Neuroscience

Taking a Peek at the Building Blocks of Brain Computing – Technology Networks

Synapses are specialized devices where learning and memory occur. The efficient transmission of synaptic signals relies on the delicate structure and complex molecular composition of the synapses. However, the small size (several hundred nanometers in diameter) and heterogeneous nature of the synapses pose significant challenges in direct observation of the molecules inside synapses.

Based on the proposed processing technique for in situ cryo-electron tomography, researchers from University of Science and Technology of China (USTC) and Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences (CAS) became the first scientists to observe individual GABAA receptors and their organization on the synaptic membrane, endowing the brain's ability for information processing.

"The advance of this study comes from the in situ cryo-electron microscopy, a method that preserves the cells in native states and has an order of magnitude of higher resolution compare to the super-resolution optical microscopy," said TAO Changlu, postdoctoral fellow from USTC and the study's co-first author, now associate investigator at SIAT.

This image processing technique is able to automatically locate the membrane proteins in their cellular context. "To ensure that we detect every receptor on the postsynaptic membrane, we oversampled the synaptic membrane and classified all the sampled 3D images without any template" said LIU Yuntao, graduate student from USTC and the study's co-first author, now postdoctoral fellow at UCLA. "We even used the negative control that sampling the presynaptic membrane to validate our observation."

Once the receptors were detected, researchers suddenly realized that the receptors are not randomly distributed on the membrane: they tend to keep the same 11-nm "social distancing" from each other. Intriguingly, the receptors can rotate freely, even though constrained by distance.

"The social distancing among receptors could arise from their interactions with scaffolding molecule--gephyrins", said BI Guoqiang, professor of neuroscience at USTC and senior author of the paper.

The scaffolding molecules form a 5-nm thick density sheet to support and regulate GABAA receptors on the membrane. Together, they form an absorbing semi-ordered structure called "mesophasic assembly".

A mesophasic state is in between the liquid and solid, which might be induced by the multivalent interaction between receptors and their scaffolding molecules and attract the readily-releasable vesicles containing neurotransmitters. The inhibitory synapses could store information by arranging the GABAA receptors in such a low-entropy Goldilocks state.

This semi-ordered structure differs from the previously proposed hexagonal lattice organization of GABAA receptors and gephyrins. Notably, each synapse tends to contain one mesophasic assembly, rather than multiple nano-domains as observed in excitatory synapses with super-resolution optical microscopy.

"This work represents the first nanometer-resolution observation at the inhibitory synaptic receptors and a critical step towards resolving the atomic details of the brain.", said ZHOU Hong, director of the Electron Imaging Center for NanoMachines at the California NanoSystems Institute at UCLA, also senior author of the paper.

Reference: Liu YT, Tao CL, Zhang X, et al.Mesophasic organization of GABAA receptors in hippocampal inhibitory synapses.Mesophasic organization of GABAA receptors in hippocampal inhibitory synapses. Nat Neurosci. 2020. doi:10.1038/s41593-020-00729-w

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

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Taking a Peek at the Building Blocks of Brain Computing - Technology Networks

Neuroscience

Study pinpoints neural basis for the interplay between a close relationship with God and enhanced sense of … – PsyPost

A recent study offers new evidence that having a close relationship with God serves the psychological purpose of enhancing ones sense of control. The study was published in Cognitive, Affective, and Behavioral Neuroscience.

Spiritual belief is a fundamental aspect of human culture, dating back to ancient times. Psychology researchers have explored this tendency toward supernatural belief, suggesting that a close relationship with God offers humans a sense of control and a coping mechanism

Study authors Shira Cohen-Zimerman and colleagues wanted to explore this interplay between a belief in God and a sense of control and to investigate the possibility that the constructs share a neural basis.

To do this, researchers conducted a lesion-mapping study among a sample of veterans who had served in Vietnam. The researchers were interested in exploring damage to the ventromedial prefrontal cortex (vmPFC), an area of the brain that has been linked to emotionally meaningful religious experiences in addition to a sense of control. They accordingly divided their sample into veterans with vmPFC lesions, veterans with posterior cortex lesions, and veterans with no brain injury.

All participants responded to 17 items assessing their personal relationship with God (e.g., I can talk to God on an intimate basis.). They also completed a measure of sense of control which used the item, How often do you feel powerless to get what you want out of life?.

The researchers matched their participants according to age, handedness, and general intelligence pre-injury.

The analysis found that subjects with damage to the right vmPFC demonstrated an enhanced personal relationship with God when compared to subjects with posterior lesions or no lesions at all. The group with right vmPFC damage also showed greater perceived sense of control, compared to the group without brain injury.

Next, the researchers conducted mediation analysis to further examine the interplay between lesions in the vmPFC, sense of control, and closeness with God. They found that a stronger relationship with God mediated the relationship between lesions in the right vmPFC and increased sense of control.

This pattern of results, the authors report, supports a model of right vmPFC damage enhancing participants sense of control through enhancing their personal relationship with God.

As Cohen-Zimerman and team emphasize, their study is the first to pinpoint a neural basis for the interplay between a close relationship with God and a sense of control.

Our findings indicate the importance of the close link between belief in God and a sense of control, and strengthen theories claiming that religion originated, at least in part, from the desire to avoid the threatening experience of perceiving the world as random and chaotic, the authors highlight.

The authors further note that while functional imaging studies show that activation of vmPFC is associated with enhanced religious experience, this does not necessarily contradict their finding that damage to this area increased subjects personal relationship with God.

In our view, the vmPFC does not directly enhance ones personal relationship with God. In contrast, given that patients with stronger lesions in this area reported a personal relationship with God, we infer that it is likely that other, intact brain areas, enabled the strong personal relationship with God observed in these patients, and that the vmPFC normally plays an inhibitory role in modulating this effect.

The researchers propose that their findings may have implications for patients dealing with brain injuries, particularly those with damage to the vmPFC. Such patients might improve their sense of control after injury by drawing on their faith.

The study, Neural underpinning of a personal relationship with God and sense of control: A lesion-mapping study, was authored by Shira Cohen-Zimerman, Irene Cristofori, Wanting Zhong, Joseph Bulbulia, Frank Krueger, Barry Gordon, and Jordan Grafman.

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Study pinpoints neural basis for the interplay between a close relationship with God and enhanced sense of ... - PsyPost

Neuroscience

Neuroscience Antibody or Research Reagents Market Size And Forecast (2020-2026)| With Post Impact Of Covid-19 By Top Leading Players- NEOBIOSCIENCE,…

COVID-19 Impact on Global Neuroscience Antibody or Research Reagents Market Professional Survey Research Report 2020-2027

Overview Paragraph

Starting with the basic information, the report provides a complete summary of the global Neuroscience Antibody or Research Reagents market. The summary discusses the outlook and specifications of products and services in the market and their application. The report also provides detailed information on the technology used for manufacturing and production. The report provides information on the production procedures that can increase productivity and efficiency of the overall system. The report classifies the global Neuroscience Antibody or Research Reagents market into segments based on knowledge of the market. The report covers the key market players present in different regions and also studies the strategies used by them to enhance their presence and value in the Neuroscience Antibody or Research Reagents market. The report predicts future trends and scope of the market for the forecast period 2020-2027.

Key Players

NEOBIOSCIENCE, Genscript, Thermo Fisher Scientific, Wuhan Fine Biotech Co., and Ltd.

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Market Dynamics

The report covers various factors that are responsible for the rapid growth and expansion of the Neuroscience Antibody or Research Reagents market. The report provides information on the dynamic nature of the market, analyzes the pricing economic models, dynamics of demand and supply, market driving forces, market growth restraints, etc. The report covers factors such as the favourable government initiatives and policies, mounting population, geographical changes, etc changes can impact the stability of the market during the forecast period. The report assesses the internal and external factors that can cause abnormalities in the market. The report also focuses on the opportunities, challenges, and threats witnessed by the market participants present in the Neuroscience Antibody or Research Reagents market.

Segmental Analysis

The report divides the global Neuroscience Antibody or Research Reagents market into some key segments based on attributes, features, applications, and types. This information would help the new market entrants and emerging players to understand the overall structure of the market and get information on the various products and services available in the market. This information would also help the market entrants to understand the emerging trends that can dominate the market in the future. The Neuroscience Antibody or Research Reagents port includes detailed information on the critical market segments that can lead or drive the overall Neuroscience Antibody or Research Reagents market during the forecast period. The report also covers the regional segments of the Neuroscience Antibody or Research Reagents market. The major regional markets that are expected to drive the product demand in the future are also mentioned in the market report.

Regional Analysis for Neuroscience Antibody or Research Reagents Market

North America (the United States, Canada, and Mexico)

Europe (Germany, France, UK, Russia, and Italy)

Asia-Pacific (China, Japan, Korea, India, and Southeast Asia)

South America (Brazil, Argentina, Colombia, etc.)

The Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria, and South Africa)

The objectives of the report are:

To analyze and forecast the market size of Neuroscience Antibody or Research Reagents Industry in the global market.

To study the global key players, SWOT analysis, value and global market share for leading players.

To determine, explain and forecast the market different attributes of the products or services. This information would help the companies to understand the prominent trends that are emerging in the market and would also provide a wider by type, end use, and region.

To analyze the market potential and advantage, opportunity and challenge, restraints and risks of global key regions.

To find out significant trends and factors driving or restraining the market growth.

To analyze the opportunities in the market for stakeholders by identifying the high growth segments.

To critically analyze each submarket in terms of individual growth trend and their contribution to the market.

To understand competitive developments such as agreements, expansions, new product launches, and possessions in the market.

To strategically outline the key players and comprehensively analyze their growth strategies.

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Key questions answered in the report:

What is the growth potential of the Neuroscience Antibody or Research Reagents market?

Which product segment will grab a lions sh are?

Which regional market will emerge as a frontrunner in the coming years?

Which application segment will grow at a robust rate?

What are the growth opportunities that may emerge in the Neuroscience Antibody or Research Reagents industry in the years to come?

What are the key challenges that the global Neuroscience Antibody or Research Reagents market may face in the future?

Which are the leading companies in the global Neuroscience Antibody or Research Reagents market?

Which are the key trends positively impacting the market growth?

Which are the growth strategies considered by the players to sustain hold in the global Neuroscience Antibody or Research Reagents market

List of Tables and Figures

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Neuroscience

Study focuses on efficacy of cognitive rehabilitation across a range of neurological conditions – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Nov 11 2020

A new text by Kessler Foundation scientists focuses on the efficacy of cognitive rehabilitation across a variety of neurological conditions, with specific emphasis on treatment-related changes in the brain detectable via neuroimaging.

"Cognitive Rehabilitation and Neuroimaging: Examining the Evidence from Brain to Behavior," (DOI:10.1007/978-3-030-48382-1) is authored by John DeLuca, PhD, Senior Vice President of Research and Training, Nancy Chiaravalloti, PhD, director of the Centers for Neuropsychology, Neuroscience, and Traumatic Brain Injury Research, and Erica Weber, PhD, research scientist in the Center for Traumatic Brain Injury Research.

The authors conduct cognitive rehabilitation research at Kessler Foundation, home to the Rocco Ortenzio Neuroimaging Center, a research-dedicated facility, and collaborate with researchers in the U.S. and the international community.

Because the nature of cognitive impairment and rehabilitative interventions differ across populations, content is divided by neurological condition, with experts addressing aging, stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, and multiple sclerosis (MS).

The use of neuroimaging in cognitive rehabilitation trials is covered, as well as the need to design trials to establish Class I evidence for new treatments.

Neuroimaging has advanced cognitive rehabilitation by enabling us to examine brain processes and correlate them with alterations in behavior and anatomical structures. Using specialized techniques such as structural and functional magnetic resonance imaging, diffusion-weighted imaging, and electroencephalography, we are documenting how cognitive interventions effect changes in neural activation and connectivity that correlate with improvements in language, memory, attention, and motor function.

Through advancements in neuroimaging analysis, we are learning more about the neuroplasticity of the brain in MS and schizophrenia, which will challenge researchers to apply these approaches to populations where more investigation is needed, such as children with brain injuries and individuals with brain tumors."

John DeLuca, PhD, Senior Vice President of Research and Training, Kessler Foundation

Source:

Journal reference:

DeLuca, J., et al. (2020) Cognitive Rehabilitation and Neuroimaging. Springer. doi.org/10.1007/978-3-030-48382-1.

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Study focuses on efficacy of cognitive rehabilitation across a range of neurological conditions - News-Medical.Net

Neuroscience

Pattern separation may not be present in the human hippocampus – News-Medical.Net

Nov 9 2020

NEUROSCIENCE EXPERTS from the University of Leicester have released research that breaks with the past fifty years of neuroscientific opinion, arguing that the way we store memories is key to making human intelligence superior to that of animals.

It has previously been thought and copiously published that it is pattern separation in the hippocampus, an area of the brain critical for memory, that enables memories to be stored by separate groups of neurons, so that memories dont get mixed up.

Now, after fifteen years of research, Leicester Universitys Director of Systems Neuroscience believes that in fact the opposite to pattern separation is present in the human hippocampus. He argues that, contrary to what has been described in animals, the same group of neurons store all memories. The consequences of this are far reaching, as such neuronal representation, devoid of specific contextual details, explains the abstract thinking that characterizes human intelligence.

In contrast to what everybody expects, when recording the activity of individual neurons we have found that there is an alternative model to pattern separation storing our memories. Pattern separation is a basic principle of neuronal coding that precludes memory interference in the hippocampus. Its existence is supported by numerous theoretical, computational and experimental findings in different animal species but these findings have never been directly replicated in humans. Previous human studies have been mostly obtained using Functional Magnetic Resource Imagining (fMRI), which doesnt allow recording the activity of individual neurons. Shockingly, when we directly recorded the activity of individual neurons, we found something completely different to what has been described in other animals. This could well be a cornerstone of humans intelligence.

Professor Rodrigo Quian Quiroga, Director of Systems Neuroscience, Leicester University

The study, No pattern separation in the human hippocampus, argues that the lack of pattern separation in memory coding is a key difference compared to other species, which has profound implications that could explain cognitive abilities uniquely developed in humans, such as our power of generalization and of creative thought.

Professor Quian Quiroga believes we should go beyond behavioral comparisons between humans and animals and seek for more mechanistic insights, asking what in our brain gives rise to humans unique and vast repertoire of cognitive functions. In particular, he argues that brain size or number of neurons cannot solely explain the difference, since there is, for example, a comparable number and type of neurons in the chimp and the human brain, and both species have more or less the same anatomical structures. Therefore, our neurons, or at least some of them, must be doing something completely different, and one such difference is given by how they store our memories.

The study No pattern separation in the human hippocampus by Rodrigo Quian Quiroga is published in the journal Trends in Cognitive Sciences.

Source:

Journal reference:

Quiroga, R.Q. (2020) No Pattern Separation in the Human Hippocampus. Trends in Cognitive Sciences. doi.org/10.1016/j.tics.2020.09.012.

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Pattern separation may not be present in the human hippocampus - News-Medical.Net

Genetics

Flaws emerge in modeling human genetic diseases in animals – The Conversation US

My lab, based at the University of Southern California Keck School of Medicine, uses zebrafish to model human birth defects affecting the face. When I tell people this, they are often skeptical that fish biology has any relevance to human health.

But zebrafish have backbones like us, contain by and large the same types of organs, and, critically for genetic research, share many genes in common. My group has exploited these genetic similarities to create zebrafish models for several human birth defects, including Saethre-Chotzen Syndrome, in which the bones of the skull abnormally fuse together, and early-onset arthritis.

Similar to fish, our bodies develop under the control of about 25,000 genes. The trick is finding out what each gene does. Stunning advances such as CRISPR-based molecular scissors, for which the Nobel Prize in chemistry was just awarded, allow us to precisely change genes, and designer chemicals can silence particular genes. In a recent study from our group published in Nature, however, we find that these tools are still far from perfect. Although CRISPR now allows us to efficiently generate lab animals that can pass human disease mutations onto the next generation, claims that simply injecting CRISPR into embryos or silencing genes with designer chemicals can accurately model human genetic disease are being questioned.

Finding the precise mutation that causes a particular birth defect or a late-onset disease can be tedious work. The human genome is made up of 3 billion building blocks called DNA nucleotides, and changing just one of these can cause devastating birth defects.

To figure out if we have identified the right disease-causing mutation in humans, we typically engineer the same change into the genome of a lab animal. We then breed these animals to generate babies with the disease mutation and look for the appearance of defects similar to those in human patients.

We study zebrafish because they are small, which means we can grow thousands of different genetically modified animals. We routinely use CRISPR to engineer fish that pass on a gene-breaking mutation to the next generation.

We then study the appearance of defects similar to those in humans lacking these genes in essence creating personalized zebrafish avatars of genetic disease. As zebrafish embryos are transparent and develop rapidly outside the mother, they are particularly useful for understanding how human disease mutations disrupt normal development.

Even in zebrafish, engineering animals to lack particular genes can be a time-consuming process. In my lab, we first create gene mutations in embryos, grow these fish to adulthood and then breed fish together to look at defects in the next generation.

This whole process can take a year or longer. Unsurprisingly, many labs are attempting shortcuts. Some are injecting large quantities of CRISPR molecular scissors into animals and then looking for defects in these same animals. Others are using chemicals to turn off, or silence, genes in the embryo rather than permanently changing the genes.

More and more frequently studies like this are calling into question the accuracy of these shortcuts. In animals that have been injected with CRISPR molecular scissors, not every cell is changed in the same way. And the chemicals used to silence genes appear to have unintended consequences, poisoning the embryo in a generic way.

For example, researchers in Spain recently reported that a gene called prrx1a was critical for the proper development of the heart. To figure this out, they silenced prrx1a in zebrafish with chemicals. Then, in a second experiment, they injected CRISPR molecular scissors into zebrafish embryos and examined them just one day later for heart defects.

In contrast, we completely removed the prrx1a gene and looked at generations of fish lacking this gene. Hearts in these mutant fish developed perfectly normally, showing that prrx1a was not critical for heart development. Instead, we showed that the heart defects seen upon chemical treatment in the Spanish study were due to a general poisoning of the embryos unrelated to the prrx1a gene. Animals simply injected with CRISPR also showed defects not seen upon complete removal of the prrx1a gene, although the exact reasons for these differences remain a source of active debate.

And not just our group has noticed these flaws. Using similar gene removal as we reported, the group led by Didier Stainier refuted a study that had used CRISPR injection and gene silencing to link the tek gene to blood vessel development. Given the number of studies relying on gene silencing in lab animals, as opposed to engineering the DNA mutations, the causative genes for many human diseases may need to be reevaluated.

The desire for speed in research must not come at a cost of accuracy and reproducibility.

The good news is that, with the ease of CRISPR, we now know how to engineer the right types of mutations in lab animals to validate human disease mutations. By creating lab animals such as zebrafish that have the mutations engineered into their genomes and then observing whether their offspring develop the same diseases as patients with the mutations, we can be confident in having identified the right human disease gene.

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Getting it right is important for accurately counseling prospective parents of their genetic risks for certain birth defects, as well as identifying the relevant genes that can be targeted to prevent or even reverse disease.

Science is constantly evolving. While the ability to engineer the genome with CRISPR is opening up endless possibilities for human genetics, researchers must also recognize the limitations of new technologies. Although rapid, directly injecting CRISPR or silencing genes with chemicals gives misleading results too often. In order to confidently identify causative mutations linked to human disease, we will need to continue to study lab animals engineered to carry and pass on the same DNA changes as found in human patients.

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Flaws emerge in modeling human genetic diseases in animals - The Conversation US

Genetics

Exploring Genetic Variation and COVID-19 Clinical Variability – Technology Networks

One of the biggest challenges that scientists and healthcare professionals are facing during the COVID-19 pandemic is the high rate of clinical variability. Whilst some patients present as asymptomatic, others are developing more severe symptoms such as pneumonia, and some cases are ultimately proving fatal. Why?The answer remains elusive; however, extensive research is exploring the possible contribution our genetics may be having. Genetic variation differences in the DNA sequences that make up our genome can impact our response to infectious diseases.

GoodCell uniquely measures and monitors inherited and acquired genetic variations in stem cells and other nucleated cells in our blood over time. Technology Networks recently spoke with Dr Salvatore Viscomi, chief medical officer at GoodCell, and attending physical at Baystate Health, to explore factors that might influence COVID-19 risk, and to discuss how the company is working to identify at-risk individuals through genetic variation analysis.

Molly Campbell (MC): For our readers that may be unfamiliar, can you discuss why medicine is moving towards a personalized approach, and why this is important considering genetic variation?Salvatore Viscomi (SV): Healthcare has traditionally taken the approach of one size fits all in defining individual risk for a disease and prescribing therapy for it. Understanding the differences between individuals on a molecular level optimizes assessment of an individuals susceptibility to a certain disease and predicting response to pharmacological therapy. Genomics plays the most important role in the emergence of personalized therapy. Identifying the inherited and acquired genetic variation will direct personalized screening and prevention plans and inform bespoke medical therapies.

MC: We know that there is high clinical variability across COVID-19 patients. How might genetic variation be contributing here, and what published evidence exists to support this?SV: Understanding immune response is critical to identifying individuals at high risk of severe morbidity and mortality. Emerging research suggests that accumulated genetic variation in our blood cells may be associated with a dysfunctional inflammatory response to COVID-19 leading to its pulmonary, cardiac and coagulopathic complications.

In a recent study published by JAMA Cardiology, researchers demonstrated an association between the presence of accumulated genetic change in our blood cells and a pro-inflammatory immune response that resembles the exaggerated cytokine release syndrome (CRS) manifested in COVID-19-positive patients. Direct evidence has emerged more recently; a study published in Cancers examined patients hospitalized with COVID-19 and found a significantly higher prevalence of accumulated genetic variation in all age groups compared to age-matched control groups.

MC: What impact might genetic variation in COVID-19 patients have on efforts to develop therapeutics or preventives, such as vaccines?SV: Identifying highly susceptible individuals through blood testing could have many applications. As an initial wave of vaccines move through Phase III trials and potentially come to market, we would have the data to determine prioritization of vaccinations when one is available. Business and government sectors need insight into risk factors that can inform inoculation strategies for societys most vulnerable, inform decisions around who should and should not be on the front lines, and give people more control when making personal decisions about how to mitigate individual risk. The broader field of genetics offers a window into the potential to correlate inherited and acquired gene mutations with immune response for the betterment of society, providing a more robust and accurate set of risk factors unique to every individual.

Furthermore, in high-risk individuals, targeting inflammation may be a clinical strategy to mitigate its clinical consequencesin COVID-19. For example, we may identify patients who are most responsive to pro-inflammatory inhibitors. Implementing measures intended to reduce subjects exposure to the infection or likelihood of contracting such infection through self-isolation, quarantine or social distancing may be advised.

MC: Can you explain the aims of GoodCell, and what the company does in terms of "banking blood for life"?SV: GoodCells mission is to extend and improve the quality of life through technology powered by our own cells. Blood is the author of our bodies, and can both cure as well as cause disease. Through our proprietary data aggregation and analytics technology platform, which aims to decode our blood cells and harness their insights to advance population and personal health, we empower individuals to identify, track and mitigate health risks. By getting ahead of their health risks, we enable the potential for a better life. In addition, through our personal biobanking service, long-term storage of your healthiest cells provides the opportunity for potential use in future therapeutics if you need them you are your best donor.

MC: Does GoodCell measure other "omics" parameters outside of genomics (DNA measurements and analysis), such as proteomics or metabolomics?SV: GoodCells platform leverages the power of blood to assess risk as such, we of course look at acquired and inherited genetic changes, but there are many more opportunities afforded by blood to understand and assess risk including routine blood chemistry tests, tests for biomarkers of disease, including emerging capabilities in liquid biopsy for earlier detection of solid tumor cancers. Ultimately, we are always looking to incorporate novel health and data insights into our product platform to better inform both an individuals health, as well as population-based health. Transcriptomics, epigenomics and metabolomics are but a few of the opportunities we are evaluating.

MC: What work is GoodCell currently conducting in the COVID-19 space?SV: GoodCell is currently engaged in a research collaboration with the New York Blood Center to evaluate how specific acquired and inherited genetic variation contribute to COVID-19 severity and recovery. We are analyzing genetic variation in asymptomatic/mildly symptomatic patients compared to hospitalized/ICU patients. GoodCell will evaluate the genetic variation in the collected samples using our proprietary assay platform to identify and validate their association with COVID-19 morbidity and mortality.

Salvatore Viscomi was speaking to Molly Campbell, Science Writer, Technology Networks.

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Exploring Genetic Variation and COVID-19 Clinical Variability - Technology Networks

Genetics

Precision Genetics Launches Combination Test to Detect COVID-19 and the Flu – PRNewswire

GREENVILLE,S.C., Nov. 10, 2020 /PRNewswire/ --Precision Genetics, a leader in the molecular laboratory and technology industries, announces today the launch of a new diagnostic test that simultaneously detects SARS-CoV-2 and Influenza A/B strains in upper respiratory tract specimens. The test is available to health systems, providers, employers, and academic institutions alike.

Precision Genetics' capabilities are essential for accurately detecting patients with COVID-19 and/or the flu. "By utilizing our high-complexity laboratory and testing methods, we can quickly and accurately distinguish between these viral infections," said Nate Wilbourne, founder and CEO of Precision Genetics. "Our goal as a molecular laboratory is to ensure the highest levels of quality and efficiency to our clinical partners."

The addition of this combination test comes just in time for the flu season. "Most current testing looks only for COVID-19. As influenza infection rates rise, testing individuals only for Covid-19 is insufficient to distinguish between various viral illnesses of the upper respiratory tract," said John Wrangle, M.D,Chief Medical Officer of Precision Genetics. "Knowing which virus a patient is infected with may help treating physicians, health professionals and health departments decide on the best course of treatment, surveillance and contact tracing."

About Precision Genetics

Precision Genetics is a high-complex molecular laboratory and technology company performing COVID-19 testing, COVID-19/Flu combination testing and pharmacogenomics testing for employer safety and wellness, pre-surgical risk analysis and mental health.

For more information on how your organization can benefit from our quick and reliable testing capabilities, please visit us at https://precisiongenetics.com, send inquiries to [emailprotected], or call our team at (877) 843-6544 (ext 4).

SOURCE Precision Genetics

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Precision Genetics Launches Combination Test to Detect COVID-19 and the Flu - PRNewswire

Genetics

The Value of a Molecular Diagnosis of Epilepsy – Medical Device and Diagnostics Industry

When discussing a diagnosis of epilepsy, advances in genetic testing are proving that it is indeed all about the details. Comprehensive genetic testing is making it possible to drill down into those details. When testing is based on whole genome sequencing (WGS) technology, it is possible to identify genetic changes, or variants, in the 370-plus seizure-associated genes found amongst the 20,000 or so genes within the human genome or, more importantly, the large number of variants located within or spanning those genes. A single-method approach for detecting multiple variant types from a single patient sample can more accurately lead to a diagnosis, resulting in more-tailored medical management and providing a better basis for improved long-term outcomes and family planning.

In the United States, epilepsy is the fourth most common neurological condition, surpassed only by migraine, stroke, and Alzheimers disease. Each year, 150,000 people on average will develop epilepsy (48 out of 100,000) and its prevalence is currently estimated at around 2.2 million people (or 7.1 out of every 1,000 people). Epilepsy is a spectrum condition characterized by unpredictable seizures that can cause or co-occur with other health problems. There is a wide range of seizure types and the ability to control them varies from person-to-person, even within families. The cause of epilepsy is often unknown, but it is most often related to brain injury or genetics. However, the word epilepsy itself has nothing to do with the cause, severity, or type(s) of an individuals seizures.

Genetic seizure disorders span multiple classes. They can include specific syndromes in which a seizure is the only symptom as well as occur as part of broader neurodevelopmental conditions that present with additional features, such as intellectual disability. Seizures may also be present as a symptom of metabolic conditions and/or other disorders. Seizure disorders share symptoms (phenotypes) with many other conditions, which often make it difficult to determine the inheritance pattern from the family history. Causal variants may be inherited from a parent or simply show up new (de novo) in a persons DNA. In some cases, variants in multiple genes may together contribute to the clinical symptoms. Many different types of variants have been shown to cause seizure disorders.

This is why definitively diagnosing the genetic cause of epilepsy can be challenging. Traditionally, this is accomplished through multiple, sequential tests. This step-wise method typically begins with what is known as a chromosomal microarray, which involves structural analysis of a persons chromosomes and checks to make sure there are no large imbalances (extra or missing pieces) that could cause epilepsy. If the microarray does not reveal a positive result, the next step is usually single-gene or multi-gene panel testing, depending on the specific nature of the individuals symptoms. If no causal variant is identified with those tests, the final step is exome testing, if the patients insurance allows for multiple genetic tests. This results in a long process of repeated rounds of testing, with each individual round limited by the types of variants that can be detected, leaving gaps in variant coverage and detection, and therefore leaving gaps in the ability to properly diagnose a patient. That is because, as a general rule, microarray, panel, and exome tests individually do not perform well at detecting a broad spectrum of changes (variants) in genetic material.

Comprehensive testing based on WGS technology has the ability to detect a wide range of variant types not covered by traditional microarray, panel-based, or exome tests, as well as the ability to reanalyze patient data in the future without resequencing. Combining WGSs consistent, comprehensive sequence coverage with proprietary algorithms allows for the detection of variants without any size limitations. The result is more-comprehensive testing of the entire spectrum of variants and genes associated with genetic epilepsy. All of this is accomplished with a single blood draw (or saliva sample) and a turnaround time of six to eight weeks.

The ability to quickly establish a genetic cause of epilepsy utilizing WGS can provide the information necessary to control an individuals seizures as soon as possible. The longer a patient experiences uncontrolled seizures, the more likely they will suffer irreparable damage to the brain. Depending on their frequency and length, uncontrolled seizures can interfere with daily activities and can negatively impact someones quality of life. The sooner that clinicians can identify an individuals cause of seizures and treat it appropriately, the better the prognosis for the long-term management of disease.

Above: Image of aa sample collection kit from Variantyx.

In some cases, a genetic diagnosis may help guide the selection ofanti-seizure medications, as there are some well-known links between certain medications and specific genetic epilepsy disorders. Some medicines work better while others may cause adverse side-effects, all of which can be determined by pinpointing of the variant causing the disease. Comprehensive genetic testing may also bring to light the risk of epilepsy to other family members, including the risk of passing the disorder on to a child. A genetic diagnosis can also assist individuals and families in finding and accessing the proper resources, from advocacy groups to connections with families sharing in similar struggles, and in opening up the door to participation in clinical studies for individuals with a related genetic diagnosis.

In summary, a single-method approach for the detection of a genetic cause of epilepsy is achievable by identifying multiple-variant types from a single patient sample through WGS technology. The result is a cost-effective, comprehensive analysis of an individuals DNA summarized in a single, unified clinical report. Obtaining a genetic diagnosis through WGS may end what is often referred to as the diagnostic odyssey or the search for an answer by an individual or family as well as provide information to guide treatment and maximize a patients quality of life.

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The Value of a Molecular Diagnosis of Epilepsy - Medical Device and Diagnostics Industry

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Fulgent Genetics to Participate in the Credit Suisse 29th Annual Virtual Healthcare Conference – Yahoo Finance

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The U.S. presidential election has come to a close, and Wall Street isnt opposed to the administration change. Last week saw the S&P 500 notch its second-best performance during an election week on record, even as Trumps chances of getting re-elected became slimer and slimer.Weighing in for Oppenheimer, Chief Investment Strategist John Stoltzfus noted, What appears clear so far is that the equity markets are not averse to a change of administration stateside at least so long as the Republicans maintain control over the Senate. Checks and balances on the Hill have been known to be important to investors over the course of history. The present in our view is no exception.There is, however, some uncertainty surrounding the Senate, with the two runoff elections for seats in Georgia scheduled for January 5, only 15 days before Inauguration Day. That said, Stoltzfus points out that continued better-than-expected Q3 results from S&P 500-listed companies, economic data tied to job gains and a sharp decline in the unemployment rate have also been helping to prop stocks up.Taking Stoltzfus outlook into consideration, we wanted to take a closer look at three stocks earning a round of applause from Oppenheimer, with the firms analysts forecasting over 100% upside potential for each. Using TipRanks database, we learned that the rest of the Street is in agreement, as all three boast a Strong Buy analyst consensus. Strongbridge Biopharma (SBBP)First up we have Strongbridge Biopharma, which is focused on developing therapies for rare diseases with significant unmet needs. Ahead of a key regulatory filing, Oppenheimer believes that SBBP's $2.12 share price reflects an attractiveentry point.Representing the firm, analyst Hartaj Singh points out that investor focus has landed squarely on Recorlev, the company's investigational cortisol synthesis inhibitor, in Cushing's syndrome. The company is gearing up to file an NDA for the therapy in Q1 2021, and the analyst is optimistic about its potential approval.In the LOGICS study, the therapy met its primary endpoint, with SBBP reporting the number of cases of a loss of mean urinary free cortisol (mUFC) response was 54.5% higher among patients who withdrew to placebo versus those who remained on Recorlev. Additionally, there was a rapid reversibility of the Recorlev treatment benefits on cholesterol following the switch to placebo given the 8-week time frame.Meanwhile, in the SONICS study, a significant benefit on mUFC normalization was observed in 30% of the patients and several cardiovascular secondary measures. It should also be noted that none of the 44 patients who were randomized discontinued due to adverse events.Post-LOGICS, we continue to view Recorlev as a differentiated treatment for Cushing's, both compared to off-label ketoconazole and the branded treatment landscape. Management reiterated its confidence in the drug's positioning, based on market research with payors and physicians. Given LOGICS reaffirming the clinical benefit profile observed in SONICS, we are encouraged by its potential to become a mainstay treatment for the disease, Singh explained.Whats more, management is not anticipating an AdComm meeting, and Singh thinks speculation on labeling both from a safety and efficacy perspective may increase prior to the potential PDUFA decision. To this end, he expects more visibility as the NDA filing and acceptance gets closer.Adding to the good news, the launch of Keveyis, the company's FDA-approved treatment for hyperkalemic, hypokalemic and related variants of Primary Periodic Paralysis (an ultra-rare neuromuscular disorder), is progressing well despite the COVID-19 pandemic, according to Singh.With quarterly sales of ~$8.0 million, above our estimate of ~$7.8 million, the growing trajectory of the launch has been encouraging, with additional room for long-term growth highlighted by management. We anticipate more credit could be ascribed to these efforts, following additional updates from life-cycle management strategies, the analyst commented.To this end, Singh rates SBBP shares an Outperform (i.e. Buy) along with a $7 price target. What's in it for investors? Upside potential of 233%. (To watch Singhs track record, click here)All in all, other analysts echo Singhs sentiment. 3 Buys and no Holds or Sells add up to a Strong Buy consensus rating. With an average price target of $8, the upside potential comes in at 272%. (See SBBP stock analysis on TipRanks)Molecular Templates (MTEM)Molecular Templates works to bring the next generation of immunotoxins called engineered toxin bodies (ETBs), which are a novel class of therapeutics with unique biology and a differentiated mechanism of action, to market. Although one of its trials was put on a partial clinical hold, Oppenheimer still believes its long-term growth narrative is strong.The Phase 2 monotherapy trial evaluating lead candidate MT-3724, an ETB that targets CD20 (a B-cell marker that is expressed in 90 percent of B-cell non-Hodgkins lymphoma (NHL)), was placed on partial clinical hold on November 4 following a treatment-related fatality. Management pointed to capillary leak syndrome (CLS) as the cause of the patient death. MT-3724 is being evaluated in three ongoing Phase 2 trials, one monotherapy and two combination.It should be noted that six patients (fatality patient and five treated in DLBCL monotherapy study) received the drug from the same batch, and the first five completed the study without evidence of CLS. Later PK analysis found peak drug exposure (Cmax) 3-4x expected levels in five out of six patients receiving the therapy from the lot. Management plans to investigate what caused the higher Cmax levels.Oppenheimers Kevin DeGeeter told clients, We would look to accumulate MTEM shares into any weakness based on expectation: 1) manufacturing batch inconsistency may have resulted in excess Cmax in limited number of patients providing clear path to remedy the problem, 2) limited read through on immunogenicity from MT-3724 (only product on first-gen ETB backbone) to other pipeline programs, and 3) guarded expectation for commercial opportunity of MT-3724 prior to clinical hold with market opportunity focused primarily on salvage patients.Even if the CLS is determined to be dose-related, the five-star analyst argues there may still be a path forward for MT-3724, as the monotherapy study is evaluating a dose of 50 g/kg while combination studies are assessing a 10-25 g/kg dose.Reflecting another positive, the hold doesnt impact studies for products on the second-generation ETB backbone, including MT-5111, TAK-169 and MT-6402. In addition, the company is set to provide a clinical update on CTX001, a potential treatment for sickle cell disease (SCD).DeGeeter opined, Our investment thesis is based, at least in part, on continued partnering of ETB platform to large biotechs for targets outside of MTEM's core oncology focus. Despite the clinical hold on MT-3724, MTEM remains in active discussions with potential partners. We'd view additional partnering deals as validation of the platform's overall safety profile.In line with his optimistic approach, DeGeeter rates MTEM an Outperform (i.e. Buy) along with a $20 price target. This figure indicates 123% upside potential from current levels. (To watch DeGeeters track record, click here)Are other analysts in agreement? They are. Only Buy ratings, 3 to be exact, have been issued in the last three months. Therefore, the message is clear: MTEM is a Strong Buy. Given the $18.33 average price target, shares could soar 108% in the next year. (See MTEM stock analysis on TipRanks)Provention Bio (PRVB)At the forefront of the autoimmune disease space, Provention Bio is working to improve the lives of patients from all over the world. With the company making significant headway in its efforts to gain approval for one of its therapies, Oppenheimer thinks that now is the time to snap up shares.On November 2, Provention Bio announced that the rolling submission of a BLA to the FDA for regulatory approval of teplizumab for the delay or prevention of clinical type 1 diabetes (T1D) in at-risk individuals had been completed. The submission included chemistry, manufacturing and controls (CMC) and administrative information modules. Now, the FDA has 60 days to review the final submission to determine if the BLA is complete, and then, a PDUFA date will be set.Writing for Oppenheimer, analyst Justin Kim points out that the BLA acceptance will be a key milestone for PRVB. We believe the external validation and review of the application would reflect favorably on the significant efforts Provention has made towards completion of this filing, namely manufacturing scale-up. As a potential advisory committee meeting and regulatory decision offer subsequently greater validation, we have confidence into these events based on teplizumab's established clinical profile.Going forward, Kim believes the therapys commercialization will become a central theme in 2021. Based on teplizumab's 14-day infusion cycle, logistics and physician/patient reception of the modality, especially during the COVID-19 pandemic, are attracting major attention, according to the analyst.Should the candidate ultimately be granted approval, screening and awareness work could reflect a significant tailwind, in Kims opinion. With it already having established meaningful relationships across key T1D advocacy groups and foundations, Provention is well-positioned and connected to build momentum for screening and identification initiatives. The analyst added, While the hurdle to execute successfully is high, reward, in our view, would be commensurate.When it comes to the long-term opportunity, the TN-10 population criteria remains a key area of focus for Kim, as these opportunities may not only expand the market opportunity for teplizumab but also significantly solidify its positioning the treatment paradigm. He also mentions that re-dosing paradigms and adjunctive use post-transplant for teplizumab are other points of strength.Summing it all up, Kim stated, PRVB remains underappreciated in our universe, potentially given macro themes around COVID-19 and intensified focus on momentum names. However, as continued execution carries PRVB through successful regulatory, pre-commercial, and commercial milestones, we believe the shares could enter a period of significant re-rating.Everything that PRVB has going for it prompted Kim to leave his Outperform (i.e. Buy) rating as is. Along with the call, he keeps the price target at $29, suggesting 106% upside potential. (To watch Kims track record, click here)Turning to the rest of the Street, the bulls have it on this one. With 4 Buys and no Holds or Sells assigned in the last three months, the word on the Street is that PRVB is a Strong Buy. At $28.75, the average price target implies 104% upside potential. (See PRVB stock analysis on TipRanks)To find good ideas for stocks trading at attractive valuations, visit TipRanks Best Stocks to Buy, a newly launched tool that unites all of TipRanks equity insights.Disclaimer: The opinions expressed in this article are solely those of the featured analysts. The content is intended to be used for informational purposes only. It is very important to do your own analysis before making any investment.

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Fulgent Genetics to Participate in the Credit Suisse 29th Annual Virtual Healthcare Conference - Yahoo Finance