del Tronto
The other panels of Figure 11 show histograms of the correlation coefficients between model and observed data
for the four seasons; in most of the cases the coefficients are higher than 0.85
considering that the model grid points can be quite far from the stations
and that the local bathymetry is not resolved with great detail
we show in the left lower panels of the figure the comparison between the time series of measured and observed elevation in four of the stations
for the month of January in SanBenedetto del Tronto and Sciacca
The tidal behavior has been thoroughly investigated in Palma et al. (2020)
where it has been shown that the model reproduces both the barotropic and the baroclinic tide very well
It was also shown in that work that tides significantly modulate the transport
not only through the Strait of Gibraltar and the Strait of Sicily
but also through the Corsica Channel and the Strait of Otranto
The tidal effects also modify some characteristics of the circulation inside the basin; in some cases
topographic waves are excited and get trapped by the bathymetry
producing diurnal rotations of the currents
Examples of this phenomenon have been found in the Sicily Channel (on the Adventure Bank and on the Malta Plateau)
in the Corsica Channel and in the Strait of Otranto
in different areas of the basin (Channel of Sicily
spectral analysis of the average kinetic energy reveals the presence of spectral peaks corresponding to periods of approximately 8 and 6 h
which can be interpreted as harmonics (overtides and compounds) of the diurnal and semi-diurnal tide components
We have found similar results analyzing the 2020 forecasts
the mean kinetic energy power spectrum (not shown) for the region over the Adventure Bank shows dominant diurnal components
which are accompanied by significant semidiurnal components
and also by quite strong peaks corresponding to nonlinear harmonics (periods of 8 and 6 h)
We have described the main features of MITO
a new operational system for the forecasting of the Mediterranean circulation that is running since 2018
and performed a detailed evaluation of its performances
by comparing the forecasts of the year 2020 with a variety of experimental data
The model-data comparison revealed that the hydrological structure and the circulation are generally in good agreement with the observations
The model was also found to correctly reproduce robust mesoscale structures
and the tide-induced sea level variability in coastal areas
This indicates that the MITO system could be successfully used to nest higher resolution coastal models
and will be the object of future development
The first naturally concerns the inclusion of data assimilation
which could improve the quality of the initial conditions
We have found that the surface temperature shows a larger bias (albeit generally well below 1°C) during the summer phase
including for example the quality of the atmospheric forcing
especially for what concerns the short-wave radiation
which is the component of the total heat flux that modulates the diurnal variability of the SST
Other errors could contribute to the cold bias
such as atmospheric forecast errors due to a bad cloud cover representation or to numerical schemes
Note also that the diurnal SST cycle reproduced by the model is in qualitative agreement with the observation
Another issue that could be interesting to consider is the fact that the extinction coefficient of short-wave radiation
may instead have seasonal and regional variability
Satellite products could be of help in addressing this issue
Salinity in the surface layer has also been found to have a bias with respect to experimental data in some regions
indicating that the components of the E-P-R budget should be further examined to improve the agreement with the observations
The inclusion of additional tidal components could also be envisaged
to have a more complete representation of the tidal forcing
thanks to its high resolution and to the capability of describing the linear and nonlinear dynamics induced by tidal forcing
may represent a useful tool in support of a wide spectrum of applications focusing on coastal areas
We finally note that the archive of short-term forecasts produced through the years
high-resolution description of the evolution of the Mediterranean dynamics
will allow in the future for the investigation of the basin variability on time scales of climatic interest
Such archive could also be used as a training set for machine learning applications
for the exploration of alternative forecasting approaches
All the authors contributed to writing the paper
The authors gratefully acknowledge the financial support from MISE, and from the EU-CEF DYDAS (Dynamic Data and Analytic Services) Project (https://www.dydas.eu/)
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Received: 11 May 2022; Accepted: 28 July 2022;Published: 26 August 2022
Copyright © 2022 Napolitano, Iacono, Palma, Sannino, Carillo, Lombardi, Pisacane and Struglia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use
*Correspondence: E. Napolitano, ZXJuZXN0by5uYXBvbGl0YW5vQGVuZWEuaXQ=
†These authors have contributed equally to this work
The Alfa Romeo Mito was the Biscione's first and only B-segment car
the small SUV born as the Milano and available with both mild hybrid and electric powertrain
Many see connections between the two models
with the Junior representing the direct successor to the Mito
Argentine designer 'father' of the small car produced from 2008 to 2018
he told our colleagues at Motor1 Argentina some time ago
Díaz has in fact revealed how at the time an Alfa Romeo Mito cabrio was designed and built as a concept
with a retractable canvas roof and four seats
The Argentinean designer told the story on his social profiles:
there was a project for a Mito Cabrio
but (Sergio) Marchionne (CEO of Fiat Chrysler Automobiles at the time
Marchione's vision went elsewhere and was very broad
There was not enough money to complete the range. Alfa 's problem was always marketing: the SUV Kamal was ready for production in 2006
but the project was cancelled thinking that the SUV trend was over."
An Alfa Romeo Mito Cabrio would have been able to compete with rivals such as the Mini Cabrio
the DS 3 Cabrio and even larger models such as the Audi A3 Cabrio.
we quote what Diaz told Motor1 Argentina during an interview last April
Alfa Romeo needs it: it is positioned in a segment that Alfa Romeo must preside over
doing it on a platform already used by Peugeot, Opel, Jeep and Fiat cuts production costs a lot
But you have to be careful about two things: this is a segment that the Chinese are entering very strongly in Europe and around the world
with vehicles equipped with better technology than the Europeans
Here I am not just talking about Alfa Romeo products or Stellantis
I am talking on a European level: the Chinese have better technology
The success or otherwise of a car is decided by the market
The Mito was a smaller car that could attract future Alfisti
I don't know if the typical customer of the Junior is the same as in the days of the Mito
Alfa Romeo is a brand that does not need ornamentation
It is a car that must be defined by the Trilobo
the central grille and the two side air intakes
On the Junior the Trilobo is almost blurred
You have to see it on the road: the front has too many parts and too many false air intakes
I think of those details as something that is not premium
When you start making holes and eventually cover them with plastic
there's the same problem as with the Tonale: a front that's not there and the side that's not very expressive
Alfa Romeo was also characterised by always having a 'shoulder' on the rear wing
here (on the Junior) the shoulder is very small
The rear of the Junior looks completely anonymous to me
There are photos of a Vinfast car produced two years ago and belonging to the same segment as the Junior
Here's the New Alfa Romeo Stelvio Before You're Supposed to See It
The Toyota Corolla Looks Even Better With White Wheels
Trump's Tariffs Could Force Stellantis to Sell Alfa Romeo and Maserati
The New Audi A6 Plug-In Hybrid Has a Decent Electric Range
The Current Alfa Romeo Giulia Will Survive Through 2026 in the US
New Alfa Romeo Stelvio: First Official Look
Croix’s Technica Series rods were conceived and delivered to give anglers “the upper hand in the trickiest of trout-fishing situations.” Its responsive
paired with the use of carbon fiber and Mito’s graphene technology
“The best way to describe Technica’s action is balanced,” says Jason Brunner
a softer lower end and mid-section stores energy and produces a smooth-loading
soulful in-hand feel while helping the caster make efficient mends and protect light tippets and small flies
the taper maintains the perfect amount of stiffness for picking up long lengths of line when recasting
downstream dry fly feeds and fast tip recovery for turning over long leaders in the wind"
“We learned a lot about the rod-performance attributes of Mito’s graphene with the 3-year development of Evos
when we began the job of designing Technica
we knew we could bend the rules of traditional moderate-action design.”
But Mito’s graphene is said to greatly impacts how the rod casts
“The addition of functionalized graphene to our established SCVI
SCIV and SCII carbon fiber matrix increases rod recovery by 20%,” Brunner says
“The benefit is a stable loop with maximum line speed
while the overall result is a blank that possesses all the feel
finesse and tippet protection of a moderate-flexing rod
with the speed and power of a medium-fast action.”
Mito’s R&D team realized that offering a prepreg option could be helpful for other customers
Mito is currently exploring working with partners to offer prepreg already infused with E-Go
The March issue of Kadokawa's Dragon Age magazine announced on Friday Kei Hozumi and Mito will launch a new series Seishun wa Sankakukei no Loop (Youth is a TrianglularLoop) in the April issue on March 7
The series will follow a love triangle between three childhood friends
Hozumi launched The Elf Sisters Can't Wait for the Night manga in Kadokawa's Dragon Age magazine in September 2021. Kadokawa shipped the sixth compiled book volume on December 9. Seven Seas publishes Hozumi's The Elf Sisters Can't Wait for the Night manga
Seven Seas will ship the second compiled book volume on May 27
Mito concluded the Sheep Princess in Wolf's Clothing manga with the fifth compiled book volume in May 2023. Seven Seas publishes Mito's Sheep Princess in Wolf's Clothing yuri manga in English
Seven Seas shipped the fourth compiled book volume on November 12
and will ship the fifth and final compiled book volume on February 11
U.S.) announces a product line expansion by core sporting customer St
Mito shared how the fly fishing rod company incorporated its functionalized graphene into the composite rods to enable faster recovery
increase torsional rigidity and improve strength-to-weight ratios
Croix’s Technica Series rods were conceived and delivered to give anglers “the upper hand in the trickiest of trout-fishing situations.” Its responsive
paired with the use of carbon fiber and Mito’s graphene technology
endless loop stability and accuracy
“The best way to describe Technica’s action is balanced,” says Jason Brunner
downstream dry fly feeds and fast tip recovery for turning over long leaders in the wind
“We learned a lot about the rod-performance attributes of Mito’s graphene with the 3-year development of Evos
released in 2023,” Brunner continues
we knew we could bend the rules of traditional moderate-action design.”
But Mito’s graphene is said to greatly impacts how the rod casts
“The addition of functionalized graphene to our established SCVI
SCIV and SCII carbon fiber matrix increases rod recovery by 20%,” Brunner says
“The benefit is a stable loop with maximum line speed
finesse and tippet protection of a moderate-flexing rod
with the speed and power of a medium-fast action.”
Mito’s R&D team realized that offering a prepreg option could be helpful for other customers
and CIO interviews of medium and large enterprises exclusively from Medical Tech Outlook
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Metrics details
essential for energy metabolism and linked to the regulation of longevity
The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied
but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes
Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects
identifying 75 non-mitochondria-targeted nuclear genes
We found that the uncharacterized gene CG11837—a putative ortholog of human DIMT1—regulates insect lifespan
as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans
whereas its overexpression extends median lifespans in fruit flies and C
elegans and enhances oxidative phosphorylation gene activity
DIMT1 overexpression protects human cells from cellular senescence
these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals
The Cell: A Molecular Approach (Sinauer Associates
Mitochondrial-associated metabolic disorders: foundations
Genomic signatures of mitonuclear coevolution in mammals
drives evolution of OXPHOS complexes in bivalves
Evolutionary rate correlation between mitochondrial-encoded and mitochondria-associated nuclear-encoded proteins in insects
Coordination of gene expression between organellar and nuclear genomes
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
How many species of insects and other terrestrial arthropods are there on Earth
Phylogenomics resolves the timing and pattern of insect evolution
Large-scale RNAi screen identified Dhpr as a regulator of mitochondrial morphology and tissue homeostasis
Highly accurate protein structure prediction with AlphaFold
A platform for experimental precision medicine: the extended BXD mouse family
Data on RNA-seq analysis of Drosophila melanogaster during ageing
A genome‐wide identification and analysis of the homeobox genes in the brown planthopper
Nilaparvata lugens (Hemiptera: Delphacidae)
Contact chemosensory genes identified in leg transcriptome of Apis cerana cerana (Hymenoptera: Apidae)
High throughput profiling of the cotton bollworm Helicoverpa armigera immunotranscriptome during the fungal and bacterial infections
Coordination of host and endosymbiont gene expression governs endosymbiont growth and elimination in the cereal weevil Sitophilus spp
An orthologous gene coevolution network provides insight into eukaryotic cellular and genomic structure and function
Evolutionary rate covariation reveals shared functionality and coexpression of genes
Identification of novel genes associated with longevity in Drosophila melanogaster—a computational approach
Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Absence of effects of Sir2 overexpression on lifespan in C
Sir2 mediates longevity in the fly through a pathway related to calorie restriction
Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16
Structural and catalytic roles of the human 18S rRNA methyltransferases DIMT1 in ribosome assembly and translation
Human DIMT1 generates N26,6A-dimethylation–containing small RNAs
Ribosomal biogenesis regulator DIMT1 controls β-cell protein synthesis
18S rRNA methyltransferases DIMT1 and BUD23 drive intergenerational hormesis
The genetic basis of adaptation to copper pollution in Drosophila melanogaster
The exceptional sensitivity of brain mitochondria to copper
a conserved lipid-droplet-associated metalloproteinase
is required for mitochondrial function in Drosophila
BUSCO update: novel and streamlined workflows along with broader and deeper phylogenetic coverage for scoring of eukaryotic
and annotation for large-scale eukaryotic metagenomics
GetOrganelle: a fast and versatile toolkit for accurate de novo assembly of organelle genomes
MitoZ: a toolkit for animal mitochondrial genome assembly
MAFFT multiple sequence alignment software version 7: improvements in performance and usability
trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses
IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies
Insect mitochondrial genomics: implications for evolution and phylogeny
The STRING database in 2021: customizable protein–protein networks
and functional characterization of user-uploaded gene/measurement sets
Cytoscape Automation: empowering workflow-based network analysis
Metascape provides a biologist-oriented resource for the analysis of systems-level datasets
REVIGO summarizes and visualizes long lists of gene ontology terms
Trimmomatic: a flexible trimmer for Illumina sequence data
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
ShinyGO: a graphical gene-set enrichment tool for animals and plants
Shen, X.-X. Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes. figshare https://doi.org/10.6084/m9.figshare.22637761 (2024)
OrthoDB v9.1: cataloging evolutionary and functional annotations for animal
Animal diversity web as a teaching & learning tool to improve research & writing skills in college biology courses
Keesey, T. M. PhyloPic; https://www.phylopic.org/
Download references
Liu for quantifying mitochondrial morphology
using the resources of the Information Technology Center and the State Key Laboratory of Computer-Aided Design & Computer Graphics at Zhejiang University
This work was supported by the National Key R&D Program of China (2022YFD1401600 to X.-X.S.); the National Science Foundation for Distinguished Young Scholars of Zhejiang Province (LR23C140001 to X.-X.S.); the National Natural Science Foundation of China (32071665 to X.-X.S.
and 31922074 to Y.C.); the Fundamental Research Funds for the Central Universities (226-2023-00021 to X.-X.S
and 2021FZZX001-31 to Y.C.); the Zhejiang Provincial Natural Science Foundation of China (LZ23C140003 to J.H.
and LR21C120002 to S.X.); the General Program of the National Natural Science Foundation of China (32371236 to Y.Z.); the New Cornerstone Science Foundation (S.W.); the Key International Joint Research Program of the National Natural Science Foundation of China (31920103005 to X.-x.C.); the National Science Foundation (DEB-2110404 to A.R.); and the National Institutes of Health/National Institute of Allergy and Infectious Diseases (R01 AI153356 to A.R.)
These authors contributed equally: Mei Tao
Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province
Centre for Evolutionary and Organismal Biology
CAS Key Laboratory of Insect Developmental and Evolutionary Biology
CAS Center for Excellence in Molecular Plant Sciences
Shanghai Institute of Plant Physiology and Ecology
Zhejiang Provincial Key Lab of Genetic and Developmental Disorders
ZJU-Hangzhou Global Scientific and Technological Innovation Center
Department of Biological Sciences and Evolutionary Studies Initiative
performed computational analyses and experiments
is a scientific consultant for LifeMine Therapeutics
The other authors declare no competing interests
reviewer(s) for their contribution to the peer review of this work
A detailed description of the analyses performed in each step of the workflow is provided in the Methods
After identifying 75 non-mt-nuProtein genes based on the protein-protein association network (Fig. 3b)
we further examined the connectivity (that is
the number of edges connecting the examined gene to other genes) for each of the 75 non-mt-nuProtein genes within three largest Clusters 1-3
which displayed the highest connectivity levels in their respective clusters
which ranked as the second-highest in connectivity within the largest Cluster 2 that contains 50 genes ( ~ 67%) out of the 75 non-mt-nuProtein genes
were used to investigate their impact on mitochondrial morphology
Illustration of the simplified organelle components
determined and stained from the control (Cg-GAL4 > UAS-mitoGFP) early third-instar larval fat body
we measured and averaged the length of mitochondria from each of five randomly selected areas (25μm x 25μm) in the early third-instar larval fat body
n = 4 biologically independent experiments for each genotype
P values were calculated using a two-tailed t test
Source data
Protein structures of fruit fly CG11837 and human DIMT1 were retrieved from the Alphafold2 database (https://alphafold.ebi.ac.uk/)
The efficiencies of knockdown of CG11837 and its orthologs on both sexes
Note that the worm was not assessed for two sexes
Fruit fly used D42-GAL4/+ and UAS-CG11837-RNAi/+ as two genetic controls; mosquito
and brown planthopper used dsGFP as controls; worm used empty vector as a control
n = 3 biologically independent experiments for each genotype
NS P > 0.05; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001
The efficiency of overexpression of CG11837 in fruit fly and E02H1.1 (an ortholog of CG11837) in worm
Fruit fly used Actin-GAL4 tsGAL80/+ and UAS-CG11837/+ as two genetic controls; worm used the N2 Bristol strain as a control
All examined organisms are 3-day-old adults
Source data
Western blot verifying the overexpression of DIMT1 in human skin fibroblasts
n = 3 biologically independent experiments
P value was calculated using a two-tailed t test
Senescence-associated β-galactosidase (SA-β-gal.) activity assay without (left panel) and with (right panel) X-ray
Cells were irradiated without or with 5 Gy X-ray
cells were re-seeded to 6-well plates and the next day
Source data
KEGG pathway enrichment (left panel) and expression level of all OXPHOS genes (right panel) between CG11837 knockdown and control male adults of 3-day-old mosquitos and 13-day-old beetles
A two paired Wilcoxon test was used to test whether the two sets of values (sample size = 80) are significantly different
KEGG pathway enrichment (left panel) and expression level of all OXPHOS genes (right panel) between CG11837 overexpression and control male adults of 3-day-old fruit files
Source data
Note that expression levels of all OXPHOS genes for young and aged insects were calculated based on publicly available wild type adult whole body transcriptome data
Nilaparvata lugens: female; Apis cerana: female; Sitophilus oryzae: unknown sex; Helicoverpa armigera: unknown sex; Drosophila melanogaster: female + male
Whiskers represent 1.5× interquartile range
Two-tailed paired Wilcoxon test was used to test whether the two sets of values are significantly different
full legends for Supplementary Tables 1–8 in Excel format
Legends and descriptive captions of all the supplementary tables are listed in the Supplementary Information
Numerical source data for Extended Data Fig
Unprocessed western blot for Extended Data Fig
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DOI: https://doi.org/10.1038/s43587-024-00641-z
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Mito City Civic Centre was officially opened to the public in July 2023 and has since emerged as the new community hub of the city. We provided structural design services for this new building after winning the design proposal with Toyo Ito, a laureate of the Pritzker Architecture Prize.
Spanning approximately 23,000m², the new civic centre boasts an array of facilities designed to cater to the diverse needs of citizens and the provision of retail space. These facilities include a 2,000-seat main theatre, a 482-seat medium theatre, a versatile small hall, conference rooms, exhibition rooms and various rentable spaces.
Structural design services for a new large-scale timber building.
New steel connectors for both the beams and the truss system.
A concrete core structure surrounded by timber and steel beams and columns.
If you'd like to speak to one of our property experts about any of the issues raised on this page or a potential collaboration then please get in touch by completing the form.
Max Mito’s business trip to luxury villas in Morocco was a red flag to finance staff
EVP’s Misha Saul called in the cops after investing
A now deleted Instagram post by StrongRoom AI’s lead designer Isabella Jorgensen in September 2023 captioned “Peter’s Moroccan extravaganza” with a brown love heart emoji left members of the company’s finance department seething
Jorgensen had just returned from a well-documented trip with her boyfriend and boss Max Mito
the new fund launched by Mito Technology is entirely dedicated to investing in start-ups that innovate in climate technology
the new fund launched by Mito Technology focuses on technologies for reducing ci Co2 emissions
in reducing the impact in the fields of mobility
Mito Tech Ventures is the first VC fund in Italy in line with Art
9 of the SFDR regulation,’ Mito Technology announced in a note
30% of the carried interest will be linked to the achievement of quantified environmental impact targets
which renews the experience gained with the fund called Progress Tech Transfer
also has among its subscribers CDP Venture Capital and FEI (European Investment Fund) with EUR 45 million subscribed
of which EUR 30 million from CDP Venture Capital and EUR 15 million from FEI
They are joined by companies in the environment and energy sectors
major professional pension funds and family offices
Mito Tech Ventures is looking for technologies with a level of technological maturity (TRL higher than 4) in the sustainability sector and early-stage start-ups (pre-seed
those that are still in the initial investment phase
The Fund offers companies still at an early stage not only the economic resources needed to develop the project
relationships and knowledge needed to transform the results of scientific and technological research into economic initiatives capable of growing and developing
The fund has a target fundraising of EUR 90 million (EUR 55 million at first closing; second closing within 24 months of launch); a hard-cap and EUR 120 million; it intends to invest in approximately 25-30 companies
Mito Tech Ventures follows the experience of Progress Tech Transfer the first venture capital fund launched by MITO Technology in December 2018 with an initial endowment of 41.6 million euros subscribed by the European Investment Fund (EIF) – with funds from InnovFin – Eu Finance for Innovators
a financial instrument developed under Horizon 2020 –
The fund closed its investment period in 2023 one year ahead of schedule
The fund has already concluded 10 follow-on rounds
many of them international; it counts the presence of women among the founders in more than one third of the portfolio start-ups
and has concluded 10 proof-of-concept investments originated by universities and public research bodies scattered throughout Italy; about 50% of the portfolio start-ups are already present on international markets
already incubated in I3P and supported in the seed stage by the business angels of the Club degli Investitori
Waterview is the first in the world to develop a solution for the real-time analysis of contextual meteorological conditions
aimed at providing the infrastructure manager with essential information for timely decision-making
as well as images from cameras routinely installed on critical infrastructure
the company is able to provide its customers (including local authorities
companies managing road networks and telephone infrastructures
and energy companies) with a reliable interpretation of the environmental conditions affecting the infrastructure itself
while also providing predictive indications (e.g
and the speed of snowfall).speed of growth of the snow layer on road surfaces
presence and propagation of gaseous emissions in the vicinity of waste collection centres
risk of failure due to the formation of ice sleeves on high-voltage electricity transmission lines)
a start-up company launched in September 2021 and led by Stefano Buono
Newcleo operates in the field of clean and safe nuclear energy
aiming to revolutionise the design and construction of Generation IV modular reactors
capable of reducing the production of waste and using as fuel those generated by old reactors
it carries out most of its research and development activities in Turin
The company has already raised over EUR 400 million in capital to date and currently generates a turnover of EUR 50 million through the work of a team of around 700 people
An Italian high-tech company operating in the field of manufacturing machines and production lines for photovoltaic cells and modules
Rise Technology has developed and patented iSplash (Industrial Selective PLAting for Solar Heterojunction): an innovative technology applicable to photovoltaics and in the future also in the semiconductor and biomedical fields
which aims to eliminate the use of silver pastes from the photovoltaic cell manufacturing process with a reduction in production cost of at least 30% and in the carbon footprint of 90%
while also mitigating the geopolitical problems related to the supply of critical raw materials
For the field of green industry tech there are: Mat3D
a spinoff of the Universities of Modena and Reggio Emilia and of Parma
Mat3D develops and produces innovative advanced polymer resin-based materials for additive manufacturing production processes with high performance (e.g.
in terms of thermo-mechanical resistance) and advanced functional properties specific to different application sectors
Mat3D has its main workplace at the University of Turin’s Innovation Centre and its legal and commercial office in Reggio Emilia
from where it serves a number of Italian companies in the world of manufacturing
a start-up born within the IRCCS Policlinico San Matteo Foundation in Pavia
which produces high-tech polypropylene-based fabrics for the manufacture of high-performance products with antimicrobial and antibacterial properties
which will allow huge cost savings for their washing
a lower environmental impact and better safety conditions in the case of use in critical environments
transforms by-products and low-value residues from the agro-industry into functional products with high added value and low environmental impact
Sqim has developed unique proprietary processes
based on the controlled fermentation of selected mycelia
and is currently on the market with specific brands for the fashion vertical and the interior design market
a spin-off of the National Research Council (at the Institute for Membrane Technology)
the company has developed a patented technique for the surface treatment of membranes currently available on the market for the treatment of industrial wastewater
thanks to the anti-fouling properties of the coating applied to their surface
considerably lengthens the useful life of the membranes themselves
a spin-off of the National Research Council – Institute of Photonics and Nanotechnology based in Padua – has developed special lenses that
a pathology that develops around the age of 40 in almost all people
it will be possible to develop glasses that autonomously restore focus for users
guaranteeing optimal visual comfort and making it easier for people with presbyopia to perform precision work tasks
a proof-of-concept project developed with the University of Brescia and the National Inter-University Consortium for Materials Science and Technology (INSTM)
aims to develop a patented technology for recovering lithium and cobalt from spent batteries of various origins (from electronic devices to cars)
with processes that guarantee a lower environmental impact and without the use of environmentally hazardous chemical solvents
The project is led by a team of researchers who can boast a unique track-record in managing research projects funded by the European community
Naturbeads aims to combat environmental pollution caused by the uncontrollable spread of industrially used microplastics
it specialises in the production of biodegradable microbeads made from cellulose
Founded in 2018 by a team of scientists and engineers
the company has developed a unique product that has already been successfully tested by major industrial clients to replace microplastics in multiple applications (from cosmetics to paints)
The solutions proposed by Naturbeads are radically sustainable: they are based on the sourcing of raw materials from certified forest or agricultural waste
and rely on a production process that is much more efficient and less carbon-intensive than current standards
avoiding the use of aggressive chemical solvents in the treatment of its semi-finished products
that produces and develops wearable robotic systems and exoskeletons for rehabilitation
assistance and increased power of movement in the service of people
It specialises in exoskeletons for upper and lower limbs used to improve mobility
strength capacity and recovery of motor functions
Valuematic is a spin-off of Scuola IMT Alti Studi Lucca
which intends to bring to the market a solution to make cloud computing more sustainable
working on the optimisation of energy consumption to allow an optimal allocation of the necessary computing resources
The start-up has developed a technology for automatic scaling of computational resources in the cloud that combines AI and proprietary modelling to provide better and longer-term predictions of computing times than solutions currently on the market
The technology can also be adapted on systems that use computational resources asynchronously
such as multiprocessor systems or mobile phones
has developed a revolutionary sensor for measuring free neutrons that can be used to detect the presence of water in the environment
with applications ranging from measuring moisture in agricultural soils
to measuring available water reserves in snowfields or glaciers
The company was awarded an EIC Accelerator in 2023
the only Italian company to obtain such an award in that year
In carbon tech there is Htms that has developed a technology to improve the energy efficiency and heat transfer capacity of fluids currently used in heating and cooling systems installed in large industrial and commercial buildings
allows for a 15-20% increase in heat transfer capacity compared to commercial standards available today in the heating
For the transport and mobility area there is Bluebrake founded in 2015 in Milan
is a company that employs more than thirty professionals and has twelve patents with international extension that concern braking on light vehicles
with particular reference to the e-bike sector
The company’s mission is to develop innovative solutions that make these vehicles safer and smarter
in order to facilitate the transition towards more sustainable mobility
both for the transport of people and goods (cargo-bikes)
The company ranks among the very few in the world able to provide high-performance and high-security solutions
and is already firmly projected on international markets
a Turin-based start-up whose mission is to reduce road accidents caused by aquaplaning
The company develops hardware and software solutions
including DAI (Digital Aquaplaning Information)
a true platform for detecting and calibrating vehicle dynamics on the road
with the aim of making driving safer in low-grip conditions
also with a view to the advent of systems of progressive autonomy in vehicle driving
the first electric jet outboard propulsion system for the marine industry
DeepSpeed innovates the on-water mobility sector
by drastically improving efficiency compared to today’s existing propulsion systems (propeller or inboard jet) and significantly reducing emissions related to current propeller-based ship propulsion standards
The project was awarded a ‘Seal of Excellence’ by the European ‘Horizon2020’ programme
The company has also integrated E-Drive Lab
a spin-off 10 from the University of Parma
which produces innovative electric storage systems specifically designed for the marine sector
aims to bring to the market the best results of the research carried out in the field of artificial intelligence applied to medical images
which enable the creation of personalised medicine solutions
as well as predictive diagnosis and early therapies on the onset of diseases such as Alzheimer’s
designed and developed the Endorail medical device to support difficult gastrointestinal endoscopy procedures
saving time and costs and increasing safety in clinical practice
as well as ensuring greater comfort and reduced invasiveness on the patient
the company was granted FDA (US Food and Drug Administration) certification for its Endorail product
thanks to which it can also start marketing in the US market
which is crucial for its growth prospects worldwide
is engaged in the development of next-generation optical spectrometers based on Brillouin spectroscopy
on the basis of changes in reflected or scattered light
makes it possible to measure fundamental properties of matter and biological systems such as cells and tissues in a non-destructive and high-resolution manner
an innovative SME based in Trieste that focuses on the development of state-of-the-art telecommunications systems for small satellites
Founded in 2014 as a spin-off of the University of Trieste and based in Area Science Park
Picosats is revolutionising the aerospace industry by introducing miniaturised and flexible solutions that enable cheaper access to space
Mito Technology was founded in 2009 as a platform for matching technology supply and business demand for innovation
In fifteen years it has established itself as a reality in the field of technology transfer
working alongside private and public operators
Mito Technology’s business model has evolved and
a venture capital fund with a focus on technologies for sustainability
spinoffs and technologies with a high proximity to go-to-market (Technology Readiness Level – TRL: from 5 to 9)
all originating from the world of scientific and technological research in the phase defined as “early stage” of their approach to the market and funding
Mito Technology belongs to Cleantech for Italy
the Italian declination of the European initiative Cleantech for Europe
an association that promotes a zero-emission future through innovation and dialogue with policy makers
Mito Technology has a strong team with heterogeneous and complementary skills ranging from deeptech
innovation finance to intellectual property management and valorisation
Some of the team members have also gained a lot of experience in international corporate contexts and have
the ability to intervene pragmatically both in deal management and in supporting the founding teams of the investee start-ups
The Mito Technology team includes Andrea Basso
Francesco De Michelis as managing director
Leonardo Massa as investment director and Valentina Sesti as associate
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93 players have played in at least one LIV Golf event
since the vast riches offered by Saudi Arabia’s bottomless Public Investment Fund was a significant reason for many deciding to join the league
it got us thinking about just how much each player has made since they jumped ship
we will break down the LIV Golf earnings from each season played so far
as well as an overall table including every player
The golfer that tops that particular list is not the golfer you think it is!)
here’s a quick reminder of what’s on offer…
The first year of LIV Golf saw eight tournaments played across the globe
and that has become 14 for each season since
For the 2025 season, there are 54 players competing in the league, with 13 teams of four complemented by two wildcards: Anthony Kim – who made his long-awaited return to golf in 2023 – and Chieh-Po Lee
who earned a spot through the LIV Golf Promotions event
Each of the 13 regular season events has a $25m purse
with $20m for the individual competition and $5m for the team competition
This is split among the 54 players, from $4m for coming first and $50k to those bringing up the rear. Only the PGA Tour’s flagship event, the Players Championship, has a bigger prize pot
with some money going to the players and a percentage going into the team pot
The amount won by each team has changed over the years – and you can see the full breakdowns below – but the prize fund is split 60/40
with 60% of the team’s winnings going directly to a team operating fund
while the remaining 40% is distributed in 10% shares to each of the four players
the top three players in the individual standings each season will receive a huge bonus payday
A total of 68 players played in the inaugural season – then called the LIV Golf Invitational Series – which began at Centurion Club
and ended with the Team Championship in Miami
And it was a good start to life on LIV for this man…
*Includes $18m bonus for winning individual standings **Includes $8m bonus for finishing second in individual standings ***Includes $4m bonus for finishing third in individual standings
DJ’s 4 Aces GC also dominated the team standings…
A total of 52 players took part in the 2023 LIV Golf season
which was now 13 regular events followed by the Team Championship
It was Bryson DeChambeau’s Crushers GC who came out on top in the Team Championship
A total of 58 players took part in the 2024 LIV Golf season
who was rumored to have signed for anything from $450m to $650m
*Includes $18m bonus for winning individual standings **Includes $8m bonus for finishing second in individual standings ***Includes $4m bonus for finishing third in individual standings
Rahm and his Legion XIII team also did well in the team standings…
Here’s how much all 93 players to have played in at least one LIV Golf event has earned in the individual standings…
because we’ll keep it updated after each LIV Golf event
Alex has been in the golf industry since 2007 and has helped shape a number of publications in that time
He joined Today’s Golfer in January 2025 to lead the brand’s news division.
He is a keen golfer who claims to play off 12 and enjoys traveling the world to try new courses
and Royal Portrush – with special mentions for Okehampton and Bude & North Cornwall
where he first fell in love with the game.
He uses a combination of Ping
and once bought the Nike SQ driver which he absolutely did not immediately regret
Rob Jerram Digital Editor
By Alex Perry and Rob Jerram
"Where We Were Born," choreographed by Mito
is performed by the seven dancers of her Co
choreography is not something fixed but rather something fluid," said Japanese choreographer Ruri Mito
"Its essence remains strong and unchanging
yet it evolves in tandem with shifts in the body and perception."
at PS21: Center for Contemporary Performance
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Aaron Simon Gross can be reached at agross@berkshireeagle.com.
A series of nine new "Hatchlings" will begin lighting up the city of North Adams on Friday, as Vanessa Till Hooper's luminous public art displays take residence until October.
In a new Berkshires-inspired fragrance line, former Pittsfielder Renée Junewicz captures the flowers outside her bedroom window, the scent of her mother's rose garden and the inside of Louisa May Alcott's Orchard House.
The 19th annual Berkshire International Film Festival features premieres, documentaries and appearances by Kenneth Cole, Bob Mackie and more over four days of film and conversation.
David Roussève returns to the stage with “DaddyAF,” a deeply personal work-in-progress showing, 8 p.m. May 3 at Mass MoCA, of a solo show exploring love, aging, identity and resilience through dance and the virtuosity of an aging body.
Berkshire Opera Festival presents "Young Verdi in Love," a concert tracing Verdi’s early romantic works, 2 p.m. April 27, at Saint James Place in Great Barrington, ahead of this summer’s 'La Traviata.'
R.B. Schlather’s "Giulio Cesare," featuring Ruckus and a full cast, continues at Hudson Hall with performances on April 23, 26, 27, 30 and May 2.
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INJ tokens are required for the token sale and for gas fees
participants’ $INJ will be converted in a proportion of 50% $NEPT and 50% $NEPT/$INJ LP based on their contribution to the sale
offering different locking tiers and built-in staking utility features and rewards
Vesting for team and investors is 36 months with a linear unlock
a few top airdrop recipients are expected to have vesting periods after an initial unlock
Upon successful completion of the sale event
participants will be able to claim their $NEPT
which can be used to stake for account health boosts
They can either redeem the LP tokens for $NEPT and $INJ or they can keep their LP tokens in the $NEPT/$INJ market to earn yield
If the sale does not reach its subscription goal
Neptune Finance is a next-generation credit network and high-yield lending protocol designed to provide capital efficiency for lenders
Cover Chew Tee-Ming co-founded Mito Health in June 2023 with Kenneth Lou
Joel Kek and Ryan Ware to offer more comprehensive and individualised health screenings (Photo: Darren Gabriel Leow) Chew Tee-Ming co-founded Mito Health in June 2023 with Kenneth Lou
Joel Kek and Ryan Ware to offer more comprehensive and individualised health screenings (Photo: Darren Gabriel Leow)
Read more: Finding the Blueprint for longevity: Inside Bryan Johnson’s mission to cheat death
Ware currently runs through the first draft of the plan and makes the necessary edits
The goal is to automate this tedious process further
to cut down the cost of the screening and the time needed to create the plan
Above Mito Health co-founders: chief medical officer Dr Ryan Ware
chief technology officer Joel Kek and chief product officer Chew Tee-Ming (Photo: Mito Health) Mito Health co-founders: chief medical officer Dr Ryan Ware
chief technology officer Joel Kek and chief product officer Chew Tee-Ming (Photo: Mito Health)
Chew says the company has nearly doubled its customer base every month
Given Singapore’s strict regulations around marketing healthcare services
Mito Health relies heavily on word-of-mouth and referrals to grow its client base
Chew’s interest in personal health grew after he exited his previous company, the personal finance firm Seedly which he also co-founded with Lou. “After exiting, I got a nutrition coach to advise me on eating better and exercises to do,” he says. “I also met with Monk’s Hill Ventures’ Peng T Ong
who shared a few books with me including David Sinclair’s Lifespan: Why We Age―and Why We Don't Have To.” Around that time
Johnson also started making global headlines for his extreme
US$2 million-a-year methods he hopes can keep death at bay
“We thought there’s an opportunity here,” says Chew
Read more: The dark side of the Blue Zone: Living longer comes with the burden of loneliness
On how different the fundraising landscape is now compared to Seedly days
“Most investors today focus on business models that can generate money from day one
it was the kind of business where we weren’t going to earn back money
So we focused on getting more users and investors were okay with that.”
Eyeing the larger US market, where there is also a stronger interest in longevity, Mito Health participated in the startup accelerator Y Combinator programme in San Francisco from July to September 2024.
Chew shares more about starting and exiting from Seedly and his advice for early-stage entrepreneurs
Read more: Why running a startup is like playing 3-D chess, says Reach52’s Edward Booty
What led to your decision to exit Seedly?
Chew Tee-Ming (TM): We got acquired twice: the first time was by ShopBack three years into the business and the second time by Compare Asia Group
I went to Switzerland for a holiday with my wife and I remember thinking
“Do I want to work on Seedly forever?” The answer became clear to me
As long as our team was being taken care of and the company mission lived on
I also realised after working on Seedly for seven years that the mission was meaningful
but it was going to be a Singapore-only business
While I didn’t know what I was going to do next
So it was largely because of personal aspirations
TM: We met when I was in Silicon Valley for the National University of Singapore (NUS) Overseas Colleges programme
A university senior was asking around if anyone could host this guy coming to visit and I offered to house him in my spare room
and he told me how he was closing down the wire-charging business he was running at the time.
which gave us S$10,000 to develop an expense tracker
We later got S$80,000 in investments from East Ventures
after a 15-minute meeting with its founding partner Willson Cuaca
We were shocked that he would invest in us because we were students
How should early-stage founders approach the fundraising process
TM: The pre-product phase will be challenging if you don’t have any previous record of starting a company
ensure your team is solid and that you are the right people to address the problem you’re looking to solve
it’s easier to convince the necessary investors
you need to be able to convince investors how you plan to correct your strategy and what you’ve learned from the current strategy.
we don’t just want investors with a lot of money and nothing else to offer
so we want investors with overseas experience who can help bring us into our next market
Founder Stories is Tatler’s content series dedicated to discovering the untold stories and challenges of today’s entrepreneurs on their climb to the top
What it’s like to fundraise for a high-growth startup while pregnant, according to ThoughtFull’s Joan Low
My First: How Cerebro evolved from struggling edtech startup to online learning leader
Seven Olympian strategies for staying strong and winning against the odds
MITO — The Ibaraki prefectural government and others are creating “Reiwa-era versions” of dishes from “Shokusai-roku (Record of food variety)
a collection of recipes left behind by Tokugawa Nariaki
the ninth lord of the Mito domain in Edo-period
Some of the dishes were unveiled at an event held on Thursday
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“Shokusai-roku” contains about 300 late Edo-period recipes
which have been analyzed by a research group led by Ibaraki University Professor Masaya Araki
The prefectural government came up with the idea of getting chefs to create new specialty dishes using food produced in the prefecture
Eleven talented chefs from the prefecture have been working on the project since October based on a modern translation of the book
eight chefs presented nine dishes of Japanese
Chef Yasuaki Kobayashi of Motoyu Yamada-ya Ryokan presented “ukeiri tofu no shiyo,” a combination of grated yam
Kobayashi combined grated ayu (sweetfish) meat with tofu and floated it in a broth with grated turnip to represent “shiga,” a phenomenon that occurs in winter on the Kuji River
where sherbet-like ice flows on the surface
Chef Takaaki Otsu of Restaurant Otsu created a modern version of gobo mochi (rice cake with burdock root)
a dish in which burdock root and glutinous rice are kneaded together and deep fried
The roasted meat of Hitachinokuni wild mallard was served with gobo-mochi mixed with the mallard meat and covered in a sauce made from mallard offal and other ingredients
“I was surprised at the great potential of Shokusai-roku,” Araki said
She said that the cuisines were creative and tasty
and that historical resource should resonate with foreigners as well
Each of the restaurants will continue to make improvements and consider adding the dishes to their menus
Our weekly ePaper presents the most noteworthy recent topics in an exciting
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