Neuroscience

Malvern Festival of Ideas announces guest speaker Professor Colin Blakemore – Malvern Gazette

MALVERNS popular festival of ideas is returning once again with a new guest speaker once called 'one of the most powerful scientists in the UK'.

Colin Blakemore, professor of neuroscience and philosophy at the School of Advanced Study at the University of London and emeritus professor of neuroscience at the University of Oxford is the opening speaker at this years festival.

Professor Blakemore is the former chief executive of the British Medical Research Council as well as having hundreds of papers published in research journals.

He has been president of the British Neuroscience Association, the Physiological Society, the British Association for the Advancement of Science (now the British Science Association) and the Society of Biology.

The Observer newspaper once referred to him as One of the most powerful scientists in the UK. In parallel with his academic career, he has also has championed the communication of science and engagement with the public.

He has presented the BBC Reith Lectures and the Royal Institution Christmas Lectures.

In addition, he has written and presented many other programmes about science and written or edited several popular science books. He has also been honorary president of the Association of British Science Writers.

READ MORE: Vets closes due to major water leak

The theme of this years festival, is A Brave New World? and explores what can be done to look positively at the future as well as to what extent can ideas around social policy, economics, medicine, science, politics, psychology, arts, foreign policy and faith lead to a better world.

Speakers include the Labour peer professor baroness Ruth Lister, Dr Irene Guijt, head of research and publishing at Oxfam, Anthony Painter, leader of the research and impact team at the RSA, author and economics commentator Grace Blakeley, and philosopher Dr Julian Baggini. There will be a session on artificial intelligence and its impact on society with Dr Subramanian Ramamoorthy of Edinburgh University and Ivan Bartoletti. The weekend concludes with Peter Tatchell speaking on the future of LGBT+ rights.

All these talks take place at the Chase School and there is a family day at Malvern Cube on Saturday, March 7 with story teller and author Bernadette Russell.

For more information go to malvernfestivalofideas.org.uk/

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Malvern Festival of Ideas announces guest speaker Professor Colin Blakemore - Malvern Gazette

Neuroscience

BioXcel Therapeutics Announces FDA Clearance of IND Application for BXCL501 for the Treatment of Opioid Withdrawal Symptoms – GlobeNewswire

NEW HAVEN, Conn., Feb. 05, 2020 (GLOBE NEWSWIRE) -- BioXcel Therapeutics, Inc. (BTI or Company) (Nasdaq: BTAI), a clinical-stage biopharmaceutical company utilizing artificial intelligence approaches to identify and advance the next wave of medicines in neuroscience and immuno-oncology, today announced that its Investigational New Drug (IND) application for BXCL501, the Companys proprietary sublingual thin-film formulation of dexmedetomidine (Dex), has received clearance from the U.S. Food and Drug Administration (FDA) for the treatment of opioid withdrawal symptoms.

The FDA clearance of our IND application for opioid withdrawal, a fourth indication, is an important step in our plans to build a neuroscience franchise around the multiple therapeutic opportunities with BXCL501, commented Vimal Mehta, Chief Executive Officer of BTI. Opioid overdose is reported as the number one cause of death for those under 50 years old in the U.S., and the distressing and challenging symptoms that come with opioid withdrawal are a primary reason for relapse. There is an urgent need for better treatment options to help manage the debilitating withdrawal symptoms and aid this underserved population from continued opioid abuse. BXCL501, our investigational non-opioid therapy, may offer key advantages to treating symptoms due to its intrinsic potency and favorable delivery method. We believe this study will build on the encouraging results we observed in our intravenous (IV) Dex trial, which appeared effective in reducing opioid withdrawal symptoms.

Opioid withdrawal is an emotional and physiological medical condition that may be driven by the excessive drive of noradrenergic neurons that originate from the locus coeruleus in the brainstem. BXCL501 selectively activates alpha-2a adrenergic receptors, which decreases excessive neuronal firing, alleviating the physiological symptoms of opioid withdrawal.

The RELEASE trial is a multicenter, randomized, double-blind, placebo-controlled, ascending-dose Phase 1b/2 study designed to evaluate the safety, pharmacokinetics, tolerability and efficacy of BXCL501 in patients experiencing symptoms of opioid withdrawal. This study will enroll subjects with opioid use disorder who are physically dependent on opioids. Patients will be randomized into multiple dose cohorts of BXCL501, or matching placebo, administered twice daily for five days. The study will assess opioid withdrawal symptoms using both the Clinical Opiate Withdrawal Scale and Short Opiate Withdrawal Scale of Gossop over a 10-day period.

About BXCL501BXCL501 is a potential first-in-class, proprietary sublingual thin film of dexmedetomidine, a selective alpha-2a receptor agonist for the treatment of acute agitation. BTI believes that BXCL501 directly targets a causal agitation mechanism and the Company has observed anti-agitation effects in multiple clinical studies across multiple neuropsychiatric indications. BXCL501 has also been granted Fast Track Designation by the U.S. Food and Drug Administration for the acute treatment of agitation.

A Phase 1b safety and efficacy study of BXCL501 yielded positive dose-response data. BXCL501 is being evaluated in the SERENITY program, consisting of two Phase 3 studies for the acute treatment of agitation in patients with schizophrenia (SERENITY I) and bipolar disorder (SERENITY II). BXCL501 is also being evaluated in a Phase 1b/2 trial for the treatment of agitation associated with dementia, and the Company is preparing to initiate the Phase 1b/2 RELEASE trial of BXCL501 for the treatment of opioid withdrawal symptoms.

About Opioid Drug Withdrawal:

According to the Centers for Disease Control and Prevention (CDC), the misuse of and addiction to opioids is a serious national crisis and is the leading cause of death in the U.S. for those under 50 years old. Between 1999-2017, almost 400,000 people died from an overdose involving an opioid, with greater than 47,000 deaths occurring in 2017 alone. The CDC estimates the total "economic burden" of prescription opioid misuse alone in the U.S. is $78.5 billion a year, including the costs of healthcare, lost productivity, addiction treatment and criminal justice involvement. Opioid withdrawal is a condition characterized by symptoms such as anxiety, agitation, sleep problems, muscle aches, runny nose, sweating, nausea, vomiting, diarrhea and drug craving that occur after stopping or reducing the use of opioids in anyone with physical dependence on opioids.

About BioXcel Therapeutics, Inc.BioXcel Therapeutics, Inc. is a clinical stage biopharmaceutical company utilizing artificial intelligence to identify improved therapies in neuroscience and immuno-oncology. BTI's drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indices. BTI's two most advanced clinical development programs are BXCL501, a sublingual thin film formulation designed for acute treatment of agitation resulting from neuropsychiatric disorders, and BXCL701, an orally administered systemic innate immunity activator designed for treatment of a rare form of prostate cancer, pancreatic cancer and advanced solid cancers in combination with other immuno-oncology agents. For more information, please visit http://www.bioxceltherapeutics.com/.

Forward-Looking StatementsThis press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include but are not limited to the effects of BXCL501 treatment on opioid withdrawal symptoms and the timing of clinical development initiatives and trials for BXCL501. When used herein, words including anticipate, being, will, plan, may, continue, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon BTI's current expectations and various assumptions. BTI believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. BTI may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, its limited operating history; its incurrence of significant losses; its need for substantial additional funding and ability to raise capital when needed; its limited experience in drug discovery and drug development; its dependence on the success and commercialization of BXCL501 and BXCL701 and other product candidates; the failure of preliminary data from its clinical studies to predict final study results; failure of its early clinical studies or preclinical studies to predict future clinical studies; its ability to receive regulatory approval for its product candidates; its ability to enroll patients in its clinical trials; its approach to the discovery and development of product candidates based on EvolverAI is novel and unproven; its exposure to patent infringement lawsuits; its ability to comply with the extensive regulations applicable to it; its ability to commercialize its product candidates; and the other important factors discussed under the caption Risk Factors in its Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2019, as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SECs website at http://www.sec.gov and on the Companys website at http://www.bioxceltherapeutics.com.

These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While BTI may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing BTIs views as of any date subsequent to the date of this press release.

BioXcel Therapeutics, Inc.www.bioxceltherapeutics.com

Investor Relations:John Grazianojgraziano@troutgroup.com1.646.378.2942

Media:Julia Deutschjdeutsch@troutgroup.com1.646.378.2967

Source: BioXcel Therapeutics, Inc.

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BioXcel Therapeutics Announces FDA Clearance of IND Application for BXCL501 for the Treatment of Opioid Withdrawal Symptoms - GlobeNewswire

Neuroscience

Researchers reveal new activity above the surface in brain-cell receptors – News-Medical.net

Like buoys bobbing on the ocean, many receptors float on the surface of a cell's membrane with a part sticking above the water and another underwater, inside the cell's cytoplasm. But for cells to function, these receptors must be docked at specific regions of the cell. Most research has focused on the 'underwater' portions. That's where the cell's molecular machines swarm and interact with a receptor's underwater tails, with those interactions then fueling signals that dive deep into the nucleus, changing the cell's course.

New work by a team of Thomas Jefferson University researchers reveals new activity above the surface, in brain-cell receptors that govern learning and chronic pain. In the study, the authors show that the 'above water' portion of proteins can help dock the proteins at synapses, where neurons mediate flow of information throughout the brain. This discovery opens the possibility of using this docking site as a target to develop treatments for chronic pain and other diseases more effectively. The study was published January 29th in Nature Communications.

"The extracellular spaces - the parts 'above the water' - have been largely overlooked," says senior author Matthew Dalva, PhD, professor and vice chair of the Department of Neuroscience and director of the Jefferson Synaptic Biology Center in the Vickie & Jack Institute for Neuroscience - Jefferson Health. Dr. Dalva and his team looked at the NMDAR receptor on brain cells and pinpointed the spot where this receptor interacts with a neighbor to initiate signaling. "When trying to develop new therapy, finding the bullseye is half the problem," says Dr. Dalva.

Finding a key interaction that sits above the cell's surface, could make it more accessible to therapeutics.

The kinds of receptor interactions we're talking about are different than when a receptor binds to its ligand outside of the cell, which is well documented. Here we're describing the kinds of biochemical exchanges - kinase phosphorylation fueled by free-floating ATP - that we thought, until recently, were exclusive to the inside of cells."

Dr. Matthew Dalva, senior author

The researchers focused on the synaptic protein called NMDA-type glutamate receptors (NMDARs), which help regulate the strength of synaptic connections between neurons. It's important that the synapse connects strongly, but not too strongly, in order to prevent creating an overly excitable connection.

A key mechanism controlling synaptic strength is the increase in NMDAR function due to direct molecular interaction with another synaptic protein called the EphB receptor tyrosine kinase. Dr. Dalva and colleagues had previously shown that the phosphorylation of EphB on the "outside" or extracellular portion of the molecule can lead to a direct interaction with NMDARs. And that chemical exchange causes the receptors to cluster and drive neuronal plasticity and chronic pain (PlosBiology 2017). Their new work identifies a specific region of the NMDAR or bullseye, necessary for these proteins to interact.

This specific bullseye could have important medical implications, as disruption of the EphB-NMDAR interaction has been associated with Alzheimer's, and in chronic pain can be due to too much of this interaction. As a trans-synaptic organizer and NMDAR binding protein, the EphB receptor is a key regulator of these events.

However, despite discovery of this interaction over a decade ago, the exact spot where NMDAR interacts with EphB has been a mystery. Here, the researchers demonstrate that specific amino acids in the hinge region of the NDMAR are required to interact with EphB2. Importantly, the amino acids in the hinge region are required for proper NDMAR mobility and stabilization at the synapse.

"There is growing evidence that extracellular interactions may play key regulatory roles in diseases ranging from pain to cancer and even malaria," says Dr. Dalva. "As we begin to define what these exchanges look like, we'll be able to study them, understand their contribution to disease and potentially use them to find better medical interventions."

Source:

Journal reference:

Washburn, H.R., et al. (2020) Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility. Nature Communications. doi.org/10.1038/s41467-020-14345-6.

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Researchers reveal new activity above the surface in brain-cell receptors - News-Medical.net

Immunology

Quality Medical Management Services USA, LLC Signs Lease for Brand New, Expanded State-of-the-Art Space at Current 333 East Shore Rd Manhasset…

The new Manhasset office will now feature approximately 7,700 square feet of leading-edge technology and facilities.

Tarrytown, NY, Feb. 06, 2020 (GLOBE NEWSWIRE) -- Quality Medical Management Services USA, LLC, an affiliate of ENT and Allergy Associates, LLP, today announced that it has doubled down on its pledge to provide superior ENT, Allergy and Audiology healthcare services to the patients of Nassau County by signing a 10 year lease with East Shore Realty, LLC for a brand new, expansive clinical office at its current clinical office location at 333 East Shore Rd, Manhasset, NY, 11030.

This expansion allows ENTA physicians and other medical professionals to serve their patients needs with the increased benefit of 12 ENT exam rooms, 4 Allergy rooms, 3 audiology booths, a complete hearing aid dispensary, a full complement of allergy exam rooms for on-site testing and injections, and many other advantages. The Manhasset office will now feature approximately 7,700 square feet of leading-edge technology and facilities.

The expansion and renovations will be spearheaded by Nicole Monti-Spadaccini, Senior Vice President and Chief Operating Officer of QMMS USA. Ms. Monti currently oversees and directs the entire day to day operations for ENT and Allergy Associates, LLP.

This newly expanded and modernized location will complement the Practices other current Nassau County offices, in Garden City (990 Stewart Avenue, 6th floor, Suite 610, Garden City, NY, 11530) and Lake Success (3003 New Hyde Park Road, Suite 409, Lake Success, NY, 11042).

Philip Perlman, M.D., the senior ENTA partner in this office commented, Manhasset is an exciting place to live and work. Our neighborhood offers a dynamic environment that lends itself to young and old alike, singles and families wanting to take full advantage of the area. Our newly expanded office is now geared for further population growth and our patients deserve no less.

I have been practicing medicine in Nassau County for many years, added ENTA physician partner Mike Ditkoff, M.D. and I can tell you that we are extremely excited about what this new lease and facility upgrade will mean for patients in our communities.

Luke Donatelli, M.D, ENT physician in Manhasset commented, This expansion will offer extra comfort, extra convenience and truly state-of-the-art facilities. It further enhances our ability to provide what we already offer, which is the finest ear, nose, throat, allergy and audiology care possible. We are extremely pleased with this new lease.

Robert Glazer, EVP Chief Executive Officer of QMMS USA We are constantly looking for ways to improve the patient experience at our clinical locations. At our Manhasset office, we had the opportunity to upgrade and enhance without needing to move.Our expanded space provides additional exam rooms and procedure rooms as we look to recruit more high-quality otolaryngologists to this location. This is truly the best of all worlds. He continued With this expansion we are adding full time allergy, asthma and immunology services with the addition of Dr. Irum Noor to our clinical team. Dr. Noor will be supported by a team of well-educated and experienced nurses. In addition, we are subsequently expanding our audiology services, which combine the medical expertise of our ENT physicians and the diagnostic and rehabilitative skills of our licensed Doctors of Audiology to provide the most comprehensive care possible.

This expanded and improved facility is yet another example of ENTAs singular focus on both our patients healthcare, and the quality of their doctor visit experience, noted Robert Green, M.D., President of ENTA, Among other things, this new space means more comfort for everyone, and thats very important.

To learn more about ENTA, find a local office or book an appointment, download the ENT and Allergy Associates mobile app, visit http://www.entandallergy.com or call 1-855-ENTA-DOC.

About ENT and Allergy Associates LLP

ENT and Allergy Associates LLP (ENTA) has more than 220 physicians practicing in 46 office locations in Westchester, Putnam, Orange, Dutchess, Rockland, Nassau and Suffolk counties, as well as New York City and northern/central New Jersey. The practice sees over 90,000 patients per month. Each ENTA clinical location provides access to a full complement of services, including General Adult and Pediatric ENT and Allergy, Voice and Swallowing, Advanced Sinus and Skull Base Surgery, Facial Plastics and Reconstructive Surgery, Disorders of the Inner Ear and Dizziness, Asthma, Clinical Immunology, Diagnostic Audiology, Hearing Aid dispensing, Sleep and CT Services. ENTA has clinical alliances with Mount Sinai Hospital, Montefiore Medical Center, Northwell Health, and a partnership with the American Cancer Society.

Story continues

To learn more about QMMS USA, LLC, visit http://www.qmmsusa.com

About QMMS USA, LLC: Backed by over 20 years of experience, Quality Medical Management Services USA (QMMS USA) offers healthcare consultancy services in the area of medical staff operations, practice management, ancillary service revenue enhancement, compliance, records management, and business applications. QMMS USA provides a seasoned team to offer leading edge healthcare business management. QMMS USA implements best practices throughout to ensure success.

Jason CampbellENT and Allergy Associates, LLP9149842531jcampbell@entandallergy.com

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Quality Medical Management Services USA, LLC Signs Lease for Brand New, Expanded State-of-the-Art Space at Current 333 East Shore Rd Manhasset...

Immunology

UHS board considers thesis reports – The News International

UHS board considers thesis reports

LAHORE:The 154th meeting of Advanced Studies and Research Board of the University of Health Sciences (UHS) was held here on Thursday with Gujranwala Medical College, Gujranwala, Principal Prof Dr Maroof Aziz Khan in the chair.

The board considered the thesis reports of Dr Mahwish Farzana, MD (radiology), Dr Ayman Nasieb, MS (cardiothoracic Surgery), Dr Matiur Rahman, MS (cardiac surgery) and Dr Salik Nazeer Qaisrani, MS (urology). The synopses of the following students were also considered for registration in various postgraduate courses: Dr Ghanwa Saeed, MPhil (immunology), Mahwish Asif, MPhil (microbiology), Faiqa Munir, MPhil (human genetics and molecular biology), Dr Syed Muhammad Saad Gardezi, MPhil (pharmacology), Dr Hafsa Faiz, MPhil (pharmacology), Dr Hammad Hassan, MPhil (science of dental materials), D. Huda Mehmood, MDS (prosthodontics), Dr Zoha Rahim, MD (gastroenterology), Dr Muhammad Asad Munir, MS (orthopaedics), Dr Mehreen Gul, MS (Obst. & Gynae.) and Dr Umair Rahim Khan, MS (plastic surgery).

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UHS board considers thesis reports - The News International

Genetics

Genetics researchers target cadmium reduction in cacao – Valley News

The 28th annual International Conference on the Status of Plant and Animal Genome Research took place Jan. 11-15, in San Diego, and the Jan. 12 cacao genomics workshop included a presentation on the attempt to reduce the cadmium content of the bean used for chocolate.

Jim Dunwell of the University of Reading in the United Kingdom addressed the situation including potential solutions in Molecular Genetic Approaches to Reducing Cadmium Accumulation in Cocoa. Dunwell said that the European Union recently implemented a cadmium limit which took effect in January 2019.

During the processing of chocolate, were trying to get rid of cadmium, Dunwell said.

Chocolate is one of the major products with high cadmium levels, and rice grown in China also has high levels of cadmium.

Its something which is not good for anybody, Dunwell said. It accumulates in your body over your life.

The source of cadmium could be natural such as volcanic soils, and the use of phosphate fertilizers, mining activity or industrial pollution can also create cadmium in the soil.

There are hot spots geographically where cacao grown in those areas produce beans that exceed the limit, Dunwell said.

The four nations with the greatest cacao production are in western Africa, where the cadmium levels in the soil are the lowest. Although those four nations account for approximately 72% of the worlds chocolate production, some of the highest-quality chocolate is from South American cacao and many of those areas have cadmium levels which exceed the European Union limit. The initial maximum levels allow for a higher cadmium concentration in darker chocolate but no more than 0.00008%; the lowest maximum level is 0.00001% and the limit for cocoa powder is 0.00006%.

Africa and Asia the range is not too bad, but if you look at the Latin American, South American region the rate is much more, Dunwell said. Its a threat to the livelihoods of particularly sensitive areas of challenged parts of South America.

Efforts have been made to track the source of cadmium in those areas.

Some of them are natural geological sources, Dunwell said.

Other sources are due to fertilizers.

Agriculture in many areas depends on the use of fertilizers, Dunwell said. Certain phosphate fertilizers in parts of the world have high levels of cadmium in them.

The cadmium level in phosphate fertilizers varies depending on the source of the phosphate. Russian phosphate has lower cadmium levels, which creates the political risk that Russia will use that advantage as a bargaining tool.

European agriculture doesnt want to be dependent on Russian fertilizers, Dunwell said.

Some of the research involves adjustment of cadmium levels in the soil.

If you can stop the cadmium from getting into the plant thats probably the best way to start, Dunwell said. Plants dont need cadmium at all.

Biochar binding of the soil is one potential solution.

There is lots of agronomic interest and agronomic activity, but so far it hasnt been proven, Dunwell said.

Adjusting the pH level of soil is complicated by the different levels throughout the world.

Theres a very narrow pH window which you have to calculate, Dunwell said.

A focus on cacao plant rejection of cadmium through the root stock or through transporter genes is part of the research.

If we can do that in the long term, we can put that into a breeding program, Dunwell said. Cadmium comes in as a kind of hitchhiker. There is no cadmium-specific transporter.

Most of the genetic work that has been done in the past uses rice as a model system.

The idea was to identify the region looking at other species, Dunwell said. Rice is the precedent in terms of gene editing.

Cadmium is believed to be transported into the plant through the Natural Resistance-Associated Macrophage Protein transcriptome. Cacao has five NRAMP genes.

Its at one gene that does one thing, Dunwell said.

A mutagenesis process in the research utilizes downregulation of Heavy Metal ATPase genes, and when the HMA gene NtHMA4 is downregulated a reduction of more than thirtyfold is achieved.

Mutagenesis has been used conventionally, Dunwell said.

The NRAMP and HMA genes from were isolated in several accessions which differ in cadmium update.

We looked at variations between the different accessions that we have, Dunwell said.

Variants of different transcriptome length were then spliced. The researchers also used the NRAMP5 gene to transport cadmium from cacao into yeast.

You can test these variants from different cacao accessions, Dunwell said.

The cadmium will have an inhibitory effect on the yeast, Dunwell said. It stops yeast growing, but it allows the uptake of cadmium into yeast.

The purpose of that was for comparison rather than for adding cadmium to yeast, and the experiment confirmed that NRAMP5 encodes a protein capable of cadmium transport.

We know theyre in the right part of the yeast cell, Dunwell said. Were also interested in cadmium isotope variation. Plants can discriminate between these isotopes.

Cadmium in nature has eight isotopes.

We should consider cadmium not as one element but as a series of elements with different isotopes, Dunwell said.

Joe Naiman can be reached by email at jnaiman@reedermedia.com.

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Genetics researchers target cadmium reduction in cacao - Valley News

Genetics

Genetic Variants Linked to Disparity Between a Persons Internal Gender and Their External Sex – Technology Networks

Some of the first biological evidence of the incongruence transgender individuals experience, because their brain indicates they are one sex and their body another, may have been found in estrogen receptor pathways in the brain of 30 transgender individuals.

Twenty-one variants in 19 genes have been found in estrogen signaling pathways of the brain critical to establishing whether the brain is masculine or feminine, saysDr. J. Graham Theisen, obstetrician/gynecologist and National Institutes of Health Womens Reproductive Health Research Scholar at theMedical College of GeorgiaatAugusta University.

Basically and perhaps counterintuitively these genes are primarily involved in estrogens critical sprinkling of the brain right before or after birth, which is essential to masculinization of the brain.

Variants investigators identified may mean that in natal males (people whose birth sex is male) this critical estrogen exposure doesnt happen or the pathway is altered so the brain does not get masculinized. In natal females, it may mean that estrogen exposure happens when it normally wouldnt, leading to masculinization.

Both could result in an incongruence between a persons internal gender and their external sex. The negative emotional experience associated with this incongruence is called gender dysphoria.

They are experiencing dysphoria because the gender they feel on the inside does not match their external sex, Theisen says. Once someone has a male or female brain, they have it and you are not going to change it. The goal of treatments like hormone therapy and surgery is to help their body more closely match where their brain already is.

It doesnt matter which sex organs you have, its whether estrogen, or androgen, which is converted to estrogen in the brain, masculinizes the brain during this critical period, saysDr. Lawrence C. Layman, chief of the MCG Section of Reproductive Endocrinology, Infertility and Genetics in theDepartment of Obstetrics and Gynecology. We have found variants in genes that are important in some of these different areas of the brain.

These brain pathways are involved in regions of the brain where the number of neurons and how connected the neurons are typically differ between males and females.

They note that while this critical period for masculinizing the brain may seem late, brain development actually continues well after birth and these key pathways and receptors already need to be established when estrogen arrives.

While its too early to definitively say the gene variants in these pathways result in the brain-body incongruence called gender dysphoria, it is interesting that they are in pathways of hormone involvement in the brain and whether it gets exposed to estrogen or not, says Layman.

He and Theisen are co-corresponding authors of the study in the journalScientific Reports.

This is the first study to lay out this framework of sex-specific development as a means to better understand gender identity, Theisen says. We are saying that looking into these pathways is the approach we are going to be taking in the years ahead to explore the genetic contribution to gender dysphoria in humans.

In fact, they already are exploring the pathways further and in a larger number of transgender individuals.

For this study, they looked at the DNA of 13 transgender males, individuals born female and transitioning

to male, and 17 transgender females, born male and transitioning to female. The extensive whole exome analysis, which sequences all the protein-coding regions of a gene (protein expression determines gene and cell function) was performed at the Yale Center for Genome Analysis. The analysis was confirmed by Sanger sequencing, another method used for detecting gene variants.

The variants they found were not present in a group of 88 control exome studies in nontransgender individuals also done at Yale. They also were rare or absent in large control DNA databases.

Reproductive endocrinologist/geneticist Layman says his experience with taking care of transgender patients for about 20 years, made him think there was a biological basis. We certainly think that for the majority of people who are experiencing gender dysphoria there is a biologic component, says Theisen. We want to understand what the genetic component of gender identity is.

While genetics have been suggested as a factor in gender dysphoria, proposed candidate genes to date have not been verified, the investigators say. Most gene or gene variants previously explored have been associated with receptors for androgens, hormones more traditionally thought to play a role in male traits but, like estrogen in males, also are present in females.

MCG investigators and their colleagues decided instead to take what little is known about sex-specific brain development that estrogen bath needed in early life to ensure masculinization of the brain to hone in on potential sites for relevant genetic variances. Extensive DNA testing initially revealed more than 120,000 variants, 21 of which were associated with these estrogen-associated pathways in the brain.

Animal studies have helped identify four areas of the brain with pathways leading to development of a male or female brain, and the investigators focused on those likely also present in humans. Laboratory studies have indicated that disrupting these brain pathways in males and females during this critical period results in cross sex behavior, like female rodents mounting and thrusting and males taking on a more traditional female posture when mating. These cross sex behaviors, which also have been documented in non-human primates, emerge during the natural sex hormone surge of puberty.

While sex specific brain development has not been thoroughly evaluated in humans, as with animals, the effects typically play out most at the time of puberty, a time when sex hormones naturally surge, when the general awareness of our sexuality really begins to awaken and when the complex state of gender dysphoria may become easier for adolescents to articulate, the investigators say. Layman notes that many individuals will report experiencing gender incongruent feelings as early as age 5.

Theisen notes that we all are full of genetic variants, including ones that give us blue eyes versus brown or green, and the majority do not cause disease rather help make us individuals. I think gender is as unique and as varied as every other trait that we have, Theisen says.

The investigators suggest modification of the current system for classifying variants that would not imply that a variant means pathogenic, or disease causing.

Last year, the World Health Organization said that genderincongruenceis not a mental health disorder and six years before thatThe Diagnostic and Statistical Manual of Mental Disorders, replaced gender identity disorder with general dysphoria.

About 0.5 to 1.4% of individuals born male and 0.2 to 0.3 % of individuals born female meet criteria for gender dysphoria. Identical twins are more likely than fraternal twins to both report gender dysphoria.

Gender affirming therapies, like hormone therapies and surgeries along with mental health evaluation and support, help these individuals better align their bodies and brains, the physician-scientists say.

Transgender individuals experience increased rates of discrimination, sexual violence and are at increased risk of depression, substance abuse and attempted suicide. About 26% report use of alcohol or other drugs to help cope; 19% have been denied medical care by a physician or other provider, some report verbal harassment in a medical environment and insurance companies do not consistently cover the cost of gender affirming hormone or surgical therapies.

A problem, the investigators say, is an overall lack of understanding of the biologic basis of gender dysphoria.

While their study of 30 individuals they now have data on more than 30 others appears to be the largest to date, the sample size prompted them to classify the published findings as preliminary.

Reference: Theisen et al. (2019).The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants. Scientific Reports.DOI: https://doi.org/10.1038/s41598-019-53500-y.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Genetics

Hemp Genetics CEO: Stable THC Levels Will Come With Breeding Innovation (OPINION) – Greenhouse Grower

Photo Courtesy Chuck Zimmerman/AgWired.com

Society at-large is literally bursting at the seams with interest in hemp and CBD, and the traditional, John Deere-tractor-and-a-bag-of-GMO-seed segment of the agriculture world has not been spared.

You can jump on your Google machine and pull up report after report of long-downtrodden ag regions known for legacy production of tobacco and cotton and other commoditized, low value crops turning acres over to hemp in large numbers. The Carolinas are a hotbed for this type of thing, from what were hearing anyways.

But really its happening all over the countryside, and its not going to stop anytime soon, not with the most conservative estimates pitting an acre of high-CBD hemp biomass fetching anywhere from $250 to $500 at market (after accounting for production costs, the bulk of which are to pay expensive hand labor crews to harvest the plants).

Comparably, soy farmers that have the benefit of large scale, mechanized planting and harvesting equipment were making around $160 per acre average on their crop back in 2012, whereas today they are reportedly taking a $20 an acre loss on average on production.

Thats largely the result of the market-depressing 2019 commodities Trade Wars, which has many farmers looking to hemp as a way to get themselves and the family farm out of the roller coaster international trade market and its wild fluctuations.

And lets not even mention the horrible spring planting season this past year for most commodity crops, where a ton of acres didnt even get planted and remained fallow for all of 2019.

Its all a long way of making the point that, you cant really blame a lot of these farmers for looking to hemp to change their fortunes. Farming is, after all, a business at the end of the day.

But, I digress. Lets get to the point of this article:

Long the gathering place for corn, soybean, sorghum, and other large-scale, commercial crop breeders and researchers working both for and with the multinational seed companies, this year the American Seed Trade Association (ASTA) held a Hemp and Seed Opportunities & Challenges session at the groups annual winter meeting in downtown Chicago, IL.

Those in attendance that mid-December afternoon report there was lots of interest in the session. I was mostly interested in hearing what one featured speaker, New West Genetics CEO Wendy Mosher, had to say to the group, which I found a recording of on ag media veterans Chuck and Cindy Zimmermans AgWired site (Thanks, Chuck and Cindy!).

The reason seeing Moshers name on the agenda peaked my interest: Growers weve come to know in this space have reported the genetics in hemp (and legal cannabis) as uneven performing at best, often generally unreliable for the marketed phenotypes promised and, at worst, either non-germinating or non-compliant on the 0.3% THC content requirement established in USDAs now-infamous Interim Final Rulemaking.

As CEO Mosher herself, an expert in the field, pointed out in her address to ASTA, theres just so little replicated, independent breeding data on all of these genetic varieties and crosses and hybrid strains of cannabis sativa she describes the current hemp breeding world as still in the 1950s compared to other technologically advanced ag seed segments like corn and soy.

Anyways, the reason I was interested in hearing from Mosher is I had heard of her outfit, New West Genetics, before. The name kept coming up in conversations with growers and in web searches as we did our preliminary homework on the genetic side of the hemp market.

New West is notable in the hemp genetics game and should be on any prospective hemp growers radar for many reasons, perhaps chiefly among them having the first US-bred commercial variety of hemp (NWG ELITE) to be earn classification as a certified variety by the Association of Seed Certifying Agencies (AOSCA). I would also add that theyve assembled a top-notch team of traditional and non-traditional breeding expertise, which you can check out here. Im no grower myself, but if I were, these are the type of genetics providers Id look to work with.

The hemp seed breeder CEO started off her address to ASTA with a plea for more participation from the ag seed industry, saying hemp breeding desperately needs the seed industries expertise and professionalism.

We need the seed industry to be participating so we can keep things as optimized as we can, she added.

Currently, she says, her group New West Genetics is focused on creating mechanized, stable varieties for the modern hemp market, which is pretty much exclusively for the flower and processing market, with some modest demand (for the grain).

With CBD based-products projected to be a $1.8 billion industry by 2022, and consumers becoming more aware of the high Omega 3 to low Omega 6 ratios in hemp Mosher says its the closest ratio to fish oil found in a plant-based formulation the hemp market seems like it is here to stay for the foreseeable future, and opportunity for farmers on both the flower and the grain side abound.

Mosher had one particular point that I found fascinating, mostly because it debunked one of the long-held beliefs I had come to take as fact, that the THC percentage levels of finished hemp flower were the direct result of environmental factors like heat stress, light, climate, etc.

All of the research that we have done thus far, and, again, its initial, but all of it has proven the exact opposite, Mosher says. Weve found that the genetics are controlling a little over 80% of the traits of the cannabinoids, as opposed to something like yield which is more 50-50. This is great news, because with well-bred seed we can create stable THC content across regions. And, of course, CBD (levels) as well.

Mosher also says New West has uncovered in its research trials from 2019 that some of the major commercial varieties on the market are not compliant (with the 0.3% THC requirement).

Yet, there is good news on the breeding side as well.

We want to find a balance between the two markets (flower and grain) and make mechanically harvestable varieties that are also enhanced for CBD, she says. And youre going to see enhanced CBD varieties that are diaceous next year, in 2020. Weve got them coming to market, weve just got to bulk up (the numbers).

New West is perhaps unlike some others Ive encountered in the industry in that the group is not actively lobbying for a loosening of the 0.3% THC or lower requirement in the IFR, or asking for an allowance of up to 1% THC as has become common during the USDA comment period, which was recently extended to Jan. 30.

While Mosher admits the requirement is the greatest risk for producers, from our perspective, she believes it can be managed and even conquered consistently by sourcing certified, replicated genetics.

Right now the way it (testing) works is you estimate about a 20-30 day window from maturity and you start to test for THC content, starting weekly and then as you see the THC content start to climb you start testing more frequently so you can catch it before it crosses the threshold, she explains. We see that as a result of using non-compliant genetics, but everyone in the industry sees it a little differently.

The consequences of missing that (0.3%) window is severe, because if it happens your crop cannot enter the stream of commerce, she adds. This hasnt been a huge deal up until this point because before the IFR not everybody was being tested, right? Now, they want every plot tested so its becoming more and more of a risk to not use compliant, proven genetics.

In concluding her address to ASTA, Mosher stressed the need for a mechanized harvesting solution so growers can more economically harvest the crop, as well as a need for more education on the grain side as to using hemp grain and protein in animal feed, bedding, and other sustainable applications.

Matthew J. Grassi is the Technology Editor for Greenhouse Grower and American Vegetable Grower, both Meister Media Worldwide brands. See all author stories here.

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Hemp Genetics CEO: Stable THC Levels Will Come With Breeding Innovation (OPINION) - Greenhouse Grower

Physiology

Designer wants to push the limits of human performance in space – AroundtheO

Olivia Echols says her dream job probably doesn't exist yet because it's so futuristic. But the graduate program in sports product design at the University of Oregon Portland is helping her prepare for it.

From 3D body scanning and computer-aided design to physiology and biomechanics, the program gave her a wide range of knowledge and experience in the world of design. Echols graduated in June 2019 and has been working on the Future Design Team at Adidas.

Echols grew up with a love for sewing and making her own clothes, which inspired her to pursue a career in designing apparel. After earning her bachelors degree in apparel design from Oregon State University in 2013, she worked at Nike in technical design and materials innovation for four years.

She decided to go into the sports product design graduate program in order to further develop her skills and shift her career back to design.

I wanted to grow my process and aesthetic and see whats possible, Echols said.

Echols said getting her masters at UO Portland has been invaluable, as shes currently in a design position helping the team at Adidas come up with concepts for items that will reach the market in five to seven years.

Its a different perspective to have gone back to school and now be working again, Echols said. It felt like a reset, and I feel like a stronger designer for it.

The program went beyond apparel and taught Echols and her classmates how to design just about anything for athletes, from footwear and transportation to gloves. They also got to work with the latest technology, including software programs, scanners, 3D printers, laser cutters, vacuum forming machines and more.

Susan Sokolowski, the program director and an associate professor of sports product design, said developing future female and minority design innovation leaders is important to the graduate program, as the sports industry has historically been focused on male leaders and products for men.

Olivia represents the next generation of design innovators. She is an amazing teammate, incredible maker and thinker, Sokolowski said. We support our students to develop their why and point of view of how they can change the industry with new products for untapped markets and users.

For Echols, those physical environments are not limited to Earth.

For her capstone project, Echols designed and produced workout apparel meant for astronauts in space, taking physiology and biomechanics into account. During her spring break last year, she even went to space camp in Houston to learn more about how to design for the way bodies change and perform in space.

The program also gave her opportunities to travel internationally. She and a classmate were selected as finalists in the Woolmark Performance Challenge, a competition for early career designers to develop creative sports products with merino wool. Echols got to travel to London for a workshop at the Woolmark offices.

It was super cool and inspiring, and theres so much going on there, not only in fashion but on the tech side, Echols said. She also got to pitch her ideas to a panel of professionals at a conference in Denver called Outdoor Retailer.

Kiersten Muenchinger, an associate professor of product design in the School of Art + Design, said the graduate program is the only one in the world thats focused on the design and innovation of sports industry products like footwear, apparel and equipment.

Portland is the international hub of design innovation in sports product, Muenchinger said. Both Nike and Columbia Sportswear developed in the Portland area and inspired many international and local brands to follow.

Muenchinger called Echols a leader.

She is comfortable innovating by conducting her own research and applying materials and manufacturing innovations in the areas she researches, Muenchinger said.

Muenchinger said she hopes Echols and the other sports product design students and alumni continue to innovate to help people perform at their peak, in whatever physical environments they encounter.

Echols is inspired to push the boundaries of human performance on Earth and in space.

Its exciting to be entering the industry right now as a woman because I think theres a renewed sense of creating products for women, and Im excited to work at companies with women in leadership roles, she said.

By Emily Lindblom, University Communications

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Designer wants to push the limits of human performance in space - AroundtheO

Physiology

Gut bacteria linked to muscle function in the colon, says mice study – NutraIngredients.com

Researchers fromCrick University in London and the University of Bern in Switzerland have identified how the contraction and relaxation of muscles in the colon, which is regulated by nerve cells, is influenced by the bacteria in our gut.

The study, published inNature,when such microbes are present, a specific gene called Ahr is activated in intestinal nerves, resulting in healthy contraction and relaxation of the colon. This relationship can be disrupted in cases of intestinal disorders, like irritable bowel syndrome (IBS).

"There is a clear link between the presence of microbes in the colon and the speed at which food moves through the system. If this relationship goes off-kilter it could cause considerable harm," says Yuuki Obata, lead author and postdoc in the Development and Homeostasis of the Nervous System Laboratory at the Crick.

The study help explain how nerve cells sense the microbes in the gut and how they could coordinate their function with other gut tissues.

"Disturbances of intestinal motility are extremely common and cause a lot of suffering in patients after surgical operations or in conditions such as irritable bowel syndrome,"explains Andrew Macpherson, Professor of Medicine and Director of Gastroenterology at the University Hospital of Bern.

"This work provides a foundation to unravel why patients that are colonised with different groups of microbes are susceptible to these intestinal problems."

Brigitta Stockinger, co-lead author and group leader in the AhRimmunity Laboratory at the Crick, adds:"By drawing on different teams at the Crick and internationally with Bern University, we've combined expertise on the gut and how environmental signals from microbiota and diet are passed to cells, to gain understanding of how gut physiology and digestion are affected by these signals."

Vassilis Pachnis, co-lead author and group leader in the Development and Homeostasis of the Nervous System Laboratory at the Crick, adds that this is the first study to demonstrate howAhR is used by intestinal nerve cells to sense the presence of microbes and regulate peristalsis therefore promoting healthy digestion.

He adds: "Inthe future, the use of microbial products that change the activity of AhR in nerve cells could help us alleviate the consequences of abnormal gut peristalsis that is often associated with gastrointestinal diseases."

Source: Nature

Obata, Y., Castao, ., Boeing, S.et al.

"Neuronal programming by microbiota regulates intestinal physiology"

https://doi.org/10.1038/s41586-020-1975-8

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Gut bacteria linked to muscle function in the colon, says mice study - NutraIngredients.com