Category Archives: Molecular Genetics

Three years ago, Government Executive created the Government Hall of Fame with a simple purpose: to recognize those peoplesome world-famous, others virtually unknownwho have made historic advances in achieving governments aim of serving the American people. Since then, a distinguished group of heroes, ranging from Clara Barton to Anthony Fauci, have been inducted into the hall.

This year, were taking the Hall of Fame to a whole new level by combining it with the Federal 100, an annual list prepared by FCW of women and men who personify whats possible in the federal government, especially in the area of information technology. Since Government Executive and FCW have joined forces under the GovExec corporate banner, we decided it was only natural to bring the two prestigious awards programs together in one gala. That event, An Evening of Honors, will take place on May 12 at the Washington National Cathedral.

Here are the members of the Class of 2022 of the Government Hall of Fame:

Francis Collins

An M.D. and a Ph.D. in physical chemistry, Collins devoted much of his life to molecular genetics and made several important discoveries, which led to his appointment in 1993 to lead the agency managing the Human Genome Project. The National Human Genome Research Institute finished its work in 2003. In 2009, President Obama appointed him director of the National Institutes of Health, where he served under three different administrations. He retired at the end of 2021. Collins was awarded the Presidential Medal of Freedom by President George W Bush in 2007.

Patricia Roberts Harris

Harris was the first African-American woman to hold a Cabinet position. She served as secretary of Housing and Urban Development and later headed the Department of Health, Education and Welfare (which became Health and Human Services while she was leading it) in the Carter administration. Earlier in her career, Harris served as ambassador to Luxembourg, the first Black woman to be named to such a post. She arranged for an endowment to be created afterher death in 1985 to provide stipends for Howard University students to participate in public service internships.

Walter Hollis

Hollis served for 56 years at the Defense Department, including 26 years as the deputy undersecretary of the Army for operations research until his retirement at the age of 80 in 2006. He was the highest ranking civil servant in the Army and in charge of Operations Research, Systems Analysis and Operational Test and Evaluation. This made him an extremely influential figure in the system development and procurement process. Collins was highly respected for his willingness to buck the Army hierarchy to avoid costly mistakes.

Shirley Ann Jackson

A renowned theoretical physicist, Jackson is the first African-American woman to receive a doctorate from M.I.T. in any subject. In 1995 she became both the first woman and first African-American to serve as chairperson of the Nuclear Regulatory Commission. During her tenure, she instituted crackdowns on the nuclear power industrys violations and assured NRCs commitment to public health and safety.She was awarded the National Medal of Science, the nations highest honor for contributions in science and engineering, by President Obama in 2016.

Charles McGee

A member of the famed African American fighter pilot unit known as the Tuskegee Airmen, McGee flew a total of 409 combat missions in World War II, the Korean conflict and the Vietnam War. In the process, he won the Distinguished Flying Cross, the Legion of Merit, the Bronze Star, the Air Medal and the Presidential Unit Citation. In 2020, President Trump promoted him from the rank of colonel to brigadier general. McGee died at the age of 102 in 2022.

Ely S. Parker

In 1857, Parker, a Seneca Indian who was educated as both a lawyer and an engineer, was appointed by the Treasury Department to oversee the construction of a customs house in Galena, Ill. There he became acquainted with Ulysses S. Grant, and served on the generals staff during the Civil War. In that role, Parker made the formal copy of the terms of surrender presented at Appomattox. When Grant was elected president, he appointed Parker commissioner of Indian affairs, the first Native American to hold the post.

Elmer Staats

Staats shaped the Government Accountability Office (then known as the General Accounting Office) over four presidential administrations. In a federal career spanning 50 years, he worked in the Bureau of the Budget beginning under President Franklin Roosevelt in 1939. After several promotions, he became comptroller general in 1966. There he broadened GAOs work, conducting high-impact oversight of federal elections, Vietnam War spending, energy, consumer protection and other issues.

Marshalyn Yeargin-Allsop

A pioneer in tracking the prevalence of autism among children, Yeargin-Allsop is chief of the developmental disabilities branch at the Centers of Disease Control and Prevention. After joining the CDC in 1981, she saw the need for better information on developmental disabilities among children. She devised an innovative study to address the issue, leading to a movement to provide better services to children with such disabilities. Yeargin-Allsop was the recipient of the 2018 career achievement award in the Service to America Medals program.

IN GOOD COMPANY

The members of the distinguished class of 2022 join those who have already been inducted into the Government Hall of Fame:

THE SELECTION COMMITTEE

This years inductees into the Government Hall of Fame were chosen by a panel made up of former federal officials and public administration experts:

See more here:
Presenting the Government Hall of Fame Class of 2022 - GovExec.com

Transcript:

Estelamari Rodriguez, M.D., MPH: Hello, and welcome to Cure Expert Connections on exon 20 [EGFR mutations] in non-small cell lung cancer. Im Estelamari Rodriguez, M.D., MPH, and Im associate director of community outreach and co-lead of the Thoracic Disease Group of the University of Miami Sylvester Comprehensive Cancer Center. Id like to welcome Katina Bland. Please introduce yourself, Katina.

Katina Bland: Absolutely. Thank you for having me, Dr. Rodriguez. My name is Katina Bland, and I am pleased to be here today with you. I am a member of the Exon 20 Groups advisory council, and I also am the chair of the Speakers Bureau. I have the privilege of also being the care partner for my beloved husband, Martell Bland, who also was an exon 20 patient with ICAN [International Cancer Advocacy Network]. My husband and I established the educational program called the Martell and Katina Bland Patient Education Program.

Estelamari Rodriguez, M.D., MPH: Thank you for all youve done. I really believe that, we have known about EGFR mutations for a long time, but we are finding that there are subgroups of patients with EGFR mutations that we didnt know how to treat because we didnt understand that all these receptors, all these mutations, can respond differently to treatment. I just wanted to cover a little about the significance of EGFR mutations. EGFR has been well established as a very common driver mutation for non-small cell lung cancer. It accounts for about 20% to 25% of mutations in non-small cell lung cancer. The EGFR [exon] 20 insertion mutation, which we previously had lumped together with all the EGFRs, we have known that patients who have this exon 20 insertion mutation either get missed in the process of diagnosis or they get treated with the existing EGFR targets that were previously used for the common mutations, and they were not responding as well.

There has been a lot of research in exon 20 insertion mutations to understand what would be the best target for these patients. These are seen in 4% to 12% of EGFR-mutated cases. We know that the more common [mutations] that have been tested in the larger trials with the older generation drugs are deletion 19, and L858R on exon 21, but this particular exon 20 insertion is important to recognize because now we have treatment options. Katina, I wanted to ask you a bit about when your husband was diagnosed. How was that discussion of understanding his mutation, and at what point had they figured that out for him?

Katina Bland: Well, we figured that out relatively soon because our oncologist ordered NGS testing for him and that was critical. NGS stands for next-generation sequencing testing. It is absolutely critical that we use that form of testing because that is more accurate than any other form of testing you may have heard of, including something thats known now as PCR [polymerase chain reaction] testing. Most people have heard of that as it relates to the COVID-19 era now. PCR testing leaves quite a bit undiagnosed, maybe 50% of EGFR exon 20 insertion mutations are not caught with PCR testing. It is critical that the platform for testing and the standard needs to be the NGS testing because biomarker testing is the way to go, to have your tissue and your liquid biopsies tested in that method.

Estelamari Rodriguez, M.D., MPH: Im glad to hear that you and your husband had that information at the beginning of the treatment because, unfortunately, many patients either dont get the right test up front or it gets missed because theres an urgency to treat, and patients have been started on chemo [chemotherapy] and immunotherapy, where we know that patients who have driver mutations will be better with targeted therapy. It is very critical to have this at the time of diagnosis. Just to summarize what you said, the NCCN [National Comprehensive Cancer Network], which sets the standards for cancer care in the United States and internationally, has outlined comprehensive molecular testing, molecular profiling of the tumor, as standard. We have about nine targets that today are considered druggable, for which we have a drug, and we have many that are in development. Having as much information as possible about the tumor genetics and the molecular drivers will open doors for treatments that are available today.

Some of the treatments we will discuss today are very recent. If you dont do this test, when the drug gets approved, you will have missed the opportunity. You mentioned something really important; I think its very hard for patients. You get these reports that, even for physicians, are very hard to comprehend. Sometimes they have a summary slide, and you dont know what type of test was done. Was it an immunohistochemistry, which is a very simple expression of a protein? Or was it a PCR, which you mention can be just a single gene evaluation? Or was it an in-depth next-generation sequencing, which is more comprehensive and looks at the whole genome of that tumor? Those are the ones that would allow us to pick specific findings like the EGFR 20 insertion.

Transcript edited for clarity.

More:
Overview of EGFR Exon 20 and Molecular Testing in NSCLC - Curetoday.com

Next generation sequencing (NGS) is a novel procedure for sequencing genomes at low costs and high speed with improved efficiency.The global next generation sequencing market accounted for $3,567 million in 2015, and is anticipated to reach $12,801 million by 2022, registering a CAGR of 19.9% from 2016 to 2022.NGS also known as deep sequencing and parallel sequencing is a technology that has revolutionized molecular biology and genomics research. It is a high throughput, non-Sanger based sequencing method.

Next generation sequencing has made sequencing of genomes very rapid and cost-effective. Through this method, billions of DNA strands can be sequenced efficiently. Next generation sequencing has made it possible to conveniently sequence whole genomes, and analyze various DNA-protein interactions. This technique allows the researcher to focus, study, and interpret deep sequence target regions. Next generation sequencing can be utilized through varied interventions such as oncology, biomarker studies, drug discovery, understanding reproductive health, and personalized genomics.

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Market Statistics:

The file offers market sizing and forecast throughout 5 primary currencies USD, EUR GBP, JPY, and AUD. It helps corporation leaders make higher choices when foreign money change records are available with ease. In this report, the years 2020 and 2021 are regarded as historic years, 2020 as the base year, 2021 as the estimated year, and years from 2022 to 2030 are viewed as the forecast period.

The Centers for Medicare and Medicaid Services report that US healthcare expenditures grew by 4.6% to US$ 3.8 trillion in 2019, or US$ 11,582 per person, and accounted for 17.7% of GDP. Also, the federal government accounted for 29.0% of the total health expenditures, followed by households (28.4%). State and local governments accounted for 16.1% of total health care expenditures, while other private revenues accounted for 7.5%.

This study aims to define market sizes and forecast the values for different segments and countries in the coming eight years. The study aims to include qualitative and quantitative perspectives about the industry within the regions and countries covered in the report. The report also outlines the significant factors, such as driving factors and challenges, that will determine the markets future growth.

Technological advancements in sequencing platforms, surge in applications of next generation sequencing, and increase in genome mapping programs drives the global next generation sequencing market. In addition, rise in awareness pertaining to next generation sequencing and rise in investment in research, development, and innovation supplement the market growth. However, lack of skilled professionals, ethical & legal limitation related to next generation sequencing, and standardization concerns in sequencing procedures impede the market growth. Furthermore, use of cloud computing as a potential data management service and untapped emerging economies offer lucrative opportunities for the market players.

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The next generation sequencing market is segmented based on product, application, technology, end user, and geography. Based on product, the market is segmented into consumables, platforms, and services. The consumables product segment is further classified on the basis of sample preparation consumables and other consumables. The sample preparation consumables are further segmented into DNA fragmentation, end repair, A-Tailing & size selection, library preparation & target enrichment and quality control. The platform NGS product segment is bifurcated into HiSeq, MiSeq, Ion Torrent, SOLiD, Pacbio Rs II & Sequel System, and other sequencing platforms. The services segment is divided into sequencing services and data management. In the NGS product segment, consumables occupied dominant share in 2015, and the segment is expected to maintain this trend during the forecast period. This is attributed to the fact that they are widely used throughout the sample preparation process and other pre-requisite steps of NGS.

Based on application, this market is bifurcated into biomarkers & cancer, diagnostics, reproductive health, personalized medicine, agriculture & animal research, and other applications. The biomarkers & cancer application was the highest revenue contributor in 2015, while the personalized medicine segment is anticipated to grow at the highest rate. The growth for this segment is due to increase in investment in R&D throughout the world along with surge in awareness about NGS applications in precision medicine. Based on technology, the next generation sequencing technology market is classified into sequencing by synthesis, ion semiconductor sequencing, sequencing by ligation, pyrosequencing, single molecule real time sequencing, and other technologies. Sequencing by synthesis technology held the greatest share in 2015 and this trend is estimated to continue throughout the study period as this technology allows both short and long insert paired end reads for high resolution genome sequencing and structural variation detection, sequence assembly & others respectively..

Geographically, this market is analyzed across North America, Europe, Asia-Pacific, and LAMEA. North America accounted for the largest market share in the next generation sequencing market in 2015, and is expected to retain its dominance throughout the forecast period. This is primarily attributed to the higher buying power, availability, and applications that favor the utilization of NGS in this region. There is also an increase in agreements and collaborations between different market players and health centers to promote and utilize NGS in this region. However, Asia-Pacific is expected to emerge as a lucrative area with maximum growth potential, owing to the improvement in R&D facilities, available disposable income, and rapidly developing economic conditions.

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Product development is the key strategy adopted by market players. The report provides a comprehensive analysis of the key players that operate in the global next generation sequencing market.

KEY PLAYERS PROFILED

Illumina, Inc.Thermo Fisher Scientific, Inc.Pacific Biosciences of California, Inc.Beijing Genomics InstituteQiagen N.V.454 Life Sciences Corporation (Roche Holding AG)Agilent Technologies, Inc.Perkinelmer, Inc.Genomatix GmbHPierianDx.

A release on June 8th, 2021, by the Bureau and Economic Analysis and U.S. The Census Bureau reports the recovery of the U.S. market. The report also described the recovery of U.S. International Trade in July 2021.In April 2021, exports in the country reached $300 billion, an increase of $13.4 billion. In April 2021, imports amounted to $294.5 billion, increasing by $17.4 billion. COVID19 is still a significant issue for economies around the globe, as evidenced by the year-over-year decline in exports in the U.S. between April 2020 and April 2021 and the increase in imports over that same period of time. The market is clearly trying to recover. Despite this, it means there will be a direct impact on the Healthcare/ICT/Chemical industries.

KEY MARKET BENEFITS

The study provides an in-depth analysis of the global next generation sequencing market along with the current trends and future estimations to elucidate the imminent investment pockets.The report presents quantitative analysis of the market for the period of 2014-2022 to enable stakeholders to capitalize on the prevailing market opportunities.Extensive analysis of the market based on product type assists in understanding the trends in the industry.Key market players along with their strategies are thoroughly analyzed to understand the competitive outlook of the industry

Next generation sequencing Market Key Segments:

By Product

ConsumablesSample Preparation ConsumablesDNA Fragmentation, End Repair, A-Tailing and Size SelectionLibrary Preparation & Target EnrichmentQuality ControlOther ConsumablesPlatformsHiSeqMiSeqIon TorrentSOLiDPacbio Rs II and Sequel SystemOther Sequencing PlatformsServicesSequencing ServicesRNA SequencingWhole Exome SequencingWhole Genome SequencingTargeted SequencingChip SequencingDe Novo SequencingMethyl SequencingData Management ServicesNGS Data Analysis ServicesNGS Data Analysis Software & WorkbenchesNGS Storage, Management and Cloud Computing Solutions

By Application

DiagnosticsBiomarkers and CancerReproductive HealthPersonalized MedicineAgriculture and Animal ResearchOther Applications

By Technology

Sequencing by SynthesisIon Semiconductor SequencingSequencing by LigationPyrosequencingSingle Molecule Real Time SequencingOther Technologies

By End User

Academic & Government Research InstitutesPharmaceutical CompaniesBiotechnology CompaniesHospitals & Clinics

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By Geography

North AmericaU.S.CanadaMexicoEuropeGermanyFranceUKItalySpainRest of EuropeAsia-PacificJapanChinaAustraliaIndiaSouth KoreaTaiwanRest of Asia-PacificLAMEABrazilTurkeySaudi ArabiaSouth AfricaRest of LAMEA

Other players in the value chain include (profiles not included in the report)

Eurofins ScientificGatc Biotech AGMacrogen, Inc.Oxford Nanopore Technologies, Ltd.Bio-Rad Laboratories, Inc.DNASTAR, Inc.Biomatters Ltd.Partek Inc.New England Biolabs, Inc.Myriad Genetics, Inc.

Table of Content:

Key Questions Answered in the Market Report

How did the COVID-19 pandemic impact the adoption of by various pharmaceutical and life sciences companies? What is the outlook for the impact market during the forecast period 2021-2030? What are the key trends influencing the impact market? How will they influence the market in short-, mid-, and long-term duration? What is the end user perception toward? How is the patent landscape for pharmaceutical quality? Which country/cluster witnessed the highest patent filing from January 2014-June 2021? What are the key factors impacting the impact market? What will be their impact in short-, mid-, and long-term duration? What are the key opportunities areas in the impact market? What is their potential in short-, mid-, and long-term duration? What are the key strategies adopted by companies in the impact market? What are the key application areas of the impact market? Which application is expected to hold the highest growth potential during the forecast period 2021-2030? What is the preferred deployment model for the impact? What is the growth potential of various deployment models present in the market? Who are the key end users of pharmaceutical quality? What is their respective share in the impact market? Which regional market is expected to hold the highest growth potential in the impact market during the forecast period 2021-2030? Which are the key players in the impact market?

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Next Generation Sequencing (NGS) Market Analysis by Growth Developments, Competitive Research Outlook and Strategies 2021 to 2030 Queen Anne and...

Precision Medicine MarketReport mainly improves market size,and provide detailed product mapping and investigation of various market scenarios. Our expert analysts provide a thorough analysis and breakdown of the market presence of key market leaders. We strive to stay updated with the recent developments and follow the latest company news related to the industry players operating in the global Precision Medicine market. This helps us to comprehensively analyze the individual standing of the companies as well as the competitive landscape. Our vendor landscape analysis offers a complete study to help you gain the upper hand in the competition.

The rising incidence of chronic and unusual diseases triggers the need to build technically innovative methods for accelerated medical data aggregation and review. The bioinformatics program helps in data processing by rendering successful therapeutic approaches. As a consequence, the growing volume of data in the healthcare sector would fuel demand for bioinformatics, raising competition in the industry for precision medicines

Development of cost-effective research approaches for genomics and molecular genetics, and growing the usage of extensive data are some of the main drivers that drive the market demand.

Precision MedicineMarket Size USD 60.33 billion in 2019, Precision Medicine Market Growth CAGR of 10.3%, Precision Medicine Industry trends High incidence of cancer.

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The creation of bioinformatics tools and applications would promote the production of immunotherapy and thus boost the study of microbiomes, thus advancing the area of precision medicine. Besides, the development of high-throughput technologies such as next-generation sequencing and microarray will pave the way for market growth in bioinformatics, which will further drive market demand in the coming years.

Based on technology, drug discovery is projected to grow with a CAGR of 9.8% in the forecast period, due to the growing emphasis of bio-pharmaceutical players on developing precision medicine for treating diseases, including cancer, which will further boost the market growth.

The diagnostic companies expected to grow with a CAGR of 10.4% in the forecasted period, owing to a wide variety of applications for which big players in the precision medicine industry are engaged in various investment programs.

The oncology application is the major contributor to the Precision Medicine Market. The segment is growing due to the rising frequency and prevalence of cancer worldwide, which will intensify the demand for precision medicine as an essential form of therapy coupled with developing tailored treatments for patients with cancer dependent on their genetic makeup over traditional chemotherapy.

North America dominated the market for Precision Medicine in 2019. The regions consistent focus on cost-effective and innovative procedures that are adopted in the area is driving the market.

Key participants include Biocrates Life Sciences, Tepnel Pharma Services, Menarini Silicon Biosystems, NanoString Technologies, Quest Diagnostics, Qiagen, Teva Pharmaceutical, Eagle Genomics, Novartis, and Pfizer, among others.

The report further offers a complete value chain analysis along with an analysis of the downstream buyers and upstream raw materials. The study focuses on global trends, regulatory frameworks, and macro- and micro-economic factors. The report also provides an extensive analysis of the segment and sub-segmented expected to dominate the market over the projected period. The report offers a forecast estimation of the market with regards to the analysis of the market segmentation, including product type, end-user industries, application spectrum, and other segments.

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For the purpose of this report, Emergen Research has segmented into the global Precision Medicine Market on the basis of technology, end-use, application, and region:

Competitive Outlook:

The global Precision Medicine market is highly consolidated due to the presence of a large number of companies across this industry. These companies are known to make hefty investments in research and development projects. Also, they control a considerable portion of the overall market share, thus limiting the entry of new players into the sector. The global Precision Medicine market report studies the prudent tactics undertaken by the leading market players, such as partnerships and collaborations, mergers & acquisitions, new product launches, and joint ventures.

Market Taxonomy:

Chapter 1: Methodology & Scope

Chapter 2:

Executive Summary

Chapter 3:

Industry Insights

Chapter 4:

Regional Landscape

Chapter 5:

Company Profile

Key questions addressed in the report:

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Precision Medicine Market Study Report Based on Size, Shares, Opportunities, Industry Trends and Forecast to 2027 - Digital Journal

April 29, 2022

A genetic study of 2,155 purebred and mixed-breed dogs combined with 18,385 owner surveys has challenged existing notions about dog breed stereotypes and personality types.The study identified 11 locations along the canine genome that were strongly associated with behavior, none of which were specific for breed, suggesting that these personality traits predate modern canine breeding by humans.

Using a really powerful model, these findings provide compelling support for the fact that complex traits, like behavior or personality, may have some genetic contribution, but that contribution is distributed across so many genes with really tiny effects," said Arizona State University School of Life Sciences Assistant Professor Noah Snyder-Mackler, who contributed to the study in a collaboration with investigators at the UMass Chan Medical School, includingElinor Karlsson, who led the study that was published in a recent issue of Science. "This means that while we can predict how biddableBiddability refers to a dog's ability to respond to human direction. a dog is on average, we will do a pretty terrible job predicting the biddability of a single dog based on their genotype, and definitely not their breed. It points to the fact that much of these complex traits are strongly impacted by the lived experiences of each individual.

Noah Snyder-Mackler

Canine behavioral disorders are often proposed as a natural model for human neuropsychiatric disorders. Compulsive disorders, for instance, are often observed to manifest similarly in both humans and dogs. Thanks to the power of current DNA sequencing technology and the close relationship between pet and owner, canine genome-wide association studies (GWAS) have the potential to identify unique genetic areas in the dog genome that could lead to new insights into similar genes in humans. Karlsson and colleagues show that large-scale GWAS in dogs can yield genetic loci associated with behavioral traits.

Although friendliness is the trait we commonly associate with golden retrievers, what we found is that the defining criteria of a golden retriever what makes a golden retriever a golden retriever are its physical characteristics, the shape of its ears, the color and quality of its fur, its size; not whether it is friendly, said Karlsson, associate professor of molecular medicine at UMass Chan Medical School.

While genetics plays a role in the personality of any individual dog, the specific dog breed is not a good predictor of those traits, explained Karlsson, who is also the director of the Vertebrate Genomics Group at the Broad Institute of the Massachusetts Institute of Technology and Harvard University. A dogs personality and behavior are shaped by many genes as well as their life experiences. This makes them difficult traits to select for through breeding. For the most part, pure breeds are only subtly different from other dogs. A golden retriever is only marginally more likely to be more friendly than a mixed-breed or another purebred dog, such as a dachshund.

The story of how modern-day dog breeds emerged is a relatively short one in evolutionary terms, contrasted against the history of dog domestication from prehistoric wolves. Genetic research pegs the change from wolf to dog at about 10,000 to 15,000 years ago. Humans didnt begin intentionally breeding dogs until roughly 2,000 years ago, when they were being selected for work roles such as hunting, guarding and herding. It wasnt until the Victorian era in the 1800s that humans began selecting dogs consistently for the physical appearance and aesthetic traits that today we commonly associate with modern breeds.

Yet modern dog breeds are often credited with characteristics and temperaments (bold, affectionate, friendly, trainable) that correlate to their ancestral function (herding, guarding or hunting). Likewise, the breed ancestry of dogs is assumed to be predictive of temperament and behavior. DNA tests are even marketed as tools for dog owners to learn about a pets individual personality. However, there is a lack of genetic studies linking behavioral tendencies to ancestry or other genetic, heritable factors.

By pairing genome-wide association mapping technologies with pet owner surveys obtained through Darwins Ark, an open-source database of owner-reported canine traits and behaviors, Karlsson and first author Kathleen Morrill, a PhD student in the Morningside Graduate School of Biomedical Sciences at UMass Chan, explored the complicated relationship between modern canine breeds and behavioral characteristics.

Genome-wide association studies (GWAS) are an approach used in genetics research to try to associate specific areas of variation in the human genome that align with certain phenotypes. Taking whole genome sequences from hundreds of thousands of people with the same disease, for instance, researchers look for common genetic variations among these people to pinpoint broad areas in the genome that may be predictive or causative for specific diseases.

Karlsson, Morrill and their colleagues applied this same strategy to correlate areas of the canine genome with certain behavioral traits or characteristics. Pet owners who participate in Darwins Dogs provide scientists with saliva samples from their dogs. Researchers run whole genome sequencing on these samples to generate a robust genetic data set for investigation. Additionally, for this study, owners filled out 12 short surveys totaling 117 questions about their pets behaviors and physical traits. Combined, this data provides the basis for scientists to associate genetics with owner-reported behavior.

Given a large enough sample size, GWAS are a really powerful tool for learning about genetics, said Morrill. We only get that size by looking at all dogs not just purebred dogs, but mixed-breed dogs too. We compare all these DNA sequences computationally, using complex algorithms, to identify areas of differences and commonalities that might be of interest.

Karlsson and Morrill collected more than 2,000 canine genomes and 200,000 survey answers through Darwins Dogs. Because of existing stereotypes about dog behavior and breeds, Karlsson and Morrill designed the study to account for possible owner bias, in part, by establishing standard definitions for reporting and rating canine behavioral traits such as biddability (a dog response to human direction), dog-human sociability (a dogs comfort with people, including strangers) and toy-directed motor patterns (a dogs interest and interaction with toys), among others. Physical and aesthetic trait standards were pulled from those published by the American Kennel Club.

Genetic research pegs the change from wolf to dog at about 10,000 to 15,000 years ago. Photo courtesy of Noah Snyder-Mackler

Behavioral data was analyzed across owner-reported breeds and genetically detected breed ancestries. The results of these tests, which included data from 78 breeds, showed that while breed explained some minor variation in behavior, its contributions were relatively small (9%). For certain behavioral traits, such as toy-directed motor patterns, age was a better predictor of behavior: Younger dogs were more likely to score higher in this category. For specific survey items, such as lifts leg to urinate, a dogs sex was the best predictor of behavior. Physical traits like coat color were more than five times more likely to be predicted by breed than behavioral traits.

Additionally, investigators failed to find behaviors that were exclusive to any one breed. Even in Labrador retrievers, which had the lowest propensity for howling, 8% of owners reported their Labradors sometimes howl. Likewise, while 90% of greyhound owners reported that their dogs never bury their toys, three owners described greyhound dogs as frequent buriers.

Complementing the survey analysis of breeds to measure breed-behavioral propensities, the researchers also leveraged the genetic ancestry of highly mixed-breed dogs to test whether behavior is heritable in a breed-dependent manner. In some cases, heritable behavioral traits like biddability are somewhat more likely to correlate with breed, even if mixed a few generations back. In the case of purebred dogs, ancestry can make behavioral predictions somewhat more accurate. For less heritable, less breed-differentiated traits, like agonistics threshold, which measures how easily a dog is provoked by frightening, uncomfortable or annoying stimuli, breed is almost useless as a predictor of behavior.

A comparison of dog genomes was performed to identify genetic variations tracking along breed, as well as along individual physical and behavioral traits. Karlsson and Morrill identified 11 locations on the dog genome strongly associated with behavioral differences, none of which were specific for breed, and another 136 suggestively associated with behavior. The genetic differences between breeds such as golden retrievers, Chihuahuas, Labrador retrievers, German shepherd dogs and others, primarily affected genes that control coat color, fur length and other physical traits far more than breed differences affected behavioral genes.

Overall, Karlsson and Morrill found that behavioral characteristics were influenced by multiple factors, including environment and individual genetics, but that modern breed classification played a modest role in the outcome.

The majority of behaviors that we think of as characteristics of specific modern dog breeds have most likely come about from thousands of years of evolution from wolf to wild canine to domesticated dog, and finally to modern breeds, said Karlsson. These heritable traits predate our concept of modern dog breeds by thousands of years. Each breed inherited the genetic variation carried by those ancient dogs, but not always at exactly the same frequencies. Today, those differences show up as differences in personality and behavior seen in some, but not all, dogs from a breed.

For ASU's Snyder-Mackler, the study represents a significant opening salvo demonstrating the power of using modern genomic tools to study companion animals to gain new insights intothe causes and consequences of variation in the social environment, from the molecular to the organismal levels.

"This study would not have been possible without the Herculean efforts to generate a massive behavioral dataset and combine that with whole genome sequencing of almost 2,000 dogs without spending an arm and a leg. This was achieved by using some really cool computational approaches to try and gain as much information from each dog with as little sequencing as possible, which we found worked better than the most common approach to genotyping microarrays," said Snyder-Mackler.His lab focuses on studies that allow him to probe questions central to human health, aging and evolutionary biology, often using companion animals or field animal research.

Next up is another huge citizen science canine effort now underway called the Dog Aging Project, where, according to Snyder-Mackler, "We are trying to understand what makes dogs tick (and age). Our lab uses molecular tools to try and identify how age and the environment interact to alter the dog immune system.So this new study has provided a really powerful roadmap to carrying out future studies in larger cohorts, which Dr. Karlsson is leading as part of the Dog Aging Project."

The project promises to explore what exactly are "dog years," other than the conventional wisdom of one dog year equal to about seven human years. What is known is that big dogs typically age more rapidly, an estimated 10 times faster than humans. By contrast, little dogs have a longer life span and can often live up to 20 years old.

Given that dogs share the human environment and have a sophisticated health care system but are much shorter-lived than people, they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy life span.

Snyder-Mackler and collaborators outlined the goals of their efforts in a recent Nature paper. The Dog Aging Project is an interdisciplinary, open-data, community science project that consists of a team of more than 100 staff, students, faculty and veterinarians from more than 20 academic institutions, along with over 30,000 canine participants and their owners.

The study investigators also include Kate E. Creevy, Joshua M. Akey, Matt Kaeberlein and Daniel E. L. Promislow, and afford great opportunities for Snyder-Mackler lab ASU graduate students, such as Brianah Mccoy and Layla Brassington, who are helping to lead efforts to better understand the role of the environment, diet, drugs and the epigenome on dog aging.

"I wanted to work at the interface of the public and academic science, and the Dog Aging Project is a great way to do that. So I hopped on the project," said Mccoy, who is a nontraditional student and among the first ASU Online students to pursue a PhD, having spent some time at the National Institute of Aging and Harvard Medical School prior to joining the Snyder-Mackler lab. Mccoy is particularly interested in diet and longevity, and is studying asubset of participating dogs that will be selected to be part of a new clinical study to explore the potential of the drug rapamycin to improve health.

Brassington is a master's degree student now in the molecular and cellular biology program at ASU who hopes to graduate in winter 2022.

"I read about the Dog Aging Project, and I was super excited to find a project that looked at health-related changes due to the environment," she said. She will be examining the environmental air quality and pollution levels of ozone, carbon monoxide and others nationwide.

Both are now working hard with the citizen science effort, generating experiments, and hope to publish their first data from the Dog Aging Project later this year.

The Dog Aging Project is actively looking for more participants. If you are a dog owner wanting to get involved, you can learn more at dogagingproject.org.

Written by JimFessenden,UMass Chan Medical School Communications, with contributions from Joe Caspermeyer, ASU.

Top photo: Kristoff, one of Sparky's Service Dogs, keeps watch at the feet of his handler Taylor Randle on Hayden Lawn on Sept. 8, 2016, as they hang out with other puppies being trained by students. Photo by Charlie Leight/ASU News

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Dog study shows there's a lot more to behavior than just breed - ASU News Now

A forest fire broke out in Katraj Ghat on Friday night. (Express Photo/Pavan Khengre) A PETA India member takes part in street theatre style graphic demonstration in Fergusson college road to show how animals are abused (caged, Shackled, force-fed chemicals and electrocuted) and killed in laboratories while experimented on during World Week For Animals in Laboratories on Friday. New Pimpri Chinchwad Police Commissioner Ankush Shinde (right) takes over on Thursday. (Express photo by Rajesh Stephen) A wrestling match is in progress during a village fair kaka bhairavnath god festival at Kharadi gaon on Wednesday. (Express) RSS Chief Mohan Bhagwat along with Industrialist Baba Kalyani and Sunita Kalyani during the inauguration of Dr. Dada Gujar mother and child hospital on Friday at Malwadi Hadapsar. (Express photo/ Ashish Kale) A Memorandum of Understanding (MoU) was signed between Maharashtra University of Health Sciences, Nashik and Indian Drug Research Association and Laboratory Pune for establishment of Late Dr.K C Gharpure Genetics & Molecular Biology Laboratory for Cancer Diagnosis and Clinical research, under the guidance of Lieutenant General Madhuri Kanitkar (Retd.), PVSM, AVSM, VSM, on Friday at Gharpure trust bungalow, Shivajinagar. (Express photo/Ashish Kale) MP Prakash Javdekar, Maharashtra opposition leader Devendra Fadnavis and MLA and State BJP chief Chandrakant Patil during the release of Deepstambh, a book written on Lt. Prof. Farande at Bhandarkar Institute on Tuesday. Express Photograph by Arul Horizon. 19/04/2022, Pune. A forest fire broke out in Katraj Ghat on Friday night. (Express Photo/Pavan Khengre) Passanger face dificulties due to PMPML sudden strike. The services of Pune Mahanagar Parivahan Mahamandal Limited (PMPML) were hit on Friday morning as private contractors providing services to the transport body went on strike without prior notice. (Express/Pavan Khengre) Restaurants, Marriage lawns and Banquet halls have been demolished during PMCs Anti-encroachment drive on Wednesday on DP road from Rajaram bridge to Mhatre bridge area. (Express/Ashish Kale)

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Thomas Insel, who directed the National Institute of Mental Health (NIMH), is busy promoting his new book, which carries the odd title of Healing: Our Path from Mental Illness to Mental Health. It is a curious title and a curious endeavor, given that his thirteen years in charge of the nations mental health research produced such uniformly dismal results. When the New York Times recently interviewed him about the book, the headline spoke of him as the Nations Psychiatrist. If he is that, the outlook for those with serious mental illness is a dark one.

Having overseen the expenditure of more than twenty billion dollars during his term of office, Insel confesses that none of that money has produced any clinical advances that help patients, and that is an understatement. And yet he has the chutzpah to promote himself as having the answer to the countrys mental health problemswhich turns out to be more of the same singular emphasis on neuroscience and genetics that characterized research at NIMH under his leadership. As the clich would have it, repeating the same behavior that has proved counterproductive in the past is the very definition of insanity.

NIMH was born in the aftermath of the Second World War, a conflict that showed, once again, that modern industrial warfare is inimical to mental health, with hundreds of thousands of troops succumbing to combat-related mental disorders. For the first three decades of its existence, the new institute pursued an eclectic approach to the problems posed by major mental illness, funding social and behavioral research alongside biological and pharmacological studies. That broad-spectrum approach was abruptly abandoned under Reagans presidency. Research that suggested connections between mental illness and social factors was distinctly unwelcome politically, and faced with threats to the organizations funding, the leaders of NIMH embraced a research agenda that focused narrowly on biological psychiatry.

In many ways, Insels time as director of NIMH thus followed what had been its standard approach for more than two decades. But the shift from what one president of the American Psychiatric Association called a bio-psycho-social approach to the problem of mental illness to a bio-bio-bio approach was particularly marked under Insels leadership, and has been continued under his successor, Joshua Gordon (whose own research prior to his appointment was on neural activity in mice). Funding genetics and neuroscience has become the Institutes mantra, regardless of its failure to deliver positive results.

Since the appearance of the third edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM) in 1980, American psychiatry has been fixated on defining mental illness on a purely symptomatic basis. The presence of a certain number of symptoms in a tick-the-boxes fashion is supposed to result, in a purely mechanical fashion, in a diagnosis of schizophrenia, major depression, or bipolar disorder (not to mention a host of other mental disorders). It was an approach that, in the face of a parade of embarrassing studies that showed the profession could not agree on diagnosis, tried to ensure inter-rater agreement while quite deliberately ignoring the issues of whether psychiatrists labels corresponded to real diseases in nature.

When the American Psychiatric Association contemplated a fifth revision of this elephantine manual at the turn of the century, its proponents boasted that the new edition would break from this model. With the backing of the neuroscientific research NIMH had been funding under Steven Hyman, the director who preceded Thomas Insel, and with Insels renewed commitment to this line of research, the expectation was that DSM-5 would transform psychiatrys whole approach to diagnosis, using neuroscience to classify mental disorders on the basis of what caused each of the mental disorders it distinguished.

But the science that would permit this simply didnt (and doesnt) exist. We remain almost wholly in the dark about the causes of mental illness and the task force charged with constructing the new manual was forced back on the same symptomatic approach the profession had embraced in 1980. None of the hugely expensive neuroscience NIMH had funded had shown what the etiology of mental illness was. It was more than slightly ironic, then, that it was Insel who took the lead in denouncing the new DSM as a monstrosity. In interviews at the time, he voiced his disgust in no uncertain terms.

On April 29, 2013, a week before DSM-5 was officially published, Insel complained publicly that the final product involves mostly modest alterations of the previous edition. That was not intended as a compliment. In the rest of medicine, he suggested, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. . . symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best course of treatment. DSM-5 set itself up as psychiatrys Bible, he reflected, but Biology never read that book, and Patients with mental disorders deserve better.

It was simply astonishing, he averred, that psychiatrists should practice in this fashion. Most of his psychiatric colleagues actually believe [that the diseases they diagnose using the DSM] are real. But theres no reality. These are just constructs. There is no reality to schizophrenia or depression. Henceforth, Insel announced, NIMH would alter its approach to studying mental illness, since we cannot succeed if we use DSM categories as the gold standardThat is why NIMH will be re-orienting its research away from DSM categories. In particular, he suggested, we might have to stop using terms like depression and schizophrenia, because they are getting in our way, confusing things.

One sees what motivated such a statement (and it must have been greeted with glee by the Scientologists), but the phrasing was distinctly unfortunate. The labels may need to go (with who knows what consequences for psychiatrys reputation). Yet the distress and pathology those traditional labels seek to capture will not disappear with them.

Insels comments incited a furor, with both medical and scientific journals and the mass media hastening to report his skepticism. He had hoped to use the controversy to advance his own pet project, something he called Research Domain Criteria (or RDoC), an attempt to install a research framework based on biology, and more particularly on a nebulous notion that related mental illness to a mysterious something called brain circuits. But RDoC was not ready for prime time. No other entity engaged in psychiatric research endorsed his hobby horse, and it has faced fierce criticism since Insel stepped down as NIMH director in 2015.

In 1886, the American alienist Pliny Earle had lamented that In the present state of our knowledge, no classification of insanity can be erected on a pathological basis, for the simple reason that, with but slight exceptions, the pathology of the disease is unknown Hencewe are forced to fall back upon the symptomatology of the disease. Nearly a century and a half later, and despite billions of dollars devoted to neuroscience, nothing, it seems, had substantially changed.

The other major hobby-horse Insel funded during his years as director was the study of genetics. It seemed, on the surface, a promising bet. Dating all the way back to the late nineteenth century, psychiatrists had speculated that mental illness had strong genetic roots. Till the closing years of the twentieth century, such claims rested on evidence from family studies, most notably studies of fraternal and monozygotic twins. These were often plagued by methodological problems and rendered suspect by the ideological commitments of some of the central researchers, but better-conducted studies toward the end of the twentieth century and a greater distance from a prior association with Nazi researches led many biological psychiatrists to expect that imminent scientific advances would uncover strong genetic links to major mental illnesses.

The discovery of the PCR (polymerase chain reaction) technique in 1983, which allowed researchers to make millions to billions of copies of a specific DNA sample, was the first of two major breakthroughs on this front. A year after Insel became NIMH director in 2002, this breakthrough was followed by another major scientific advance, the decoding of the human genome. Taken together, these developments fueled expectations that the genetic underpinnings of disorders like schizophrenia and bipolar disorder would soon be uncovered, and NIMH poured resources into such studies.

Confounding researchers expectations, the expected genetic connections have essentially failed to materialize. In the words of two leading psychiatrists, Rudolf Uher and Michael Rutter, molecular genetic studies of psychiatric disorders have done a lot to find very little. In fact, in the era of genome-wide association studies, psychiatric disorders have distinguished themselves from most types of physical illness by the absence of strong genetic associations. The field as a whole, as the eminent geneticist Kenneth Kendler puts it, has had to absorb some painful lessons and acknowledge that despite our wishing it were so, individual gene variants of large effect appear to have a small to non-existent role in the etiology of major psychiatric disorders.

Given the results of nearly twenty years of work, it is now clear that there is no Mendelian gene or set of genes that explain schizophrenia. As that reality became apparent, researchers more and more relied upon an approach called genome-wide association studies (or GWAS). It is an approach that makes no assumption about where genetic associations might lie, but simply scours hundreds of thousands of sites looking for possible linkages and does so for a whole range of psychiatric disorders. The result has been a muddle, one that has disappointed the hopes and expectations of these researchers that a clear picture of the genetics of mental disorder would appear. Studies examining many tens of thousands of patients and controls have failed to show clear genetic links, and even aggregating hundreds of genetic sites, each of which are individually of small effect, explains less than eight percent of the observed variance. Worse still, an individual can harbor many of these genetic variations without ever developing mental illness. Various genes had been hypothesized to be particularly likely to be linked to particular forms of mental disorder. But these so-called candidate genes have been shown to have no closer relationship to the development of schizophrenia than random sets of control genes. That has proved to be as true for bipolar disorder as for major depressive disorder and schizophrenia.

Indeed, these GWAS studies have produced a still more confounding result than these. For rather than revealing one set of vulnerabilities for schizophrenia and others for bipolar disorder or major depressive disorder, most such risks as it identified seemed common to a whole range of mental disorders. The high degree of genetic correlationamong attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia, the international Brainstorm Consortium reported, provides important evidence that current clinical boundaries do not reflect distinct underlying pathogenic processes. . . This suggests a deeply interconnected nature for psychiatric disorders.

In the abstract, negative scientific findings can be seen as just as valuable as positive ones, acting as correctives to ones original hypotheses and suggesting the need to reappraise research strategies. That is not the message Dr. Insel seems to take from these results. If anything, he suggests, the United States should double down on brain research. His successor as director of NIMH, Joshua Gordon, seems to be of the same mind, insisting in the pages of the New York Times that researchers, having identified hundreds of relevant genes, are starting to understand those genes in the context of the brain, promising in a decade or two to provide a pathway to better therapies.

Psychiatry has been offering promissory notes of this sort for well over a hundred years, and has consistently dishonored them. There are ample grounds for skepticism about these latest assurances from Dr. Gordon and the man who dubs himself Americas psychiatrist. The more sensible conclusion to draw from the absence of progress either in understanding the etiology of major mental disorders or in advancing therapeutics is that putting all ones eggs in the biological basket is a dangerous gamble. If genetics were the royal road to comprehending where mental illness comes from, its effects would have to be exceedingly powerful, and the research of the past twenty years makes that an extremely difficult position to sustain.

Quite unexpectedly, under the weight of the genetic evidence, existing distinctions between disorders are crumbling, and the notion that such artificial constructs identify distinct diseases has become ever-more implausible. The enlightenment genetic researchers have produced threatens to undermine the standing and legitimacy of the diseases that psychiatrists had believed in for more than a centuryconcepts that have woven themselves deeply into the ways the lay public had been taught to view mental illness. To acknowledge that the distinctions between schizophrenia and bipolar disorder may be spurious, and that those constructions might have to be abandonedbut with what to put in their places?threatens the very foundations of the psychiatric professions claims to expertise. If such fundamental building blocks of the psychiatric universe crumble on close inspection, what is left?

Two years after denouncing DSM-5, Insel stepped down from his position as director of NIMH. In the aftermath, he gave an interview to an online MIT magazine. He was asked to summarize his accomplishments while heading the institute, and responded insouciantly, I spent 13 years at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that I realize that while I think I succeeded in getting lots of really cool papers published by cool scientists at fairly large costI think $20 billionI dont think we moved the needle in reducing suicide, reducing hospitalizations, improving recovery for the tens of millions of people who have mental illness.

The current situation is even more dire than the one Insel conjures up here. People with serious mental illness live, on average, fifteen to twenty-five years less than the rest of us, and that gap seems to be widening, not narrowing. While genetics and neuroscience have flourished within the confines of universities, their therapeutic payoff has been minimal or non-existent. This may change, but it is equally possible that those sponsoring these programs may tire of funding investigations that show few signs of producing practical advances. Meanwhile, advances in psychopharmacology since the introduction of the first antipsychotics and antidepressants in the 1950s have essentially stalled, and the major drug companies have largely abandoned research in this area. In the words of the former head of neuroscience at Eli Lilly and Amgen, Psychopharmacology is in crisis. The data are in, and it is clear that a massive experiment has failed: despite decades of research and billions of dollars invested, not a single mechanistically novel drug has reached the psychiatric market in more than 30 years. Steven Hyman, Insels predecessor as the head of NIMH and now director of the Stanley Center for Psychiatric Research at Harvard has made the same point: the discovery of chlorpromazine and related compounds in the 1950s seemed to promise both therapeutic progress and significant probes of brain function. Looking back, the picture is painfully different. The efficacy of psychotherapeutic drugs plateaued by 1955. And that efficacy is limited indeed, with none of the drugs helping much with the devastating negative symptoms of schizophrenia, and the drugs side-effects remaining as troublesome as ever.

In the face of this damning record accrued during the period he oversaw the countrys basic research into the causes and remedies for serious mental illness, Insel is unrepentant. He and his successor continue to fixate on biology and biology alone. In my judgment, that is a profound error, and it threatens to undermine still further the prospects for progress in the mental health arena. The foolish monism that NIMH has embraced has meant that the phenomenological and social dimensions of mental illness have all but disappeared as questions worthy of serious and sustained attention. That is an imbalance that has had profoundly negative effects on psychiatry, and more importantly, on the prospects of advancing the clinical care of patients. Given Insels role in these developments, I suggest that his is the last voice we should be listening to when we ponder how to deal with the devastation mental illness brings in its train.

***

Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussionbroadly speakingof psychiatry and its treatments. The opinions expressed are the writers own.

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Thomas Insel and the Future of the Mental Health System - Mad In America - Mad in America

USC professor outlines the characteristics of a longevity diet based on a range of nutrition research from studies in laboratory animals to epidemiological research in human populations.

Professor Valter Longo leads a review of research in animals and humans to identify how nutrition affects aging and a healthy lifespan.

According to University of Southern California (USC) Leonard Davis School of Gerontology Professor Valter Longo, examining a variety of nutrition research from studies in laboratory animals to epidemiological research in human populations offers a clearer picture of the ideal diet for a longer, healthier life.

Published on April 28, 2022, in the journal Cell, in a research article that includes a literature review, Longo and coauthor Rozalyn Anderson of the University of Wisconsin describe the longevity diet, a multi-pillar approach based on studies of various aspects of diet, from food composition and calorie intake to the length and frequency of fasting periods.

We explored the link between nutrients, fasting, genes, and longevity in short-lived species, and connected these links to clinical and epidemiological studies in primates and humans including centenarians, Longo said. By adopting an approach based on over a century of research, we can begin to define a longevity diet that represents a solid foundation for nutritional recommendations and for future research.

Longo and Anderson reviewed hundreds of studies on nutrition, diseases, and longevity in laboratory animals and humans and combined them with their own studies on nutrients and aging. The analysis included popular diets such as the restriction of total calories, the high-fat and low-carbohydrate ketogenic diet, vegetarian and vegan diets, and the Mediterranean diet.

Professor Valter Longo. Credit: University of Southern California/Stephanie Kleinman

The article also included a review of different forms of fasting, including a short-term diet that mimics the bodys fasting response, intermittent fasting (frequent and short-term), and periodic fasting (two or more days of fasting or fasting-mimicking diets more than twice a month). In addition to examining lifespan data from epidemiological studies, the team linked these studies to specific dietary factors affecting several longevity-regulating genetic pathways shared by animals and humans that also affect markers for disease risk. These include levels of insulin, C-reactive protein, insulin-like growth factor 1, and cholesterol.

The authors report that the key characteristics of the optimal diet appear to be moderate to high carbohydrate intake from non-refined sources, low but sufficient protein from largely plant-based sources, and enough plant-based fats to provide about 30 percent of energy needs. Ideally, the days meals would all occur within a window of 11-12 hours, allowing for a daily period of fasting. Additionally, a 5-day cycle of a fasting or fasting-mimicking diet every 3-4 months may also help reduce insulin resistance, blood pressure, and other risk factors for individuals with increased disease risks.

Longo described what a longevity diet could look like in real life: Lots of legumes, whole grains, and vegetables; some fish; no red meat or processed meat and very low white meat; low sugar and refined grains; good levels of nuts and olive oil, and some dark chocolate.

The next step in researching the longevity diet will be a 500-person study taking place in southern Italy, Longo said. The longevity diet bears both similarities and differences to the Mediterranean-style diets often seen in super-aging Blue Zones, including Sardinia, Italy; Okinawa, Japan; and Loma Linda, California. Common diets in these communities known for a high number of people age 100 or older are often largely plant-based or pescatarian and are relatively low in protein. But the longevity diet represents an evolution of these centenarian diets, Longo explained, citing the recommendation for limiting food consumption to 12 hours per day and having several short fasting periods every year.

In addition to the general characteristics, the longevity diet should be adapted to individuals based on sex, age, health status, and genetics, Longo noted. For instance, people over age 65 may need to increase protein in order to counter frailty and loss of lean body mass. Longos own studies illustrated that higher protein amounts were better for people over 65 but not optimal for those under 65, he said.

For people who are looking to optimize their diet for longevity, he said its important to work with a healthcare provider specialized in nutrition on personalizing a plan focusing on smaller changes that can be adopted for life, rather than big changes that will cause an harmful major loss of body fat and lean mass, followed by a regain of the fat lost, once the person abandons the very restrictive diet.

The longevity diet is not a dietary restriction intended to only cause weight loss but a lifestyle focused on slowing aging, which can complement standard healthcare and, taken as a preventative measure, will aid in avoiding morbidity and sustaining health into advanced age, Longo said.

Reference: Nutrition, longevity and disease: From molecular mechanisms to interventions by Valter D. Longo and Rozalyn M. Anderson, 28 April 2022, Cell.DOI: 10.1016/j.cell.2022.04.002

The article, Nutrition, longevity and disease: from molecular mechanisms to interventions, was co-authored by Professor Rozalyn M. Anderson of the University of Wisconsin School of Medicine and Public Health. This work was supported in part by awards to Longo, including the Associazione Italiana per la Ricerca sul Cancro (IG#17605 and IG#21820.), the BC161452 grant of the Breast Cancer Research Program (US Department of Defense), and the National Institute on Aging-National Institutes of Health grants P01 AG055369. Anderson is supported by NIH-NIA RF1AG057408, R01AG067330, R01AG074503, Veterans Administration Merit Award BX003846, and by Impetus Grants and the Simons Foundation. This work was made possible by support from the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.

Longo is the founder of and has an ownership interest in L-Nutra; the companys food products are used in studies of the fasting-mimicking diet. Longos interest in L-Nutra was disclosed and managed per USCs conflict-of-interest policies. USC has an ownership interest in L-Nutra and the potential to receive royalty payments from L-Nutra. USCs financial interest in the company has been disclosed and managed under USCs institutional conflict-of-interest policies.

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Do You Want a Long Healthy Lifespan? The Characteristics of a Longevity Diet - SciTechDaily

Sidney Altman was born on May 7, 1939, in Montreal, the second son of Victor and Ray (Arlin) Altman. His mother was a textile worker; his father ran a grocery store.

The family had little money, but Dr. Altman, in an autobiographical sketch for the Nobel Institute, credited his parents with setting a good example that stayed with him for the rest of his life. It was from them, he wrote, that I learned that hard work in stable surroundings could yield rewards, even if only in infinitesimally small increments.

Dr. Altman became fascinated by science as a boy first by news of the detonation of the first atomic bomb, when he was 6 years old, and then by seeing the periodic table of the elements, which, he wrote, gave him a sense of the elegance of scientific theory and its predictive power.

He had intended to enroll at McGill University in his hometown, but he changed course when he was accepted by the Massachusetts Institute of Technology. He studied physics at M.I.T., but in his final semester, out of curiosity, he took an introductory course in molecular biology and found it compelling.

After M.I.T., he spent 18 months in a graduate physics program at Columbia University, but he said he was not really happy there. He wanted to be an experimental scientist and there was no opportunity at Columbia, so he quit and went back to Canada.

The next summer, he was offered a job writing about science for an institute in Boulder, where he could also take summer courses.

One night he wound up at a party talking to George Gamow, a well-known physicist, cosmologist and writer. Dr. Altman explained that he was dissatisfied with physics but fascinated with biophysics. Dr. Gamow suggested that he go to the University of Colorado in Denver, which had a good biophysics department.

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Sidney Altman, Who Stumbled on a Breakthrough in Genetics, Dies at 82 - The New York Times

1Department of Virology and Molecular Biology, National Animal Health Diagnostic and Investigation Center, Sebeta, Oromia, Ethiopia; 2Department of Veterinary Laboratory Technology, Ambo University, Ambo, Oromia, Ethiopia

Correspondence: Morka Dandecha, Department of Veterinary Laboratory Technology, Ambo University, Ambo, Oromia, Ethiopia, Tel +251-910309600, Email [emailprotected]

Background: Newcastle disease is a major viral disease of poultry. The virus is a major problem for chickens in Ethiopia and there is a scarcity of updated information on the virological and molecular status of confirmation of Newcastle disease outbreak cases in the country.Methods: Newcastle disease outbreaks were investigated from February 2021 to October 2021 in central Ethiopia to isolate and detect the virus by cell culture and reverse transcriptase PCR. A total of 44 pooled tissue specimens were sampled from sick and recently dead chickens showing typical clinical signs of Newcastle disease. Virus isolation were performed using DF-1 cells and detection of the virus was done by real-time PCR.Results: Out of 44 collected tissue samples, 38.63% (17/44) were positive on DF-1 cells. The result shows 17 of the clinically sick and dead chickens were positive for the virus by reverse transcriptase polymerase chain reaction. Based on the sample type, 54.54% (6/11) of the brain samples, 36.36% (4/11) of the intestines, 54.54% (6/11) of lung and trachea, 9% (1/11) of pooled liver, kidney, heart, and spleen samples were positive. Viruses were isolated in the proportions 37.5% (6/16), 25% (2/8), 50% (2/4), 25% (1/4), 50% (2/4) and 50% (4/8) from Sebeta, Bishoftu, Sululta, Nifas Silk, Kolfe and Yeka, respectively.Conclusion: This study showed that Newcastle disease is a major viral disease causing death of chickens in the study area. Therefore, any control approach should focus on the appropriate characterization of the virus strain causing the outbreak in the study area.

Keywords: central Ethiopia, chickens, isolation, Newcastle diseases virus, RT-PCR

Ethiopia is gifted with numerous livestock populations. The total poultry population in the country is 56.06 million.1 This poultry population contains both exotic and indigenous chickens. They are widely distributed in rural and peri-urban areas where they play important roles in income generation, food production and social interactions.2 The production of these chickens is affected by different obstacles such as disease, management problems and genetics of the chickens. The primary cause of the reduction of production and productivity of the chickens is a viral disease.3 Newcastle disease is the most common viral disease of these birds and is often responsible for various disorders, including gastrointestinal, nervous system, respiratory system and non-gastrointestinal disorders.4,5 Newcastle disease virus (NDV) is an RNA virus with a negative sense and composed of six genes, which are generated through RNA editing.68

Newcastle disease virus affects a widespread range of poultry globally.9 It is a major cause of economic harm worldwide.10 In many undeveloped countries, it is widespread and causes great problems in poultry farming.11,12 In Ethiopia, the disease was first reported in 197213 and it can cause up to 80% death in poultry farms. The virus affects the nervous, respiratory and digestive systems.14,15 The clinical signs and severity of NDV can vary depending on the strain of the virus. According to variation in strains, the death of chickens in a flock ranges from 90100%.14,16,17 There is recurrent occurrence of the disease in commercial poultry farms in different parts of Ethiopia. But, confirmations of outbreaks are uncommon and inadequate data exist on the type of virus responsible for these outbreaks. Generally, information about the isolation and molecular detection of the virus from chickens is insufficient in Ethiopia in general and in the study area in particular. Therefore, the objectives of this study were the isolation and molecular detection of Newcastle disease virus from outbreak cases in the study area.

The study was performed from February 2021 to October 2021 in a selected area of central Ethiopia (Bishoftu, Addis Ababa, Sululta and Sebeta) where NDV outbreaks occurred in commercial poultry farming system, as indicated in Table 1.

Table 1 Detail About the Study Areas

Chickens of both sexes and all ages managed under commercial poultry farm systems were included. Chickens that had experienced an outbreak of Newcastle disease were used for outbreak investigation.

A cross-sectional study design was performed during an active outbreak to isolate and detect NDV from suspected outbreak cases. The study focused on suspected cases of ND. Before the beginning of any outbreaks, proper information channels from concerned bodies regarding the outbreaks were collected through different contact addresses. Depending on the reported outbreak case of ND, a field investigation was conducted at the area of outbreaks, clinical information was recorded and appropriate samples were collected from chickens showing signs suggestive of ND infection.

Representative tissue specimens were collected from different organs. About 44 tissues from ill and recently dead chickens showing distinctive clinical signs of ND were sampled. Necropsy examination was performed and affected tissues, i.e. brain, lung and trachea, pooled tissue of liver, spleen, kidney and heart, and intestines were sampled from the same chickens. Collected samples were submitted to the laboratory using an icebox and stored at 80C for further processing.

Tissue specimens were processed by chopping them into small pieces and grinding with sterile sand in mortar and pestle at the virus isolation laboratory. Four tissue specimens, i.e. four brain, four lung and trachea, four pooled tissue of spleen, kidney, liver and heart and four intestines that were sampled from the same outbreak case were pooled to increase the concentration of virus. The suspension of tissue samples (10% (w/v)) were mixed with sterile phosphate buffer saline (PBS) which contains penicillin (100 IU/mL) and streptomycin (1000 g/mL). The suspension was filled into a sterile Falcon tube and centrifuged at 3000 rpm, +4C for 20 minutes. The supernatants were collected and filtered with 0.45 L then 0.1 mL of the samples were inoculated onto confluent DF-1 cells which were cultured on 24-well plates and maintained with DMEM containing 2% calf serum and incubated at 37C for one week with daily follow-up. The cytopathic effect (CPE) was determined based on a characteristic of NDV on the cell line. Samples that did not show a cytopathic effect were continued up to the third passage. The samples that revealed characteristics of the cytopathic effect were harvested for molecular detection of the virus.

Viral RNA extraction was conducted on all positive cell culture samples using Qiagen viral RNA mini kit according to the manufacturers instructions. To detect NDV in the isolated samples the specific prime designed M-gene of Newcastle disease virus was used and specific Forward Primer M+4100- 5-AGT GAT GTG CTC GGA CCT TC-3, Reverse Primer M-4220- 5CCT GAG GAG AGG CAT TTG CTA-3, Probe M+4100- 5FAM- TTC TCT AGC AGT GGG ACA GCC -TAMRA 3 were used to detect M-gene based NDV. Master mix reagents per 25 L reaction were used from Qiagen one-step RT-PCR kit: 5 L PCR buffer (5x), 0.5 L of each primer forward and reverse (20 pmol), 1 L of probe (6 pmol), 0.8 L of deoxynucleotide triphosphates, 1.25 L of 25 mM MgCl2, 0.5 L of 13.3 u/L of RNase inhibitor (Promega), 1 L Qiagen enzyme mix, 6.45 L Rnase free water and 8 L of extracted RNA. Real-time PCR was performed using an Applied Biosystems 7500 fast real-time PCR machine. For amplification, reverse transcription at 50C for 30 min and at 95C for 15 min was followed by 40 cycles of denaturation at 94C for 10 s, annealing at 52C for 30 s and extension at 72C for 10 s.18 Probe-based fluorescent dye signals were calculated at the extension step of each cycle, and the cycle threshold (Ct) for each sample was observed. The samples that have a Ct value <35 were positive and samples that have >35 Ct value were negative for M genes based on rRT-PCR.19

The common clinical signs suggesting Newcastle disease recorded in this study were twisting of the head (Figure 1A), depression (Figure 1B), paralysis of wings (Figure 1C) and paralysis of legs and twisting of the head (Figure 1D). During outbreak investigation of 9 poultry farms a total of 13,000 chickens reared under semi-intensive and intensive poultry farms were examined for Newcastle disease. Out of 13,000 chickens observed 2443 chickens were showing clinical signs and 1233 chickens had died. Overall rates of 18.8%, 9.5% and 50.5% morbidity, mortality and case fatality, respectively were observed in the study area (Table 2).

Table 2 Status of NDV in the Study Area

Figure 1 Clinically diseased chickens suspected of NDV infection. Symptoms include (A) twisting of the head, (B) depression, (C) paralysis of the wings and (D) paralysis of the legs and twisting of the head.

The NDV infected chickens were examined and gross pathological changes were recorded. Postmortem examination of recently dead and humanely killed chickens infected with NDV showed hemorrhagic ulcer in the intestine wall (Figure 2A), enlarged spleen (Figure 2B), degeneration and multifocal necrosis in the liver (Figure 2C) and pin-point hemorrhages in proventriculus (Figure 2D).

Figure 2 Gross pathological lesions of NDV-infected chickens. (A) intestine of infected chicken showed hemorrhagic foci that appeared dark red from external view, (B) enlarged spleen, (C) degeneration and multifocal necrosis in the liver, (D) proventriculus of infected chickens showing ecchymotic hemorrhages.

The present study revealed that among 44 pooled tissue samples of naturally infected chickens, NDV was isolated from 17 (38.63%), as indicated in Table 3. Cytopathic effect was observed in all inoculated samples with clear, small plaques on the DF-1 cell line early from the 3rd day of inoculation. An initial cytopathic effect was observed as small round cells which reflected the light. The foci and syncytia formation occur after a time which causes cell death and detachment from tissue culture plate (Figure 3B arrows).

Table 3 Number of Samples Collected and Cultured Positive Samples from Different NDV Suspected Outbreak Investigations of Chickens

Figure 3 ND virus grown on DF-1 cells. (A) uninfected monolayer of DF-1 cell and (B) DF-1 cells infected by NDV showing cytopathic effect (arrows).

In this finding, the virus was isolated from different tissue organs collected from field outbreaks. The descriptions of the isolates by sample type are presented in the Table 4.

Table 4 Newcastle Disease Isolation Rate from Tissue Samples of Chickens

A total of 17 isolate samples of RNA were extracted and tested by reverse transcriptase-polymerase chain reaction (RT-PCR) for M gene-based NDV and all of the isolates were positive by RT-PCR. The samples and control RT-PCR amplification curve are indicated in Figure 4B. Ct values ranging from 20.734.00 of positive samples, 22.0 ct value of positive control and no ct value for negative control were observed by Applied Biosystems 7500 PCR machine and are indicated in Figure 4B.

Figure 4 Amplification plot result of rRT-PCR. (A) shows rRT-PCR positive samples result with ct value and (B) shows positive and negative controls.

Newcastle disease is a severe viral infection existing worldwide including Ethiopia. The current study was performed for isolation and molecular detection of the virus from active outbreaks.

The current study revealed that distinctive clinical signs of NDV such as twisting of the head and neck, paralysis of wings and legs, depression, ruffling of feather and gasping were observed in the affected chickens. This result was in agreement with the results of previous studies.2022 A previous report18 shows enlargement and inflammation of eyes, diarrhea, dizziness and lack of appetite were reported which is a slight variation from this finding. However, the clinical signs of Newcastle disease vary depending on the host organs affected.

From a total of 13,000 chickens observed during outbreaks, 2443 were identified as diseased chickens and 1233 had died. The overall morbidity, mortality and case fatality rates observed in infected chickens in the study area were 18.7%, 9.5% and 50.5%, respectively. According to one study21, 21.21% mortality was reported from chickens exposed to outbreaks of ND. Similarly, Saidu and Abdu23 reported a 97.7% mortality rate which is higher than the present finding. This variation might be associated with the immunity status of the chickens and strain of the virus.

Necropsy was conducted on infected chickens with NDV and gross pathological changes were recorded. Postmortem finding of infected chickens with NDV showed hemorrhagic ulcer in the intestine wall, enlarged spleen, degeneration and multifocal necrosis in the liver and pin-point hemorrhages in proventriculus. These results were in line with some other reports.21,2426 Hemorrhagic laryngotracheitis, congestion and edema of the lungs have been reported27; the reported lesion is different from the present study, and this variation may be due to different strains of NDV that can affect different organs of the chickens. In this study, the observed lesions were indicative of ND depending on the observed gross pathological lesions. Nevertheless, pathogenicity examinations are obligatory to be conducted to estimate the virulence of the virus.7

The current study showed that from 44 pooled specimens of necropsy examination, NDV was isolated from 38.63% (17/44) samples using DF-1 chicken fibroblast cell line. Isolation of virulent NDV from infected chickens confirms the presence of NDV in the study area. The isolated virus from clinical samples reveals characteristics of NDV cytopathic effect, i.e. rounding of cells, formation of syncytia and cell death. Relatively large number of syncytia was found in the isolates which is related with the virulence of the virus. This finding was in close agreement with previous reports16,27 which found that NDV was isolated from suspected birds and the same CPE characteristics were reported in their findings. In the present study, the virus was isolated from different organs of infected chicken samples, with 54.54% from the brain, 54.54% from the lung and trachea, 36.36% from the intestine and 9% from pooled liver, kidney, spleen and heart. According to one report16, NDV was isolated 100% from the spleen, brain, trachea and colon by using chicken embryo fibroblast cell, which is higher than the present study. This variation may be due to the virus load in those organs during infection.

Reverse transcriptase real-time PCR was used, due to its high sensitivity, high specificity, efficiency and mostly its capacity for detecting the virus. Newcastle disease virus was detected from pooled tissue of 17/44 (38.63%) examined chickens. All 17 isolated viruses were positive by reverse transcriptase real-time PCR. The amplification of matrix gene from isolate samples confirmed the chickens were exposed to Newcastle disease. This finding was in agreement with a report28 which isolated and identified the virus from suspected Newcastle disease in Ethiopia by reverse transcriptase real-time PCR.

The present study revealed that NDV was isolated and detected from active outbreaks in the study areas. It is the primary viral disease in poultry farms in these areas and causes significant economic losses. The current finding also showed that NDV is the most important viral infection causing the death of birds managed in the different production systems in the study areas. Fast identification and isolation of the virus are very important for the prevention and control of the infection. The occurrence of ND in poultry farms of the study area should be considered as the causative agent of poultry death in the study areas. Therefore, further molecular characterization is required to identify the strain of virus circulating in the study area. Awareness training for chicken farmers about the impacts of Newcastle disease infection and regular strategic vaccination are essential.

The data obtained from field and laboratory results were recorded, coded and entered into a Microsoft Excel spreadsheet. Statistical analysis was performed by Statistical Package for Social Sciences (SPSS) version 20. Descriptive statistics including frequencies and percentages were used and results were summarized using tables.

An ethical clearance certificate for this research was obtained from National animal health diagnostic and investigation center (Reference ARSERC/EC010/2020).

The authors would like to thank the national animal health diagnostic and investigation center for full laboratory access and opportunity during the laboratory work.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

The authors report no conflicts of interest in this work.

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