the largest accelerator of medical technology companies in the world
had collaborated with Asia Pacific Medical Technology Association (APACMed) to recognise and honor the latest revolutionary medical technologies from around the globe at the forum staged on September 5th and 6th
a Taiwanese Medical device company APrevent
developing solutions for voice disorders emerged as the 2024 MedTech Innovator Asia Pacific Accelerator Program Lead Winner and awarded $175,000
KA Imaging (Canada) and Qritive (Singapore)
are awarded $10,000 each for their exclusive innovations and contribution to the MedTech industry
2024 MedTech Innovator Asia Pacific Accelerator celebrated the APAC cohort companies' stellar innovations
An expert panel of MedTech executives discussed the latest innovations in depth with the achievers
Johnson & Johnson MedTech Asia Pacific; Vy Tran
MedTech Innovator has been a catalyst for groundbreaking healthcare Solutions
The accelerator works closely with stakeholders across the industry to foster the growth of early to mid-stage startups
Till date MedTech Innovator has fostered the growth of 717 companies that have collectively raised over $8 billion in follow-on funding and introduced 345 products to the market
more than 400 companies applied for the Asia Pacific Program
and 20 were selected to complete the four-month Accelerator Program
and digital health companies from around the globe made up the Asia Pacific cohort
an unparalleled network of over 600 global peers
and over $300,000 in cash and in kind prizes
a Taiwan-based company has developed innovative solutions for voice and speech disorders and is the first Taiwanese company to win the MedTech Innovator Asia Pacific Accelerator Program Grand Prize
“APrevent’s VOIS offers a significant improvement for the lives of patients suffering from glottic insufficiency or vocal fold paralysis
reduce complications and enhance recovery through a minimally invasive procedure,” said Paul Grand
breakthrough innovations in the MedTech field were recognized
“APACMed is proud to partner with MedTech Innovator Asia Pacific
supporting our shared goals to identify
foster and mentor medtech innovation in the region to advance patient care,” said Harjit Gill
Head of Business Development – Asia Pacific
Johnson & Johnson MedTech said “Johnson & Johnson MedTech will continue to support MedTech Innovator APAC Accelerator in advancing new technologies for patients in our region
which we view as one of the most promising areas for medtech innovation.”
MedTech Innovator Asia Pacific unites best-in-class startups with investors
and allied service professionals in the medtech industry to help drive commercialization of life-changing technologies in the region
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communications@biospectrumasia.com
+65 90150305
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Transwestern’s Paul Wittorf had quite the promotion recently when he went from SVP of the Houston office to executive managing partner and market leader for Transwestern’s North Texas operations
We sat down for a quick Q&A to get to know him better
Paul: My first job was working a bee farm in Navasota, TX. My first real estate job was leasing Esperson Buildings in Downtown Houston
Bisnow: How did working on a bee farm prepare you for a career in commercial real estate
Bisnow: As someone who has a fatal bee-sting allergy
Paul: To gain the trust of Transwestern employees
clients and the broader real estate community in DFW
Bisnow: What is something you love about commercial real estate
Paul: It’s a tie between crème brulee and bread pudding
Paul: I can ride a unicycle while juggling
Paul: The best thing about working in commercial real estate and specifically in Texas is the people
We are also fortunate to be in such a business-friendly state
which will contribute to the growth of our industry in the future
Texas is a great place to be in the commercial real estate business
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What: Ronald McDonald House of Dallas Under the Moonlight Gala
Where: 141 Manufacturing Street mixed-use development
The 411: Supporters of Ronald McDonald House of Dallas donned their cutest
most colorful spring dresses on May 5 for the Cinco de Mayo-themed fiesta
Attendees gathered at sunset for the organization's first in-person gala since the pandemic pause
along with Holly and Paul Wittorf and honorary chairs Haylie and Bert Crouch
a home-away-from-home for families of seriously ill children who travel to Dallas seeking medical treatment in area hospitals
Cinco de Mayo was the perfect way to bring back the beloved gala
said RMHD chief development officer Diane Fullingim
the Under the Moonlight gala had been the pinnacle of our spring fundraising season
raising over $3.5 million for the House since 2005,” she said
“Getting to have the event in-person this year after such a long absence was an absolute blessing
and that excitement was palpable in the room."
Guests enjoyed the music of a mariachi band and noshed on authentic Mexican cuisine and sipped Osadía tequila tastings
The industrial space had been transformed by event producer extraordinaire Hamilton A
with hundreds of bright tissue paper blooms
A competitive auction included such fabulous items as a private suite for 21 at the Kenny Chesney concert at AT&T Stadium
a one-week luxury home escape in 30A Florida
While exact figures were not made available
the organization says it "smashed" its fundraising goals
from gorgeous weather to The Masters golf tournament
All that and more found its way onto chic chapeaus and sky-high hats at Mad Hatter's 2025
themed "Celebrating Spring in the South." The epic fundraising luncheon sponsored by the Women’s Council of the Dallas Arboretum assists with the development
and Women's Council president Therese Rourk welcomed fashionably dressed guests to Ginsburg Plaza at the Dallas Arboretum on April 17
Kristyn Potter (@acaeventdesigns) captured the flirty
while a lively and talented trio comprised of students from Lake Highlands High School Jazz Ensemble kept spirits high
The Mad Hatter's extensive silent auction drew plenty of interest
Those interested in competing for blue ribbons paraded their expertly crafted millinery before judges Amanda Shufeldt
before the jazz trio led a vibrant second line into Rosine Hall for the fashion show
The Taste of the Masters group.Photo by ASHGPHOTO
Presented by NorthPark Center and produced by Jan Strimple
with NBC 5 anchor Laura Harris serving as emcee
the fresh fashions were as light as a spring breeze
with beauty by Glossier and jewelry from Eiseman Jewels
The hat winners then got their own turn on the runway:
Emcee — and self-proclaimed Georgia peach —Laura Harris.Photo by ASHGPHOTO
Guests were then invited to sit down to a lovely lunch of chilled avocado soup and mixed greens topped with sous-vide chicken
all drizzled with peach-hot honey dressing
A Bananas Foster tart proved a sweet ending to a positively enchanting day at the Dallas Arboretum
Metrics details
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by clonal expansion of myeloid blasts in the bone marrow (BM)
the prognosis for AML patients remains poor
and there is a need to identify novel molecular pathways regulating tumor cell survival and proliferation
but expression correlates with survival in AML patients and patients with higher expression have poorer outcomes
Silencing FBXO21 in human-derived AML cell lines and primary patient samples leads to differentiation
knockdown of FBXO21 leads to up-regulation of cytokine signaling pathways
Through a mass spectrometry-based proteomic analysis of FBXO21 in AML
we identified that FBXO21 ubiquitylates p85α
a regulatory subunit of the phosphoinositide 3-kinase (PI3K) pathway
for degradation resulting in decreased PI3K signaling
dimerization of free p85α and ERK activation
These findings reveal the ubiquitin E3 ligase
plays a critical role in regulating AML pathogenesis
specifically through alterations in PI3K via regulation of p85α protein stability
Little is known about the molecular mechanism of FBXO21
and it has not yet been studied within the context of malignant hematopoiesis
knockdown (KD) of FBXO21 in AML patient samples and patient derived cells lines led to apoptosis and decreased proliferation at a greater degree compared to normal human CD34 + HSPC
Silencing of FBXO21 in AML increased expression of inflammatory cytokines and chemokines
we utilized a mass spectrometry based proteomic approach to identify p85α as a substrate of FBXO21
p85α is targeted for ubiquitination by FBXO21
and stabilization of p85α leads to apoptosis
the data suggest that FBXO21 plays a key role leukemia progression and maintenance but has a limited role in normal hematopoiesis suggesting FBXO21 as a potential therapeutic target for drug discovery
D Western blot probing for FBXO21 in two independent HBM samples compared to patient-derived AML (MOLM-13
A–J (MOLM-13: n = 3 biological replicates
AML Patients: n = 3 technical replicates) MOLM-13 cells and 4 AML primary samples (2 de novo
2 relapse) were infected with lentiviral shRNAs against shFBXO21 and shNTC were analyzed at 72 h post puromycin selection by (A
B) western blot for knockdown in (A) AML patient derived cell line
(C) proliferative ability of MOLM-13 cells by cell count
E) (left) representative flowcytometry plot and (right) bar graph of Annexin V and propidium iodide (PI) for percent of (1) AnnexinV+/PI− and (2) AnnexinV+/PI+ apoptotic cells in (D) MOLM-13 and (E) AML primary cells
Cells were analyzed by flowcytometry for (F) (right) representative flowcytometry plot and (left) bar graph of CD11b (MOLM-13) and (G) (right) representative flowcytometry plot and (left) bar graph of CD15 (AML primary cells) expression
Colony forming ability by CFU assay in (H) MOLM-13 and (I) AML primary cells
J Survival of sub-lethally irradiated NSG mice transplanted with 5 × 105 MOLM-13 cells infected with shRNAs against shFBXO21 and shNTC
3 technical replicates) MOLM-13 cells were infected with retrovirus expressing FBXO21
and Empty control were analyzed after sorting via FACS for (A) protein expression by western blot
(D) for percent of Annexin V+/PI- and Annexin V+/PI+ apoptotic cells
(E) (left) representative flowcytometry plot and (right) bar graph of CD15 expression by flow cytometry
and (F) survival of sub-lethally irradiated NSG mice transplanted with 5 × 105 cells infected with an Empty control or a plasmid overexpressing FBXO21
G MTT assay in MOLM-13 NTC and shFBXO21.55 following treatment with between 0.1-1000 nM cytarabine for 48 h
and (I) AML primary cells with FBXO21 KD and shNTC
and (J) MOLM-13 FBXO21 and Empty were treated with 50 nM cytarabine for 48 h
stained with Annexin V and PI for Annexin V+/PI− and Annexin V+/PI+ apoptotic cells
Together these finding demonstrate that levels of FBXO21 impact survival
A Volcano plot showing fold change of expressed genes from MOLM-13 cells with silenced shFBXO21 and shNTC
B Gene ontology analysis showing pathways known to be associated with significantly upregulated (p < 0.05
≥1-fold change) and downregulated (p < 0.05
≤1-fold change) genes using DAVID bioinformatics database
C Localization of significantly upregulated genes (405)
D Cytokine array for supernatant of MOLM-13 cells with shFBXO21 KD and shNTC
membranes showing the change in inflammatory cytokines and quantified intensities relative to internal standards
CXCL10 secretion was evaluated by enzyme-linked immunosorbent assay (ELISA) in (E) MOLM-13 cells with silenced shFBXO21 and shNTC
(F) AML primary cells with silenced shFBXO21 and shNTC
and (G) MOLM-13 cells expressing FBXO21 and Empty control
A Schematic of TMT MS and K-ε-GG IP/MS using MOLM-13 cells infected with shRNAs against shFBXO21 and shNTC
B Volcano plots showing fold change of expressed proteins from shFBXO21 compared to shNTC cells
C Gene ontology analysis showing pathways known to be associated with significantly upregulated (p < 0.05
≥1.3-fold change) proteins using DAVID bioinformatics database
Western blot for previously known FBXO21 substrates (ASK1
EID1) and other MAPK pathway proteins (D) in MOLM-13 cells and (E) AML primary cells
proteins involved in cytokine signaling pathways
and RNA-seq data comparing overlap of differentially expressed proteins and genes
G Western blot in MOLM-13 cells for validation of upregulated proteins of interest identified via the combination of proteomic and genomic analysis
the combination of proteomic and genomic analysis yielded two potential novel FBXO21 substrates in AML
A Western blot of endogenous immunoprecipitation of FBXO21 in MOLM-13 cell line
B Western blot of GFP and HA immunoprecipitation in HEK293T cells transiently transfected with plasmids expressing GFP-tagged p85α and/or HA-tagged FBXO21/∆FBXO21
C Western blot of shNTC/shFBXO21.55 MOLM-13 cells treated with 20 μM MG132 or DMSO
D Western blot of Ubiquitin immunoprecipitation in shNTC/shFBXO21.55 HEK293T cells transiently transfected with p85α and 2
E Western blot of Ubiquitin immunoprecipitation in Empty/FBXO21/∆FBXO21 HEK293T cells transiently transfected with p85α and 5 or 10 μg Ubiquitin
F HEK293T cells were transfected with GFP-tagged p85α
After immunopurification with anti-GFP/anti-HA
in vitro ubiquitylation of p85α was performed in the presence of E1
Samples were analyzed by western blot with the indicated antibodies
these results demonstrate that FBXO21 directly mediates the ubiquitylation and degradation of p85α in AML
3 technical replicates) MOLM-13 cells were infected with retrovirus expressing p85α and Empty control were analyzed after sorting via FACS by (A) western blot
(C) for percent of Annexin V+/PI- and Annexin V+/PI+ apoptotic cells
Western blot in MOLM-13 cells with silenced shFBXO21 and shNTC for (F) PI3K pathway proteins and (G) native gel for PI3K complex proteins
H Schematic highlighting FBXO21 mediated alterations within PI3K signaling pathway
Together these finding suggest that p85α overexpression directly leads to ERK activation and elevated CXCL10 expression
and elevated CXCL10 has a negative impact on AML cells
This suggests that loss of FBXO21 leads to decreased canonical PI3K signaling and promotes dimerization of p85α leading to cell death and differentiation of AML cells by elevated CXCL10 via ERK activation
led to activation of ERK and increased CXCL10 suggesting that p85α is either indirectly or directly activating ERK
we found that silencing of FBXO21 leads to decreased canonical PI3K signaling with decreased activation of AKT
as well as decreased interaction with the catalytic sub-unit p110
Excess free p85α due to overexpression and stabilization of p85α protein promoted dimerization of p85α
Future studies are needed to decipher the signaling cascade altered by FBXO21 silencing and p85α overexpression
It is unknown whether p85α dimers can activate ERK or decreased AKT phosphorylation promotes ERK activation
Addition of CXCL10 to the media led to an anti-proliferative effect
however previous studies have shown inhibition of AKT signaling can also inhibit suggesting multiple players in the signaling cascade maybe contributing to the anti-proliferative effects
These findings identify a novel role of FBXO21 in regulating PI3K signaling in AML
These findings identify a novel role for FBXO21 in PI3K signaling by ubiquitination of p85α
Although p85α is a regulatory sub-unit of PI3K signaling and lacks kinase activity
excess free p85α following silencing leads to dimerization and decreased interaction with its catalytic sub-unit p110
the data suggest targeting FBXO21 could inhibit canonical PI3K signaling and impedes growth of AML
but may also impede growth of other cancer sub-types dependent on canonical PI3K signaling
Lentivirus was produced according to manufacturer instructions
Cells were treated with 1 μg/ml of puromycin 48 h post infection
cells were treated for 48 h with 50 nM cytarabine
cells were treated for 4 h with 20 µM MG132
For CFC assay cells were plated 100 cells/well of a 24-well plate in Methocult (H4434
5 × 105 MOLM-13 cells were transplanted into sub-lethally (250 cGy) irradiated 6–10 week old NSG mice (#005557
All experiments performed were approved by the Institutional Animal Care and Use Committee of the University of Nebraska Medical Center in accordance with NIH guidelines
staining was performed following BioLegend apoptosis staining protocol
Antibodies listed in supplemental materials and methods
Total RNA was harvested from cells using the Monarch Total RNA Miniprep Kit (New England Biolabs
RNA sequencing and analysis was performed by Novogene
Cytokine arrays were performed in accordance with the manufacturer’s protocol (R&D Systems
Proteome Profiler Array: Human Cytokine Array Kit)
CXCL10 ELISA assays were performed per manufacturer’s protocol (R&D Systems
HEK293T cells were transfected with plasmids encoding HA-FBXO21
or GFP-p85α were immunopurified from the whole cell extracts using Anti-HA (Sigma) or Anti-GFP (MBL International) beads overnight at 4 °C
The immunopurified HA-FBXO21 or HA-ΔFBXO21 (0.5 µg) proteins were incubated with immunopurified GFP-p85α (0.5 µg)
Ubiquitylation reactions were performed in 100 mM NaCl
and stopped with 2× laemmli buffer (10 min at 95 °C)
All experiments were performed in triplicate unless noted and statistical analyses were performed using unpaired two-tailed Student’s t test assuming samples of equal variance
Error bars depict the standard deviation ± mean
the p value was calculated using a Log-rank (Mantel-cox) test
The remaining data needed to evaluate all conclusions are available within the Article and/or Supplementary Information
The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability
Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression
The SCF ubiquitin ligase: insights into a molecular machine
Regulation of normal and malignant hematopoiesis by FBOX ubiquitin E3 ligases
Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia
FBXO21 mediates the ubiquitylation and proteasomal degradation of EID1
A comprehensive method for detecting ubiquitinated substrates using TR-TUBE
Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21
Lys29-linkage of ASK1 by Skp1-cullin 1-Fbxo21 ubiquitin ligase complex is required for antiviral innate response
Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability
F-box protein interactions with the hallmark pathways in cancer
Ubiquitin E3 ligase FBXO21 regulates cytokine-mediated signaling pathways
but is dispensable for steady-state hematopoiesis
Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group
Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel
Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths
Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation
The emerging role of CXCL10 in cancer (Review)
Downmodulation of ERK activity inhibits the proliferation and induces the apoptosis of primary acute myelogenous leukemia blasts
Survival of acute myeloid leukemia cells requires PI3 kinase activation
PI3 kinase alpha and delta promote hematopoietic stem cell activation
Oncogenic activity of the regulatory subunit p85β of phosphatidylinositol 3-kinase (PI3K)
Pan-cancer analysis on the role of PIK3R1 and PIK3R2 in human tumors
Class IA PI3K regulatory subunits: p110-independent roles and structures
Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer
Interleukin-6 activates phosphoinositol-3′ kinase in multiple myeloma tumor cells by signaling through RAS-dependent and
GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia
Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival
High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability
Naturally occurring neomorphic PIK3R1 mutations activate the MAPK pathway
dictating therapeutic response to MAPK pathway inhibitors
The MLL recombinome of acute leukemias in 2017
and prognosis in adult acute myeloid leukemia
Mll rearrangements in haematological malignancies: lessons from clinical and biological studies
ERK signaling mediates the induction of inflammatory cytokines by bufalin in human monocytic cells
GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses
The PI3K-Akt-mTOR signaling pathway in human acute myeloid leukemia (AML) cells
PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF
The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation
The crossregulation between ERK and PI3K signaling pathways determines the tumoricidal efficacy of MEK inhibitor
Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML
Loss of FBXO9 enhances proteasome activity and promotes aggressiveness in acute myeloid leukemia
UBR5 HECT domain mutations identified in mantle cell lymphoma control maturation of B cells
Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system
The ProteomeXchange consortium in 2017: supporting the cultural change in proteomics public data deposition
Download references
We would like to thank the University of Utah Flow Cytometry Shared Resource Laboratory
Division of Hematology Biorepository at Huntsman Cancer Institute
UNMC Flow Cytometry Research Facility and UNMC Mass Spectrometry and Proteomics Core Facility for expert assistance
The UNMC core facilities are administrated through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffett Cancer Center’s National Cancer Institute Cancer Support Grant
Human CD34+ cells were available with the support of Cooperative Centers of Excellence in Hematology NIDDK Grant # DK106829
KJW was supported by the UNMC Internal Fellowship
SMB is supported by the National Institutes of Health P20GM121316
RKH and SMB are supported by the UNMC Pediatric Cancer Group
This publication was supported by the Huntsman Cancer Institute at the University of Utah
supported by the National Cancer Institute of the National Institutes of Health (NIH) under award number P30CA042014 and Fred & Pamela Buffett Cancer Center Support Grant from the National Cancer Institute under award number P30CA036727
These authors contributed equally: Kasidy K
Division of Hematology & Hematopoietic Malignancies
Department of Biochemistry and Molecular Biology
and SMB conceived and designed the experiments
CMG and SMB performed experiments and analysis
NTW provided technical and/or material support
All authors reviewed the manuscript before submission
The authors declare no competing interests
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
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DOI: https://doi.org/10.1038/s41375-023-02020-w
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– Everything has changed for 45-year-old Jennifer Johnson
A year sober and clean from alcohol and drug addiction
she’s built an unshakable support system spurring her toward a better life
Jennifer’s mom had cancer when she was young
contributing to feelings she was attempting to escape
she was free to do what she wanted with little risk of getting caught or punished
At a very young age she started using drugs
“That’s normal around here,” Jennifer said
and for years she didn’t think anything was wrong
she was an exotic dancer and got paid to drink
This fed her increased dependance on alcohol
“I just thought I was having a good time,” Jennifer said
“My mother told me I couldn’t party for a living
and during that time experienced a shattered vertebrae in her neck due to a car accident
amphetamines were introduced to her through a group of friends
she had gotten pregnant and curbed drug and alcohol usage long enough to have the baby
Jennifer and the father split up when the baby was very young due to continuous drug and alcohol usage from both
she went through a period of using cocaine
which drove a wedge between her and her mother due to frequent stealing
Jennifer decided to check herself into rehab
and after some time she was pregnant with another child
due to various circumstances relating to her addiction
she was unable to have custody of either child
Her drug usage then spiraled for many years
“I had learned all the tricks to get away with it,” she said
making it possible to use drugs without people’s knowledge
things began to change when she most recently got arrested on a possession charge
The judge explored sending her to The Lovelady Center recovery program
the judge instead sent her to the Mobile Day Reporting Center
This outcome was a good thing for Jennifer
who works best under pressure and needed a program more stringent
“[The judge] sent me to the DRC thinking it wouldn’t be in my favor
At the DRC you can’t get away with anything
One surprise coming to the Mobile DRC was the ability to be mentored again by Bridgette Davis
who was a previous counselor at a methadone treatment program years prior
not only willing to help herself but help others.”
“The classes were not like other classes,” said Jennifer
“The life skills were actually teaching me something I needed to know about my addiction
The stuff they taught me replaced what I thought I knew about myself
and the more I was out in the real world clean
I had no idea it would be this wonderful.” DRC classes are known for their rigorous workload and hard work needed to graduate
but most credit those elements to the program’s success
Mobile DRC Administrator Seaton Fitzgerald
who has high standards for success in the program
was impressed with Jennifer’s work: “She’s great
She’s been one person who has made my job really easy.”
family and mentors who assisted her while in the DRC program
She frequently prays for people who lack the resources and support available to her
she has completed her GED and gotten her driver’s license during her first year of sobriety
Jennifer credits Alcoholics Anonymous for continuing to set her on the right path
Jennifer is now able to help others struggling with similar addictions
“[Jennifer’s] transformation always amazes me,” said Lisa
“When I go to meetings and see the light come on in her eyes – it’s such a gift.”
a friend and fellow Mobile DRC participant
also expressed support for Jennifer: “She is an absolute inspiration
she really helped with building that foundation for a good recovery path.”
“If you’re not serious about recovery you’re not going to like it,” Jennifer said when asked about advice for other DRC participants: “If you’re serious about it
it can be the best thing you’ve ever done for your life.”
She believes state leaders need to take a close look at how individuals with drug addiction are treated: “Drug addicts in jail just feed into other drug addicts
I think something better will come if enough people get interested.”
“They’ll keep you clean long enough for your heart to catch up with your mind,” Jennifer said
the Mobile DRC program is highly effective at providing a path for recovery
Jennifer was ultimately the one who took those steps
Jennifer had many supportive people to guide her
but then the unexpected happened: she became the mentor to those needing her the most
Mobile Day Reporting Center Participant Jennifer Johnson
questions@paroles.alabama.gov
By Steve BrownReal Estate Editor
Paul Wittorf will take over in June as executive managing partner of Transwestern’s Dallas-Fort Worth office
Wittorf – who’s currently in the firm’s Houston office – will take over from longtime Transwestern exec Jack Eimer
who’s moving to a new role on the company’s national leadership team
Eimer had headed the Dallas-based operation for more than two decades
I felt the urge to do something new and different while still contributing to the Transwestern national platform,” Eimer said in a letter to Transwestern’s North Texas team
it became clear to us who the best candidate is to take our D-FW operations to even higher levels through the next generation.”
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Wittorf has been in Transwestern’s Houston office since 2000. He’s been one of the company’s top producers in leasing and marketing office buildings. In his new job in Dallas he will oversee an operation with more than 300 people that leases and manages 220 properties totaling 55 million square feet.
“We have grown our operation almost eight times its mid-1990s size,” Eimer said.
Eimer will continue to serve on the firm’s Executive Committee and Board of Directors and will continue to work in Dallas.
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Metrics details
Reduction of the greenhouse gas N2O to N2 is a trait among denitrifying and non-denitrifying microorganisms having an N2O reductase
and physiological differences among organisms within the clades may affect N2O emissions from ecosystems
To increase our understanding of the ecophysiology of N2O reducers
we determined the thermodynamic growth efficiency of N2O reduction and the selection of N2O reducers under N2O- or acetate-limiting conditions in a continuous culture enriched from a natural community with N2O as electron acceptor and acetate as electron donor
The biomass yields were higher during N2O limitation
irrespective of dilution rate and community composition
The former was corroborated in a continuous culture of Pseudomonas stutzeri and was potentially due to cytotoxic effects of surplus N2O
Denitrifiers were favored over non-denitrifying N2O reducers under all conditions and Proteobacteria harboring clade I nosZ dominated
The abundance of nosZ clade II increased when allowing for lower growth rates
but bacteria with nosZ clade I had a higher affinity for N2O
the specific growth rate is likely a key factor determining the composition of communities living on N2O respiration under growth-limited conditions
there are no reports on long-term growth of bacteria based on their N2O-reducing capacity and the selective effect of N2O as sole electron acceptor in natural communities
closely related to the dominant population in the enrichment culture during high dilution rates
An acetate-consuming N2O-reducing culture was enriched from activated sludge and cultivated in a double-jacket glass bioreactor with a working volume of 2 l (Applikon
the Netherlands) operated as a continuous stirred tank reactor (i.e.
a flow-controlled chemostat) during 195 days
Mixing was achieved with a stirrer having two standard geometry six-blade turbines turning at 750 rpm
The dilution rate was controlled by two peristaltic pumps feeding-concentrated medium and water to the system and an effluent pump controlled by a level sensor
The reactor temperature was maintained at 20 ± 1 °C using a cryostat bath (Lauda
The pH was monitored with a pH electrode (Mettler Toledo) and maintained at 7.0 ± 0.05 by titration of 1 M HCl controlled by an ADI 1030 biocontroller (Applikon)
The chemostat was operated under non-sterile conditions and cleaned approximately every 3 weeks to remove any biofilm present
The contribution of biofilm growth to the amount of biomass inside the reactor was negligible
Before terminating the chemostat experiment
a batch experiment was performed on day 192 to compare the maximum acetate conversion rate of the enrichment with either N2O or NO3− as an electron acceptor
the influent and effluent pumps of the chemostat were stopped
but flushing with N2 gas was kept constant (at 800 ml min−1)
The sparging with N2O was initially increased to obtain maximum conversion rates on N2O and then stopped before adding 1 mM NO3− and monitoring its reduction
a strain closely related to the dominant population in the enrichment culture during periods I and II
was grown under alternating N2O and acetate-limiting conditions
The chemostat reactor set-up was similar to the one described above
The substrate and mineral medium were fed simultaneously
but final concentrations in the influent were the same as in the enrichment culture
The mineral medium was adjusted to a defined medium by removing the yeast extract
The chemostat was inoculated with a pre-culture of P
stutzeri JM300 grown aerobically in a shake flask and harvested at exponential phase
Start-up of the reactor was initially in batch mode with the defined mineral medium supplemented with 30 mM NO3− to induce denitrification
and medium was added at a dilution rate of 0.044 h−1
the N2O supply rate varied to achieve N2O-limiting vs
diluted in N2 supplied at a rate of 600 ml min−1
Samples from the reactor for analysis of acetate and NH4+ were immediately filtered after sampling (0.45-μm pore size poly-vinylidene difluoride membrane
Acetate was measured with a Chrompack CP 9001 gas chromatograph (Chrompack
the Netherlands) equipped with an HP Innowax column (Algilent Technologies
was determined spectrophotometrically using cuvette test kits (Hach Lange
For the estimation of biomass concentration
the volatile suspended solids (VSS) concentration was determined by centrifuging 0.2 l of the enrichment
and then burning the pellet at 550 °C for 2 h to determine the ash content
and CO2 in the headspace of the reactor were monitored in dried gas
either by using an infrared gas analyzer (NGA 2000
USA) or through mass spectrometry (Prima BT
The N2O consumption and N2 and CO2 production rates were computed from the off-gas partial pressure and the gas supply rate
Dissolved N2O as well as dissolved CO2 and ionized species were included in the mass balances
an average of the N2O consumption and the N2 production was used to estimate the moles of electrons accepted
To monitor the microbial community structure of the enrichment
the reactor was sampled regularly for microscopy
and DNA extraction for quantitative PCR and sequencing as described below
DNA was extracted from a pellet retrieved from 2 ml of the enrichment culture at each sampling occasion
and from the activated sludge samples used as inoculum using the PowerLyzer PowerSoil DNA Isolation Kit (MoBio Laboratories)
DNA was quantified using the Qubit Fluorometer (Life Technologies Corporation)
Standard curves were obtained using serial dilutions of linearized plasmids containing fragments of the respective genes
We tested for PCR inhibitors in all DNA extracts with a plasmid-specific qPCR assay (pGEM-T; Promega) and no inhibition was detected when comparing to controls with only the plasmid added
Sequencing was performed by Microsynth (Microsynth AG) on the MiSeq platform (Illumina) using 2 × 300 bp paired-end chemistry for 16S rRNA genes and on a 454 FLX Genome Sequencer (Roche) using Titanium FLX + chemistry for the nosZ genes
The sequences obtained in this study are available at The Sequence Read Archive under the accession number PRJNA398140
using a hybridization buffer containing 35% (v/v) formamide
Slides were observed with an epifluorescence microscope (Axioplan 2
the Netherlands) and images were acquired with a Zeiss MRM camera
compiled with the Zeiss microscopy image acquisition software (AxioVision version 4.7
and nirK genes during operation of the N2O-reducing chemostat under four conditions (I–IV) with either acetate or N2O as growth-limiting factor
The nirS and nirK genes were abundant in the enrichment culture throughout the entire time of operation (Fig. 1)
except for a short period in which both genes were equally abundant (period II)
The abundance of nirS was strongly affected by the shift from nitrous oxide to acetate limitation during the low dilution rate
whereas nirK and nosZ genes were mainly affected by the change in dilution rate
Relative abundance of nosZI (a) and nosZII (b) OTUs with >10% of the sequences at any given date during operation of the N2O-reducing chemostat under four conditions (I–IV). The OTUs are listed on the right-hand side with genus/family indicated in parenthesis (see Figure S2)
Closely related OTUs are shown in shades of the same color
When the relative abundances of the main groups present in the enrichment were independently validated using FISH, the results roughly corroborated those obtained by 16S rRNA sequencing (Figure S4)
Gammaproteobacteria dominated the enrichment during periods I and II
and were later washed out and replaced by Betaproteobacteria
Microscopy did not reveal the presence of other cells than prokaryotes
this phylum is understudied and might include members with other metabolic features than what is currently described
Their presence could also indicate important microbial interactions that we cannot account for (e.g.
etc.) resulting in the co-existence of N2O-reducing denitrifiers and other organisms
We can only speculate about the Gracilibacteria living off the fermentation of byproducts excreted by denitrifiers or products of cell lysis
The rhizosphere is an example of an environment where carbon supply is high
and high growth rate or overall affinity would be a competitive advantage
It would be interesting to address the competition of nosZ clade I vs
clade II under N2O limitation under a larger range of growth rates
N2O reducers would necessarily have to harvest energy during N2O reduction
as it was the sole electron acceptor provided
Nitrous oxide (N2O): the dominant ozone-depleting substance emitted in the 21st century
Genomics and ecology of novel N2O-reducing microorganisms
Nitric oxide and nitrous oxide turnover in natural and engineered microbial communities: biological pathways
The unaccounted yet abundant nitrous oxide−reducing microbial community: a potential nitrous oxide sink
Unexpected nondenitrifier nitrous oxide reductase gene diversity and abundance in soils
Intergenomic comparisons highlight modularity of the denitrification pathway and underpin the importance of community structure for N2O emissions
Recently identified microbial guild mediates soil N2O sink capacity
Non-denitrifying nitrous oxide-reducing bacteria - an effective N2O sink in soil
Substrate oxidation and nitrous oxide utilization in denitrification
Three transcription regulators of the Nss family mediate the adaptive response induced by nitrate
nitric oxide or nitrous oxide in Wolinella succinogenes
Nitrous oxide reduction kinetics distinguish bacteria harboring clade I NosZ from those harboring clade II NosZ
Diversity and evolution of bioenergetic systems involved in microbial nitrogen compound transformations
Habitat partitioning of marine benthic denitrifier communities in response to oxygen availability
Comparison of bacterial communities of conventional and A-stage activated sludge systems
Simple model for the energetics of growth on substrates with different degrees of reduction
Barcoded primers used in multiplex amplicon pyrosequencing bias amplification
Development of a prokaryotic universal primer for simultaneous analysis of Bacteria and Archaea using next-generation sequencing Bourtzis K (ed)
PEAR: a fast and accurate Illumina paired-end reAd mergeR
VSEARCH: a versatile open source tool for metagenomics
UCHIME improves sensitivity and speed of chimera detection
SINA: accurate high-throughput multiple sequence alignment of ribosomal RNA genes
QIIME allows analysis of high-throughput community sequencing data
HMM-FRAME: accurate protein domain classification for metagenomic sequences containing frameshift errors
Spatial and phyloecological analyses of nosZ genes underscore niche differentiation amongst terrestrial N2O reducing communities
FunGene: the functional gene pipeline and repository
ARB: a software environment for sequence data
FastTree 2 - approximately maximum-likelihood trees for large alignments Poon AFY (ed)
A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach
Enrichment of a mixed bacterial culture with a high polyhydroxyalkanoate storage capacity
Insights into the phylogeny and coding potential of microbial dark matter
Anaerobic oxidation of thiosulfate to tetrathionate by obligately heterotrophic bacteria
belonging to the Pseudomonas stutzeri group
Isolation and properties of a denitrifying bacterium related to Pseudomonas lemoignei
Pathway of nitrous oxide consumption in isolated Pseudomonas stutzeri strains under anoxic and oxic conditions
Phenotypic and genotypic heterogeneity among closely related soil-borne N2- and N2O-producing Bacillus isolates harboring the nosZ gene
Soil type overrides plant effect on genetic and enzymatic N2O production potential in arable soils
Intercropping affects genetic potential for inorganic nitrogen cycling by root-associated microorganisms in Medicago sativa and Dactylis glomerata
Growth yields in bacterial denitrification and nitrate ammonification
Copper control of bacterial nitrous oxide emission and its impact on vitamin B12-dependent metabolism
Expression of nitrous oxide reductase in Paracoccus denitrificans is regulated by oxygen and nitric oxide through FnrP and NNR
Nitrous oxide reduction by an obligate aerobic bacterium
and sulfur cycling among widespread estuary sediment bacteria
Download references
This work was funded by the European Commission (Marie Curie ITN NORA
FP7-316472) and the Swedish Research Council (VR grant 2016-03551 to SH)
We like to warmly thank Koen Verhagen for carrying out preliminary work with the N2O chemostat and Gerben Stouten for his help with the off-gas measurements
The European Commission (Marie Sklodpowska-Curie ITN NORA
FP7-316472) and the Swedish Research Council (grant 2016-03551)
Department of Forest Mycology and Plant Pathology
Swedish University of Agricultural Sciences
The authors declare that they have no conflict of interest
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DOI: https://doi.org/10.1038/s41396-018-0063-7
Frontiers of Environmental Science & Engineering (2023)
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PetaGene’s PetaSuite software has been chosen to compress the huge data sets used at AstraZeneca’s Centre for Genomics Research (CGR)
The CGR investigates the underlying genetic causes of disease and aims to integrate genomics across AstraZeneca’s drug discovery platform
The scale of data required for such work is enormous. AstraZeneca’s CGR has so far processed more than 200,000 genomics datasets
generating more than a petabyte of data - equivalent to the streaming HD movies for 40 years without a break
PetaSuite is designed to accelerate data transfer for cloud computing and reduce storage costs for research projects involving genomics data
co-founder and chief commercial officer of PetaGene
which is based in Cambridge’s Hauser Forum
said: “Using genomic data for biopharmaceutical targets discovery requires large cohorts with massive multi-petabyte data sets
“The time required to transfer these data from sequencers to compute clusters as well as the cost of storage can cripple these large initiatives
“PetaSuite addresses the challenges caused by growing volumes of genomics data and achieves up to 10x reductions in storage costs and transfer times
while adhering to the industry-standard BAM and FASTQ genomics file formats.”
PetaGene says its compression software will enable the CGR to compress more than 200,000 BAM files in a 24-hour period and will add the compressed data to tiered cloud storage
the CGR can reduce its data by an average of 76 per cent or
achieve a fourfold expansion in storage capacity
The lossless compression of files reduces transfer times to less than a quarter
and the software enables unmodified analysis tools to run more quickly
vice president and head of genome analytics and bioinformatics
at AstraZenecam said: “AstraZeneca’s Centre for Genomics Research has the bold ambition to analyse up to two million genomes by 2026
Minimizing the storage footprint and transfer time of genome data while maximizing data access and compute processing is a necessity to enable us to achieve our ambition.”
PetaSuite is typically used as an intrinsic part of a client’s cloud or locally hosted analysis pipeline
Data is compressed ready to use as it is processed
and moves to the next stage of analysis without it needing to be decompressed later
AstraZeneca records 18% sales growth in Q3 of 2019 as impressive results continue