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the location of Ciacci Piccolomini d’Aragona in the sultry southeast of the Brunello di Montalcino DOCG should make it especially vulnerable to the impact of climate change
And yet this family-owned winery continues to release wines full of elegance and precision
So far and so rapidly has the star of Brunello di Montalcino risen in the wine universe that it’s easy to forget that
this was a poor area populated by subsistence farmers who sold off their grapes or made simple wines for their own consumption
Now there are over 250,” says Alex Bianchini
the Brunello estate owned by his father Paolo and his aunt Lucia
because she tells me every day we have to remember that
There has been a big development since then.”
Wine is but a recent chapter in the estate’s history
which can be traced back to the 17th century
including a palazzo built by Fabivs de’ Vecchis
The tongue-twisting name is a consequence of the marriage between Count Alberto Piccolomini d’Aragona (a descendant of Pope Pius II) and Elda Ciacci
the Ciaccis having bought the estate in 1877
who had long wanted to make wine commercially
He had planted the first vineyards in 1983 and
released the estate’s maiden wines: 20,000 bottles of Brunello and 5,000 bottles of Rosso di Montalcino
production has risen to about 300,000 bottles a year – there is a Syrah
producing a pair of Rosso di Montalcinos (including Rossofonte
and a pair of wines from the Pianrosso vineyard
including a Riserva only made in the best years
Wine may have come relatively late to the story of this estate
but already there’s a feeling of continuity and consistency to the way in which the wines are made – possibly a consequence of family ownership
As Alex Bianchini helps his father Paolo with production
his aunt Lucia runs the administration and accounting
so we do more or less everything,” Bianchini says
but the galestro soils of the Pianrosso vineyard
which Giuseppe Bianchini started planting back in 1985
have long been the source of Ciacci Piccolomini d’Aragona’s finest wines
“Pianrosso means ‘red soil’,” explains Bianchini
“These soils are really rich in iron and minerals thanks to the old volcano [Monte Amiata
However impressive the galestro soils may be
there is one inescapable fact about the Ciacci Piccolomini d’Aragona estate – in fact
it’s the first aspect that Alex Bianchini mentions when we meet: “We are the hottest area in Montalcino.” Throw in the inescapable impact of climate change and you’d expect the wines to be baked
Alex ticks off a list of beneficial factors: vineyards – certified organic since 2018 – planted at an elevation of 240m to 360m above sea level; the relatively proximity of the sea; the protection of Monte Amiata
“Perhaps during July and August it’s very hot
but we get good temperature variation,” he says
This is the perfect way to ripen the grapes in terms of aromas and colour
Those galestro soils conceal a few secrets too
Drill down and you hit clay – crucial in terms of water retention after winter or spring rains
“Two or three months without water is not a big problem,” says Bianchini
“Only two times in the last 25 years we had a problem with dry conditions
This was a problem for the young vineyards
because their roots don’t go as far down.”
The vineyards are located close to the Orcia river
which also helps to leaven the effects of the hot
although conversely it can be a problem if there’s a lot of rain in June and July
Bianchini cites 2014 as an example of this – so wet that no Pianrosso or Riserva was made
The Bianchinis plant mustard and other cover crops
then press them down into the soil – a “green manure” which Alex says can create a 2-3C temperature difference – crucial when the mercury climbs into the mid-30s at the height of summer
“The harvest time is the other secret,” he says
Now we are checking the grapes at the end of August
and sometimes the harvest can start in the first two weeks of September.”
“A lot of people older than me say this is like a harvest from the 1990s or 1980s,” Bianchini notes
but mainly for the harvest time: today is earlier; tomorrow could be later.”
Attention is now focused on the 2020 and 2019 vintages
with Ciacci Piccolomini d’Aragona about to release its classic Brunello and Pianrosso 2020
Brunello di Montalcino Vigna de Pianrosso Riserva Santa Caterina d’Oro
The name is a tribute to Giuseppe Bianchini
who died in 2004 (just before the completion of the estate’s new winery)
and who was three times garlanded as winemaker of the year in Siena’s Santa Caterina d’Oro awards
The two vintages have some similarities – picking dates
general weather patterns – but 2020’s July heat has made its wines a little softer and more generous now
while 2019 displays more structure and tannic backbone
but you’d imagine most people might drink the 2020s while they wait for the 2019s to reach their peak
Not that you can be entirely sure of how a vintage will evolve
As the Brunello di Montalcino DOCG abandons its star rating for vintages – a blunt tool at the best of times
replaced by a much more detailed and nuanced assessment of conditions – some perhaps overlooked years are getting a second chance
you can find a perfect expression of Brunello for me
and a lot of my colleagues say the same thing – but people thought it would not be perfect for long ageing.”
If there’s one more secret to be unlocked about Ciacci Piccolomini d’Aragona
it’s the estate’s laser focus on tradition in terms of ageing
and adherence to the “old regulations”: three years in wood for the classic Brunello and Pianrosso; three-and-a-half years for the Riserva
“We only use big barrels for Sangiovese,” says Bianchini
with Biondi-Santi.” The classic Brunello spends seven to eight months in bottle before release (the mandatory minimum is four); the Riserva more than 18 months
The approach is perhaps best summed up in the management of the four plots that make up the Pianrosso vineyard
the grapes are picked for the Brunello Pianrosso wine
but one bunch per vine is left behind to ripen further for another week
The yields from the Pianrosso plots are eyewateringly low at the best of times – about 5,000kg/ha
versus closer to 7,000kg/ha for the rest of the estate
because we prefer to focus on the quality,” says Bianchini
The wines of Ciacci Piccolomini d’Aragona are represented in the UK by Mentzendorff
The estate’s Brunello di Montalcino 2020 (RSP £51 per bottle)
Pianrosso 2020 (£68) and Vigna di Pianrosso Riserva Santa Caterina d’Oro 2019 (£125)
are scheduled to arrive in the UK in April 2025
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A qualitative study method illuminates patients’ fears for the future
Dry eye disease (DED) is one of the most common ocular conditions
and patients with the disease may experience a wide range of severity and progression
A recent study completed by researchers in Italy shone light on the often-overlooked aspects of DED by applying a narrative medicine approach
Researchers working on the project collected data from 38 eye care centres in Italy and one in San Marino
Respondents included adult patients with DED
their informal caregivers and ophthalmologists caring for the patient base.1 The authors collected demographic data as well as written narratives which illustrated quality-of-life (QoL) factors via an anonymous collection portal
171 patients diagnosed with DED participated in the research
as did 37 informal caregivers (family members or friends)
27% reported severe DED and 14% stated that they were not informed about the severity of their DED
163 patient narratives and 35 caregiver narratives were analysed
and 81 ophthalmologists composed 111 parallel charts to illuminate the clinical factors of the patients’ experiences
from the IRCCS San Raffaele Scientific Institute
University Vita-Salute San Raffaele in Milan
spoke with Ophthalmology Times Europe about the research
also presented the results as a poster at the 2024 Tear Film & Ocular Surface Society (TFOS) Conference in Venice
“The narrative medicine approach was a bit of a challenge for us as researchers because it was something that we were not so used to
It is very commonly used in other medical fields
where studying the impact on QoL of both diseases and treatments is much more common,” Dr Aragona said
Narrative medicine is also quite different from questionnaires
which use precisely selected and defined terms to reach a quantitative conclusion
Narrative medicine gives respondents a greater degree of freedom
“Patients were prompted to write sentences which answered questions like ‘What are your overall feelings about your experience of dry eye disease
Your treatment?’ and ‘What are your most frequent fears about your future?’” Dr Aragona said
we completed an evaluation of the terms that were used most commonly.”
Analysis of the narratives revealed common themes
All parties frequently mentioned the physical experience of DED
and the burden of using eye drops and other avenues of relief multiple times per day
Patients and caregivers reported drastic impacts of DED at home and in the workplace: daily activities
Caregivers who assumed those patients’ responsibilities reported feelings of overwhelm
The economic impact of DED was magnified by patients’ limited ability to work
and many patients said the cost of their treatment affected their families’ budgetary needs
I have to treat this disease for the rest of my life?’” Dr Aragona recalled
“They said it feels like they have all the existing burdens of daily life
This points toward durability as a priority for future treatments
such as anti-inflammatory drugs that could work for a longer period of time or be more active on the pathogenesis of the disease.”
Dr Aragona highlighted the inclusion of caregivers in the narrative research project
The family members and friends who serve as informal caregivers are frequently excluded from QoL research
but this study revealed new findings on caregivers’ perception of DED
“The most surprising result was related to the caregivers
We found that 35% of caregivers surveyed considered dry eye disease to be a disabling condition,” Dr Aragona said
“The patients only made this kind of evaluation in 19% of cases.”
Many of the caregivers surveyed said that caring for their family members with DED necessitated major life changes
Dr Aragona recalled the experience of one young woman who left her university
putting her studies on pause in order to care for a parent with DED
we haven’t had so many data regarding the broader impact on patients’ families,” Dr Aragona said
Caregivers reiterated a common response from patients which emphasised the doctor-patient relationship
70% said that the therapeutic alliance with their doctor is fundamental to the treatment’s success
“Both caregivers and patients said they prioritised a relationship with a doctor who could really understand their problems and suffering
I think most of the patients felt a bit lost,” Dr Aragona said
I have experienced that patients who come to me say they feel as though other ophthalmologists did not believe in their levels of pain and suffering..
Dry eye is a really complex disease where there are critical symptomatic aspects
which are sometimes not in accordance with the clinical signs.”
11% said they craved a sense of constancy or consistency in the therapies used to treat DED
Patients were encouraged to share their fears for the future
and the most common responses included a worsening of the condition and treatments losing efficacy or not being completely effective
while only 5% of patients said they hope DED sees heightened awareness in the future
22% of caregivers advocated for increased research efforts and improved treatment access
Caregivers were also less likely to describe patients’ QoL as “good,” and more likely to describe patients’ QoL as “poor” (Figure)
Future therapeutics may require a different approach than traditional treatments for ocular pain
Newer research is assessing pain independently of other clinical [observations]
I think this is becoming a more important aspect that we consider in our evaluations of dry eye disease
and there’s still space to improve,” Dr Aragona said
“I think that we are starting to better understand the different pathological connections between ocular pain
ocular surface diseases and dry eye disease
I hope that there will soon be more therapeutic approaches which focus on pain as patients with dry eye disease experience it
There is a difference between pain related to dry eye symptoms and pain derived from the sensitisation of the central nervous system.” Some of the ophthalmologists surveyed echoed Dr Aragona’s sentiments: 26% said that DED awareness should be raised among their colleagues and patients
Dr Aragona said that narrative medicine projects such as this one could help pinpoint patients’ therapeutic needs in a way that traditional clinical research does not
After presenting the research at the TFOS Congress
reactions from her colleagues indicated a growing interest in narrative medicine
“The study received a really good reception from the audience of international ophthalmologists
and there was great interest in narrative medicine as a new way to study patients’ quality of life,” she said
“The day after the presentation of the posters
one opinion leader in dry eye came back to me and asked for more details on the narrative medicine approach
and said that it was a novel idea he would consider more.”
Patients who participated in the project reported positive outcomes from sharing their stories
which could bode well for the future of narrative medicine
65% of patients described writing as a positive experience (46% of caregivers and 47% of ophthalmologists reported the process was a positive experience)
One patient said she hoped sharing her story could help other patients: “Many people like me
“I have met other women my age who did not know it is a disease
to avoid bothering others.” Dr Aragona said that narrative medicine could help shape future therapies and help researchers understand aspects of DED which are missed in questionnaires or clinical trials
“I do think and hope narrative medicine will be used more broadly in the future to evaluate therapeutics’ impact on patients,” Dr Aragona said
Dr Aragona has concluded her PhD project at Vita-Salute San Raffaele University and is currently an ophthalmologist in IRCCS San Raffaele Scientific Institute in Milan
Her everyday activity deals with patients affected by dry eye disease
Join ophthalmologists across Europe—sign up for exclusive updates and innovations in surgical techniques and clinical care
Editorial Advisory Board members bring research findings to ARVO
Ophthalmology Times and Modern Retina editorial advisory boards are present and presenting at the 2025 ARVO meeting
Higher Molar Dose and Its Translation into Clinical Practice
LuxIA receives CE-MDR certification
LuxIA is designed to screen adult diabetic patients for more-than-mild diabetic retinopathy
EMA CHMP adopts positive opinion for teprotumumab (Tepezza, Amgen) marketing authorisation application
the European Commission will issue a decision on the first severe thyroid eye disease treatment
The future of microbial keratitis treatment is bright
Ultraviolet light’s potential in ocular care extends beyond structural reinforcement to antimicrobial applications
Vision- and life-threatening neuro-ophthalmological presentations
Paediatric diagnoses of juvenile idiopathic intracranial hypertension
609-716-7777
one curiosity lingered as I waited for U.S
After working in the dairy industry for 35+ years
I am finding City Pulse a challenging and rewarding new start
Helping businesses get their message out is an exciting and gratifying experience
Joe Aragona joined the show to discuss his priorities in the House this year
The state’s 103rd Legislative session began on Wednesday
with Republicans taking the majority in the House of Representatives
But Democrats still hold a majority in the state Senate
requiring bipartisan efforts in the Legislature to get bills passed into law
MichMash host Cheyna Roth and Gongwer News Service’s Zach Gorchow discuss the first day back in session and some of the new legislative developments being drafted
Gorchow sits down with Republican state Rep
Joseph Aragona to discuss his goals for this new Legislature and the likelihood for bipartisanship
Subscribe to MichMash on Apple Podcasts, Spotify, NPR.org or wherever you get your podcasts
Roth noted that a coveted spot for a bill is to be House or Senate Bill No. 1, and this year’s Senate Bill 1 is Freedom of Information Act (FOIA) expansion — something we’ve talked about a lot on this show
It’s an issue that was killed during lame duck last year
and one that Gorchow said is hard to be optimistic about this session after multiple terms of inaction and with Republicans in control of the House
“When a minority party becomes the majority party
See the House Democrats last term,” Gorchow said
adding that there are no firm commitments from House Republicans yet on this issue
it’s “a clear message from the Senate that they want this done quickly.”
a second term House Republican serving Clinton Township in Macomb County
says while he’d be supportive of FOIA expansion
his priorities this year will revolve around updating Michigan’s tipped wage and sick leave policies
as well as on expanding government oversight via the House Oversight Committee
“We’re trying to bring a higher value for the tax dollars that people give state government throughout Michigan,” Aragona said
referring to House Republicans’ oversight priorities
“These subcommittees are meant to try and encompass the breadth of state government
and [to address] issues we’ve seen in the past where we haven’t gotten answers.”
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Michigan Republican lawmakers are proposing to end state taxes on tips
(Advance Local file photo)Jim Lowney | For NJ Advance Media
.st1{fill-rule:evenodd;clip-rule:evenodd;fill:#2a2a2a}By Michael Kransz | mkransz@mlive.comLANSING
MI - Servers and bartenders would keep more of their pay under a proposal by Republican state lawmakers to stop taxing tips
said tips would no longer be considered taxable income in Michigan under the bill he introduced Sept
Tips would still be subject to federal taxes
but former President Donald Trump and Vice President Kamala Harris have each pledged to end federal taxes on tips if they are elected this November
“This is Trump’s idea that Vice President Harris stole
so now I’m stealing it for Michigan,” said Aragona
Trump in June announced his plan to exclude tips from federal taxes
Aragona challenged his Democrat colleagues
who hold majorities in the state House and Senate
they’d pass it to show that this isn’t just a campaign gimmick by Harris
but I’m betting they won’t do that because they know that if the vice president really wanted to get rid of taxes on tips
she could go to Congress and make it happen right now instead of just making promises,” he said
The effect of ending taxes on tips could be severely diminished by changes starting next year that will see the state’s lower $3.93 an hour wage for tipped workers gradually phased out
Related: Michigan restaurant servers urge lawmakers to save tips at Capitol rally
Those workers will earn about $6 an hour plus tips starting Feb
with that pay gradually increasing each year until it reaches the standard minimum wage in 2030
Many servers and bartenders have warned customers will tip less or not at all if they become minimum wage workers
Others have said potential menu price increases caused by the higher wages could also change tipping habits
About 70% of readers who responded to MLive’s recent, unscientific survey said they will tip less if servers make minimum wage
Related: Most readers will tip less if servers make minimum wage, MLive survey finds
The transitioning of tipped workers to minimum wage earners stems from a Michigan Supreme Court ruling this summer
Aragona’s bill would define a tipped employee as someone working in an occupation where the worker regularly receives more than $30 a month in tips
Workers would deduct proven tips from their adjusted gross income on their state income taxes
Aragona said removing taxes on tips would result in better service and more people wanting to work in the industry
“Quality waitstaff hustle for their money,” he said
“Getting rid of taxes on tips will give them an incentive to work more and provide better customer service
It will help with staffing issues because more people will want to work in restaurants
Fifteen other Republican state representatives have co-sponsored Aragona’s bill
which remains in the Michigan House’s Tax Policy Committee
Related: How we got here: Michigan’s minimum wage and pay for tipped workers set for drastic changes
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Volume 3 - 2009 | https://doi.org/10.3389/neuro.08.015.2009
This article is part of the Research TopicNeuroeconomicsView all 13 articles
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations
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Obituaries
FL passed away peacefully in her home on July 24
2023 in the presence of her most cherished loved ones
PA to her late parents of Maria Elizabeth Marino and Anthony Marino
She is the youngest of three siblings; brother
She was raised in Philadelphia mostly by her mother
Her father passed away when she was only 4 years old
Frank Joseph Aragona and her two children; son
Both Marianna and Frank grew up in South Philadelphia and were high school sweethearts
They were wed in September of 1970 and have been happily married for over 52 years
and Gina while residing in Pennsylvania and then New Jersey
Marianna and Frank both retired and moved south to Florida
she dedicated 18 years of service to the Federal Government Defense Logistics Agency of Philadelphia as a management assistant and budget analyst
In the early to mid 90s Marianna was a realtor for Prudential of Springfield
The remainder of her career was spent in New Jersey as a sales and design consultant for Ethan Allen and Diamond Furniture
She also performed visual merchandising for Levitz
Marianna and Frank often visited nearby Walt Disney World
Marianna and Frank went on a Mediterranean cruise and on an Alaskan cruise
Marianna's number one passion was to be by "her" Rialto Bridge in Venice
She was fortunate to make her dream come true not once
Marianna spent many summers in Atlantic City
She loved the beach and walked the Atlantic City Boardwalk
Her favorite venues were the Steel Pier with the Diving Horse and Funcade
Her fond memories were associated with being at her Aunt Jenny's house on S
Marianna and Frank had several family pets
Their two dogs were both pugs named Rosie and Bobo whom she dearly loved
she went above and beyond for her two children
She loved making mashed potatoes and made the best chicken cutlets
Marianna was someone who possessed the natural ability to make people laugh
She always gave her "spiel" as she would never hold back or refrain from expressing her opinions on just about anything
Her qualities included creative writing and storytelling
Marianna was diagnosed with stage 3B breast cancer and then in 2013 was discovered to have stage 4 metastatic cancer
She courageously battled with the side effects of cancer in recent years
July 31 from 10-11 AM at Pagano Funeral Home
Online condolences may be made by visiting www.paganofuneralhome.com
Pennsylvania19060DE: (302) 792-8485PA: (610) 485-6200
paganofh@gmail.com
one of the greatest and fiercest NHRA Competition eliminator racers of the modern era
10 surrounded by family after a long and brave battle with cancer
in a variety of open-wheeled dragsters and altereds with a variety of non-traditional powerplants
2018-19) are tied for most in the class alongside other greats such as David Rampy
and he is just one of three drivers to win back-to-back Comp crowns in the points-earning era (Dean Carter
into the class and scored his first national event win in St
then he spent the next two decades terrorizing the class
Among his greatest wins was a victory at the prestigious NHRA U.S
but he also showed his versatility by winning in Super Comp at the fall 2015 Charlotte event
His 15 wins in Comp are tied for fourth most behind fellow class legends Rampy
“The things I love about Comp are the challenge and the chess game
It’s not as simple as everybody thinks; you gotta know what your opponents can do
Aragona bravely battled the disease and even returned to the winner’s circle in June 2022 at the Division 1 event in Atco
after his diagnosis and fell just short of winning the Summit Racing Equipment NHRA Nationals when a fuel-line fitting shook loose
perhaps Aragona’s fiercest competitor over the last two decades
probably the biggest advocate for Comp eliminator I ever met,” he said
“He was a key member of the SCRA [NHRA’s Sportsman Racing Advisory Committee] and was a rep for a Division 1 forever
He was a guy who lived and breathed Competition eliminator
I don't know of anybody who put more into the category than Frank did
he still wanted to be involved in the SRAC."
the recently retired director of Division 1 where Aragona did the bulk of his racing
“Frank’s involvement with the SRAC went beyond the rules of the class
He knew more about everyone else's index than he did his own
He'd be the first person to volunteer to jump in on class index concerns and always tried to make sure the class got the attention it deserves
We are all better for having him a part of the SRAC
If a racer had any issues Frank would accompany them to the tower for the discussion
Always learning and looking for ways to improve racing
"I am honored and proud to have been inducted into the Northeast Division Hall of Fame at the same time as Frank last week at the D-1 banquet
I'm glad I was able to know Frank and call him a friend.”
Massel also addressed Aragona's competitive side on the racetrack and his nature off the track
we had some fierce rivalries over the years
and then we’d go to the next race and shake hands and hug
and that's kind of how Frankie was," said Massel
"He was a friend to everybody at the track
and he was your enemy when you staged up alongside him
“Not only did he compete with multiple cars
One of the things I really appreciate is that his uncle did his motors
They didn't go like everybody else down the road with a small-block V-8
You always knew he was gonna be in the race
He did a great job conserving his index and a great job hitting the Tree
He drove both sides of the racetrack as good as anybody.”
“I respected him for who he was as a racer and what he's accomplished
and it kind of mirrors the relationship I had with my dad and drag racing
the class’ all-time GOAT (81 wins) and 100-time NHRA national event winner
also had tremendous things to say about Aragona
“I raced with his daddy a little bit when I first started
but Frankie was a fierce competitor,” said Rampy
“He really put forth a lot of effort into it
We always seem to wind up racing each other a whole lot
and you definitely never took that for granted
AUG 18-19 Lucas Oil Series Divisional Event
Metrics details
it remains unclear how mechanical forces affect their behaviour in vivo
Here we develop a mouse model in which the consequences of stretching on skin epidermis can be studied at single-cell resolution
Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA sequencing
we show that stretching induces skin expansion by creating a transient bias in the renewal activity of epidermal stem cells
while a second subpopulation of basal progenitors remains committed to differentiation
Transcriptional and chromatin profiling identifies how cell states and gene-regulatory networks are modulated by stretching
Using pharmacological inhibitors and mouse mutants
we define the step-by-step mechanisms that control stretch-mediated tissue expansion at single-cell resolution in vivo
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Growth on demand: reviewing the mechanobiology of stretched skin
Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment
Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage
Appreciating force and shape—the rise of mechanotransduction in cell biology
Mechanical forces and growth in animal tissues
Emerging views of the nucleus as a cellular mechanosensor
Mechanical forces direct stem cell behaviour in development and regeneration
Plasticity of epithelial stem cells in tissue regeneration
The osmotic tissue expander: a three-year clinical experience
Cell adhesion and mechanics as drivers of tissue organization and differentiation: local cues for large scale organization
α-Catenin as a tension transducer that induces adherens junction development
A single type of progenitor cell maintains normal epidermis
Distinct contribution of stem and progenitor cells to epidermal maintenance
Defining the clonal dynamics leading to mouse skin tumour initiation
Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling
Spatiotemporal coordination of stem cell commitment during epidermal homeostasis
Homeostatic epidermal stem cell self-renewal is driven by local differentiation
Defining stem cell dynamics and migration during wound healing in mouse skin epidermis
AP-1: a double-edged sword in tumorigenesis
p53/p63/p73 in the epidermis in health and disease
C/EBPα and β couple interfollicular keratinocyte proliferation arrest to commitment and terminal differentiation
Klf4 is a transcription factor required for establishing the barrier function of the skin
GRHL3/GET1 and trithorax group members collaborate to activate the epidermal progenitor differentiation program
Single-cell transcriptomics reveals that differentiation and spatial signatures shape epidermal and hair follicle heterogeneity
Single-cell transcriptomics of traced epidermal and hair follicle stem cells reveals rapid adaptations during wound healing
SCENIC: single-cell regulatory network inference and clustering
Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics
Polarization of myosin ii refines tissue material properties to buffer mechanical stress
YAP and ERK mediated mechanical strain-induced cell cycle progression through RhoA and cytoskeletal dynamics in rat growth plate chondrocytes
Actomyosin bundles serve as a tension sensor and a platform for ERK activation
Mechanobiology of YAP and TAZ in physiology and disease
its cofactors and the link to signal transduction
The roles of YAP/TAZ and the Hippo pathway in healthy and diseased skin
cortical cytoskeleton and cell shape in epidermal spindle orientation
Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions
A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors
Noncanonical hedgehog pathway activation through SRF–MKL1 promotes drug resistance in basal cell carcinomas
Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification
Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
Competition for space induces cell elimination through compaction-driven ERK downregulation
The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin
Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin
Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells
Hippo pathway effector Yap promotes cardiac regeneration
Lack of Diaph3 relaxes the spindle checkpoint causing the loss of neural progenitors
A global double-fluorescent Cre reporter mouse
The incompatibility of living systems: characterizing growth-induced incompatibilities in expanded skin
Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis
Distinct modes of cell competition shape mammalian tissue morphogenesis
Accurate expression profiling of very small cell populations
The Sequence Alignment/Map format and SAMtools
HTSeq—a Python framework to work with high-throughput sequencing data
GREAT improves functional interpretation of cis-regulatory regions
Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities
normalization and visualization of single-cell RNA-seq data in R
Pooling across cells to normalize single-cell RNA sequencing data with many zero counts
Computational assignment of cell-cycle stage from single-cell transcriptome data
Dimensionality reduction for visualizing single-cell data using UMAP
Comprehensive integration of single-cell data
Download references
We acknowledge the animal facility at ULB (Erasme campus)
Vanderwinden and LiMiF for the help with confocal microscopy
and colleagues who provided reagents mentioned in the text
scRNA-seq was performed at the Brussels Interuniversity Genomics High Throughput core and the Genomics Core Leuven
is supported by a long-term postdoctoral fellowship of the HFSPO (LT000380/2015-L) and an FNRS fellowship
is supported by a Royal Society EP Abraham Research Professorship and a Wellcome Trust Senior Investigator Award (098357/Z/12/Z)
is supported by a long-term fellowship of the HFSPO (LT000092/2016-L)
acknowledge core funding to the Gurdon Institute from the Wellcome Trust (092096) and CRUK (C6946/A14492)
FWO postdoctoral fellowship number 12W7318N and Marie Skłodowska-Curie fellowship number 12O5617N
a research grant from the Fondation Contre le Cancer
the foundation Baillet Latour and a consolidator grant of the European Research Council (ERC-EXPAND
Sanger Institute–EBI Single-Cell Genomics Centre
Electron Microscopy Platform of VIB Bio Imaging Core
The Wellcome Trust–Cancer Research UK Gurdon Institute
Wellcome Trust–Medical Research Council Stem Cell Institute
Department of Applied Mathematics and Theoretical Physics
helped with experiments and animal follow-up
All authors read and approved the final manuscript
The authors declare no competing interests
Peer review information Nature thanks Carien Niessen
reviewer(s) for their contribution to the peer review of this work
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
dashed yellow lines denote dermal-epidermal boundary and boxed area in pink
orange and green are shown at higher magnification
Ultrastructural analysis of cell–cell adhesion
Quantification of the intercellular spacing on images as in h and l
Quantification of the width of the desmosomes as in i and m
Quantification of the width of the number of hemidesmosomes per μm in j and n
TEWL measurements from n = 3 CD1 mice in CTRL and at different time point during expansion
Immunohistochemistry for the adherens junctions (AJ) component β-catenin
Representative images of AJ component p120-catenin (t) and E-cadherin (v) colour-coded for the signal intensity with ImageJ
Protein expression is visualized as a colour gradient going from black to yellow
with black as indicator of no expression and yellow as indicator of maximal expression
Quantification of the average integrated density signal for p120-catenin (u) and E-cadherin (w)
Each data point is the average of 3 sections per mouse (n = 3 mice per condition)
The quantifications are made on n = 3 different animals per condition on 10 different samples per mouse and represented as mean + s.e.m
Source data
Representative images of the tight junction (TJ) components ZO-1 (a) and Claudin-1 (c) and of Vinculin (e) colour-coded for the signal intensity with ImageJ
Quantification of the average integrated density signal for ZO-1 (b)
The number of mice per condition is indicated
inflammatory cells stained with CD45 (g) and macrophages stained with CD68 (i) (green) and Hoechst for nuclei (blue) on tissue sections
Percentage of CD45 (h) and CD68 (j) positive cells on the total dermal cells quantified based on the nuclear staining
mRNA expression analysis for the indicated gene in Untreated (Unt.
black) skin and skin treated with Dexamethasone (Dexa.
Fold change is expressed compared to one Unt
Maximum intensity projection of confocal pictures showing immunostaining for K14 (red)
BrdU (green) and Hoechst for nuclei (blue) 4 h following BrdU administration on whole mount epidermis
Proportion of basal cells that are BrdU positive (n = 3,694 cells counted from 3 mice for Untreated and n = 3,764 cells from 3 mice for the Dexamethasone treatment)
Source data
Panel n shows the results of one-progenitor model and the CTRL data
p shows the results of two-progenitor model and the CTRL data
These results show both the enhanced accuracy of the two-progenitor model over the one-progenitor model
despite involving the same number of fit parameters
Source data
while the two parameters in panel (f) represent variation in the net rates
Representative orthogonal confocal sections immunostained for Krt14 (red)
Krt10 (green) following short-term BrdU (white) incorporation identifying cells biased for renewal (Krt14+Krt10−)
cells primed for differentiation (Krt14+Krt10+) and differentiated cells (Krt14−Krt10+)
Percentage of the type of divisions in CTRL (108 divisions from n = 4 mice) and EXP D2 (254 divisions from n = 4 mice) based on short-term BrdU tracing and staining as in h
Source data
Immunohistochemistry on paraffin sections for c-FOS in control and EXPD4
Quantification of the number of cells c-FOSL+ in the basal layer related to q
Immunofluorescence on tissue sections for pSTAT3 in green and K14 (red) to identified the epidermis
Quantification of the number of cells positive for pSTAT3 in the basal layer related to s
3 sections quantified per n = number of mice and total number of cells indicated in parentheses d
Source data
showing the graph-based clustering results annotated by cell type
the IFE stem cells cluster are in red (IFE SCs#1) and dark red (IFE SCs#2)
the IFE committed cells (IFE CCs) cluster is in pink and the differentiated IFE cells (IFE DIFF.) are in green
The differentiated cells from the infundibulum (INF
the proliferating cells of the infundibulum (PROLIF
INF.) are in plum and the sebaceous gland cluster (SG) is in orange
The IFE stress cells (STRESS) are in dark grey and the cluster of stem cells stretch (SCs STRETCH) in yellow
UMAP plot of the CTRL sample colored by normalized gene expression values for genes identifying the IFE (c) versus infundibulum (d)
the sebaceous gland (e) and the proliferating cells (f)
Undifferentiated (g) and more differentiated cells (h) in the IFE identified the SCs cluster (i)
the CCs cluster (j) and the differentiated stage (k)
Gene expression is visualized as a colour gradient going from grey to yellow with grey as indicator of no expression (that is
expression values below or equal to the 50th percentile for that sample) and yellow as indicator of maximal expression
Table showing the specific marker genes used to annotate the different clusters
Integrated UMAP graphic representation of the IFE cells in CTRL
The proliferating stem cells (PROLIF.) are in light blue
the stem cells clusters are in red and dark red (SCs#2)
the committed cells (CCs) cluster is in pink and the differentiated cells (DIFF.) are in green
The stress cells (STRESS) are in dark grey and the cluster of stem cells stretch (SCs STRETCH) in yellow
Predicted cell-cycle phases assigned using the cyclone function from scran tool and visualized in the UMAP
cells in G2/M are in orange and cells in S phase are in red
Percentage of cells in the different cycling phase calculated on the total number of cells
UMAP plot colored by normalized gene expression values for the indicated gene and in the indicated sample
Gene expression is visualized as a colour gradient going from grey to yellow with grey as indicator of no expression and yellow as indicator of maximal expression
UMAP plots coloured by the degree of regulon activation for TFs differentially activated (AUC rank-sum test FDR corrected p-value <0.05) in the different conditions
Colour scaling represents the normalized AUC value of target genes in the regulon being expressed as computed by SCENIC
Heat map representation of the top 20 gene expression changes along the inferred pseudotime trajectory computed with Slingshot for the CTRL IFE
Heat map representation of the top 20 gene expression changes along the inferred pseudotime homeostatic trajectory computed with Slingshot for the EXP D1 IFE
Heat map representation of the top 20 gene expression changes along the inferred pseudotime trajectory computed with Slingshot characterizing the stress state for the EXP D1 IFE
Columns represent cells ordered by their position along the pseudotime trajectory; rows represent genes whose expression profiles show highest correlation (FDR-correted p-value <0.01) with the pseudotime variable
calculated using a generalized additive model (GAM)
The colour scaling of the cells represents the normalized expression value of a gene in a particular cell
Scheme of the genetic strategy to delete Diaph3 in the epidermis
Protocol to delete Diaph3 during stretch-mediated tissue expansion
Orthogonal views of confocal analysis of immunostaining for K14 (red) marking basal cells and Phalloidin (green) to visualize F-actin and Hoechst for nuclei (blue) in whole mounts of IFE in CTRL from a CD1 mouse
EXP D1 from a CD1 or Krt14-cre-DIAPH3fl/fl (Diaph3 cKO) mouse
Percentage of cells with F-actin fibres in the apical side of basal cells related to c (n = 4 mice per condition)
Orthogonal views of confocal analysis of immunostaining for K14 (red) marking basal cells
BrdU (green) and Hoechst for nuclei (blue) in whole mounts of IFE from Krt14-cre-DIAPH3fl/+ (Diaph3 WT) and Krt14-cre-DIAPH3fl/fl (Diaph3 cKO) mice during expansion
Epidermal Diaph3 cKO were born at a Mendelian ratio and did not present obvious pathological phenotypes
Immunostaining for the basal marker K14 (red) and the suprabasal markers K1 and K10 (green) in Diaph3 WT and Diaph3 cKO mice in EXP D2 and EXP D4
Epidermal thickness of Diaph3 WT and Diaph3 cKO mice in EXP D2 and EXP D4 (three measurements taken with ImageJ on two sections per mouse
n = at least 3 mice for the different conditions)
Scheme of the genetic strategy to delete Myh9 in the epidermis
Protocol to delete Myh9 during stretch-mediated tissue expansion
Immunohistochemistry for MYH9 in untreated and Tamoxifen induced Krt14-creER-MYH9fl/fl mice
Orthogonal views of confocal analysis of immunostaining for K14 (white)
BrdU (red) and Hoechst for nuclei (blue) in whole mounts of IFE in Myh9 WT and Myh9 cKO mice during expansion
Epidermal thickness of Myh9 WT and Myh9 cKO mice in EXP D2 and EXP D4 (three measurements taken with ImageJ on two sections per mouse
Analysis of adherens junctions in Diaph3 cKO and Myh9 cKO mice
Representative images of adherens junction (AJ) component α-catenin (m)
the α18 tension sensitive form of α-catenin (α18-catenin) (o) and Vinculin (q)
colour-coded for the signal intensity with ImageJ
Quantification of the average integrated density signal for α-catenin (n)
Each data point is the average of 3 sections per mouse (n = 5 mice per condition)
Source data
Protocol for Trametinib or Pimasertib treatment in CD1 mice operated to place the expander and scarified at D2
Immunohistochemistry for pERK on paraffin sections of epidermis form CD1 mice untreated or treated with the indicated drug at EXP D2
Quantification of the proportion of BrdU positive cells during expansion at the indicated time point in CD1 mice untreated or treated with Trimatenib or Pimasertib (n = at least 3 mice per condition as indicated
total number of cells analysed indicated in parentheses)
Immunohistochemistry for FOSL1 (e) and immunofluorescence for JUN (f) on sections of epidermis from CD1 mice untreated or treated with the indicated drug at EXP D2
Epidermal thickness measured with ImageJ on tissue sections at EXP D8 in CD1 mice untreated or treated with the indicated drug (n = 5 mice untreated
3 measurements on at least 2 sections per mouse)
Immunostaining (white) for YAP1 on skin sections in the control and in EXP D1
White arrows indicate nuclear localization
Quantification of YAP1 subcellular localization
bars and error bars represent the mean and s.e.m
similar level of YAP1 in nucleus than in cytoplasm
less YAP1 in nucleus than in cytoplasm (n = 150 cells for all samples except n = 120 for EXP D8)
Quantification of MAL subcellular localization
similar level of MAL in nucleus than in cytoplasm
less MAL in nucleus than in cytoplasm (n = 150 cells for all samples except n = 120 for EXP D8)
Immunostaining (white) for MAL (k) and JUN (l) on skin sections in the control and in EXP D1
Scheme of the genetic strategy to delete YAP-TAZ in the epidermis (m) and protocol to delete YAP and TAZ in stretch-mediated tissue expansion (n)
Immunohistochemistry for YAP (top) and TAZ (bottom) in Krt14-creER-YAP-TAZfl/fl mice before and after Tamoxifen administration
BrdU (green) and Hoechst for nuclei (blue) in whole mounts of IFE in YAP-TAZfl/fl (YAP-TAZ WT) or Krt14-creER-YAP-TAZfl/fl (YAP-TAZ cKO) mice at the indicated time point following expansion
Epidermal thickness of YAP-TAZ WT and YAP-TAZ cKO mice in EXP D2 and EXP D4 (three measurements taken with ImageJ on two sections per mouse
Protocol to inhibit MAL with the CCG203971 small molecule during stretch-mediated tissue expansion
Quantification of MAL subcellular localization in EXP D2 and EXP D4 mice treated or not with the MAL inhibitor
less MAL in nucleus than in cytoplasm (n = 150 cells per condition)
BrdU (green) and Hoechst for nuclei (blue) in whole mounts of IFE in mice treated with the MAL inhibitor or with vehicle control (untreated) at the indicated time point following expansion
Epidermal thickness of CD1 mice in EXP D2 and EXP D4 treated or not with the MAL inhibitor (three measurements taken with ImageJ on two sections per mouse
Source data
The number of counted divisions is indicated in parenthesis from n = number of mice
Source data
Source data
Notes on the modeling of the clonal data related to Fig
ATAC-seq peaks upreagulated during expansion
Peaks showing chromatin region with increased accessibility in EXP D2 (n=1 mouse) compared to CTRL (n=1 mouse)
Differential peaks are defined as peaks having at least a twofold change compared to control and being called peak in the expanded condition and contain at least 3 reads per million
Motif enrichment analysis on ATAC-seq peaks upregulated during expansion
Transcription factor motifs enriched in the ATAC-seq peaks that were upregulated by more than 2-fold in EXP D2 (n=1 mouse) compared to CTRL (n=1 mouse) as determined by Homer analysis using known motif search (3262 target sequences
Marker genes for clusters identified in CTRL
Genes differentially expressed in the different clusters in CTRL
Differentially expressed SCENIC regulons in CTRL
SCENIC analysis on the different clusters in CTRL
Wilcoxon rank-sum test FDR corrected p-value < 0.05
Differentially expressed genes CTRL vs EXP D1 SCs populations
P-values are FDR adjusted Wilcoxon rank-sum tests
Differentially expressed regulons CTRL vs EXP D1 SCs populations
Differentially expressed genes EXP D1 vs EXP D2 Treatments
Differentially expressed regulons EXP D1 vs EXP D2 Treatments
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Idaho (CBS2) — Colder weather is here and that means the start of cold and flu season
gave CBS2's Ashley Carter some helpful tips to stay healthy this flu season
"The biggest thing is prevention right
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getting in to see your doctor when you need to can be tricky
Saltzer Health is extending their hours at their family medicine clinics to help bridge that gap
Finding a primary care provider should always be your first step
but if you can't get in to see your primary care provider when the flu strikes
Saltzer Health has a few options that may help
Their extended hours through winter is a big help
but you can also see one of their advanced practice providers
Those could be nurse practitioners and physician assistants
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Wearing a serious demeanor as he peered into his log books earlier this summer at Summit Motorsports Park
three-time Comp eliminator champion Frank Aragona Jr
initially seemed to give off a "Do Not Disturb" vibe
swiftly disassembling the initial impression
and he didn't hold back once the conversation began to roll
a typical hernia operation had revealed a very untypical cancerous tumor that had nestled into the muscle around his stomach
"Only one in a million people get this very rare form of cancer
but I got this angiosarcoma," said Aragona
"If you knew me and would have seen me in March
you would have thought it might be the last time
Aragona wasted no time once the diagnosis was made
With the help of friends and family in the drag racing community and beyond
he sought out the best cancer treatment facilities across the country and spoke with them all
finally landing on Memorial Sloan Kettering Cancer Center in New York
where the now-New Jersey resident had grown up
"All fingers pointed back to the doctor in New York," said Aragona
husband to Beatrice and father to Frankie III and Emma
but you have a very aggressive form of cancer
The tumor had grown from 3cm to 8cm in a little more than a month
Aragona and his medical team began a return attack
He entered a rigorous course of chemo therapy
he received the treatment for nine hours a day
Aragona did this every 18 days for three rounds
and ahead of what was to be the fourth and final round
it was determined that his white blood cell count was too low
"But it turned out that they had slowed the tumor down and actually stopped it," he said
"They did the surgery to take it out and found it was only 10cm
and I didn't even need any more chemo or radiation
They had to cut a whole section of my right stomach muscle out and a little bit into the left to get everything
so I was supposed to recuperate for eight weeks
but I was very fortunate that the pathology came back that they got everything
Aragona missed the first Northeast Division race of the season
he had an appointment with his doctor to assess the progress of his healing
he mentioned to the doctor — in front of his wife and the head nurse — that there was another division race coming up
It would be seven weeks and five days after the operation
and Aragona stated that he would like to compete
'No.' But I felt good; I was just very sore," he recalled
"The doctor told me I was going to feel sore for a year
and that it was always going to feel different than it had before
you can do it.' My wife and the nurse were like
'Don't tell him that!' But we went to Cecil County
Aragona raced only his dragster in Comp at Cecil County Dragway in May
he entered Comp with his dragster again at Maple Grove Raceway
he felt ready to return to the seat of his championship Bantam altered
Although it was a little trickier to climb into
and 2019 Comp eliminator world champion knew he was ready
He immediately raced to the final round at the Lebanon Valley Dragway division race
Later in June and for the first time since the diagnosis last December
Aragona brought out both his dragster and his altered to race at the Summit Racing Equipment NHRA Nationals
He logged another runner-up for the season there in Comp in Norwalk
"I was hoping to get a win [by then]," admitted Aragona
"I was very happy that I always lived my life
they were the only thing on my mind — so we just did everything that we had to do
It's kind of surreal that I'm here racing two cars
I was diagnosed with a life-threatening disease that has a 35% survival rate
Aragona finally got his first post-cancer win this past weekend at the Atco Dragway divisional event
and before he even got back to the pit area
his phone was blowing up with congratulations on his 40th NHRA Lucas Oil Drag Racing Series victory
"I'm going to tell you something about friends and family," said an emotional Aragona
I couldn't go because of the surgery — but my dad and my cousin said that they would take the kids
The kids had an entourage with them on the starting line
It was pretty amazing being home and seeing that
People from all over the country contacted me when they found out about the cancer
People I don't even know were telling me they had been watching me race for years and that I had to get better
there were 'win lights for Frankie' shirts
Jackie Fricke made decals and took her name off the car and put my name on it
Atco photos courtesy of Diane Kubicke and David Smith
Ambassador Giancarlo Aragona was born in Messina
He graduated in law from the University of Messina on 14 November 1964 and entered the diplomatic service on 28 March 1969
He served as First Secretary at the Italian Embassy in Vienna from 1971 to 1974
as Consul at the Italian Consulate in Freiburg from 1974 to 1977
and as Counsellor at the Italian Embassy in Lagos until 1980
he worked in the Directorate General for Political Affairs and in the Department for Development Co-operation
After leaving his post as Counsellor at the Italian Embassy in London
he joined the Italian Permanent Mission to NATO in Brussels as Deputy Chief of Mission
Following a period as Diplomatic Advisor in the Ministry of Defence from December 1992 to April 1994
he was called to the position of Deputy Chief of Cabinet of the Foreign Minister
he was Chief of Cabinet of the Foreign Minister
By Seattle Mag April 24
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He created a flurry of anticipation this past May after announcing his plans to open a contemporary Spanish restaurant in downtown Seattle. And today, Spinasse's Jason Stratton welcomes his newest project into the world: Aragona
After a weekend of practice runs on friends and family
the sprawling restaurant — perched high enough above the city bustle to create stellar views of the waterfront — is ready to roll
and Portland transplant Clare Gordon will be doing desserts
Dinner starts at 5 pm. Regular hours can be found on the Aragona website.· Aragona [Official Site]· All Aragona Coverage [~ESEA~]· All Eater Inside Coverage [~ESEA~]
There are a lot of thankless jobs in horse racing—outrider
hotwalker come to mind—but few of them are as open to public scrutiny as the morning-line oddsmaker
The work of the morning-line oddsmaker is visible daily
its correctness able to be assessed by anyone interested enough to pay attention
And while a sharp morning line is seldom the subject of commentary
the linemaker who gets it wrong also gets an earful
David Aragona became the oddsmaker for New York Racing Association about a year ago
following a stint as a handicapper at Timeform US
He started going to the races when he was in primary school
taken there by his father and his uncle.
"My father had all these VHS tapes of the Breeders' Cup and the Kentucky Derby," he recalled
"and I'd watch them and educate myself
A regular handicapper as a teenager growing up in northern New Jersey
racing took a back seat to education when he attended New York University
Sign up for BloodHorse Daily
"The blog developed a little bit of a following through Twitter
and I made some connections," said Aragona
"Marc Attenberg at Timeform reached out to me in early 2015 as a kind of informal consultant
and that led to my working with them on a part-time basis
I started working for them full time."
Aragona does analysis of NYRA races and major national races for Timeform
along with video analysis for NYRA and DRF
He also makes regular appearances on Talking Horses
NYRA's in-house handicapping show.
He acknowledged making the morning line for the Belmont is not exactly the same as making it for a $40,000 claimer on a Wednesday afternoon
you get a bit of an opportunity to weigh public opinion more than you usually do," he said
"I can log on to social media to see what people are saying and what direction they're leaning
I probably wouldn't have made Tacitus the favorite
given that War of Will won the Preakness and Tacitus lost the Kentucky Derby (presented by Woodford Reserve [G1])
and everybody seems convinced that he's the horse that will relish the Belmont distance."
and I exceeded my own expectations," he said
"I don't track as closely anymore."
He often has to wear two hats when he's assessing a card: his linemaker hat
assessing how he thinks the public will bet; and his handicapper hat
"I generally do the morning line first," he said
"then put it aside for a little while and come to handicap with a different set of eyes."
And while he generally finds it relatively easy to ignore the social media critics
he will mute people that start slinging mud
"That's not my style," he said
And when someone whose opinion I respect has a criticism
"It's easy to do a pretty good job when the racing is straightforward
especially at Aqueduct," he continued
"It's a lot more complicated when you have turf racing and first-time starters and 2-year-olds at Belmont and especially at Saratoga
but sometimes it's just impossible."
David Aragona posts his picks & plays each live race day
David Aragona is a Daily Racing Form handicapper and morning line oddsmaker for NYRA races
TimeformUS past performances, available from Daily Racing Form, offer a revolutionary set of tools for analyzing pace, speed figures, and form. Learn more about TimeformUS and get PPs
Clear favorite Tiote (#3) may win at a short price
but haven't been thrilled with his first couple of starts and wonder how much upside is left here
Poppy's Ticket (#1) offers some appeal among the firsters
but will pull in support due to the presence of Irad
The 5 consecutive gate works leading into the debut are also unconventional
Want to instead take a shot with Don Luis (#7) off a layoff
but Marisa Monserrate does have a $2.98 ROI with all starters over 5 years
Thought this colt showed some potential on debut last year and was just badly overmatched in his second start
Appears to be training well for the return and intriguingly attracts John Velazquez while shipping to New York when there were surely easier spots available at the recently opened Finger Lakes meet
Don't have much trust left for Bendoog (#6)
who possesses the ability to beat a field like this but has struggled to find the winner's circle recently
breaking slowly and lugging in on his riders
Jose Lezcano figures to get aggressive here
but those tactics could be dependent on the break
he didn't run as badly as it looks last time
where he got involved in a fast pace and understandably faded as the race fell apart
His TimeformUS Speed Figures make him look far more competitive here than his price will suggest
Also don't mind him pairing back up with Jose Ortiz
who has gotten some better results out of him in the past
Pretty intrigued by this switch back to turf for On Command (#7)
especially now that she appears to be in career best form since the trainer switch to the still underrated Amelia Green
Filly ran a bit better than it looks in both turf starts last year
contesting fast paces going distances that are just too far for her
Strikes me as one that will take well to turf sprinting
and may be catching some key rivals in a vulnerable state as they return from layoffs
Nothing against the returning Clement pair
but each ended their campaigns on sour notes
Love Appeals (#3) has had a very light worktab for the return
and Dontlookbackatall (#5) has to prove that she can still recapture top form as a 5-year-old
Not totally convinced that we're ever going to see General Partner (#5) put it all together after he showed so much promise early in his career
Thought his big fig last summer at Saratoga was aided by a favorable pace setup and track bias
Did catch a sharp rival off the claim last time
and now figures to be a short price again just because of connections
Drake's Passage (#1) is obviously the main rival
but he's not the most reliable sort either after disappointing twice at the end of last year
Any rain that falls before this race may not suit him
and don't love the rail draw for a horse that seems to prefer racing freely in the clear
Will instead go back to Reddington (#4) one more time
$3.16 ROI) second off the claim in dirt routes over 5 years
He was oddly live on the board last time and didn't get an ideal trip and Castellano kept to a right-handed stick
allowing him to lug in through upper stretch
Was still maintaining big strides to the wire once he got clear late
and may benefit from more aggressive handling with the switch to Ricardo Santana
Feels like there is opportunity in this Vagrancy
since I'm not thrilled with either of the two fillies than I pegged as ML favorites
It's far from clear that Almostgone Rocket (#2) is still the same horse that we saw last summer after she was so disappointing off the layoff last time
and I'm not convinced that Haulin Ice (#5) can reproduce her Oaklawn form in New York
The other Saffie runner R Disaster (#1) is more interesting to me after she was involved in a suicidal pace last time at Gulfstream and still tried to battle back last when challenged by the classy Nic's Style
She should play out as the speed of the speeds from the rail
will try to beat those speeds with Socially Selective (#6)
Can't say that I've ever been a huge fan of this mare
but she just seems to fit this race really well
losing some position into the lane before going to the rail in the stretch
She drew perfectly outside here and should rate and finish in a race that seems ripe to fall apart
Train the Trainer (#5) is an intriguing new face in the NY-bred ranks after debuting in a tough open company field at Santa Anita behind the highly touted Goal Oriented
but he still has to overcome shipping across the country
and he figures to get an early challenge from Merica's Back (#8)
That Maker trainee ran better than it appears last time after missing the break and then pulling his rider forward into a premature move
which could potentially set things up for Iron Max (#3) as he returns from a layoff
Colt trained really well in Saratoga last summer
but Jeremiah Englehart seemed unsure of what he really wanted to do
trying a variety of surface and distance combinations
Intrigued to see him show back up in a dirt sprint for the underrated Amelia Green
Think there's more ability here than his form would suggest
and the presence of the favorite could ensure he's still a fair price even with Prat hopping aboard
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provided the licencing rights for the iconic franchise
while Funko contributed to the design of the toys
Aragona acknowledges that this transformation requires a careful balance between retaining Kinder’s childlike charm and appealing to a more mature audience
as this is our first attempt at such a strategy
We plan to achieve this balance through tailored marketing and in-store placements,” he explains
While the toys and marketing will remain playful and childlike for younger children
older audiences will see a more sophisticated approach with digital touchpoints and mature toy designs
The collection has generated significant attention on social media
with unboxing videos showcasing the excitement of discovering different character toys
Aragona mentions that over 90% of the social media conversations surrounding the new Kinder Joy are organic
Although social media buzzes with excitement for the new collection
it appears to be unavailable at several marketplaces
When asked if this scarcity is a deliberate strategy to maintain hype and curiosity
“The brand’s initial steps towards this launch were rather slow
We were cautious about production and wanted to gauge initial reactions
we have ramped up both marketing and production.”
The Harry Potter collaboration is just the beginning
Kinder Joy is already exploring new partnerships with other beloved franchises
aiming to replicate this success while ensuring alignment with its core values
Plans are also in motion to introduce culturally relevant themes for the Indian audience
Kinder Joy joins the list of brands playing on nostalgia to continue to appeal to older demographics
and that’s especially true in Competition eliminator
after claiming a second straight and third overall championship in 2019
the numbers prove that there are few who are better at it than him
He’s just the third driver to win back-to-back points-based championships in the class and the third to score a trio of titles
“The things I love about Comp are the challenge and the chess game,” he said
“It’s not as simple as everybody thinks; you gotta know what your opponents can do
a championship was not really in the plan early in the season
“Craig Bourgeois got on a run in the beginning of the year
and everyone thought he was just going to run away with it
so my main focus at that point was just to win Indy [the U.S
After starting the year with their E/Dragster Automatic car and scoring wins at the Division 1 event at Maple Grove Raceway and the JEGS Allstars
switched to a new Ken Keir-built Bantam that they had pegged for the J/AA class
They debuted it at the Division 1 event at Lebanon Valley Dragway in June
where they won the race and the Best Engineered Car award
and then also won the next two divisional events to change the course of their season
“We knew J/AA was a good index because nobody’s really been in that class for many
we were on a cloud because that put us right into the hunt again
and it made wanting to win Indy much more interesting because it’s an extra 10 points [for the 64-car field].”
Aragona raced his way through five rounds of competition in Indy
capping the victory with a strong (-.56) 7.60 to defeat David Billinsgley in the final
and we got the right breaks — which you gotta have at the right time to win in Comp — and we used up index when we needed to
I probably didn’t need to use up as much as I did in the final
but it was 10:30 at night against a great driver like Billingsley
I’d drive it to the second turnoff if I had to.”
Aragona went to work on the numbers and knew what he needed to do better than anyone to lock up the title
which he did in Charlotte at the NTK NHRA Carolina Nationals
You look online and see you can better their score
nobody else in the country could pass us no matter what they did.”
Frank Affronti trigged a foul start against Aragona to secure the title
then Aragona went on to beat Elio Mannino for good measure
“It’s hard to compare the three championships because each is special
but I’d have to say this year was better because of winning Indy and the Allstars
and the world championship in one year — I mean
That’s pretty much all my favorites in one.”
and it was in Pomona where his season was really capped when fellow three-time Comp champ Bill Maropolus asked him to pose for a photo with he and David Rampy
he figured that I would be next [to win three]
and that I would be the one who broke the tie and won four
Aragona extended thanks to his father and to Dave Yediny
Even when I’m home I’m thinking about racing and strategy and things to do to make it better
and I thank my family for their support.”
with the Austin American-Statesman's editorial board
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JoJo Aragona had no idea that he had a diehard fan
Fresh off his 138-pound state championship for Pope John
he was wrestling in the Pittsburgh Classic on March 15
That is where he was approached by a 6-year old girl named Kamryn
who was able to name all of his accomplishments and everything he had ever done
Aragona gave Kamryn his Pittsburgh Classic medal
Aragona got a text from her mother that Kamryn had slept with the medal all three days and had even taken it to school
That is the kind of impact and legacy Aragona will leave at Pope John as he embarks on his next chapter at Rutgers
Aragona -- the winningest wrestler in Sussex County history -- is the 2018-19 New Jersey Herald Wrestler of the Year
"It feels amazing that I can engrave my name in Pope John history as hopefully one of the best wrestlers to ever come through here," Aragona said
Eddie Ventresca can come in here and do the same thing in excelling past my records to break them
Aragona finished his Pope John career with a record of 158-6
The previous all-time wins record for the Lions was 130 by Jake Rotunda while former High Point wrestler Nick Francavilla previously led Sussex County with 156 career wins
Aragona's state championship bout ended with a 7-1 win over Jacob Perez-Eli of Paulsboro as Aragona was able to live up to his billing as the No
Aragona's senior year ended with a perfect 38-0 record that included titles at the Beast of the East
District 2 and Region 1 along with the state title
Aragona also helped Pope John win two North
Non-Public B titles and a Non-Public B state title in his junior season
a couple of random events got Aragona started in wrestling
he gave me a flier to come out and try it," Aragona said
so I was always more interested in football and wrestling was kind of like the side sport that I played until eighth grade when really that all changed
so I had to quit football and I really just started pounding wrestling
Once Aragona started focus solely on wrestling
He was just 85 pounds in eighth grade before he started intensifying his workouts
His daily routine now includes getting up at 4:15 a.m
going through his school day and then going to Pope John's practice before either hitting up another practice or going home to lift
becoming the top wrestler in the county does not just happen by accident
"My mom and dad drove me mainly," Aragona said
"My dad was always pushing me to be the best I can be
and my mom was always making sure that I was staying healthy by eating the right foods
They are the main reason why I am where I am today."
Aragona will join a host of other talented New Jersey wrestlers at a program on the rise in Rutgers
Aragona will be joined in RU's recruiting class by Robert Kanniard of Wall
who won the state title at 160 pounds this year
They will join three New Jersey state champions from last year's recruiting class in Bill Janzer of Delsea
Jake Benner of Ocean Township and Kyle Lightner of Delaware Valley
The grind of the Big Ten Conference is something Aragona is looking forward to
"Definitely my top-bottom work will improve a lot just by being in the Big Ten and being in the room with all of those guys," Aragona said
everything will get tweaked to improve more
but I feel like I will become a better wrestler wrestling in the Big Ten
I can win a couple of Big Ten titles and a couple of national titles."
There is a certain buzz in the air when Pope John senior JoJo Aragona is competing in a wrestling tournament
he carries himself with the swagger you would expect from somebody with his pedigree
He always has the same bright green and gray shorts on and either a Pope John jacket or a long-sleeved shirt of his future college destination — Rutgers
Aragona is in his own world with headphones always blasting in his ears to mentally prepare himself for the battle ahead
The intensity in his eyes is something to behold
The Lions senior has taken New Jersey high school wrestling by storm since he arrived on the scene four years ago
He came to Pope John with all the talent in the world as a freshman
but now he has added the confidence and swagger to go with it
“My attitude and my mindset are the biggest factors of what’s changed,” Aragona said
“I’m just more confident in myself and going out there
That’s really all it is — just going out there and scoring as many points as I can
do my own warm-up and everything I have to do for myself to get myself right
I go out there knowing I am where I am for a reason
I just go out there to have fun and get to my attacks and score my points
I just stick to the solid basics that I do.”
Aragona is about to embark on his final journey to Atlantic City in hopes of capturing the only thing missing from his career — an individual state championship
He got that started off by dominating the Region 1 Tournament
winning it for the fourth time in his career on Saturday at West Milford
Aragona pinned his first two opponents before beating Craig Manno of St
It was actually his first decision against an NJSIAA opponent this year
Aragona beat Travis Mastrogiovanni of Blair Academy
for his only other regular decision against a New Jersey opponent
Every other win against New Jersey opponents has been by at least a major decision
His record this year stands at an unblemished 35-0 headed into Atlantic City and 153-6 for his career
He is four wins away from setting a new Sussex County wins record after High Point’s Nick Francavilla won 156 matches from 2008 to 2011
Aragona became just the second Pope John wrestler and fourth from Sussex County to win four Region 1 titles with the win over Manno in the finals
Mike Frick last accomplished the feat for the Lions from 1968-1972 before High Point legends John Gardner (1987-1990) and Francavilla did it for the Wildcats
“Everyone in the room pushes each other and we work hard,” Aragona said
“We fight for what we have and what we want on the mat
To be the second ever from Pope John is just an amazing feeling really.”
That confidence has also helped Aragona keep his edge and his laser focus he takes into each match
Even the best wrestlers can get caught by surprise by one move
It happened to two-time state champion Pat Glory of Delbarton in Atlantic City last year when he got taken to his back before recovering
Something similar happened to Aragona as a sophomore when he got upset in the District 2 semifinals by Mark DiGeronimo of Kittatinny
Aragona welcomes the challenge of every opponent
He knows that as the top ranked 138-pounder in the state and in the country he will get the best shot from everybody looking to knock him off his perch to make a name for themselves
The Rutgers commit has not let that happen so far
and he wants to be challenged at the highest level
the kids will wrestle me hard because I like when kids wrestle hard and get a little chippy,” Aragona said
When kids just like to back up and run away
I’m still going to get to my attacks and try to score
but it just doesn’t look good on their part backing up and running away
That’s really what I look forward to when I come to places like this
It all comes down to this week for Aragona after placing third in the state as a freshman (106) and a junior (120) and second as a sophomore (120)
Everything he has been working toward is a culmination of this moment
“I’m just going to take it one match at a time and one step at a time,” Aragona said
“I’m going to warm up the same way I’ve been all year
I’m going to wrestle every match the same and try to score as many points as possible