Category Archives: Human Genetics

When talking about caribou, most people probably think of some version of Santa Clauss reindeer. Although real-life reindeer sadly do not exhibit any of the fantastical traits associated with helping Santa deliver gifts all over the world, caribou their North American counterpart of the same species (Rangifer tarandus) are in fact known to perform epic long-distance migrations.

Despite this, not everyone knows that not all caribou migrate caribou that live in boreal forests are indeed mainly sedentary. Things can get even trickier when we consider populations in which only some caribou migrate, a phenomenon called partial migration.

Why these behavioral differences exist is a fascinating research question, the answer to which is strategically important for the conservation of migratory animals, which are globally imperiled.

In a recently published study, we examined these two types of behaviors in western Canadian endangered caribou and linked a caribous tendency to migrate with its genetic heritage.

The main purpose of our study was to investigate whether caribou migratory behaviour is associated with genetics. To do this, we examined single nucleotide polymorphisms (SNPs), which are fragments of DNA increasingly used by researchers in genetic studies. SNPs are highly abundant and found in genes all across an organisms entire genetic makeup. This means that they are particularly suitable for studies aimed at determining the association between genetic, ecological and behavioural characteristics.

At first, these kinds of markers were used only for model species such as humans and mice, but thanks to recent technologies, they can now be obtained and analyzed in the context of wild species at a reasonable cost.

Our research group, based at the University of Calgary, studied migratory behaviour in 139 radio-collared caribou across western Canada. These caribou belonged to populations located in different environments, ranging from tundra to forests and mountains. We examined GPS locations for each animal using several approaches, including looking at an individual animals movement and seasonal ranges (the winter and summer areas where the animals live).

As a result, we were able to tell which animals were migratory and which were not, and determined that caribou in the tundra tend to be more migratory than others, performing the longest migration (up to 500 kilometres one way). These findings also supported previous studies.

Our first step was to examine SNPs and determine groups of individuals with similar genetic characteristics. For each of the 139 caribou we tracked, we obtained around 30,000 SNPs. Our caribou mainly belonged to either a northern or southern group, which is consistent with previous studies.

Historically, two caribou genetic lineages evolved in separated glacial refugia (areas without ice, where flora and fauna survived) located north and south of the ice sheet during the ice ages. The historical northern refugia was predominantly composed of tundra habitat, where caribou migrated to follow seasonally available food.

In contrast, the southern portion of the species range was dominated by forested environments, where caribou were sedentary as a consequence of reduced seasonality of resources. Our findings showed that that caribou belonging to the northern group were more likely to migrate, indicating that migration may be associated with the genetic ancestry of caribou.

We then wanted to know whether there were specific genetic mutations associated with migratory behaviour, and consequently identified 57 SNPs associated with migration. Many of these SNPs were found in genes that may influence migration in other species. These genes included those regulating including circadian rhythms, sleep, fat metabolism and hormone production.

Overall, our findings provide initial evidence of a package of ancestral genes common across migratory groups that affects the inclination to migrate.

Migratory animals are known to positively affect biodiversity and ecosystem functioning. Upon arrival at a destination site, migrants deposit nutrients and other substances into resident communities and ecosystems. This is being affected by human activities, and there have been resultant dramatic declines in the populations of migratory ungulates. The disappearance of migratory behaviour is now recognized as a global conservation challenge, with alarming new findings for threatened caribou in particular.

Human-caused habitat alterations and climate change have both contributed to caribou decline. This, alongside the local extinction of some populations of mountain caribou, could mean the disappearance of other ecological and genetic behaviours.

If, as we report, migratory behaviour is genetically influenced, caribou could be further impacted by the permanent loss of migratory behaviour. Migratory behaviour, as well as the set of mutations contributing to it, may not be easily re-established once lost.

Genetic mutations, especially those that are beneficial, occur in evolutionary timeframes that are incompatible with the fast decline of caribou. In the face of rapid declines, novel mutations, including those influencing migration, are unlikely to emerge.

This loss could perhaps be averted with the maintenance of seasonal habitats for caribou a strategy that would facilitate migration and give caribou a better fighting chance at population persistence.

See more here:
Whether caribou migrate or stay put is determined by genes that evolved in the last ice age - The Conversation Indonesia

NEW YORK--(BUSINESS WIRE)--Kallyope, Inc., a leading biotechnology company focused on identifying and developing therapeutics involving the gut-brain axis, today announced the appointments of George Shiebler as General Counsel and Anita Kawatra as Executive Vice President, Corporate Affairs, to help steer the company as it advances a pioneering drug discovery platform, clinical trials, and pipeline of multiple programs mediated by gut-brain axis signaling across a broad range of therapeutic areas.

With novel compounds in two lead programs now in clinical development, this is an inflection point for Kallyope. As we embark upon our next phase of growth to bring forth powerful new therapeutics driven by our unique drug discovery platform, we are continuing to build a world-class team to help take our work from the lab to the real world, said Jay Galeota, president and CEO, Kallyope. George and Anita are recognized industry leaders with extraordinary track records. George brings to Kallyope comprehensive knowledge of pharmaceutical industry regulations and unmatched expertise in negotiating a wide variety of sophisticated corporate transactions. Anita has an extensive background in the life sciences, global public health, and public policy, with a strong history of success advising management and boards of startup and growing biotech companies. We look forward to benefiting from their experience and perspectives as we move forward.

George Shiebler has more than 30 years of experience as an attorney in the pharmaceutical and biotech industries. Most recently, he was Senior Vice President and General Counsel of nference, an AI-driven health technology company. Previously, he was a founding executive and General Counsel at Inheris Biopharma, and General Counsel and Chief of Staff for G&W Laboratories. Mr. Shiebler spent 23 years at Merck & Co., leading the worldwide transaction and licensing practice and overseeing multibillion-dollar public and private mergers and acquisitions, multinational joint ventures, and venture investments in startups. He holds a JD from the University of Georgia School of Law, where he was a member of the Law Review, and a bachelors degree from the University of Virginia.

Anita Kawatra has held numerous senior management positions in the life sciences over the past 20 years, following a decade in government and policy. Most recently, she was Chief Corporate Affairs Officer at nference. Previously, she was a founding executive of Inheris Biopharma and held global roles at Elan Pharmaceuticals, Prothena Biosciences, Merck & Co., and the International AIDS Vaccine Initiative. Prior to her work in biopharmaceuticals, she served in the administrations of New York City Mayor David Dinkins and New York Governor Mario Cuomo. Ms. Kawatra is a board member of the New York City Health and Hospitals Corporation, the largest public health system in the United States. In 2020, she was named among the 100 most influential Asian Americans in New York politics and policy. She holds a masters degree from Columbia University and a bachelors degree from Yale University.

About Kallyope

Kallyope, headquartered at the Alexandria Center for Life Science in New York City, is a biotechnology company dedicated to unlocking the therapeutic potential of the gut-brain axis. The companys cross-disciplinary team integrates advanced technologies in sequencing, bioinformatics, neural imaging, cellular and molecular biology, and human genetics to provide an understanding of gut-brain biology that leads to transformational therapeutics to improve human health. The companys founders are Charles Zuker, Ph.D., Lasker Award winner Tom Maniatis, Ph.D., and Nobel laureate Richard Axel, M.D. For more information visit http://www.kallyope.com.

Excerpt from:
Kallyope, Pioneers in Drug Discovery via the Gut-Brain Axis, Strengthens Senior Leadership Team with Key Appointments - Business Wire

Cyprium Therapeutics, a subsidiry of Fortress Biotech, is developing CUTX-101 for the treatment of Menkes disease

CUTX-101 has potential to be first FDA-approved treatment for Menkes disease; rolling submission of New Drug Application to FDA is ongoing and expected to be completed in mid-year 2022

MIAMI and SOLANA BEACH, Calif., March 21, 2022 (GLOBE NEWSWIRE) -- Cyprium Therapeutics, Inc. (Cyprium), a Fortress Biotech, Inc. (Nasdaq: FBIO) (Fortress) subsidiary, with support from its licensing partner Sentynl Therapeutics, Inc. (Sentynl), a wholly owned subsidiary of Zydus Lifesciences Ltd. (formerly known as Cadila Healthcare Ltd.), today announced positive data on CUTX-101, copper histidinate (CuHis), in patients with Menkes disease. The data will be presented as a Top-Rated Abstract and Poster at the 2022 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting taking place March 22-26, 2022, virtually and at Music City Center in Nashville, TN. The previously reported results are from an efficacy and safety analysis of data integrated from two completed pivotal studies in patients with Menkes disease treated with CUTX-101.

Details of the poster are as follows:

Poster Title: Safety and Efficacy of Copper Histidinate (CUTX-101) Treatment for Menkes Disease Caused by Severe Loss-of-Function Variants in ATP7APoster Number: eP195Authors:Stephen G. Kaler, M.D., M.P.H., Shama Munim, M.S., Michael Chen, Ph.D., Robert Niecestro, Ph.D., Lung S. Yam, M.D., Ph.D.Dates / Times: Posters will be available for viewing on Wednesday, March 23, 5:00 p.m. 7:00 p.m., Thursday, March 24, 9:30 a.m. - 4:30 p.m. and Friday, March 25, 10:00 a.m. 1:00 p.m. in the Exhibit Hall. Dr. Kaler will formally present the poster on Thursday, March 24 from 10:00 a.m. 11:30 a.m. CT.

The abstract can be viewed here.

The positive data that will be presented at the 2022 ACMG Annual Clinical Genetics Meeting demonstrate the efficacy and safety of CUTX-101 and its potential to be the first treatment approved by the U.S. Food and Drug Administration (FDA) for patients with Menkes disease. We continue to make progress with our rolling submission of a new drug application (NDA) for CUTX-101 which we anticipate to be completed in the middle of this year, said Lung S. Yam, M.D., Ph.D., President and Chief Executive Officer of Cyprium. We welcome the opportunity to present the positive efficacy and safety data of CUTX-101 to medical geneticists who are often involved in the diagnosis and treatment of Menkes disease, a rare, fatal pediatric disease.

In 2021, Cyprium partnered with Sentynl Therapeutics, Inc., a U.S.-based specialty pharmaceutical company owned by the Zydus Group, to bring CUTX-101 to market. Cyprium will retain development responsibility of CUTX-101 through approval of the NDA by the FDA, and Sentynl will be responsible for commercialization of CUTX-101 as well as progressing newborn screening activities.

About Menkes Disease Menkes disease is a rare X-linked recessive pediatric disease caused by gene mutations of copper transporter ATP7A. The minimum birth prevalence for Menkes disease is believed to be 1 in 34,810 live male births, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment (Kaler SG, Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease and ATP7A-related disorders based on the Genome Aggregation Database (gnomAD). Molecular Genetics and Metabolism Reports 2020 June 5;24:100602). The condition is characterized by distinctive clinical features, including sparse and depigmented hair (kinky hair), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality is high in untreated Menkes disease, with many patients dying before the age of three years old. Milder versions of ATP7A mutations are associated with other conditions, including Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy. Currently, there is no FDA-approved treatment for Menkes disease and its variants.

About CUTX-101 (Copper Histidinate)CUTX-101 is in clinical development to treat patients with Menkes disease. CUTX-101 is a subcutaneous injectable formulation of Copper Histidinate manufactured under current good manufacturing practice (cGMP) and physiological pH. In a Phase 1/2 clinical trial conducted by Stephen G. Kaler, M.D., M.P.H., at the National Institutes of Health (NIH), early treatment of patients with Menkes disease with CUTX-101 led to an improvement in neurodevelopmental outcomes and survival. In August 2020, Cyprium reported positive topline clinical efficacy results for CUTX-101, demonstrating statistically significant improvement in overall survival for Menkes disease subjects who received early treatment (ET) with CUTX-101, compared to an untreated historical control cohort, with a nearly 80% reduction in the risk of death. CUTX-101 has been granted FDA Breakthrough Therapy, Fast Track, Rare Pediatric Disease and FDA Orphan Drug Designations. Additionally, the European Medicines Agency granted Orphan Drug Designation for CUTX-101. A Cyprium-sponsored expanded access protocol for patients with Menkes disease is ongoing at multiple U.S. medical centers.

About Cyprium TherapeuticsCyprium Therapeutics, Inc. (Cyprium) is focused on the development of novel therapies for the treatment of Menkes disease and related copper metabolism disorders. In March 2017, Cyprium entered into a Cooperative Research and Development Agreement (CRADA) with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the NIH, to advance the clinical development of CUTX-101 (Copper Histidinate injection) for the treatment of Menkes disease. In addition, Cyprium and NICHD entered into a worldwide, exclusive license agreement to develop and commercialize adeno-associated virus (AAV)-based gene therapy, called AAV-ATP7A, to deliver working copies of the copper transporter that is defective in patients with Menkes disease, and to be used in combination with CUTX-101. CUTX-101 was granted FDA Breakthrough Therapy, Fast Track and Rare Pediatric Disease Designations, and both CUTX-101 and AAV-ATP7A have received FDA Orphan Drug Designation previously. Additionally, the European Medicines Agency previously granted Orphan Drug Designation to CUTX-101. Cyprium was founded by Fortress Biotech, Inc. (Nasdaq: FBIO) and is based in New York City. For more information, visit http://www.cypriumtx.com.

About Fortress BiotechFortress Biotech, Inc. (Fortress) is an innovative biopharmaceutical company focused on acquiring, developing and commercializing high-potential marketed and development-stage drugs and drug candidates. The company has nine marketed prescription pharmaceutical products and over 30 programs in development at Fortress, at its majority-owned and majority-controlled partners and at partners it founded and in which it holds significant minority ownership positions. Such product candidates span six large-market areas, including oncology, rare diseases and gene therapy, which allow it to create value for shareholders. Fortress advances its diversified pipeline through a streamlined operating structure that fosters efficient drug development. The Fortress model is driven by a world-class business development team that is focused on leveraging its significant biopharmaceutical industry expertise to further expand the companys portfolio of product opportunities. Fortress has established partnerships with some of the worlds leading academic research institutions and biopharmaceutical companies to maximize each opportunity to its full potential, including AstraZeneca plc, City of Hope, Fred Hutchinson Cancer Research Center, St. Jude Childrens Research Hospital, Nationwide Childrens Hospital and Sentynl Therapeutics, Inc. For more information, visitwww.fortressbiotech.com.

About Sentynl TherapeuticsSentynl Therapeutics is a U.S.-based biopharmaceutical focused on bringing innovative therapies to patients living with rare diseases.The company was acquired by the Zydus Group in 2017. Sentynls highly experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is committed to the highest ethical standards and compliance with all applicable laws, regulations, and industry guidelines. For more information, visit http://www.sentynl.com.

About Zydus The Zydus Group, with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global pharmaceutical company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 23000 people worldwide and is driven by its mission to unlock new possibilities in life-sciences through quality healthcare solutions that impact lives. The group aspires to become a global life-sciences company transforming lives through pathbreaking discoveries. For more information, visit https://www.zyduslife.com/zyduslife/

Forward-Looking StatementsThis press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended. As used below and throughout this press release, the words we, us and our may refer to Fortress individually or together with one or more partner companies, as dictated by context. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; risks relating to the timing of starting and completing clinical trials, including the possible disruption of trials due to the hostilities in Europe; our dependence on third-party suppliers; risks relating to the COVID-19 outbreak and its potential impact on our employees and consultants ability to complete work in a timely manner and on our ability to obtain additional financing on favorable terms or at all; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our Securities and Exchange Commission filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. The information contained herein is intended to be reviewed in its totality, and any stipulations, conditions or provisos that apply to a given piece of information in one part of this press release should be read as applying mutatis mutandis to every other instance of such information appearing herein.

Company Contacts:Jaclyn Jaffe and William BegienFortress Biotech, Inc.(781) 652-4500ir@fortressbiotech.com

Lung Yam, M.D., Ph.D.Cyprium Therapeutics, Inc. ir@cypriumtx.com

Michael HerczSentynl Therapeutics, Inc. ir@sentynl.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

See the original post:
Fortress Biotech, Cyprium Therapeutics and Sentynl - GlobeNewswire

image:Ana Victoria Lechuga-Vieco, Raquel Justo, Jos Antonio Enrquez, Jess Vzquez y Enrique Calvo. view more

Credit: CNIC

Research carried out at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) has demonstrated that mixing mitochondrial DNAs (mtDNAs) of different origins can have damaging effects over the medium and long term. mtDNA is a component of the genetic material that is transmitted exclusively from mothers to their children.

The study, published in Circulation, provides invaluable information about how to identify and avoid possible risks associated with mitochondrial therapeutic interventions. The most popular of these methods include the injection of mitochondria from a donor egg into the egg of a woman with fertility problems and mitochondrial replacement therapy aimed at preventing the transmission of disease-causing mutations to descendents, popularly known as "three-parent children". Mitochondrial replacement therapy has already been approved in the United Kingdom.

The new study shows that, while most cells do not tolerate the presence of two mitochondrial genetic variants and progressively eliminate one of the two mtDNAs, some major organs are unable to do this, including the heart, lungs, and skeletal muscle.

For lead researcher Dr. Jos Antonio Enrquez, who heads the Functional Genetics of the Oxidative Phosphorylation System (GENOXPHOS) group at the CNIC, the findings have major implications for treatments involving the transfer of donor mitochondria because they show that animals generated through these procedures appear healthy early in life but go on to suffer in later life from heart failure, pulmonary hypertension, loss of muscle mass, frailty, and premature death.

In the body, most of the DNA is contained in the cell nuclei. In humans, this is where approximately 20 000 genes of the genome are located. However, another 37 genes are located outside the nucleus. These genes are located in cellular compartments called mitochondria and constitute the mitochondrial DNA, explained Dr. Enrquez.

Nuclear DNA is transmitted from parents to their offspring, with the mother and father contributing 50% shares that mix when an egg is fertilized by a sperm.

In contrast, mtDNA is inherited only from the mother because the sperm mitochondria are destroyed in the interior of the fertilized egg. Uniparental transmission of mtDNA is found in almost all organisms. In addition, mtDNA is present in multiple copies per cell, and these copies are all essentially identical, a phenomenon known as homoplasmy.

The presence of more than one mtDNA genetic variant in the cell is called heteroplasmy. Although very rare, heteroplasmy sometimes occurs naturally as a result of mtDNA mutations and can cause several diseases. New therapeutic approaches proposed in recent years and aimed at preventing disease or treating infertility can generate a new form of heteroplasmy in people.

This new form of heteroplasmy, involving distinct non-mutated mtDNA variants, is produced when an individuals cells contain both the original recipient mtDNA and the donor mtDNA transferred during the intervention. In the GENOXPHOS group at the CNIC, we have been investigating whether this breaching of a natural biological barrier has detectable physiological effects, said Dr. Enrquez.

The researchers show that the selection between mtDNA variants coexisting in the same cell depends on their impact on cell metabolism and can be modulated by variations in gene function, drug actions, and dietary changes. All of these factors help to determine the preference for one type of mitochondrial genome over another, they write.

The question as to why mtDNA is transmitted to descendents from only one parent has yet to be answered, but until now the issue had no health implications, said first author Dr. Ana Victoria Lechuga-Vieco. The new medical therapies that breach this biological barrier can generate, intentionally or non-intentionally, mixtures of mtDNA from more than one individual in the same cell.

Before the publication of the new study, we did not know what impact this mtDNA mixing had for the individual, said Dr. Enrquez.

To address this question, the GENOXPHOS group generated mice with a single nuclear genome but with all their cells simultaneously containing two distinct mtDNA variants. This mouse strain was fertile, and young animals showed no related disease, explained Dr. Lechuga-Vieco.

But long-term analysis over the full lifetime of these mice showed that the coexistence of two mtDNA variants in the same cell compromised mitochondrial function.

We observed that cells rejected the presence of two mitochondrial genomes, and most of them progressively eliminated one of the mtDNA variants. Surprisingly, however, major organs like the heart, lungs, and skeletal muscle were unable to do this, explained Dr. Lechuga-Vieco.

Organs that could eliminate one of the mtDNA variants, like the liver, recovered their mitochondrial metabolism and cellular health, but those that could not progressively deteriorated as the animals aged, continued Dr. Enrquez.

Thus the animals, which appeared healthy in their youth, in later life suffered from heart failure, pulmonary hypertension, loss of muscle mass, frailty, and premature death.

The researchers conclude that the dangerous effects of mitochondrial therapeutic interventions identified in the new study show the need for caution in the selection of the donor mtDNA genotype.

As the authors state in their article, the results of the Circulation study also imply that Even the most promising method, for the replacement of oocyte mitochondria carrying known pathological mtDNA mutations, may fail to achieve 100% replacement.

The study shows that recipient cells have a high capacity to select and amplify the original, pre-existing mtDNA variant, which may have been undetectable before transfer of the donor mtDNA. The procedure thus has the potential to result in a mix of mtDNA from two individuals in descendent cells. The same problem arises with oocyte rejuvenation by microinjection of donor cytoplasm, pointed out Dr. Enrquez.

Similarly, added Dr. Enrquez, A similar risk can arise when purified donor mitochondria are used to treat damaged cells implicated in cardiopulmonary or neurlogical diseases.

Dr. Enrquez stressed that these risks do not mean that mitochondrial replacement therapy should be abandoned. In the same way as blood transfusions and organ transplants require careful control of compatibility between recipient and donor, Dr. Enrquez recommends that any therapeutic strategy that risks the mixing of healthy mtDNA variants from two individuals should ensure full compatibility between the donor and recipient mitochondrial genomes.

The study was supported by the following funding bodies: Ministerio de Asuntos Econmicos y Transformacin Digital (MINECO); Ministerio de Economa, Industria y Competitividad (MEIC); Human Frontier Science Program; European Molecular Biology Organization; Programa Red Guipuzcoana de Ciencia, Tecnologa e Informacin del Gobierno Vasco; and the ELKARTEK Program Department of Industry, Innovation, Commerce, and Tourism.

About the CNIC

The Centro Nacional de Investigaciones Cardiovasculares (CNIC), directed by Dr. Valentn Fuster, is dedicated to cardiovascular research and the translation of knowledge gained into real benefits for patients. The CNIC, recognized by the Spanish government as a Severo Ochoa center of excellence, is financed through a pioneering public-private partnership between the government (through the Carlos III Institute of Health) and the Pro-CNIC Foundation, which brings together 12 of the most important Spanish private companies.

Experimental study

Animals

Heteroplasmy of Wild Type Mitochondrial DNA Variants in Mice Causes Metabolic Heart Disease With Pulmonary Hypertension and Frailty

3-Mar-2022

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A CNIC study highlights the risks of mitochondrial therapeutic interventions - EurekAlert

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Genetic and morphological variation of Vespa velutina nigrithorax which is an invasive species in a mountainous area | Scientific Reports - Nature.com

Asano, T., Boisson, B., Onodi, F., Matuozzo, D., Moncada-Velez, M., Maglorius Renkilaraj, M., Zhang, P., Meertens, L., Bolze, A., Materna, M., Korniotis, S., Gervais, A., Talouarn, E., Bigio, B., Seeleuthner, Y., Bilguvar, K., Zhang, Y., Neehus, A. L., Ogishi, M., Pelham, S. J., Casanova, J. L. (2021). X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Science Immunology, 6(62), eabl4348. https://doi.org/10.1126/sciimmunol.abl4348

Bastard, P., Gervais, A., Le Voyer, T., Rosain, J., Philippot, Q., Manry, J., Michailidis, E., Hoffmann, H. H., Eto, S., Garcia-Prat, M., Bizien, L., Parra-Martnez, A., Yang, R., Haljasmgi, L., Migaud, M., Srekannu, K., Maslovskaja, J., de Prost, N., Tandjaoui-Lambiotte, Y., Luyt, C. E., Casanova, J. L. (2021). Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Science Immunology, 6(62), eabl4340. https://doi.org/10.1126/sciimmunol.abl4340

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Decoding the Genetics Behind COVID-19 Infection - National Institutes of Health (NIH)

The team headed by Professor Huu Phuc Nguyen, Chair of Human Genetics at Ruhr-Universitt Bochum (RUB), and Professor Roland Schroers, Head of the Department of Haematology, Oncology, Stem Cell/Immune Therapy at the University Hospital Knappschaftskrankenhaus, published their findings in theInternational Journal of Canceron 22 January 2022.

Optical genome mapping involves the extraction of very long DNA molecules, for example routinely collected blood samples or bone marrow material from patients. These long DNA molecules are labelled with dye molecules at more than half a million different positions in the entire human genome and are then moving through ultrathin nanochannels on a special chip. As the DNA molecules move through the nanochannels, a laser is used to make them visible and they are photographed using a fluorescence microscope. The images of the entire genome are then analysed using bioinformatic analyses. The aim is to identify and interpret changes in genetic regions that are relevant for the development of cancer, explains Dr. Wanda Gerding from the Bochum Department of Human Genetics.

Optical genome mapping thus facilitates genome-wide analysis of regions that are important for the classification and therapy of leukaemias using one methodology. Furthermore, it also allows the identification of new relevant genomic regions and new genes.

In the current study, the team compared the methodology to current standard diagnostics in patients with acute myeloid leukaemia as well as myelodysplastic syndromes. The researchers showed that the results obtained by optical genome mapping methodology were concordant in 93 per cent of samples compared toa conventional methodology, the so-called cytogenetic karyogram, where whole chromosomes are visualized. In 67 per cent of the samples, it was even possible to obtain additional genetic information.

The methodology can thus not only detect structural changes in the genome more accurately, but also has the potential to become an important component of routine diagnostics for patients with leukaemia. As a further benefit, genome research can provide data and new insights for further research work in the field of tumour biology, says Wanda Gerding.

For the project, the Human Genetics Department at RUB, headed by Professor Huu Phuc Nguyen, cooperated with the Haematology, Oncology, Stem Cell and Immunotherapy Department of the Knappschaftskrankenhaus Bochum, headed by Professor. Roland Schroers, a member of the Centre for Haematooncological Diseases (ZHOE) at RUB, and Professor Peter Reimer from the Haematology, Internal Oncology and Stem Cell Transplantation Department at Evangelische Kliniken Essen-Mitte. The close scientific cooperation of both departments was ensured by Dr. Deepak Vangala, Dr. Wanda Gerding, Dr. Verena Nilius-Eliliwi (funded by the Female Clinical Scientist programme of the RUB Medical Faculty) and medical student Marco Tembrink (Human Genetics, medical doctoral scholarship holder from FoRUM, Medical Faculty of the RUB (FoRUM RUB). The project received a positive vote from the Ethics Committee of the RUB Medical Faculty (No. 20-7063).

Reference:GerdingM, Tembrink M, Nilius-Eliliwi V, et al. Optical genome mapping reveals additional prognostic information compared to conventional cytogenetics in AML/MDS patients. Int. J. Cancer Res.2022. doi: 10.1002/ijc.33942

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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More Precise Information on the Genetic Basis of Leukemia - Technology Networks

Very low concentrations of the popular organic insecticide Spinosad have profound effects on beneficial insect species, including vision loss and neurodegeneration, new research led by the University of Melbourne and Baylor College of Medicine has found.

The study, published in eLife, used the vinegar fly Drosophila to analyse the impact of chronic exposure to low concentrations (0.2 parts per million) of Spinosad and the resulting physiological impacts on the brain and other tissues.

Spinosad is commonly used to control insect pests, including thrips, leafminers, spider mites, mosquitoes, ants and fruit flies, in both commercial and domestic settings.

Within a matter of 20 days, tiny doses of Spinosad can have an alarming impact on the brains of adult Drosophila. Observing sections of brain tissue under microscope demonstrated there was an average of 17% of the fly brains destroyed due to exposure, said Dr. Felipe Martelli from Monash University, who completed this work as part of his Ph.D. at the University of Melbourne. Neurons that serve vital functions die, leaving large vacuoles, fluid-filled sacs, in the brain. This leads to neurodegeneration, blindness and behavioural changes in adult vinegar flies. Due to the Drosophilas genetic and biochemical similarities to other insects, the research indicates that these impacts could be translated to other beneficial insects such as bees, Martelli said.

As a natural substance made by a soil bacterium, Spinosad is often thought to be less harmful to beneficial insects and is frequently used as an alternative to synthetic insecticides, according to study co-author, Professor Philip Batterham, from the School of BioSciences and Bio21 Institute at the University of Melbourne.

There is often an assumption that organic equates to safer, but our study finds this isnt the case, Batterham said. Spinosad is now registered for use in over 80 countries, and it poses a far greater risk to beneficial insects than previously thought. Concerningly, the low concentration levels used in this study is what would be commonly found in groundwater or in the air through incidental exposure.

Based on earlier work by our research group using similar techniques to this study, Spinosad was found to have a much greater negative impact on vinegar flies at far lower doses than imidacloprid, a synthetic insecticide that has been banned in Europe for its impacts on non-target insects including honeybees, Batterham said.

While this study does not aim to pin the blame on Spinosad, it does show that having an organic label doesnt always mean safer. All insecticides, no matter their source, need to be rigorously studied for any unintended ecological impacts, Batterham said.

Martellis research was enhanced by the opportunity to do experiments in the lab of a global leader in neuroscience, Dr. Hugo Bellen, corresponding author and distinguished service professor of molecular and human genetics at Baylor.

The striking biological features that are associated with low levels of Spinosad resemble some slow progressive neurological diseases in which lysosomes are expanded, also called Lysosomal Storage Disease. These genetic diseases have also been associated with Parkinsons Disease, and there are interesting similarities in the pathogenic mechanisms caused by mutations in these genes and Spinosad, Bellen said.

A collaboration between the University of Melbourne, Baylor College of Medicine and the University of Texas, this study adds to a growing body of evidence indicating that insecticides are contributing to the global decline in population sizes of many beneficial insect species.

Large-scale insecticide application is a primary weapon in the control of insect pests in agriculture but we know that around the world, insect populations are decreasing in size by about 1% each year; this decrease is largely in insects that are not pests, Batterham said.

When you look at insect species disappearing, it's almost like randomly pulling blocks out of a Jenga tower; its destabilizing ecosystems making them vulnerable to collapse.

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An organic insecticide is more damaging to non-target insects than synthetic counterparts - Baylor College of Medicine News

54gene, the health technology company advancing African genomics research for improved global health outcomes, has announced the awarding of $64,000 in scholarships to four PhD candidates in Nigeria, Uganda and South Africa. Through the African Centre for Translational Genetics (ACTG), a non-profit initiative launched by 54gene in February 2020, the grants awarded will be used to further develop translational genomics research capacity across Africa and will cover all expenses of the recipients during their postgraduate study.

The ACTGs mission is to invest in the continents health ecosystem by empowering the next generation of African genomics scientists through the provision and implementation of scholarships, grants, fellowships, internships and training programmes. The PhD scholarship awards were the primary focus for the ACTG in 2021. Following a three month pan-African call for applications and a rigorous selection process, four successful recipients were handpicked from a total of 46 applications and were awarded grants to advance their genomics research studies in the areas of cardiometabolic diseases, cancers, neurological diseases and sickle cell disorders. The four candidates that have now been awarded the PhD scholarships are studying at different institutions spread across Africa two are based at Makerere University, Uganda, one at the University of Pretoria, South Africa and the last awardee is based at Covenant University in Nigeria.

Gomera, Rejoice University of Pretoria, South Africa

Kintu, Christopher Makerere University, Uganda

Onyia, Abimbola Covenant University, Nigeria

Soremekun, Chisom Makerere University, Uganda

54gene, through the ACTG in 2020, launched the NCD-GHS Consortium composed of Nigerian geneticists in partnership with the Nigerian Institute of Medical Research (NIMR) and the National Biotechnology Development Agencys Center for Genomics Research and Innovation (NABDA-CGRI). Preliminary findings from the Consortiums landmark study into non-communicable and cardio-metabolic diseases were shared at the American Society of Human Genetics Conference in October 2021. The study found seven distinct clusters among the 50 under-studied ethnolinguistic groups in Nigeria with some groups showing evidence of shared genomic regions with northern African and European groups. In comparison to European populations, the study also replicated previous research showing lower levels of Neanderthal genome sharing in Nigerian groups.

Speaking on the scholarships, Dr. Abasi Ene-Obong, CEO of 54gene, said, Developing the next generation of genomic scientists is critical in ensuring that the knowledge, resources and insights derived from homegrown research benefits not only Africans but the global population. Access to funding as well as to our international team of genetic and biomedical specialists is a unique opportunity for these talented African researchers who, like us, want to unlock the boundless potential offered by the human genomic diversity of African populations. The funding and available resources will put them at par with their counterparts in developed countries and make them more confident in leading future research studies.

With over $45 million in investment raised by the company since its launch, the PhD candidates will receive up to $4,000 annually for four years, to cover tuition fees and living expenses. Recipients will have the opportunity to work alongside leading researchers at 54gene and its partner institutions (NIMR and CGRI), who are experts in genomic data science, bioinformatics and molecular genetics. Recipients will also be given access to state-of-the-art genomic technologies and the opportunity to co-publish novel findings in collaboration with these leading scientists. PhD candidates will also be given the opportunity to work with 54genes partner institutions post-graduation.

Aminu Yakubu, VP Research Governance and Ethics at 54gene and ACTG representative said, There is incredible African talent in the genomics space, but opportunities to undertake research and conduct desired tests is limited due to inadequate infrastructure. Supporting and powering pan-African genomics research, especially for non-communicable diseases, has been a key impact marker for 54gene since the company launched in 2019. This is why we are thrilled to offer these outstanding researchers the opportunity to carry out ground-breaking research that will contribute to future health outcomes and benefit the field of genomics research on the continent and also globally.

Prof. Babatunde Salako, Chairman NCD-GHS Steering Committee and Director-General, Nigerian Institute of Medical Research (NIMR), said, Despite the global health crisis of the past two years, genomic science has not ceased to be important, nor have our scientists allowed their thirst for ground-breaking research to become extinguished. It has been a great pleasure to serve the committee by reviewing the 46 applicants, who are some of the brightest minds on the continent. This initiative is also a massive win for Africa as we deepen our efforts to become leaders in genomic research.

As 54gene expands its operations and partnerships in the coming years, the ACTG looks forward to equally expanding the coverage of its empowerment activities to reach more student scientists, junior and senior research scientists alike in academia and research institutes. Through these efforts, the ACTG is building on the giant precedent work undertaken by organizations like the Human Hereditary and Health in Africa (H3Africa) Consortium, and the African Academy of Sciences among others.

About 54gene

54gene is a health technology company centred on advancing the field of African genomics to unlock scientific discoveries as well as improve diagnostic and treatment outcomes within Africa and the global community. Founded in 2019, the company generates genetic insights from research cohorts in the worlds most diverse populations to improve the development, availability and efficacy of therapeutics and diagnostics that will prove beneficial to all populations.

About the ACTG

The ACTG is the African Centre for Translational Genetics. It is an entity designed by 54gene to facilitate precision medicine on the African continent, provide funding for translational genetics research by African scientists and re-invest in the health ecosystem by empowering the next generation of African genomic scientists through the provision and implementation of grants, internships and training for medical researchers and students.

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54gene's African Centre for Translational Genetics awards $64,000 scholarship to further genomics research - Ventures Africa

It's one of the most common medical conditions on the planet so why are the causes ofanxiety still such a mystery? Scientists are working tounravel them.

Ithappened in a split second, like a bone snapping under pressure.

One minute I was cooking dinner, monitoring babies, bath time, work emails, phone calls, deadlines and life admin. The next, the room was spinning.

I turned, and suddenly the floor began undulating beneath my feet. Negotiating the kitchen was like walking across the Turkey Trot at Coney Island. The walls fell in towards me.

I grabbed the bench to steady myself, but my fingers were tingling and there was a high-pitched ringing in my ears. Yet, I felt like I was trapped inside a glass box: sounds outside were muffled, my vision blurred, my heart racing.

There were no broken bones, but something else cracked that day, something inside my head.

I visited my doctor in a panic but despite the drama of my symptoms, the diagnosis was remarkably straightforward: "What you are describing is commonly felt by people experiencing anxiety," the doc told me gently.

Research suggests more than 25 per cent of us encounter a clinically significant episode of anxiety at some point in life.

For some, it is a fleeting experience like mine and manyanxiety sufferersrespond well to existing treatments including cognitive behaviour therapy or medication. Yet for others, anxiety can be a crippling and chronic disability impacting all areas of life without relief.

The COVID pandemic has supercharged the numbers, with GPs and psychologists reporting a spike in patients seeking help for anxious feelings.

And while researchers emphasise the complexity of the anxiety jigsaw puzzle which can lead to diagnoses including generalised anxiety disorderor obsessive compulsive disorder there are three key areas where cutting edge research is ushering in a new way forward.

No longer is anxiety viewed as arandom condition, as sudden and uncontrollable as the symptoms it can cause.

Instead, genetics, diet and knowledge ofhowtraumatic life events can affect brain structure and development are forging promising new approaches to understanding what causes anxiety, and how to treat it.

Lets break it down.

At the QIMR Berghofer Medical Research Institute in Queensland, PhD candidate Jackson Thorp an expert in psychiatric genetics has spent years hunting for a needle in a haystack.

At the Institute's Translational Neurogenomics Lab, Thorp is using a global database of 400,000 people to identify gene variants more common in anxiety sufferers.

Using statistical analysis software to cross-check the 20,000-25,000 genes in the human genome, Thorps work aims to identify gene changes more common in people with anxiety disorders.

And just last yearThorp and his colleagues hit the jackpot.

"We found 611 genes that were linked to anxiety and many of these are also linked to depression," he says.

"This tells us genetic risk for anxiety does not come from one or two genes but hundreds. Probably even thousands of genes are responsible for increasing the risk of developing anxiety."

Research like this is so new, so pioneering, that a full picture is yet to emerge about which genes are most significant and precisely how they influence anxietys development.

The next step is to understand their role in predisposing someone to anxiety or whether specific genetic mutations could even predict it.

One of the most interesting is a gene known as DRD2, responsible for coding a dopamine receptor in the brain. This neurotransmitter is released when we associate particular activities with pleasure and is related to mental health outcomes.

Yet with Thorps research showing so many genes associated with anxiety, the reality is most of us probably have at least some genetic risk factors.

What makes one person develop an anxiety condition and not another?

"While there is a very large genetic component that does not mean you will definitely develop anxiety, it just means youre more likely to," Thorp explains.

And research reveals exactly how much more likely.

Anxiety disorders are about 30 per cent heritable, Thorp says, noting many people can see anxiety symptoms emerge repeatedly across generations of their own families.

But if genes are behind 30 per cent of our susceptibility to anxiety disorders, what influences the other 70 per cent?

A great many cases of anxiety are triggered by unknown causes, often environmental, Thorp says. "You may have a high genetic risk but if you don't have that environmental trigger then perhaps you wont develop anxiety at all," he says.

The ability for genes to turn themselves on or off in response to environmental triggers is known as epigenetics. It is common across all diseases. A genetic predisposition to diabetes, for example, does not mean you will become ill it increases your risk but how that risk interacts with lifestyle or environment can determine what happens next.

In the case of anxiety, an environmental trigger could be a one-off traumatic experience, sustained disadvantage or common lifestyle stressors.

It could even be living through COVID-19.

A spike in the numbers of people seeking help for anxiety during the pandemic shows in real time the likely role of the environment in triggering genetic susceptibility.

"If we have two people with the same environmental trigger such as the pandemic, why does one develop anxiety but not the other?" asks Thorp. "It's reasonable to ask whether one person has a higher genetic risk."

And it's possible that if it wasnt for COVID-19 that susceptibility may never have been provoked.

The way anxiety changes the structure of the brain and the neurotransmitters it releases consumes Jess Nithianantharajah, a neuroscientist from Melbournes Florey Institute of Neuroscience and Mental Health.

Nithianantharajahs goal is to understand the biological basis of anxiety and "what is really going on in the brain that changes peoples behaviour".

Unlike brain disorders like dementia which are driven by loss of brain capacity, the brain of an anxious person shows "changes in connectivity", Nithianantharajah says. "Certain circuits in the brain become over-connected or under-connected and it's interesting how connectivity changes can lead to impaired behaviours."

In straightforward terms, our human brains are wired to respond to environmental triggers, particularly those that may suggest threat.

When we feel under siege the ancient parts of our brains that developed long before we became the sophisticated humans we are today go into "fight or flight mode".

This process floods our bodies with hormones like adrenaline or cortisol from our endocrine system, as well as neurotransmitters like noradrenaline from the brain, to either fight off the threat or flee from it.

This adaptive reflex has helped humans evolve to identify and respond to danger.

Yet there can be too much of a good thing.

In an anxious brain this response is never properly turned off. Every situation begins to feel like a threat and our bodies react as if they are under fire. Those neural pathways that are meant for emergencies are used repeatedly until they become the go-to response in almost every situation.

Nithianantharajah explains the brains threat "watchman", a tiny nut-shaped structure called the amygdala that sits alongside the hippocampus and encodes danger, becomes hyper-activated.

Neurotransmitters like glutamate that fire up the brain, get out of whack with those like Gammaaminobutyric acid (GABA), designed to calm things down.

The amygdala's crucial connections with the brains pre-frontal cortex which develops until adolescence and acts like the sensible control centre of the brain are broken down, undermining rational thought processes that might tell the amygdala "hey, no worries, you can ease off because this is all good".

"Sometimes it's hard to understand what's the chicken and what's the egg," says Nithianantharajah, adding that within the next few years a toolkit of new treatments may become available to provide more targeted mental health care. "Not everyone who presents with anxiety has the same symptoms and they dont all respond to the same drug," she says.

But what sparks mixed-up connections in the first place?

Sarah Whittle, head of the University of Melbournes Social and Affective NeuroDevelopment Lab, is researching how early life experiences shape brain development and increase the risk of anxiety.

Her fascinating research shows a threatening environment, whether it comes from within the family or from the community, can cause a childs brain to develop faster than normal.

"In essence kids have to grow up quickly to look after themselves," she says. "The circuits in the brain responsible for responding to threat, and regulating emotions, are impacted. Those same circuits are specifically involved in anxiety."

It's suspected that links between the brains ancient "limbic system", including the amygdala, and the controlling prefrontal cortex, are disrupted.

On MRI brain scans Whittle can actually see the impact of this disruption.

Kids that have experienced threat tend to have stronger connectivity between these two brain regions as they develop, she says.

Like so much research into anxiety, the work Whittle does is brand new. Conclusions cannot yet be drawn. The next step is large longitudinal studies in children from diverse backgrounds. One such study involves10,000 US children representing a cross-section of the population.

Researchers will return to these children several times over the next decade, checking their brain structure, function and connectivity and comparing findings with psychological and cognitive development.

"It is crucial when looking at children or adolescents to see how the brain develops over time or we're not getting the whole picture," Whittle says. "Waves of this US study will be coming up over the next five or six years and we'll be able to look in more detail at how trajectories of brain development got off track following exposure to stress and at what age children are most vulnerable."

We have relatively little influence over the way our genes, or the early environments we encounter as children, influence our anxiety risk. But diet is another matter.

Felice Jacka is pioneeringa growing body of research that shows how diet, something over which we all have substantial control, can influence mood.

The link between the gut and the brain is well-known: we have all experienced "butterflies" when we are nervous. Jackas research in "nutritional psychiatry" at Deakin Universitys Mood and Food Centre has made a ground-breaking connection: diet can directly influence mental health.

When Jacka announced the topic would be the focus of her 2010 PhD "many people thought I was quite bananas", she says.

But she persisted. And when her research became the first to demonstrate a correlation between diet quality and the likelihood of having a clinically significant depressive or anxiety disorder Jacka became a sensation. Her work was published on the cover of the prestigious American Journal of Psychiatry and featured in Time magazine.

Further studies continue to strengthen the link, showing those who eat diets high in vegetables and fruits, wholegrains, legumes, nuts and seeds are up to 30 per cent less likely to become depressed.

And Jacka argues that none of this should come as a surprise. The impact of diet is well-established in physical health. Why should mental health be any different?

Yet she is at pains to ensure people do not see their anxiety as a failure of their eating habits: "You did not cause your anxiety," she says.Instead, Jacka wants us to feel empowered: unlike many other risk factors for mental disorders diet is easily manipulated. "Identifying factors we can modify in order to improve mental health outcomes is very, very important," she says.

The scope of Jackas findings are fascinating.

A study of 23,000 Norwegian mothers shows their diet when pregnant is linked to the emotional health of their children, independent of other risk factors.

Another significant association shows diet quality is related to the size of a brain region called the hippocampus, a structure of densely-packed neurons that is unique in its ability to add neural connections throughout life. It is influential in learning and memory as well as mental health.

Jacka saysthe hippocampus can grow or shrink in response to environmental impacts and its size has been linked to anxiety.

"People with mental disorders often have a smaller hippocampus and as they recover the hippocampus grows again," Jacka says. "As people age the hippocampus also tends to get smaller but around 60 per cent of this age-related shrinkage maybe influenced by diet quality."

Jacka conducted a three-month study comparing the impact of diet and social support on moderate-to-severe clinical depression.

"What we saw at the end of that three months was actually quite astounding,"she says. "About a third of (the dietary support cohort) went on to have full clinical remission compared with about 8 per cent in the other condition."

But why does it work?

It is suspected pathways between the gut and brain influence the release of neurotransmitters like serotonin and gamma aminobutyric acid (GABA), two of the bodys most important "feel good" chemicals.

Diet may offer a way to "hack" these chemicals, ensuring our bodies are working optimally, with plenty of happy chemicals available to support and even boost our mood.

In addition, diet influences the function of our immune systems. "And we know that low-grade immune activation, causing inflammation, is an important factor in mental and brain health," Jacka says.

While we wait for the relationship between anxiety, genes, diet and brain structure to deliver new treatments, the ongoing role of psychotherapy in managing symptoms and changing thought patterns to restructure neural pathways cannot be overstated.

Psychologist Peter McEvoy, an anxiety specialist, has devoted many hours of clinical practice to helping people confront and overcome anxiety conditions.

"What causes anxiety is a big question and it's a complex one," says McEvoy, Professor of Psychology at Curtin University, and associate editor of the academic Journal of Anxiety Disorders.

While some individuals may experience anxiety because of "a high genetic load", McEvoy says others are more vulnerable to the "environmental load" including experiences of trauma or pandemic stressors for example.

Notwithstanding these risk factors "we don't really know why one particular individual is going to develop an anxiety disorder and another isn't," he says.

But his years of experience have highlighted one key constant in anxious patients: the need for certainty.

Intolerance of uncertainty, he says, is "ripe for breeding anxiety", noting the "but what if" cycle is a feature of many anxious thoughts. Psychotherapy is excellent at helping patients question these thought cycles.

McEvoy's research into the certainty/uncertainty principle suggests that humans are hard-wired to want to predict the future, a survival instinct that allows us to plan and prevent bad things from happening.

This urge has been quite literally built into the structure of the brain, he says.

Like Nithianantharajah and Whittle, he notes the importance of the pre-frontal cortex in "planning for things and predicting things so we can modify our risk in some way".

Uncertain situations like COVID can set up a battle inside the brain between our innate need to seek certainty, and plan contingencies to keep us safe, while facing a situation that is genuinely uncertain and even out of control.

Some people, McEvoy says, become stuck in a circular pattern of worry, trying to sort out a plan, trying to prevent a bad outcome from a perceived threat, but in reality "if we pursue that goal of achieving certainty, it is likely to lead us down the pathway of excessive worry, and anxiety".

The answer, according to McEvoy, is at once practical and yet, for someone trapped in a cycle of worry, tortuously difficult to achieve: "The goal is to learn to tolerate and accept uncertainty," he says. "To focus more on the here and now and simply ask yourself 'what is controllable today?'.'

How will you know youve reached that place of comfort? For McEvoy the answer is simple: If were still going, then were coping, were resilient. And if were feeling a little exhausted by it then thats ok too.

Words and production: Catherine Taylor

Video:Zalika Rizmal andAndrew McKenzie

Illustrations : Emma Machan

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What causes anxiety? Why is it so common? And how can it be treated? - ABC News