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Tag: Genetics

  • Enhancing genomics and bioinformatics knowledge sharing

    Enhancing genomics and bioinformatics knowledge sharing

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    Newswise — The African BioGenome Project, a large-scale international research project involving Konstanz bioinformatician Abdoallah Sharaf, successfully launched its “Open Institute”. The institute’s mission: accelerating knowledge exchange in biodiversity genomics and bioinformatics.

    The “blueprints” of all living organisms are encoded in the sequences of their DNAs’ base pairs. Knowledge about these genome sequences and the identification of functional subunits, such as genes, are of great importance for biodiversity conservation efforts and for the life sciences in general. For this reason, the African BioGenome Project (AfricaBP), founded in 2021, has set itself an ambitious goal: sequencing the genomes of 100,000 animal and plant species that occur only in Africa – and to do so within 10 years. What is more, the sequencing is to be conducted exclusively in Africa.

    A second goal of the AfricaBP, therefore, is to empower African scientists and institutions to obtain the required skill sets, capacity, and infrastructure to generate, analyze, and utilize genome sequences in labs across the continent. With the successful launch of AfricaBP’s Open Institute, the project has made an essential step towards reaching this goal, as Abdoallah Sharaf and his colleagues now describe in an article in Nature Biotechnology. Sharaf is a bioinformatician in the Department of Biology at the University of Konstanz (Germany), associate professor at Ain Shams University (Egypt), and Co-Chair of the AfricaBP pilot committee.

    Central goals of the Open Institute
    “The Open Institute aims to lower some of the barriers that often prevent the advancement of biodiversity genomics and bioinformatics knowledge exchange in Africa,” says Sharaf. To do so, the AfricaBP Open Institute focuses on five key priority areas:

    • Curriculum development
    • Technology development and infrastructure
    • Promoting grassroot knowledge exchange and equitable partnerships
    • Maximizing data ownership and sovereignty
    • Scientific enterprise and industry

    In 2022, the Open Institute started hosting widely-attended workshops in cooperation with African institutions and organizations as well as global partners. So far, over 700 participants from 29 countries have been trained in cutting-edge technologies in the fields of biodiversity and genomics. As many of the participants came from African countries with active genomics research, in the future, the Open Institute will broaden its outreach to increase the participation of scientists from regions that currently have minimal genomic activity. In line with this, five more workshops on various aspects of genomics and bioinformatics are planned by the end of 2023 – two of them online, three in a hybrid format.

    Tom Kariuki, Chief Executive Officer of the Science for Africa Foundation (SFA), applauds the project: “As the SFA Foundation, we are laser-focused on improving the quantity, quality, and productivity of science in Africa, which requires a skilled scientific workforce through the development of globally competitive science leaders in Africa. The Open Institute serves our objective of training future generations of scientists who will generate data to inform policy and Africa’s development agenda.”

    This text is an adapted version of the original press release of the African BioGenome Project.

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    University of Konstanz

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  • Scientists Take Next Big Step in Understanding Genetics of Schizophrenia

    Scientists Take Next Big Step in Understanding Genetics of Schizophrenia

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    Newswise — CHAPEL HILL, NC – Genetically speaking, we are individuals different from each other because of slight variations in our DNA sequences – so-called genetic variants – some of which have dramatic effects we can see and comprehend, from the color of our eyes to our risk for developing schizophrenia – a debilitating psychiatric condition affecting many millions worldwide. For several years, scientists have studied the entire genomes of thousands of people – called genome-wide association studies, or GWAS – to find approximately 5,000 genetic variants associated with schizophrenia.

    Now, UNC School of Medicine scientists and colleagues are figuring out which of these variants have a causal effect in the development of the schizophrenia. They are finding that some of genetic variants regulate or alter the expression of genes involved in the condition.

    Published in the journal Cell Genomics, this research marks a big step forward in our understanding of the genetic basis of schizophrenia.

     “Our findings not only provide insights into the intricate regulatory landscape of genes, but also propose a groundbreaking approach to decoding the cumulative effect of genetic variants on gene regulation in individuals with schizophrenia,” said senior author Hyejung Won, PhD, associate professor of genetics at the UNC School of Medicine. “This comprehension could potentially pave a path for more precise interventions and therapies in the future. Right now, therapeutic options are limited, and some people do not respond to drugs available.”

    For this study, Won and first authors Jessica McAfee and Sool Lee, both UNC-Chapel Hill graduate students, led a team of researchers from UCLA, Harvard, the University of Michigan, and Human Technopole in Italy to explore the genetic variants already linked to the risk of schizophrenia through GWAS research. Their goal was to figure out a way to tease apart meaningless variants from those with potential for biological activity important for developing schizophrenia. This isn’t easy for a few reasons, one of which is that genetic variants are often inherited together from parents. So, right next to each other could be two genetic variants associated with the condition – one might be important for gene expression that plays a major role in the condition, but the other variant might not have any role in the condition.

    To tackle this problem, the researchers used a special technique called a massively parallel reporter assay (MPRA) – essentially a genetic sequencing technique that can parse which variants trigger gene expression and which ones don’t. To use this method, the researchers introduced the 5,000 variants into human brain cells in a dish, cells that are essential for early brain development. These variants may or may not cause the expression of their downstream gene and genetic barcode.  The barcode, a 20bp DNA sequence, is unique to each variant. This is what the group uses to distinguish the variant sequences. The MPRA revealed 439 genetic variations with actual biological effects, meaning they can alter expression of gene.

    “Traditionally, scientists have used other epigenetic data, such as transcription factor binding and biochemically defined enhancers, to identify variants with biological effects,” Won said. “However, these conventional methods failed to predict a large portion of variants we identified to have biological effects. Our work points to a wealth of unexplored variants with biological effects.”

    To understand how these variants work together to influence gene activity, Won and colleagues developed a new model that combines data from MPRA with chromatin architecture of brain cells – that is, the genetic information important for how brain cell DNA is organized. By doing this, the researchers could connect these 439 variants to how genes are turned on or off.

    “Schizophrenia is a complex condition that is highly heritable,” Won said. “To find these 439 potentially causal variants is a big step, but we still have a lot of work ahead to figure out the complicated genetic architecture that leads an individual to develop this condition. With that information in hand, we could begin to understand the biological mechanism underlying this complex disorder, which may eventually lead to targeted therapies.”

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    University of North Carolina School of Medicine

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  • Largest genetic study of epilepsy to date provides new insights on why epilepsy develops and potential treatments

    Largest genetic study of epilepsy to date provides new insights on why epilepsy develops and potential treatments

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    Newswise — The largest genetic study of its kind, coordinated by the International League Against Epilepsy (ILAE), including scientists from the ILAE Consortium on Complex Epilepsies of the Genetics Commission, has discovered specific changes in our DNA that increase the risk of developing epilepsy.

    The research, published today in Nature Geneticsgreatly advances our knowledge of why epilepsy develops and may inform the development of new treatments for the condition.

    Epilepsy, a common brain disorder of which there are many different types, is known to have genetic component and to sometimes run in families. Here, researchers compared the DNA from diverse groups of almost 30,000 people with epilepsy to the DNA of 52,500 people without epilepsy. The differences highlighted areas of our DNA that might be involved in the development of epilepsy.

    The researchers identified 26 distinct areas in our DNA that appear to be involved in epilepsy. This included 19 which are specific to a particular form of epilepsy called genetic generalized epilepsy. They were also able to point to 29 genes that are probably contributing to epilepsy within these DNA regions.

    The scientists found that the genetic picture was quite different when comparing distinct types of epilepsy, in particular, when ‘focal’ and ‘generalized’ epilepsies were compared. The results also suggested that proteins that carry electrical impulse across the gaps between neurons in our brain make up some of the risk for generalized forms of epilepsy.

    “Gaining a better understanding of the genetic underpinnings of epilepsy is key to developing new therapeutic options and consequently a better quality of life for the over 50 million people globally living with epilepsy,” said Professor Gianpiero Cavalleri, Professor of Human Genetics at RCSI School of Pharmacy and Biomolecular Science, Deputy Director of the SFI FutureNeuro Research Centre and member of the ILAE Consortium on Complex Epilepsies.

    “The discoveries we report on here could only be achieved through international collaboration,  on a global scale. We are proud of how the global community of scientists working to better understand the genetics of the epilepsies have pooled resources and collaborated effectively, for the benefit of people impacted the condition,” commented Professor Cavalleri.

    The researchers also showed that many of the current medications for epilepsy work by targeting the same epilepsy risk genes that were highlighted in this study. However, based on their data, the researchers were able to propose some potentially effective alternative drugs. These will need to be clinically tested for use in epilepsy as they are normally used for other conditions, but they are known to target some of the other epilepsy risk genes uncovered.

    “This identification of epilepsy associated genetic changes will allow us to improve diagnosis and classification of different epilepsy subtypes. This in turn, will guide clinicians in selecting the most beneficial treatment strategies, minimising seizures,” said Professor Colin Doherty, Consultant Neurologist, St James’s Hospital, Co-author and Clinical Investigator at the SFI FutureNeuro Centre, and member of the Irish Epilepsy League.

    Over 150 researchers, based across Europe, Australia, Asia, South America and North America, carried out the research. They worked together as part of the ILAE Consortium on Complex Epilepsies. The ILAE Consortium was formed by researchers in 2010, recognising that the complexity of genetic and environmental factors underlying epilepsy would require research across massive datasets, and therefore unprecedented collaboration on an international scale.

    “Undertaking such a comprehensive study is a remarkable achievement….The challenge now is to translate the findings of this research to improve the lives of people with epilepsy,” concluded Professor Cavalleri.

    “With this study, we have bookmarked parts of our genome that should be the major focus of future epilepsy research. It will form the basis for further work looking at the molecular pathways involved in seizure generation, neuronal dysfunction and altered brain activity,” said Professor Samuel Berkovic, University of Melbourne.

    “This is a major milestone for the ILAE Consortium on Complex Epilepsies, demonstrating what can be achieved when scientists openly collaborate and share data from across the world. The outputs are wide-reaching and applicable to epilepsy patients globally,” said Professor Helen Cross, President of the International League Against Epilepsy.

    Guided by the ILAE vision of a world in which no person’s life is limited by epilepsy, the driving principle behind the ILAE Consortium is that through collaboration and synergy, researchers will make more progress towards fully understanding the inherited components of epilepsy than can be realized by individual groups.


    More information: GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture, Nature Genetics (2023). DOI: 10.1038/s41588-023-01485-w

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    International League Against Epilepsy

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  • New study shows promising evidence for sickle cell gene therapy

    New study shows promising evidence for sickle cell gene therapy

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    New research published in the New England Journal of Medicine indicates that stem cell gene therapy may offer a promising, curative treatment for the painful, inherited blood disorder sickle cell disease (SCD).

    The findings from a new clinical trial, published August 31, add to the body of evidence supporting gene therapy as a treatment for sickle cell disease, which primarily impacts people of color.

    About 100,000 Americans have sickle cell disease, according to the U.S. Centers for Disease Control and Prevention. The condition, which can cause a lifetime of pain, health complications and expenses, affects one in 365 Black babies born in the U.S. and one in 16,300 Hispanic babies.

    Until recently, the only treatment options have been intensive bone marrow transplants from siblings or matched donors. But other curative therapies are now on the horizon. The University of Chicago Medicine Comer Children’s Hospital was one of three sites to enroll patients in the clinical trial, which tested a stem cell gene therapy to treat sickle cell disease.

    As part of the trial, researchers used CRISPR-Cas9 to edit specific genes in stem cells — the building blocks of blood cells — taken from each patient. The edits increased the cells’ production of fetal hemoglobin (HbF), a protein that can replace unhealthy, sickled hemoglobin in the blood and protect against the complications of sickle cell disease. The patients then received their own edited cells as therapeutic infusions.

    The therapy was the second for this disease to use CRISPR-Cas9 technology and the first to target a new genetic area and use cryopreserved stem cells with the hope of increasing access to such a treatment. Other gene therapy studies for SCD have used lentiviruses — a type of virus often modified and used for gene editing which remain in the cell long-term. No foreign material remains in stem cells edited with CRISPR-Cas9.

    Trial participants who received the CRISPR-edited stem cells reported a decrease in vaso-occlusive events, a painful phenomenon that occurs when sickled red blood cells accumulate and cause a blockage.

    “The biggest take-home message is that there are now more potentially curative therapies for sickle cell disease than ever before that lie outside of using someone else’s stem cells, which can bring a host of other complications,” said James LaBelle, MD, PhD, director of the Pediatric Stem Cell and Cellular Therapy Program at UChicago Medicine and Comer Children’s Hospital and senior author of the study. “Especially in the last 10 years, we’ve learned about what to do and what not to do when treating these patients. There’s been a great deal of effort towards offering patients different types of transplants with decreased toxicities, and now gene therapy rounds out the set of available treatments, so every patient with sickle cell disease can get some sort of curative therapy if needed. At UChicago Medicine, we’ve built infrastructure to support new approaches to sickle cell disease treatment and to bring additional gene therapies for other diseases.”

    As the scientific community continues to refine and expand the applications of gene therapy, the potential for curative treatments for diseases like sickle cell disease is becoming more of a transformative reality. The journey is ongoing, with the need for long-term follow-up and further research, but this study provides an encouraging glimpse into a future of effective genetic interventions.

    In the larger context of therapeutic development, LaBelle stressed the importance of the study’s contribution to the growing body of evidence supporting the viability of gene therapy as a treatment for sickle cell disease. Two other gene therapies for the disease are awaiting FDA approval this year.

    “The data from this trial supports bringing on similar gene therapies for sickle cell disease and for other bone marrow-derived diseases. If we didn’t have this data, those wouldn’t move forward,” he said.

    The study, “CRISPR-Cas9 Editing of the HBG1/HBG2 Promoters to Treat Sickle Cell Disease,” was published in NEJM in August 2023. Co-authors include Radhika Peddinti, along with researchers from St. Jude Children’s Research Hospital, Memorial Sloan Kettering Cancer Center, Novartis Institutes for BioMedical Research, Children’s Hospital Los Angeles, and IRCCS San Raffaele Hospital in Milan, Italy. The authors also acknowledged research coordinator Christopher Omahen and Amittha Wickrema, director of UChicago’s cell processing facility.

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    University of Chicago Medical Center

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  • Monell Center Helps Discover Epigenetic Mechanism that Causes Bitter Taste Distortion

    Monell Center Helps Discover Epigenetic Mechanism that Causes Bitter Taste Distortion

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    Newswise — PHILADELPHIA (August 22, 2023) – A bitter taste in the mouth is often a symptom or side effect of illness, which may be the result of how the body reacts to pathogens. A new study published in iScience, by Hong Wang, PhD, an Associate Member at the Monell Chemical Sense Center, and colleagues sheds light on the mechanisms involved in the complex interplay between taste perception and immune function. Their work also highlights the potential of a sequencing tool for investigating epigenetic mechanisms that affect taste-cell gene expression. Epigenetics is the study of how and when genes are expressed rather than alteration of the genetic code itself.

    In addition to being unpleasant, a bitter taste in the mouth or from food can contribute to a loss of appetite, an effect associated with ailments from the common cold to cancer. Bitter taste can also affect patients’ willingness to take certain medications, especially when they are young children. Bitter receptors are encoded by Tas2r genes, which also provide an important defense against bacteria and parasites in the mouth and gut. However, this process is not well understood.

    For this study, the team explored how inducing inflammation would affect gene regulation of these taste receptors. Using lipopolysaccharide (LPS), a compound that induces inflammation similar to that caused by bacterial infections, they found that mice showed a distinct elevated aversion to bitter tastes. The team used nerve-recording experiments to confirm that this aversion originates in the taste buds of mice, rather than in their brains.

    “Our study had very clear data showing this is actually a change at the peripheral level, not deep in the brain,” said Wang, confirming that genes in taste cells govern bitter taste distortion to this type of inflammation.

    This finding has interesting clinical implications for the study of behavioral aspects of illness, such as a loss of appetite. When people are sick they often do not feel like eating. This can affect even humans’ love for sugary treats, as other studies have noted. Mice also have a decreased preference for sweet tastes during illness and forced intake of sugar can make them sicker. These results potentially indicate a protective behavior with a biological or evolutionary basis.

    To investigate the underlying gene expression mechanisms of the bitterness response, the team used several methods of analysis. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed a significantly increased response across the majority of the Tas2r taste-receptor genes, with peak gene expression ranging from three to five days during the sickness period.

    The researchers also used single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) to explore the expression of Tas2r genes in response to LPS – the first reported instance of this method to study taste receptor gene expression. LPS markedly increased the accessibility of many Tas2r genes, indicating that the bitter taste distortion in this experiment is caused by an epigenetic mechanism, similar to how disease-causing bacteria can affect those genes.

    Finally, the study showed that LPS-induced inflammation globally affected gene expression in taste stem cells, suggesting a “remodeling” of the cells’ genome. This may leave an epigenetic memory, enabling the cells to respond faster to future infections, but may also contribute to long-lasting effects on taste responses. This finding sheds light on why cancer treatment and certain chronic illnesses can cause a lingering bitter taste in the mouth or alter the taste perception of certain foods.

    This diverse response across taste receptors has potential implications for research on how to make more effective bitter blockers for medications and other edible health and wellness products. “The spectrum of the bitter taste receptor expression is not uniform,” Wang said. “If we want to look at a bitter blocker for an individual taste receptor, we may want to take these factors into consideration, such as whether it’s for after a sickness, during a sickness, or which of the taste receptor genes is most prominently expressed.”

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    The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. Founded in 1968, Monell‘s mission is to improve health and well-being by advancing the scientific understanding of taste, smell, and related senses, where our discoveries lead to improving nutritional health, diagnosing and treating disease, addressing smell and taste loss, and digitizing chemosensory data.

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    Monell Chemical Senses Center

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  • Research aims to uncover genetic and environmental risk factors of nonalcoholic fatty liver disease

    Research aims to uncover genetic and environmental risk factors of nonalcoholic fatty liver disease

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    Newswise — DETROIT – Wanqing Liu, Ph.D., professor of pharmaceutical sciences in the Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences and of pharmacology in Wayne State’s School of Medicine, received a $3 million, five-year award from the National Institute of Environmental Health Sciences of the National Institutes of Health. The study, “Interaction between Genome and Heavy Metals in Nonalcoholic Fatty Liver Disease,” aims to discover and validate the gene Х heavy metal (GXM) interactions in human livers and to understand their role in nonalcoholic fatty liver disease (NAFLD).

    Andrea Cassidy-Bushrow, Ph.D., senior scientist and epidemiologist in the Department of Public Health Sciences at Henry Ford Health, is the co-principal investigator on the study.  

    NAFLD is the most common chronic liver disease, affecting more than 30% of the U.S. population. NAFLD is characterized by a spectrum of histological changes with multiple cells involved. There are no approved drug treatments available currently for the disease.

    “There is an urgent need to identify both the genetic and environmental risk factors of NAFLD to aid in developing diagnostic, prevention and therapeutic strategies,” said Liu. “Over the past decade, a number of genetic risk alleles have been identified, but a growing body of research demonstrates that exposure to heavy metals increases NAFLD risk. However, more research is needed to assess the correlation between various naturally occurring accumulated metals in human livers and the NAFLD histology.”

    Liu and Cassidy-Bushrow said that critical knowledge about how naturally and chronically accumulated metals interact with the liver genome and together to confer risks for NAFLD is lacking. Their preliminary studies in human liver tissues have successfully demonstrated that multiple metals are indeed correlated with NAFLD.

    “By leveraging our previously collected data, we have begun to identify numerous metal-response genes, expression quantitative traits loci and allele-specific expression loci, which are further enriched to NAFLD and its related pathways,” said Cassidy-Bushrow. “We aim to expand our study to a large-scale, highly detailed and integrated analysis to thoroughly understand the role of GXM interactions in NAFLD in humans.”

    The project also involves Hongmin Ni, M.D., associate professor of pharmacology, toxicology and therapeutics at the University of Kansas Medical Center, as a co-investigator. Ni will supply human liver tissue and isolated liver cells for a cell-specific, in vitro analysis of genome-metal interactions.

    The collaborative study will generate important data that has the potential to identify high-risk metals and their essential response genes, ultimately promoting the development of new strategies for NAFLD diagnosis, prevention and treatment, as well as advance research for other related diseases.

    The project number for this National Institute of Environmental Health Sciences of the National Institutes of Health grant is ES034410.

     

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    About Wayne State University

    Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit research.wayne.edu.

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    Wayne State University Division of Research

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  • New tool aligns data from tissue slices virtually

    New tool aligns data from tissue slices virtually

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    Newswise — SAN FRANCISCO, CA—Imagine a few roughly cut slices of bread on a plate. With just those slices, could you picture, in fine detail, the loaf they came from?

    Now, imagine several thin slices of tissue from, say, a small tumor. You’ve tested which of several genes are active at every point across each slice’s length and width. With that two-dimensional data from just a few slices, could you predict which of the genes are active throughout the entire three-dimensional structure of the tumor? Not easy, right?

    Discerning the 3D makeup of a tumor—or other tissue—using data from just a few slices is a serious computational challenge. But a new method developed at Gladstone Institutes enables researchers to do just that. This approach, published in the journal Nature Methods, could allow for much deeper understanding of biological tissue samples.

    “Without that third dimension, you can miss a lot of what’s happening in tissue,” says Gladstone Senior Investigator Barbara Engelhardt, PhD, senior author of the study. “Putting together slices in 3D space should help us begin to answer questions for which 2D data falls short. For instance, what are the precise boundaries of a tumor? Where have immune cells infiltrated the tumor? Where in the tumor would be best to inject a treatment?”

    The new method, named Gaussian Process Spatial Alignment (GPSA), is not just for tumors. It can be applied to nearly any kind of tissue and any type of data obtained from tissue slices, such as the structure of cells or which genes or proteins are switched on within them—with broad implications for research and medicine.

    Filling in the Blanks

    One of the most widely used ways to understand biological tissue—whether from a patient with an illness or an animal in a lab—is to surgically remove some of the affected tissue and analyze it. In labs around the world, technicians may slice the removed tissue into thin pieces to view under a microscope or to test for the presence of specific molecules that could aid diagnosis, guide treatment, or hint at how well a drug is working.

    However, the time, budget, and computational power needed to analyze each slice means that researchers and doctors are often limited to just a few slices from different parts of the tissue. What’s more, tissue slices become physically warped when they are cut, processed, and analyzed in a lab, making it difficult to discern exactly how the slices line up and fit together within the overall 3D structure of the original tissue.

    “The first step in going from 2D slice data to a full, 3D picture of the tissue is to computationally reverse warping so that we can realign the slices in virtual space,” says Engelhardt, who is also a professor in the Department of Biomedical Data Science at Stanford University.

    To address this challenge, the GPSA method uses what Engelhardt and her team refer to as a two-layer Gaussian process. This statistical approach harnesses data from the 2D tissue slices and, in the first layer, fits the warped 2D slice onto a 3D model of the tissue. In the second layer, GPSA attributes to each point in the 3D model some data collected from the slice, such as what genes are turned on at that point. In this way, GPSA reverses warping virtually and enables a highly precise alignment of the slices.

    During this process, the GPSA model fills in the spaces between slices with predictions of gene or protein expression for every point throughout the tissue, ultimately generating a 3D “atlas” of the tissue.

    “Say you have four slices from different locations in a person’s breast cancer tumor, and for every point on each slice you know which of 20,000 genes are turned on or off,” Engelhardt says. “GPSA creates a fully query-able 3D atlas where, for any single ‘x, y, z’ coordinate, for any of the 20,000 genes, we can dive in and ask: What genes are on and off at this position in the tumor? And how certain are we in this estimate?”

    A Highly Flexible Framework

    With GPSA, researchers can construct tissue atlases with data obtained from slices of inconsistent sizes, using different technologies, and at different scales and levels of resolution. While prior methods require the 3D scaffolds or “coordinate frameworks” to be pre-specified, GPSA estimates this 3D framework from the 2D slices alone when a coordinate framework for the tissue does not yet exist. The new method can also combine multiple types of tissue-slice data—say, both information about which genes are switched on and information about cellular structure—into a single atlas.

    In addition, when applied to slices taken from the same tissue at different points in time, GPSA can generate atlases that predict how every location within the tissue changes over time. In this way, the technique could help deepen understanding of aging, how illnesses progress, or how different tissues develop in a growing organism.

    “Flexibility is one of the main strengths of our new tool,” Engelhardt says.

    She and her team are now conducting analyses to further demonstrate that flexibility. For instance, they have developed a method that could be used by labs on a budget to determine the minimum number of tissue slices needed—and the precise locations where those slices should be cut—for GPSA to construct a tissue atlas with the desired information.

    “The goal is to maximize the insights we can gain from tissue slices, in order to allow researchers and clinicians to deeply query 3D tissues that are well-studied or tumors that are unique to a patient, and ultimately improve healthcare,” Engelhardt says.

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    Gladstone Institutes

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  • New genetic model predicts breast cancer risk

    New genetic model predicts breast cancer risk

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    • The model will allow, for the first time in Israel, the determination of a personal genetic risk score for breast cancer based on the genetic profile of each woman. This development could form the basis for the implementation of a personalized early detection policy – women at high risk of breast cancer will be advised to start screening tests for early detection from a younger age, and more frequently.
    • According to Tel Aviv University researchers: “Such a policy may save lives and enable a more efficient use of the health system’s resources.”

    Newswise — Researchers at Tel Aviv University have developed a computational model that makes it possible to predict each woman’s genetic risk of developing breast cancer based on her genetic profile. The research was based on a large-scale international study that included genomic data of about a quarter of a million women with and without breast cancer, and applied its findings to about 2000 Israeli women. The team of researchers explain that, “Our method will allow the health system to move to a personalized early detection policy – when those who are identified as being at high risk will be tested from a younger age and more frequently. Focusing the screening tests using the model may save lives and will save health system resources.”

    The research was conducted by doctoral student Hagai Levi under the guidance of Prof. Rani Elkon from the Department of Human Molecular Genetics and Biochemistry at the Tel Aviv University School of Medicine, and Prof. Ron Shamir from the Blavatnik School of Computer Science at Tel Aviv University. The research was carried out in collaboration with Prof. Shai Carmi from the Faculty of Medicine at Hebrew University, with Prof. Shay Ben Shachar – Director Of Precision Medicine and Genomics at Clalit Research Institute, and with Dr. Naama Elefant from the Hadassah University Medical Center.  The study was published in the Journal of Medical Genetics.

    Prof. Elkon explains that in 2003 the sequencing of a draft of the human genome was completed, creating new opportunities for improvement in medicine, with an emphasis on personalized medicine. The basic idea was that the better we know how to determine whether a certain person is genetically predisposed to a certain disease, the more we can take appropriate preventive measures.

    Prof. Elkon adds that since then, extensive research effort has been invested to identify genetic differences between people which may indicate a genetic susceptibility to specific diseases, especially the common ones such as  cancer, heart disease, diabetes, schizophrenia, and Alzheimer’s. Studies of this type, known as  Genome-Wide Association Studies (GWAS), compare the genomes of sick and healthy people, and find hundreds of genetic variants whose presence is associated with increased risk of having the disease being studied. Each variant by itself increases the risk to a very small degree, but when a significant number of relevant variants accumulate in the genome of a certain person, their risk of getting sick increases significantly.

    The studies assign a ‘genetic risk score’ to each participant, and in large samples, these scores typically follow a bell distribution: the majority of the population are in the middle, and at the two extremes are people with extremely high or low risk scores of having the same disease. The challenge of medicine is to identify in advance those people who have a high genetic tendency to get sick, especially of diseases that can be prevented or detected in early stages.

    The current study was based on the findings of a huge international GWAS study that identified genetic variants associated with breast cancer by analyzing the genetic profiles of approximately 130,000 breast cancer patients from dozens of medical centers in Europe and the United States alongside approximately 100,000 healthy women who served as a control group.

    The team of researchers from Tel Aviv University wanted to check if the findings of the international study could be used to reliably predict the risk of breast cancer of Israeli women, using a sample of about 1,000 patients and about 1,000 healthy women,  collected by Prof. Gad Rennert from the Carmel Medical Center. “If a genetic predisposition to breast cancer is discovered in a woman, there is something that can be done! Early detection may save lives,” emphasizes Prof. Elkon, and continues, “It is important to note that at this stage our research focused on Jewish women of Ashkenazi origin, which is the population closest genetically to the participants of the international study on which our model was based.”

    The researchers built a computational genetic model to predict the risk to the Israeli participants by determining a ‘genetic risk score’ for each woman and dividing the participants into deciles according to the risk score they received. The findings revealed that women in the top decile of the score calculated by the model have a four times higher chance of getting breast cancer compared to women in the bottom decile. In other words: the genetic risk score has a significant ability to predict the risk of breast cancer among the population examined. The researchers confirmed their findings on another sample of breast cancer patients collected by physician-researchers in the oncology and genetics departments at the Hadassah Medical Center.

    Prof. Elkon concludes: “Our research revealed that we already have the tools to identify, based on their genetic profile, Israeli women with an increased risk of developing breast cancer. According to the risk score it is possible to recommend that women at high risk of breast cancer start screening tests for early detection from a younger age, and more frequently. Such a policy may save lives and allow more efficient use of the health system’s resources. We hope that the promising results will lead to clinical use of the prediction method we developed and will improve the early detection of this disease. Our research group is now starting a follow-up study, in collaboration with Prof. Rinat Yerushalmi, Director of the Breast Oncology Unit at Beilinson Hospital, which will focus on collecting data and building a genetic model to calculate the risk of the disease for women of all ethnicities in Israel.”

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    Tel Aviv University

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  • Un estudio indica que las anomalías cromosómicas podrían dificultar el crecimiento de algunos tumores agresivos

    Un estudio indica que las anomalías cromosómicas podrían dificultar el crecimiento de algunos tumores agresivos

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    Newswise — ROCHESTER, Minnesota — Las anomalías cromosómicas son un rasgo característico de las células cancerosas. Los defectos en el genoma derivados de la separación incorrecta de cromosomas (y el ADN que contienen) en cada división celular conllevan crecimiento tumoral y resistencia al tratamiento.

    Sin embargo, lo opuesto también sucede, ya que los niveles altos de este cifrado genómico persistente y caótico, conocido como inestabilidad cromosómica, son perjudiciales para los tumores. Como resultado, las células cancerosas necesitan controlar estas anomalías para sobrevivir.

    En un estudio de investigación publicado recientemente en la revista Cell Reports Medicine, la Dra. en Ciencias Veronica Rodriguez-Bravo, bióloga molecular y de células cancerosas de Mayo Clinic, y su equipo identificaron un “freno” que usan las células tumorales que les permite sobrevivir a una alta inestabilidad cromosómica y volverse más agresivas. Los investigadores también descubrieron que los tumores cancerosos de próstata resistentes al tratamiento exhiben una inestabilidad cromosómica mayor que otros tipos de tumores. Si los tratamientos futuros se desarrollaran para continuar la inestabilidad, es decir, para impedir el efecto “freno”, esto podría detener el crecimiento y la supervivencia de las células cancerosas.  

    “Este estudio desafía el dogma de que las anomalías cromosómicas son principalmente promotoras de tumores y propone que, en realidad, estas pueden ser el talón de Aquiles de los tumores agresivos, como en el caso del cáncer prostático metastásico”, explica la Dra. Rodriguez-Bravo. “En general, estos tumores se consideran ‘invencibles’; por eso, descubrir que son selectivamente sensibles a medicamentos que derivan de aberraciones cromosómicas aún mayores en las células tumorales fue muy importante. Durante muchos años, las anomalías cromosómicas se consideraron principalmente promotoras de los tumores porque se asocian con la evolución de los tumores agresivos”.

    Los investigadores estudiaron modelos experimentales, como los modelos preclínicos en células cancerosas de la próstata y derivados de pacientes, combinados con el análisis de los datos de pacientes. El equipo descubrió que las células cancerosas de la próstata con un alto nivel de inestabilidad cromosómica activan genes específicos que impiden que las células desarrollen más anomalías cromosómicas con lo que garantizan la supervivencia de las células cancerosas y continúan propiciando el crecimiento tumoral. De esta forma, los tumores resistentes al tratamiento pueden evitar alcanzar niveles de anomalías genómicas catastróficas que los destruirían.

    “El estudio demuestra que alterar terapéuticamente el ‘freno’ como estrategia para forzar a las células cancerosas a acumular niveles letales de anomalías cromosómicas ocasiona la muerte de las células tumorales resistentes al tratamiento y mejora la supervivencia en modelos preclínicos derivados de pacientes”, afirma la Dra. Rodriguez-Bravo. “El estudio proporciona pruebas del concepto para desarrollar una nueva estrategia terapéutica contra los tumores agresivos con alta inestabilidad cromosómica”.

    Este estudio es producto de un trabajo científico en equipo en Mayo Clinic en el que participaron investigadores del Departamento de Urología y del Departamento de Bioquímica y Biología Molecular.

    “El propósito principal de nuestra investigación es descubrir las vulnerabilidades cromosómicas de los tumores agresivos, como el cáncer de próstata, para ayudar a desarrollar nuevas terapias combinadas para los pacientes”, concluye la Dra. Rodriguez-Bravo. “Estudiar los procesos fundamentales mediante la investigación oncológica básica a traslacional es clave para alcanzar ese objetivo y descubrir oportunidades ocultas”.

    La investigación contó con el respaldo de la Fundación Mayo Clinic, el Centro Oncológico Integral de Mayo Clinic y el Instituto Nacional del Cáncer de los Estados Unidos.

    Para obtener más información, visite Discovery’s Edge.

    PERIODISTAS: la Dra. Bravo ofrece entrevistas en español e inglés.

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    Información sobre Mayo Clinic
    Mayo Clinic es una organización sin fines de lucro, dedicada a innovar la práctica clínica, la educación y la investigación, así como a ofrecer pericia, compasión y respuestas a todos los que necesitan recobrar la salud. Visite la Red Informativa de Mayo Clinic para leer más noticias sobre Mayo Clinic.

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  • Transcription Factors Contribute to Subtypes of Colorectal Cancers

    Transcription Factors Contribute to Subtypes of Colorectal Cancers

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    Newswise — New research in colorectal cancers directed by investigators at the Johns Hopkins Kimmel Cancer Center suggests that expression of transcription factors — proteins that help turn specific genes on or off by binding to nearby DNA — may play a central role in the degree of DNA methylation across the genome, contributing to the development of different subtypes of these cancers. Methylation is a process in which certain chemical groups attach to areas of DNA that guide genes’ on/off switches. Studying the expression of these transcription factors in patients with colorectal cancers could reveal biomarkers to help determine overall survival in people with a subgroup of colorectal cancers who generally have better survival rates and, importantly, respond better to immune checkpoint therapy — a type of immunotherapy that releases restraints that cancer cells place on the immune response — and other treatments. Similar patterns of transcription factor expression could be seen by the researchers even in precancerous polyps, and could potentially be used by physicians to determine which patients need closer follow-up to prevent cancer development.

    A description of the work was published online July 24 in the journal Proceedings of the National Academy of Sciences.

    Aberrant DNA methylation is a well-known phenomenon occurring in cancers, explains senior study author Hariharan Easwaran, Ph.D., M.Sc., an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, but the degree of DNA methylation varies in cancers of the same tissue type. Some colon and other cancers have a very high degree of DNA methylation gains while others have much lower frequency of DNA methylation gains, he says. Traditionally, these have been described in an area of the genome known as a promoter region, which helps launch the transcription process. The exact mechanisms underlying these changes have not been clear.

    In a series of laboratory studies of genetic material taken from tubular adenomas (precancerous polyps in the colon) and colon tumors, the researchers linked cancer-specific transcription factor expression alterations to methylation alterations in colorectal cancers and their premalignant precursor lesions, which provided insights into the origins and evolution of different molecular subtypes of colorectal cancers.

    Specifically, researchers observed that some regions of the genome undergoing increased methylation tend to have binding sites for transcription factors that are downregulated, or have low expression. In some types of colon cancer, based on the types of genetic alterations associated with the cancer, transcription factors are upregulated or have higher expression.

    The findings suggest that cancer-specific methylation differences potentially evolve due to perturbation in the activity or expression of transcription factors. Similar changes in DNA methylation patterns were observed in precancerous polyps.

    “These studies highlight that the transcription factor expression changes and corresponding DNA methylation changes are early events during tumor development,” says lead study author Yuba Bhandari, Ph.D., a research associate at the Johns Hopkins Kimmel Cancer Center. “As polyps do not carry all of the key genetic changes typically found in full-blown cancer cells, the transcription factor changes may represent the earliest molecular regulators of precancerous cells, with profound impact on the genome-wide DNA methylation changes.”

    The specific set of transcription factors identified in the study may help in stratifying colorectal cancer prognosis, Easwaran adds.

    “This is particularly important, because multiple studies have shown that a certain subtype of colorectal cancers responds best to immune checkpoint blockade therapies, while others may not fare as well,” he says. “Expression profiling of relevant transcription factors may help develop better therapeutic strategies across subtypes of colorectal cancers.”

    Additional study co-authors included Rachael Powers, Sehej Parmar, Sara-Jayne Thursby, Ekta Gupta, Ozlem Kulak, Kurtis Bachman and Stephen Baylin of Johns Hopkins. Additional investigators from Janssen Research and Development in Pennsylvania and in Belgium contributed.

    The work was supported by the National Institutes of Health grants R01CA230995 and R01CA229240; National Institute of Environmental Health Sciences grant R01ES011858; National Cancer Institute grant R21CA212495; Sam Waxman Research Foundation and National Institute on Aging grant U01AG066101; Janssen Initiative; Commonwealth Grant; and Grollman Glick Scholarship.

    Baylin consults for MDxHealth. Methylation-specific PCR is licensed to MDxHealth in agreement with The Johns Hopkins University. Baylin and JHU are entitled to royalty shares received from sales. These arrangements have been reviewed and approved by The Johns Hopkins University in accordance with its conflict-of-interest policies.

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  • Researchers Identify Genes that Directly Influence What We Eat

    Researchers Identify Genes that Directly Influence What We Eat

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    Newswise — In one of the first large-scale studies of genes related to diet, researchers have uncovered almost 500 genes that appear to directly influence the foods we eat. The findings represent an important step toward using a person’s genetics to develop precision nutrition strategies that help improve health or prevent disease.

    “Some genes we identified are related to sensory pathways — including those for taste, smell, and texture — and may also increase the reward response in the brain,” said research team leader Joanne Cole, PhD, assistant professor in the Department of Biomedical Informatics at the University of Colorado School of Medicine. “Because some of these genes may have clear paths toward influencing whether someone likes a food or not, they could potentially be used to create sensory genetic profiles for fine-tuning a person’s dietary recommendations based on foods they like to eat.”

    For the study, the researchers used the UK Biobank, which contains data from 500,000 people, to perform a phenome-wide association study (PheWAS) that identified genes more strongly associated with diet than with any health or lifestyle factor. PheWAS studies are used to find associations between gene variants of interest and a spectrum of human traits and behaviors, including dietary intake.

    “The foods we choose to eat are largely influenced by environmental factors such as our culture, socioeconomic status, and food accessibility,” said Cole. “Because genetics plays a much smaller role in influencing dietary intake than all the environmental factors, we need to study hundreds of thousands of individuals to detect genetic influences amid the environmental factors. The data necessary to do this hasn’t been available until recently.”

    Cole will present the findings at NUTRITION 2023, the annual flagship meeting of the American Society for Nutrition held July 22-25 in Boston.

    One challenge in identifying diet-related genes is that what people eat correlates with many other factors, including health factors such as high cholesterol or body weight and even socioeconomic status. In the new work, the researchers applied computational methods to tease out direct effects of genetic variants impacting diet and separate those from indirect effects such as ones where a gene impacts diabetes and having diabetes requires a person to eat less sugar.

    This study design was possible because the UK Biobank not only contains in-depth genetic information but also detailed health and socioeconomic data. This allowed the researchers to test individual genetic variants for associations with thousands of traits and then eliminate indirect gene variants that were more strongly associated with other factors, such as diabetes.

    The analysis revealed around 300 genes directly associated with eating specific foods and almost 200 genes linked to dietary patterns which group various foods together — for example, overall fish intake or fruit consumption.

    “The study showed that dietary patterns tend to have more indirect genetic effects, meaning they were correlated with a lot of other factors,” said Cole. “This shows how important it is to not study dietary patterns in a vacuum, because the eating pattern’s impact on human health may be completely mediated or confounded by other factors.”

    In the short term, Cole is studying the newly identified diet-related genes to better understand their function while also working to identify even more genes that directly influence food preferences. She would like to pursue several lines of translational research based on these findings. For example, she is interested in studying whether using a person’s genetics to adapt the flavor profile of a diet designed for weight loss could improve adherence.

    It might also be possible to use these new insights to tailor foods to a person’s genetic predisposition. “If we know that a gene encoding an olfactory receptor in the nose increases a person’s liking of fruit and boosts the reward response in the brain, then molecular studies of this receptor could be used to identify natural or synthetic compounds that bind to it,” Cole said. “Then, we could see if adding one of those compounds to healthy foods makes those foods more appealing to that person.”

    Cole will present this research at 2:55 p.m. on Saturday, July 22, during the Personalizing Nutrition – Genetics and Dietary Pattern Interactions Poster Theater Flash Session in the Sheraton Boston, Fairfax (abstract; presentation details).

    Please note that abstracts presented at NUTRITION 2023 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.

     

    About NUTRITION 2023

    NUTRITION 2023 is the flagship meeting of the American Society for Nutrition and the premier educational event for nutritional professionals around the globe. NUTRITION brings together lab scientists, practicing clinicians, population health researchers, and community intervention investigators to identify solutions to today’s greatest nutrition challenges. Our audience also includes rising leaders in the field – undergraduate, graduate, and medical students. NUTRITION 2023 will be held July 22-25, 2023 in Boston. https://nutrition.org/N23 #Nutrition2023

     

    About the American Society for Nutrition (ASN)

    ASN is the preeminent professional organization for nutrition scientists and clinicians around the world. Founded in 1928, the society brings together the top nutrition researchers, medical practitioners, policy makers and industry leaders to advance our knowledge and application of nutrition. ASN publishes four peer-reviewed journals and provides education and professional development opportunities to advance nutrition research, practice, and education. Since 2018, the American Society of Nutrition has presented NUTRITION, the leading global annual meeting for nutrition professionals.

     

    Find more news briefs and tipsheets at: https://www.eurekalert.org/newsroom/nutrition2023.

     

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  • New algorithm helped to find thousands of repeated elements in bacterial genome

    New algorithm helped to find thousands of repeated elements in bacterial genome

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    Newswise — Scientists from The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS) elaborated mathematical algorithm that enabled to find dispersed repeated elements in genome with great accuracy. Authors tested this approach on genetic sequences of nine kinds of bacteria, and discovered early unknown repeats in all of them. Thus, for example, it turned out that almost 50% of genome of E. coli is presented by quite long repeats (400-600 pairs of nucleotides long). Such repeats represent a definite code, that is placed upon existing genes of bacteria over coding amino-acids. The found dispersed repeats can help to find new genetic targets, that are interesting from the point of view of biotechnology, for example, parts of DNA, impact on which will enable to increase productivity of bacterial strains. Results of the research are published in International Journal of Molecular Sciences.

    In genomes of many eucaryotic (multicellular) organisms – from yeast to human – there are repeated sequences of nucleotides that are a kind of letters, that compose DNA. Each such repeat is several hundreds of nucleotides long and they are spread all over the whole genome. In sum they form a family that can have significant number of separate copies. The amount of such families, and also position and number of repeats in each family differ in various species and so they can tell about evolution and origin of different living organisms. There are many mathematical algorithms for searching of dispersed repeats (those ones that are more or less equally spread in a genome), such algorithms that even enable to find out “corrupted” copies, those repeats, where some mutations took place and the sequences of which are different from others. However, in the process of evolution such changes can be so numerous, that it becomes impossible to find in genome two insufficiently similar sequences. In this connection scientists search new approaches for searching of dispersed repeats, spread in genomes of various organisms. It is significant to note that such families of repeats were earlier found only in genomes of eukaryotes (multicellular) organisms, whereas they were unknown in organisms of bacteria.

    Scientists from the Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS) suggested a new method of searching of dispersed repeated sequences. Principle of its work can be compared with search of mathematic matrix, consisting of columns and lines, that describes the family of repeats in the best way. The suggested approach is optimal as far as accuracy of finding “dispersed” repeats in the whole genome is concerned, because it takes into account the ability of changing nucleotides and their insertions and deletions, in other words, mutations.

    Researchers tested this algorithm on artificially generated sequences, that contained thousands of repeats each, a part of which contained mutations. A comparison with widely used in bioinformatics search systems showed that the suggested method enabled to find out repeats of one family with a greater number of mutations between them (up to the change of half of the nucleotides in a sequences) more precisely.

    Then authors of the research applied algorithm for search of repeats in genome of nine kinds of bacteria: Escherichia coli, Bacillus subtilis, Azotobacter vinelandii, Clostridium tetani, Methylococcus capsulatus, Mycobacterium tuberculosis, Shigella sonnei, Treponema pallidum and Yersinia pestis. Analysis enabled scientists for the first time to find out three families of repeats, 400-600 pairs of nucleotides long, in Escherichia coli, which in total take almost 50% of the whole genome of bacterium. Earlier in this microorganism there were known similar elements only of less length – up to 300 pairs of nucleotides – and in smaller numbers. In genetic sequences in other bacteria, they managed to find 1-2 families of repeats of the same length (400-600 nucleotides). By this less of them were found in Treponema pallidum, that can be connected with small size of a genome of this microorganism.

    “The found families of dispersed repeats are discovered in genes, and they represent a definite code placed on genes over triplet code, that provides coding of amino acid sequences by genes. By this it is not important on which DNA strand genes are situated. The obtained code can serve as a base for folding DNA in so called nucleoid, that in most degree defines expression of bacterial genes. It can be said that in bacterial DNA there is a code providing its folding into a nucleoid, and now we have obtained an ability to manage it. It opens great opportunities for creating new microorganisms, useful for people”, – tells about results of the research Eugine Korotkov, Doctor of Biological Sciences, head of the group of mathematical analysis of DNA sequences and proteins the Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS).

    The suggested approach can be used for analysis not only of bacterial genomes, but also genetic sequences of multicellular organisms, for example, animals or plants. It can help to understand evolution of genomes and their separate elements better, and also in the case of bacteria to find targets for creating new antibiotics or increasing productivity of strains that are important for biotechnology.

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    Russian Foundation for Basic Research

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  • Cutting-Edge Sensor Replicates Cell Membrane Functionalities

    Cutting-Edge Sensor Replicates Cell Membrane Functionalities

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    Newswise — CAMBRIDGE, MA — Drawing inspiration from natural sensory systems, an MIT-led team has designed a novel sensor that could detect the same molecules that naturally occurring cell receptors can identify.

    In work that combines several new technologies, the researchers created a prototype sensor that can detect an immune molecule called CXCL12, down to tens or hundreds of parts per billion. This is an important first step to developing a system that could be used to perform routine screens for hard-to-diagnose cancers or metastatic tumors, or as a highly biomimetic electronic “nose,” the researchers say.

    “Our hope is to develop a simple device that lets you do at-home testing, with high specificity and sensitivity. The earlier you detect cancer, the better the treatment, so early diagnostics for cancer is one important area we want to go in,” says Shuguang Zhang, a principal research scientist in MIT’s Media Lab.

    The device draws inspiration from the membrane that surrounds all cells. Within such membranes are thousands of receptor proteins that detect molecules in the environment. The MIT team modified some of these proteins so that they could survive outside the membrane, and anchored them in a layer of crystallized proteins atop an array of graphene transistors. When the target molecule is detected in a sample, these transistors relay the information to a computer or smartphone.

    This type of sensor could potentially be adapted to analyze any bodily fluid, such as blood, tears, or saliva, the researchers say, and could screen for many different targets simultaneously, depending on the type of receptor proteins used.

    “We identify critical receptors from biological systems and anchor them onto a bioelectronic interface, allowing us to harvest all those biological signals and then transduce them into electrical outputs that can be analyzed and interpreted by machine-learning algorithms,” says Rui Qing, a former MIT research scientist who is now an associate professor at Shanghai Jiao Tong University.

    Qing and Mantian Xue PhD ’23, are the lead authors of the study, which appears today in Science Advances. Along with Zhang, Tomás Palacios, director of MIT’s Microsystems Laboratory and a professor of electrical engineering and computer science, and Uwe Sleytr, an emeritus professor at the Institute of Synthetic Bioarchitectures at the University of Natural Resources and Life Sciences in Vienna, are senior authors of the paper.

    Free from membranes

    Most current diagnostic sensors are based on either antibodies or aptamers (short strands of DNA or RNA) that can capture a particular target molecule from a fluid such as blood. However, both of these approaches have limitations: Aptamers can be easily broken down by body fluids, and manufacturing antibodies so that every batch is identical can be difficult.

    One alternative approach that scientists have explored is building sensors based on the receptor proteins found in cell membranes, which cells use to monitor and respond to their environment. The human genome encodes thousands of such receptors. However, these receptor proteins are difficult to work with because once removed from the cell membrane, they only maintain their structure if they are suspended in a detergent.

    In 2018, Zhang, Qing, and others reported a novel way to transform hydrophobic proteins into water-soluble proteins, by swapping out a few hydrophobic amino acids for hydrophilic amino acids. This approach is called the QTY code, after the letters representing the three hydrophilic amino acids — glutamine, threonine, and tyrosine — that take the place of hydrophobic amino acids leucine, isoleucine, valine, and phenylalanine.  

    “People have tried to use receptors for sensing for decades, but it is challenging for widespread use because receptors need detergent to keep them stable. The novelty of our approach is that we can make them water-soluble and can produce them in large quantities, inexpensively,” Zhang says.

    Zhang and Sleytr, who are longtime collaborators, decided to team up to try to attach water-soluble versions of receptor proteins to a surface, using bacterial proteins that Sleytr has studied for many years. These proteins, known as S-layer proteins, are found as the outermost surface layer of the cell envelope in many types of bacteria and archaea.

    When S-layer proteins are crystallized, they form coherent monomolecular arrays on a surface. Sleytr had previously shown that these proteins can be fused with other proteins such as antibodies or enzymes. For this study, the researchers, including senior scientist Andreas Breitwieser, who is also a co-author in the paper, used S-layer proteins to create a very dense, immobilized sheet of a water-soluble version of a receptor protein called CXCR4. This receptor binds to a target molecule called CXCL12, which plays important roles in several human diseases including cancer, and to an HIV coat glycoprotein, which is responsible for virus entry into human cells.

    “We use these S-layer systems to allow all these functional molecules to attach to a surface in a monomolecular array, in a very well-defined distribution and orientation,” Sleytr says. “It’s like a chessboard where you can arrange different pieces in a very precise manner.”

    The researchers named their sensing technology RESENSA (Receptor S-layer Electrical Nano Sensing Array).

    Sensitivity with biomimicry

    These crystallized S-layers can be deposited onto nearly any surface. For this application, the researchers attached the S-layer to a chip with graphene-based transistor arrays that Palacios’ lab had previously developed. The single-atomic thickness of the graphene transistors makes them ideal for the development of highly sensitive detectors.

    Working in Palacios’ lab, Xue adapted the chip so that it could be coated with a dual layer of proteins — crystallized S-layer proteins attached to water-soluble receptor proteins. When a target molecule from the sample binds to a receptor protein, the charge of the target changes the electrical properties of the graphene in a way that can be easily quantified and transmitted to a computer or smartphone connected to the chip.

    “We chose graphene as the transducer material because it has excellent electrical properties, meaning it can better translate those signals. It has the highest surface-to-volume ratio because it’s a sheet of carbon atoms, so every change on the surface, caused by the protein binding events, translates directly to the whole bulk of the material,” Xue says.

    The graphene transistor chip can be coated with S-layer-receptor proteins with a density of 1 trillion receptors per square centimeter with upward orientation. This allows the chip to take advantage of the maximum sensitivity offered by the receptor proteins, within the clinically relevant range for target analytes in human bodies. The array chip integrates more than 200 devices, providing a redundancy in signal detection that helps to ensure reliable measurements even in the case of rare molecules, such as the ones that could reveal the presence of an early-stage tumor or the onset of Alzheimer’s disease, the researchers say.

    Thanks to the use of QTY code, it is possible to modify naturally existing receptor proteins that could then be used, the researchers say, to generate an array of sensors in a single chip to screen virtually any molecule that cells can detect. “What we are aiming to do is develop the basic technology to enable a future portable device that we can integrate with cell phones and computers, so that you can do a test at home and quickly find out whether you should go to the doctor,” Qing says.

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  • New factor in excess body weight discovered

    New factor in excess body weight discovered

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    Newswise — What determines whether we become overweight? Aside from lifestyle, predisposition plays a role, but genes cannot fully explain the inherited propensity to accumulate excess weight. A new study by Charité – Universitätsmedizin Berlin in Science Translational Medicine* shows that a kind of formatting of the DNA code in one gene that is associated with satiety is implicated in a slightly elevated risk of excess body weight – at least in women. This “epigenetic marking” is established early on during the embryonic stage.

    People who are overweight, especially those who are severely overweight, are at increased risk of a number of serious diseases such as cardiovascular disease, diabetes, and cancer. It is a growing health issue. All over the world, the number of overweight people is increasing. In the European Region, two out of three adults (59 percent) are overweight or obese, according to the World Health Organization.

    But what determines whether people will become overweight? Genetic predisposition plays a major role, alongside lifestyle. The similarity of the body mass index (BMI) in identical twins ranges from 40 to 70 percent. Even identical twins raised in different families still show the same significant similarity. Scientists have identified several genetic variants that influence a person’s body weight – and with it, the risk of developing obesity. But even taken all together, they cannot explain the heritability that has been observed. Researchers began to suspect there must be additional non-genetic factors that affect a person’s propensity to gain excess weight.

    Satiety gene is not altered, but formatted

    Researchers led by Prof. Peter Kühnen, Director of the Department of Pediatric Endocrinology at Charité, have now identified one such factor in their recent study. According to their findings, women’s risk of being overweight increases by about 44 percent if there are an especially large number of methyl groups adhering to the POMC (pro-opiomelanocortin) gene, which is responsible for the feeling of satiety. Methyl groups are tiny chemical units the body uses to mark the letters in the DNA code to activate or deactivate genes without modifying the sequence of letters in the DNA. In other words, the effect is much like highlighting a section of a text without rewriting the text itself. This type of “DNA formatting” is known as epigenetic marking.

    For their study, the team of researchers analyzed the “formatting” of the POMC gene in more than 1,100 people. They found more methyl groups attached to the satiety gene in obese women with a BMI of over 35 than in women with normal body weight. “A 44 percent increase in the risk of obesity is about the same as the effect that has been observed for individual gene variants as well,” says Kühnen. “By comparison, socioeconomic factors have a much stronger effect. They can increase the risk by a factor of two to three. As for why the methylation effect only shows up in women, we don’t know yet.”

    The POMC gene is “formatted” very early on during embryonic development, as the researchers showed by comparing methylation patterns in more than 15 sets each of identical and fraternal twins. While the “formatting” of the satiety gene was the same in most of the identical twins, there was hardly any correlation in the fraternal twins. “This indicates that the epigenetic marking of the POMC gene is established shortly after the egg and sperm cells merge, before the fertilized egg divides into two twin embryos,” explains Lara Lechner, the study’s first author, who works at the Department of Pediatric Endocrinology. This means the very early stage of pregnancy is crucial.

    What influences formatting?

    But what influences how much methylation the satiety gene undergoes – and thus, the risk that a person will become overweight? Past studies indicated that the presence or absence of certain nutrients that supply methyl groups could have an effect on epigenetic processes. These nutrients include betaine, methionine, and folic acid, all of which are typically absorbed through a person’s diet. A newly developed method involving individual human stem cells allowed the Charité researchers to simulate in the lab how the methylation pattern is determined during embryonic development and how nutrients affect it.

    “On the one hand, our studies and others as well show that folic acid, betaine, and other nutrients have a limited effect on the extent of methylation,” Kühnen notes. “We’ve observed that the ‘DNA formatting system’ is very stable on the whole, with cells compensating for minor fluctuations in the nutrient supply. On the other hand, there are indications that the variability of this ‘formatting’ develops at random. That means that it is not possible – not yet, at any rate – to externally influence whether a person has more or less methylation in the POMC region.”

    Medications may help

    At least in theory, women who are at elevated risk of developing obesity due to methylation of the POMC gene could receive medications to help them lose weight, as initial studies of four severely obese women and one man with this exact type of “formatting” of the satiety gene suggest. The subjects were given a specific drug that curbs the feeling of hunger and has already been approved to treat obese patients with a mutation of the POMC gene. Within three months after starting treatment, all five patients experienced less hunger. They lost an average of seven kilograms, or about five percent of their body weight. Some of them continued the treatment and continued to lose weight.

    “These findings show, for a start, that a POMC gene that has undergone epigenetic changes can in fact potentially be addressed through medication,” Kühnen says. “Further large controlled studies will be needed to show whether treatment with this drug would also be effective over a longer period, and if so, how effective and how safe this type of treatment is. Overall, though, a medication like this would still need to be just one piece of a holistic treatment strategy.”

     

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  • Killings of 3 women in Long Island went unsolved for more than a decade. Here’s how authorities tracked down the suspect | CNN

    Killings of 3 women in Long Island went unsolved for more than a decade. Here’s how authorities tracked down the suspect | CNN

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    CNN
     — 

    After the remains of four women were found near a beach in Long Island, New York, more than a decade ago, investigators say DNA evidence and cellphone data now point to a murder suspect – a local architect whose internet history showed him often searching the status of the case and details about the victims.

    Rex Heuermann was arrested in New York City on Thursday, more than a year after a police task force explored his possible connection to the cold case known as the “Gilgo Four,” named for the beach where the remains were found.

    Heuermann, 59, was indicted on one count of first-degree murder and one count of second-degree murder in each of three of the killings – Melissa Barthelemy in 2009, and Megan Waterman and Amber Costello in 2010, according to the indictment. He pleaded not guilty Friday during his first court appearance on Long Island and was remanded without bail.

    The defendant, who told his attorney he did not carry out the killings, is also the prime suspect in the 2007 disappearance and death of a fourth woman, Maureen Brainard-Barnes, according to a bail application from Suffolk County prosecutors. Heuermann has not been charged in the case, but the investigation “is expected to be resolved soon,” the document states.

    “Rex Heuermann is a demon that walks among us. A predator that ruined families. If not for the members of this task force, he would still be on the streets today,” Suffolk County Police Commissioner Rodney Harrison said during a news conference Friday, and offered his condolences to the victims’ families.

    “To the family members of Amber Costello, Melissa Barthelemy and Megan Waterman. I can only imagine what you’ve had to endure over the last decade regarding knowing that your killer was still loose. God bless you,” Harrison said before hugging a few people standing behind him.

    Authorities had been left with little information after a search for a missing woman in 2010 led to the discovery of multiple sets of human remains at Gilgo Beach. By the time the remains of the missing woman, Shannan Gilbert, were found the following year, at least 10 sets of human remains had been recovered across two Long Island counties.

    As they searched for a suspect in the “Gilgo Four” case, investigators combed through phone records from both midtown Manhattan and the Massapequa Park area in Long Island – places where the suspect is believed to have used a burner phone, court documents show.

    “For each of the murders, he got an individual burner phone, and he used that to communicate with the victims. Then shortly after the death of the victims, he then would get rid of the burner phone,” Suffolk County District Attorney Ray Tierney said during a news conference Friday.

    In February 2022, Harrison created a task force to focus on solving the cold case. By mid-March, Heuermann’s name showed up on authorities’ radar after a New York state investigator identified him in a database, according to Tierney.

    Investigators say they narrowed cell tower records from thousands of possible individuals down to hundreds and then to a handful of people. Next, authorities focused on residents who also matched a physical description provided by a witness who had seen the suspected killer.

    As the search pool narrowed, they zeroed in on anyone with a connection to a green pick-up truck a witness had seen the suspect driving, according to two law enforcement sources with knowledge of the case. Later, authorities learned Heuermann drives a green pickup truck registered to his brother.

    Eventually, investigators found Heuermann matched a witness’s physical description, lived close to the Long Island cell site and worked near the New York City cell sites where other calls were captured.

    Cell phone and credit card billing records show numerous instances where Heuermann was in the general locations as the burner phones used to call the three victims “as well as the use of Brainard-Barnes and Barthelemy’s cellphones when they were used to check voicemail and make taunting phone calls after the women disappeared,” Suffolk County prosecutors allege.

    The defendant’s next court appearance is scheduled on August 1.

    A major factor in the case that helped point investigators to Heuermann as a suspect is DNA evidence, which was made possible due to the latest scientific innovations in the field.

    After Heuermann was identified as a suspect in March 2022, authorities placed him and his family under surveillance and would obtain DNA samples from discarded items. A team later gathered a swab of Heuermann’s DNA from leftover crust in a pizza box he threw in the trash, according to Tierney.

    During the initial examination of one of the victims’ skeletal remains and materials discovered in the grave, the Suffolk County Crime Laboratory recovered a male hair from the “bottom of the burlap” the killer used to wrap her body, according to prosecutors. Analysis of the DNA found on the victim and the pizza showed the samples matched.

    Additionally, hair believed to be from Heuermann’s wife was found on or near three of the murder victims, prosecutors allege in the bail application, citing DNA testing. The DNA came from 11 bottles inside a garbage can outside the Heuermann home, the court document says.

    The hairs, found in 2010, were degraded and DNA testing at the time couldn’t yield results. But as technology progressed, mitochondrial DNA testing allowed investigators to make the connection, Tierney explained.

    The victims’ remains “were out in a tough environment for a prolonged period of time. So, there was not a lot of forensic evidence,” Tierney told CNN’s Anderson Cooper on Friday, and credited the FBI and one of its agents for a “phenomenal job” with extracting the evidence.

    Evidence shows Heuermann’s wife and children were out of the state when the three women are believed to have been killed, Tierney said during Friday’s news conference.

    A search of Heuermann’s computer revealed he had scoured the internet at least 200 times, hunting for details about the status of the investigation, Tierney added. Heuermann’s internet history also turned up searches for torture porn and “depictions of women being abused, being raped and being killed,” Tierney said.

    Heuermann was also compulsively searching for photos of the victims and their relatives, and he was trying to track down relatives, the district attorney said.

    Melissa Barthelemy, Maureen Brainard-Barnes, Amber Lynn Costello and Megan Waterman

    While the 10 sets of human remains found are all being investigated as victims of suspected homicide, four of the women found have garnered specific attention due to the similarities found in their deaths.

    The victims known as the “Gilgo Four” were all last seen alive between 2007 and 2010, and their remains were found along a quarter-mile stretch of road in a span of three days in December 2010.

    The women, who all worked in the sex industry, were also buried in a similar fashion, Tierney noted.

    “All the women were petite. They all did the same thing for a living. They all advertised the same way. Immediately there were similarities with regard to the crime scenes,” he said. The killer concealed their bodies by wrapping them in camouflaged burlap, the type used by hunters.

    Authorities have said they believe the death of Gilbert, whose disappearance sparked the searches that found the other victims, may have been accidental and not related to the other killings.

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  • Burner phones. Pizza crust. DNA on burlap. A New York architect was charged with killing 3 women in Gilgo Beach serial killings cold case | CNN

    Burner phones. Pizza crust. DNA on burlap. A New York architect was charged with killing 3 women in Gilgo Beach serial killings cold case | CNN

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    CNN
     — 

    A New York architect was charged with murder in connection to the killings of three of the women who became known as the “Gilgo Four,” according to the Suffolk County District Attorney, in a case that baffled authorities for more than a decade in suburban Long Island.

    Rex Heuermann – who told his attorney he is not the killer – was taken into custody for some of the Gilgo Beach murders, an unsolved case tied to at least 10 sets of human remains discovered since 2010, authorities said.

    The case was broken open thanks to cell phone data, credit card bills and DNA testing, which ultimately led them to arrest Heuermann, 59, authorities said.

    Heuermann was charged with one count of first-degree murder and one count of second-degree murder in each of the three killings – Melissa Barthelemy in 2009, and Megan Waterman and Amber Costello in 2010 – according to the indictment. A grand jury made the six charges, according to the Suffolk County District Attorney Ray Tierney.

    He is also the prime suspect in the 2007 disappearance and death of a fourth woman, Maureen Brainard-Barnes, according to a bail application from prosecutors. Heuermann has not been charged with that homicide but the investigation “is expected to be resolved soon,” the document says.

    This is the first arrest in the long-dormant case, which terrorized residents and sparked conflicting theories about whether a serial killer was responsible.

    Tierney said authorities, fearing the suspect might be tipped off they were closing in, moved to arrest him Thursday night.

    “We were playing before a party of one,” he told reporters. “We knew the person responsible for these murders would be looking at us.”

    See our live coverage here

    Authorities said once Heuermann was identified in early 2022 as a suspect, they watched him and his family and got DNA samples from items that were thrown away.

    During the initial examination of one of the victims’ skeletal remains and materials discovered in the grave, the Suffolk County Crime Laboratory recovered a male hair from the “bottom of the burlap” the killer used to wrap her body, according to the bail application.

    A surveillance team later gathered a swab of Heuermann’s DNA from leftover crust in a pizza box he threw in the trash, the district attorney said.

    Hair believed to be from Rex Heuermann’s wife was found on or near three of the murder victims, prosecutors allege in the bail application, citing DNA testing. The DNA came from 11 bottles inside a garbage can outside the Heuermann home, the court document says.

    Evidence shows Heuermann’s wife and children were outside of the state at the times when the three women were killed, Tierney said.

    The hairs found in 2010 were degraded and DNA testing at the time couldn’t yield results but improvements in technology eventually gave investigators the DNA answers they needed.

    Heuermann was in tears after his arrest, his court appointed attorney, Michael Brown, said Friday.

    “I did not do this,” Brown said Heuermann told him during their conversation after his arrest.

    Rex Heuermann

    Heuermann was remanded without bail. He entered a not guilty plea through his attorney. His next court date is scheduled for August 1.

    Police were still searching his home Friday night, according to a CNN team outside the house.

    Heuermann, who a source familiar with the case said is a father of two, is a registered architect who has owned the New York City-based architecture and consulting firm, RH Consultants & Associates, since 1994, according to his company’s website.

    In 2022, Heuermann was interviewed for the YouTube channel “Bonjour Realty.” He spoke about his career in architecture, and said he was born and raised in Long Island. He began working in Manhattan in 1987.

    CNN has reached out to Heuermann’s company for comment.

    The remains of the Gilgo Four were found in bushes along a quarter-mile stretch of Ocean Parkway in Oak Beach over a two-day period in 2010.

    The skeletal remains of Barthelemy were discovered near Gilgo Beach on December 11. Barthelemy, who was a sex worker, was last seen July 12, 2009, at her apartment when she told a friend she was going to see a man, according to a Suffolk County website about the killings.

    The remains of three other women were found on December 13, 2010: Brainard-Barnes, who advertised escort services on Craigslist and was last seen in early June 2007 in New York City; Amber Lynn Costello, who also advertised escort services and was last seen leaving her North Babylon home in early September 2010; and Waterman, who also advertised as an escort and was last seen in early June 2010 at a Holiday Inn Express in Hauppauge.

    Tierney said of the women, “They were buried in a similar fashion, in a similar location, in a similar way. All the women were petite. They all did the same thing for a living. They all advertised the same way. Immediately there were similarities with regard to the crime scenes.”

    Tierney said the killer tried to conceal the bodies, wrapping them in camouflaged burlap, the type used by hunters.

    The suspect made taunting phone calls to Barthelemy’s sister, “some of which resulted in a conversation between the caller, who was a male, and a relative of Melissa Barthelemy, in which the male caller admitted killing and sexually assaulting Ms. Barthelemy,” according to the bail application.

    The court document alleges cell phone and credit card billing records show numerous instances where Heuermann was in the general locations as the burner phones used to call the three victim,s “as well as the use of Brainard-Barnes and (Barthelemy’s) cellphones when they use used to check voicemail and make taunting phone calls after the women disappeared.”

    The district attorney said the killer got a new burner phone before each killing.

    The case against Heuermann came together in the two years since the restart of the investigation by Suffolk County Police Commissioner Rodney Harrison, authorities said.

    Harrison put together a task force including county police detectives, investigators from the sheriff’s office, state police and the FBI.

    Tierney said the task force held its first meeting in February 2022.

    “Six weeks later, on March 14, 2022, the name Rex Heuermann was first mentioned as a suspect in the Gilgo case,” Tierney said. “A New York state investigator was able to identify him in a database.”

    Investigators had gone backward through phone records collected from both midtown Manhattan and the Massapequa Park area – two areas where a “burner phone” used by the alleged killer were detected, according to court documents.

    Rex Heuermann is seen purchasing extra minutes for one of the burner cell phones connected to some of the crimes at a cellphone store in Midtown Manhattan, prosecutors allege.

    Authorities then narrowed records collected by cell towers to thousands, then down to hundreds, and finally down to a handful of people who could match a suspect.

    From there, authorities worked to focus on people who lived in the area of the cell tower who also matched a physical description given by a witness who had seen the suspected killer.

    In the narrowed pool, they searched for a connection to a green pickup a witness had seen the suspect driving, the sources said.

    Investigators found Heuermann, who matched a witness’s physical description, lived close to the Long Island cell site and worked near the New York City cell sites where other calls were captured.

    They also learned he had often driven a green pickup, registered to his brother. But they needed more than circumstantial evidence.

    When investigators searched Heuermann’s computer, they found a disturbing internet search history, including 200 searches aimed at learning about the status of the investigation, Tierney said Friday.

    His searches also included queries for torture porn and “depictions of women being abused, being raped and being killed,” Tierney said.

    The DA said the suspect was still compulsively searching for photos of the victims and their relatives.

    Heuermann was trying to find the relatives, he added.

    The murder mystery had confounded county officials for years. In 2020, they found a belt with initials that may have been handled by the suspect and launched a website to collect new tips in the investigation.

    Police said some victims identified had advertised prostitution services on websites such as Craigslist.

    The mystery began in 2010 when police discovered the first set of female remains among the bushes along an isolated strip of waterfront property on Gilgo Beach while searching for Shannan Gilbert, a missing 23-year-old woman from Jersey City, New Jersey.

    An aerial view of the area near Gilgo Beach and Ocean Parkway on Long Island where police have been conducting a prolonged search after finding 10 sets of human remains in April 2011 in Wantagh, New York.

    By the time Gilbert’s body was found one year later on neighboring Oak Beach, investigators had unearthed 10 sets of human remains strewn across two Long Island counties.

    The grim discoveries generated widespread attention in the region and sent waves of fear across some communities on Long Island’s South Shore.

    Authorities later said they believe Gilbert’s death may have been accidental and not related to the Gilgo Beach slayings.

    Still, Gilbert’s disappearance led to the discovery of others.

    Crime scene investigators use metal detectors to search a marsh for human remains in December 2011 in Oak Beach, New York.

    Additional remains were uncovered in neighboring Gilgo Beach and in Nassau County, about 40 miles east of New York City. They included a female toddler, an Asian male and a woman initially referred to as “Jane Doe #6,” investigators said.

    In 2020, police identified “Jane Doe #6” was as Valerie Mack, a 24-year-old Philadelphia mother who went missing two decades earlier.

    Mack’s partial remains were first discovered near Gilgo Beach in 2000, with additional dismembered remains found in 2011, according to the Suffolk County police.

    John Ray, a lawyer who represents the family of Shannon Gilbert – whose disappearance and search led to the discovery of “Gilgo Four” and other remains – said Friday he does not know if Heuermann is also responsible for her death.

    “We breathe a great sigh of relief,” Ray said. “We’re happy the police are finally taking a positive step in this respect, but this is just the beginning … This is just the edge of a bigger body of water, shall we say, of murder that has taken place.”

    Melissa Barthelemy, Maureen Brainard-Barnes, Amber Lynn Costello and Megan Waterman

    Ray also represents the family Gilgo Beach victim Jessica Taylor.

    “We don’t know if he is connected to Jessica Taylor’s murder,” he said.

    Jasmine Robinson, a family representative for Taylor, said she’s “hopeful for the future and hopeful that a connection is made” to resolve the other cases.

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  • Memory and Learning Genes Date Back 650 Million Years: Study

    Memory and Learning Genes Date Back 650 Million Years: Study

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    Newswise — A team of scientists led by researchers from the University of Leicester have discovered that the genes required for learning, memory, aggression and other complex behaviours originated around 650 million years ago.

    The findings led by Dr Roberto Feuda, from the Neurogenetic group in the Department of Genetics and Genome Biology and other colleagues from the University of Leicester and the University of Fribourg (Switzerland), have now been published in Nature Communications.

    Dr Feuda said: “We’ve known for a long time that monoamines like serotonin, dopamine and adrenaline act as neuromodulators in the nervous system, playing a role in complex behaviour and functions like learning and memory, as well as processes such as sleep and feeding.

    “However, less certain was the origin of the genes required for the production, detection, and degradation of these monoamines. Using the computational methods, we reconstructed the evolutionary history of these genes and show that most of the genes involved in monoamine production, modulation, and reception originated in the bilaterian stem group.

    “This finding has profound implications on the evolutionary origin of complex behaviours such as those modulated by monoamines we observe in humans and other animals.”

    The authors suggest that this new way to modulate neuronal circuits might have played a role in the Cambrian Explosion – known as the Big Bang – which gave rise to the largest diversification of life for most major animal groups alive today by providing flexibility of the neural circuits to facilitate the interaction with the environment.

    Dr Feuda added: “This discovery will open new important research avenues that will clarify the origin of complex behaviours and if the same neurons modulate reward, addiction, aggression, feeding, and sleep.”

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    University of Leicester

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  • Sea snake vision evolved to regain colour

    Sea snake vision evolved to regain colour

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    Newswise — An international team of scientists examining the genetic history of sea snakes have found that the species has enhanced their colour vision in response to living in brighter and more colourful marine environments.

    “Our research has found that the annulated sea snake possesses four intact copies of the opsin gene SWS1,” said PhD candidate Isaac Rossetto, from the University of Adelaide’s School of Biological Sciences who led the study.

    “Two of these genes have the ancestral ultraviolet sensitivity, and two have evolved a new sensitivity to the longer wavelengths that dominate ocean habitats.

    “The earliest snakes lost much of their ability to see colour due to their dim-light burrowing lifestyle.

    “However, their sea snake descendants now occupy brighter and more spectrally complex marine environments. We believe that recent gene duplications have dramatically expanded the range of colours sea snakes can see.”

    The team examined published reference genomes to examine visual opsin genes across five ecologically distinct species of elapid snakes. They looked at the gene data of Hydrophis cyanocinctus, or the annulated sea snake, a species of venomous snake found in tropical and subtropical regions of Australia and Asia.

    The team included scientists from The University of Adelaide, The University of Plymouth and The Vietnamese Academy of Science and Technology. They published their findings in the journal Genome Biology and Evolution.

    Many animals have lost opsins throughout their genealogical history as they’ve adapted to new habitats, but it is very rare to see opsin gains.

    “Humans have a similarly expanded sensitivity to colours, while cats and dogs are partially colour-blind much like those early snakes,” said Mr Rossetto.

    “It’s quite unique and interesting that these snakes appear to be gaining and diversifying their opsins, when other land-to-sea transitioned animals have done the opposite.”

    “Basically, there’s only one other case within reptiles at all where we think this has happened.”

    Newly gained colour-vision opsins have also been recorded in the semi-aquatic Helicops snake.

    Evidence of colour vision in Hydrophis snakes was first published in 2020, but this new research shows it is the result of gene duplication rather than gene polymorphism. This means expanded colour vision is more common among the species than first thought.

    “With a polymorphism, it’s a bit of a lottery – only some individuals would have that extended colour sensitivity. But now we know that there are multiple gene copies which have diverged, so colour vision is expected to be seen in all members of these species,” said Mr Rossetto.

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    University of Adelaide

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  • Enhanced stem cell culture boosts genome editing safety

    Enhanced stem cell culture boosts genome editing safety

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    Newswise — Tsukuba, Japan—Hematopoietic stem cells (HSCs) are rare cells found in the bone marrow that produce red blood cells, white blood cells, and platelets. Their correct functioning is indispensable for the growth and health of an organism. Accordingly, defects in the DNA of hematopoietic stem cells (mutations) can cause impaired blood production and severe diseases.

    Gene therapy seeks to treat such types of genetic diseases. A breakthrough technology that has driven the entire field in recent years is gene editing via clustered regularly interspaced palindromic repeats/Cas9 (CRISPR/Cas9). Using this technology, one can modify disease-causing mutations and transplant HSCs with recovered function, potentially curing the disease.

    However, the CRISPR/Cas9 system is not perfect. It only corrects mutations in a small fraction of cells and can introduce new, potentially dangerous mutations into other cells. Therefore, selecting corrected cells before transplantation is crucial.

    In 2019, the research group reported a method of expanding HSCs over a long time period using a polymer-based culture system and cytokines. In response to this problem, the authors have developed a novel culture system using a novel high-molecular-weight polymer. This system facilitates the growth of single HSCs in transplantable cell colonies that achieve high blood-producing capacity after long-time ex vivo culture. After editing a mutation in a murine immune deficiency model, the authors individually grow several hundred HSCs and screen them for clones that contain only the desired edit and are expected to engraft successfully. Using this method, the fraction of successfully corrected HSCs used for transplantation can be increased from 20%-30% to 100% while eliminating potentially dangerous mutations from the graft. We believe that this culture system might contribute to improving the efficiency and safety of genome editing in HSCs.

    ###
    This work was supported by the German Research Foundation (BE 6847/1-1 to H.J.B.), the Japan Society for the Promotion of Science (JSPS; #20K16234 to M.S.J.L., #23K15315 to H.J.B., #21F21108 and #20K21612 to S.Y.), the Kay Kendall Leukaemia Fund (A.C.W.), the Japan Science and Technology Agency (JST; #18071245 to C.C.), and the Japanese Agency for Medical Research and Development (AMED; #21bm0404077h0001 and #21bm0704055h0002 to S.Y.). The D.G.K. laboratory is supported by a Blood Cancer UK Bennett Fellowship (15008), an ERC Starting Grant (ERC-2016-STG-715371), a CR-UK Programme Foundation award (DCRPGF100008), the MRC Mouse Genetics Network Haematopoiesis Cluster (MC_PC_21043), and an MRC-AMED joint award (MR/V005502/1).

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    University of Tsukuba

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  • Controversial Chinese scientist He Jiankui proposes new gene editing research | CNN

    Controversial Chinese scientist He Jiankui proposes new gene editing research | CNN

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    Hong Kong
    CNN
     — 

    He Jiankui, the Chinese scientist who sparked global outrage in 2018 when he revealed that he had created the first gene-edited children, has put forward a new proposal for modifying human embryos that he claims could help aid the “aging population.”

    He, who in 2019 was sentenced to three years in prison in China for “illegal medical practices,” reemerged last year and surprised the global scientific community when he announced on social media that he was opening a research lab in Beijing.

    Since that time, updates on his research posted on his Twitter account have focused on proposed plans to develop gene therapy for rare disease.

    But on Thursday, he again courted controversy by posting a new research proposal that experts say is reminiscent of his earlier work, which scientists broadly decried as unethical and dangerous – with the potential to impact human DNA across generations.

    In a succinct, one page document, He proposed research that would involve gene-editing mouse embryos and then human fertilized egg cells, or zygotes, in order to test whether a mutation “confers protection against Alzheimer’s disease.”

    “The aging population is of grave importance as both a socioeconomic issue and a strain on the medical system … Currently, there is no effective drug for Alzheimer’s disease,” he wrote in an apparent nod to China’s growing demographic burden due to a rising proportion of elderly.

    Unlike the science that landed him in jail, this potential experiment involves a kind of abnormal fertilized egg cell generally considered not suitable to be implanted in a woman.

    No human embryo would be implanted for pregnancy and “government permit and ethical approval” were required before experimentation, the proposal said.

    It’s not clear whether He would get approval for such work in China, even if the proposal he put forward were deemed to have merit – and outside experts say the current proposal is not scientifically sound.

    Authorities in China took multiple steps to tighten rules and ethical standards affecting human gene editing in the wake of the revelations about his previous research. They also banned He from engaging in work related to assisted reproductive technology services and placed limits on his work with human genetic resources, according to state media.

    But the scientist’s release of a new proposal involving gene editing of embryos has scientists and medical ethics experts concerned – and confused.

    “The whole thing is, to put it bluntly, insane,” said Peter Dröge, an associate professor at the Nanyang Technological University in Singapore, who focuses on molecular and biochemical genetics.

    The proposed research could be seen as a step to explore if such a method of genetic editing could be used in a viable embryo in future, according to Dröge.

    Apart from ethical considerations, gene-editing an embryo to address a complex disease that affects people toward the end of their life and doesn’t have a clear, single genetic cause is “highly questionable,” he said.

    “He basically wants to genetically modify the human species so they don’t get Alzheimer’s,” he said. “I’m really surprised that he’s coming forward with this again.”

    Joy Zhang, founding director of the Centre for Global Science and Epistemic Justice at the University of Kent in Britain, said the proposal seemed to be “more of a publicity stunt than a substantiated research agenda.”

    “However, we do need to take these public claims with vigilance, as it may nevertheless misguide patients and their families, and tint the reputations not just of science in China, but global research effort in this area,” she said.

    In response to questions from CNN, He said he was “collecting feedback from scientists and bioethicists now” and did not have a timeline for the study.

    “I will make a revision to the Alzheimer’s disease proposal later. I will not conduct any experiments until I get the government permit, and also get the approval by an international ethics committee with bioethicists from USA and Europe,” he told CNN via email.

    “I want to emphasize that this is a preclinical study, no embryo will be used for pregnancy in this study. The research will be open and transparent, and all experiment results and progress will be posted on Twitter,” he said.

    He did not address questions on whether he was limited from conducting certain work in China.

    CNN also approached China’s Ministry of Science and Technology and National Health Commission for comment.

    In 2018, He, formerly a researcher at the Southern University of Science and Technology in Shenzhen, claimed he had used a gene-editing tool called CRISPR to modify human embryos of twin girls in the hopes of protecting them from HIV. A third genetically edited baby was also born from He’s experimentation, a court in Shenzhen later said.

    The research sparked a fierce uproar over the ethics of using new and potentially dangerous technology in people and the risk of unintended mutations being passed on not only to the children but potentially any future offspring. It also raised concerns about cracking open the door to a potentially species-changing future of “designer children.”

    In recent media interviews, He has indicated he feels he acted “too quickly” in conducting the research and has given sparse details on the children, besides indicating they were living “normal” lives.

    Genetic manipulation of human embryos – both viable and nonviable ones – is typically tightly controlled globally and some countries ban all such research, experts say.

    But there is robust global debate around allowing genome editing of human embryos to treat serious genetic conditions or expanding research.

    Scientists say genome editing, including in adults, shows promise for one day treating diseases that are currently difficult to treat or cure, like cystic fibrosis or sickle cell disease.

    Chinese law does not allow gene-edited human embryos used in research to be implanted into humans, or developed for more than 14 days. All gene editing for reproductive purposes has also long been banned.

    Since 2019, a broader raft of regulation of China’s biosciences field has added more legal controls and ethical standards to such research, including a major update to national bioethics guidelines earlier this year.

    There’s also been sharp backlash against He within China’s scientific community.

    In March, over 200 Chinese scholars released a statement in response to his public activities, including what they said was He’s “misleading marketing campaign” over his claimed research plans on rare disease.

    They condemned He’s “attitude and refusal to reflect on his criminal actions of violating ethics and regulations of gene editing,” and called for regulatory authorities to launch a new investigation into He’s “alleged re‐violation of scientific integrity, ethical norms, laws and regulations.”

    “The ethical boundaries shall not be crossed,” they wrote.

    As for the future of He’s research, Canadian bioethicist Françoise Baylis of Dalhousie University said numerous questions should be considered, from whether He has the requisite scientific expertise to test the hypothesis, to whether he can be trusted to follow the rules for research involving humans.

    “It is possible for people to learn from their mistakes and to change their behavior … but many are concerned, however, that He Jiankui may not have learned from his past mistakes,” Baylis said.

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