An international team of researchers from Bristol and China has prepared biocompatible protocells that generate nitric oxide gas a known reagent for blood vessel dilation - that when placed inside blood vessels expand the biological tissue.

In a new study published today in Nature Chemistry, Professor Stephen Mann and Dr Mei Li from Bristols School of Chemistry, together with Associate Professor Jianbo Liu and colleagues at Hunan University and Central South University in China, prepared synthetic protocells coated in red blood cell fragments for use as nitric oxide generating bio-bots within blood vessels.

Coating the protocells led to increased levels of biocompatibility and longer blood circulation times. Critically, the team trapped an enzyme inside the protocells which, in the presence of glucose, produced hydrogen peroxide. This was then used by haemoglobin in the protocell membrane to degrade the drug molecule hydroxyurea into nitric oxide gas.

When placed inside small pieces of blood vessels, or injected into a carotid artery, the protocells produced sufficient amounts of nitric oxide to initiate the biochemical pathways responsible for blood vessel vasodilation.

Although at a very early stage of development, the new approach could have significant benefits in biomedicine, cellular diagnostics and bioengineering.

Professor Stephen Mann, Co-Director of the Max Planck Bristol Centre for Minimal Biology at Bristol, said: This work could open up a new horizon in protocell research because it highlights the opportunities for creating therapeutic, cell-like objects that can directly interface with living biological tissues.

Associate Professor Jianbo Liu at Hunan University added: We are all really excited about our proof-of-concept studies but there is a lot of work still to be done before protocells can be used effectively as bio-bots in therapeutic applications. But the potential looks enormous.

Enzyme-mediated nitric oxide production in vasoactive erythrocyte membrane-enclosed coacervate protocellsby Liu S, Zhang Y, Li M, Xiong L, Yang X, He X, Wang K, Liu J and Mann S. in Nature Chemistry.

Max Planck Bristol Centre for Minimal BiologyThe Max Planck-Bristol Centre for Minimal Biology, a partnership between the University of Bristol and the Max Planck Society for the Advancement of Science (MPG) in Germany, aims to advance the future of health and medicine by understanding the fundamental nature of life.

Minimal biology is a new emerging field at the interface between the physical and life sciences. It aims to design and build artificial cells, minimal genomes, virus-like nanodevices and new cellular scaffolds, and seeks to understand the foundations of life and how it arose from non-living matter.

Led by Bristol ProfessorsImre Berger(Biochemistry),Stephen Mann(Chemistry) andDek Woolfson(Chemistry and Biochemistry), and ProfessorsJoachim Spatz(Heidelberg),Tanja Weil(Mainz) andPetra Schwille(Munich) at Max Planck Institutes in Germany, the Centre is based in theSchool of Chemistryat the University of Bristol. A paramount objective is to train early career scientists in minimal biology and biodesign.

What is Minimal Biology?Minimal biology is an emerging research field at the interface between the physical and life sciences. It applies principles and methods from the former to construct new systems that mimic or augment living cells and organs.

About Bristol BioDesign InstituteBristol BioDesign Institute(BBI) is the University of Bristol's Specialist Research Institute for synthetic biology. With wide-ranging applications from health to food security, BBI combines pioneering synthetic biology approaches with understanding biomolecular systems to deliver the rational design and engineering of biological systems for useful purposes.

This is delivered through multidisciplinary research which brings together postgraduate and postdoctoral researchers, academics, policy makers and industry, whilst also engaging the public with emerging solutions to global challenges.

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November: Biofriendly protocells | News and features - University of Bristol

Embryology

Prioritising IVF treatment in the post COVID 19 era: a predictive modelling study based on UK national data – DocWire News

November 25, 2020 medical

Hum Reprod. 2020 Nov 23:deaa339. doi: 10.1093/humrep/deaa339. Online ahead of print.

ABSTRACT

STUDY QUESTION: Can we use prediction modelling to estimate the impact of coronavirus disease 2019 (COVID 19) related delay in starting IVF or ICSI in different groups of women?

SUMMARY ANSWER: Yes, using a combination of three different models we can predict the impact of delaying access to treatment by 6 and 12 months on the probability of conception leading to live birth in women of different age groups with different categories of infertility.

WHAT IS KNOWN ALREADY: Increased age and duration of infertility can prejudice the chances of success following IVF, but couples with unexplained infertility have a chance of conceiving naturally without treatment whilst waiting for IVF. The worldwide suspension of IVF could lead to worse outcomes in couples awaiting treatment, but it is unclear to what extent this could affect individual couples based on age and cause of infertility.

STUDY DESIGN, SIZE, DURATION: A population based cohort study based on national data from all licensed clinics in the UK obtained from the Human Fertilisation and Embryology Authority Register. Linked data from 9589 women who underwent their first IVF or ICSI treatment in 2017 and consented to the use of their data for research were used to predict livebirth numbers.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Three prediction models were used to estimate the chances of livebirth associated with immediate treatment versus a delay of 6 and 12 months in couples about to embark on IVF or ICSI.

MAIN RESULTS AND THE ROLE OF CHANCE: We estimated that a 6-month delay would reduce livebirths by 0.4%, 2.4%, 5.7%, 9.5% and 11.8% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, while corresponding values associated with a delay of 12 months were 0.9%, 4.9%, 11.9%, 18.8% and 22.4%, respectively. In women with known causes of infertility, worst case (best case) predicted chances of livebirth after a delay of 6 months in women aged <30, 30-35, 36-37, 38-39 and 40-42 years varied between 31.6% (35.0%), 29.0% (31.6%), 23.1% (25.2%), 17.2% (19.4%) and 10.3% (12.3%) for tubal infertility and 34.3% (39.2%), 31.6% (35.3%) 25.2%(28.5%) 18.3% (21.3%), and 11.3% (14.1%) for male factor infertility. The corresponding values in those treated immediately were 31.7%, 29.8%, 24.5%, 19.0% and 11.7% for tubal factor and 34.4%, 32.4%, 26.7%, 20.2% and 12.8% in male factor infertility. In women with unexplained infertility the predicted chances of livebirth after a delay of 6 months followed by one complete IVF cycle were 41.0%, 36.6%, 29.4%, 22.4% and 15.1% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, compared to 34.9%, 32.5%, 26.9%, 20.7% and 13.2% in similar groups of women treated without any delay. The additional waiting period, which provided more time for spontaneous conception, was predicted to increase the relative number of babies born by 17.5%, 12.6%, 9.1%, 8.4% and 13.8%, in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively. A 12-month delay showed a similar pattern in all subgroups.

LIMITATIONS, REASONS FOR CAUTION: Major sources of uncertainty include the use of prediction models generated in different populations and the need for a number of assumptions. Although the models are validated and the bases for the assumptions are robust, it is impossible to eliminate the possibility of imprecision in our predictions. Therefore, our predicted live birth rates need to be validated in prospective studies to confirm their accuracy.

WIDER IMPLICATIONS OF THE FINDINGS: A delay in starting IVF reduces success rates in all couples. For the first time, we have shown that while this results in fewer babies in older women and those with a known cause of infertility, it has a less detrimental effect on couples with unexplained infertility, some of whom conceive naturally whilst waiting for treatment. Post COVID 19, clinics planning a phased return to normal clinical services should prioritise older women and those with a known cause of infertility.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, Merck KGaA, Guerbet and iGenomics. SB is Editor-in-Chief of Human Reproduction Open. None of the other authors declare any conflicts of interest.

PMID:33226080 | DOI:10.1093/humrep/deaa339

Embryology

Future Visioning the Role of CRISPR Gene Editing: Navigating Law and Ethics to Regenerate Health and Cure Disease – IPWatchdog.com

November 25, 2020 medical

As society adjusts to a new world of social distance and remote everything, rapid advancements in the digital, physical, and biological spheres are accelerating fundamental changes to the way we live, work, and relate to one another. What Klaus Schwab prophesized in his 2015 book, The Fourth Industrial Revolution, is playing out before our very eyes. Quantum computing power, a network architecture that is moving function closer to the edge of our interconnected devices, bandwidth speeds of 5G and beyond, natural language processing, artificial intelligence, and machine learning are all working together to accelerate innovation in fundamental ways. Given the global pandemic, in the biological sphere, government industrial policy drives the public sector to work hand-in-glove with private industry and academia to develop new therapies and vaccines to treat and prevent COVID-19 and other lethal diseases. This post will envision the future of gene editing technologies and the legal and ethical challenges that could imperil their mission of saving lives.

There are thousands of diseases occurring in humans, animals, and plants caused by aberrant DNA sequences. Traditional small molecule and biologic therapies have only had minimal success in treating many of these diseases because they mitigate symptoms while failing to address the underlying genetic causes. While human understanding of genetic diseases has increased tremendously since the mapping of the human genome in the late 1990s, our ability to treat them effectively has been limited by our historical inability to alter genetic sequences.

The science of gene editing was born in the 1990s, as scientists developed tools such as zinc-finger nucleases (ZFNs) and TALE nucleases (TALENs) to study the genome and attempt to alter sequences that caused disease. While these systems were an essential first step to demonstrate the potential of gene editing, their development was challenging in practice due to the complexity of engineering protein-DNA interactions.

Then, in 2011, Dr. Emmanuelle Charpentier, a French professor of microbiology, genetics, and biochemistry, and Jennifer Doudna, an American professor of biochemistry, pioneered a revolutionary new gene-editing technology called CRISPR/Cas9. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and Cas9 stands for CRISPR-associated protein 9. In 2020, the revolutionary work of Drs. Charpentier and Doudna developing CRISPR/Cas9 were recognized with the Nobel Prize for Chemistry. The technology was also the source of a long-running and high-profile patent battle between two groups of scientsists.

CRISPR/Cas9 for gene editing came about from a naturally occurring viral defense mechanism in bacteria. The system is cheaper and easier to use than previous technologies. It delivers the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, cutting the cells genome at the desired location, allowing existing genes to be removed and new ones added to a living organisms genome. The technique is essential in biotechnology and medicine as it provides for the genomes to be edited in vivo with extremely high precision, efficiently, and with comparative ease. It can create new drugs, agricultural products, and genetically modified organisms or control pathogens and pests. More possibilities include the treatment of inherited genetic diseases and diseases arising from somatic mutations such as cancer. However, its use in human germline genetic modification is highly controversial.

The following diagram from CRISPR Therapeutics AG, a Swiss company, illustrates how it functions:

In the 1990s, nanotechnology and gene editing were necessary plot points for science fiction films. In 2020, developments like nano-sensors and CRISPR gene editing technology have moved these technologies directly into the mainstream, opening a new frontier of novel market applications. According to The Business Research Company, the global CRISPR technology market reached a value of nearly $700 million in 2019, is expected to more than double in 2020, and reach $6.7 billion by 2030. Market applications target all forms of life, from animals to plants to humans.

Gene editings primary market applications are for the treatment of genetically-defined diseases. CRISPR/Cas9 gene editing promises to enable the engineering of genomes of cell-based therapies and make them safer and available to a broader group of patients. Cell therapies have already begun to make a meaningful impact on specific diseases, and gene editing helps to accelerate that progress across diverse disease areas, including oncology and diabetes.

In the area of human therapy, millions of people worldwide suffer from genetic conditions. Gene-editing technologies like CRISPR-Cas9 have introduced a way to address the cause of debilitating illnesses like cystic fibrosis and create better interventions and therapies. They also have promising market applications for agriculture, food safety, supply, and distribution. For example, grocery retailers are even looking at how gene editing could impact the products they sell. Scientists have created gene-edited crops like non-browning mushrooms and mildew-resistant grapes experiments that are part of an effort to prevent spoilage, which could ultimately change the way food is sold.

Despite the inability to travel and conduct face-to-face meetings, attend industry conferences or conduct business other than remotely or with social distance, the investment markets for venture, growth, and private equity capital, as well as corporate R&D budgets, have remained buoyant through 2020 to date. Indeed, the third quarter of 2020 was the second strongest quarter ever for VC-backed companies, with 88 companies raising rounds worth $100 million or more according to the latest PwC/Moneytree report. Healthcare startups raised over $8 billion in the quarter in the United States alone. Gene-editing company Mammouth Biosciences raised a $45 million round of Series B capital in the second quarter of 2020. CRISPR Therapeutics AG raised more in the public markets in primary and secondary capital.

Bayer, Humboldt Fund and Leaps are co-leading a $65 million Series A round for Metagenomi, a biotech startup launched by UC Berkeley scientists. Metagenomi, which will be run by Berkeleys Brian Thomas, is developing a toolbox of CRISPR- and non-CRISPR-based gene-editing systems beyond the Cas9 protein. The goal is to apply machine learning to search through the genomes of these microorganisms, finding new nucleases that can be used in gene therapies. Other investors in the Series A include Sozo Ventures, Agent Capital, InCube Ventures and HOF Capital. Given the focus on new therapies and vaccines to treat the novel coronavirus, we expect continued wind in the sails for gene-editing companies, particularly those with strong product portfolios that leverage the technology.

Despite the projected growth in market applications and abundant investment capital, there is a danger that legal and ethical concerns related to genetic research could put the brakes on gene-editing technologies and product programs emanating therefrom. The possibility of off-target effects, lack of informed consent for germline therapy, and other ethical concerns could cause government regulators to put a stop on important research and development required to cure disease and regenerate human health.

Gene-editing companies can only make money by developing products that involve editing the human genome. The clinical and commercial success of these product candidates depends on public acceptance of gene-editing therapies for the treatment of human diseases. Public attitudes could be influenced by claims that gene editing is unsafe, unethical, or immoral. Consequently, products created through gene editing may not gain the acceptance of the government, the public, or the medical community. Adverse public reaction to gene therapy, in general, could result in greater government regulation and stricter labeling requirements of gene-editing products. Stakeholders in government, third-party payors, the medical community, and private industry must work to create standards that are both safe and comply with prevailing ethical norms.

The most significant danger to growth in gene-editing technologies lies in ethical concerns about their application to human embryos or the human germline. In 2016, a group of scientists edited the genome of human embryos to modify the gene for hemoglobin beta, the gene in which a mutation occurs in patients with the inherited blood disorder beta thalassemia. Although conducted in non-viable embryos, it shocked the public that scientists could be experimenting with human eggs, sperm, and embryos to alter human life at creation. Then, in 2018, a biophysics researcher in China created the first human genetically edited babies, twin girls, causing public outcry (and triggering government sanctioning of the researcher). In response, the World Health Organization established a committee to advise on the creation of standards for gene editing oversight and governance standards on a global basis.

Some influential non-governmental agencies have called for a moratorium on gene editing, particularly as applied to altering the creation or editing of human life. Other have set forth guidelines on how to use gene-editing technologies in therapeutic applications. In the United States, the National Institute of Health has stated that it will not fund gene-editing studies in human embryos. A U.S. statute called The Dickey-Wicker Amendment prohibits the use of federal funds for research projects that would create or destroy human life. Laws in the United Kingdom prohibit genetically modified embryos from being implanted into women. Still, embryos can be altered in research labs under license from the Human Fertilisation and Embryology Authority.

Regulations must keep pace with the change that CRISPR-Cas9 has brought to research labs worldwide. Developing international guidelines could be a step towards establishing cohesive national frameworks. The U.S. National Academy of Sciences recommended seven principles for the governance of human genome editing, including promoting well-being, transparency, due care, responsible science, respect for persons, fairness, and transnational co-operation. In the United Kingdom, a non-governmental organization formed in 1991 called The Nuffield Council has proposed two principles for the ethical acceptability of genome editing in the context of reproduction. First, the intervention intends to secure the welfare of the individual born due to such technology. Second, social justice and solidarity principles are upheld, and the intervention should not result in an intensifying of social divides or marginalizing of disadvantaged groups in society. In 2016, in application of the same, the Crick Institute in London was approved to use CRISPR-Cas9 in human embryos to study early development. In response to a cacophony of conflicting national frameworks, the International Summit on Human Gene Editing was formed in 2015 by NGOs in the United States, the United Kingdom and China, and is working to harmonize regulations global from both the ethical and safety perspectives. As CRISPR co-inventor Jennifer Doudna has written in a now infamous editorial in SCIENCE, stakeholders must engage in thoughtfully crafting regulations of the technology without stifling it.

The COVID-19 pandemic has forced us to rely more on new technologies to keep us healthy, adapt to working from home, and more. The pandemic makes us more reliant on innovative digital, biological, and physical solutions. It has created a united sense of urgency among the public and private industry (together with government and academia) to be more creative about using technology to regenerate health. With continued advances in computing power, network architecture, communications bandwidths, artificial intelligence, machine learning, and gene editing, society will undoubtedly find more cures for debilitating disease and succeed in regenerating human health. As science advances, it inevitably intersects with legal and ethical norms, both for individuals and civil society, and there are new externalities to consider. Legal and ethical norms will adapt, rebalancing the interests of each. The fourth industrial revolution is accelerating, and hopefully towards curing disease.

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Future Visioning the Role of CRISPR Gene Editing: Navigating Law and Ethics to Regenerate Health and Cure Disease - IPWatchdog.com

Genetics

Jared Wareham: Are Balanced Trait Genetics a Long-Term Answer? – Drovers Magazine

November 25, 2020 medical

Genetic progress has helped drive our industry forward and each segment along the value chain hasbenefited from technological advancements in genetics followed by breeder integration. But, have we moved the needle far enough with regard to total beef system profitability?

There are opportunities to take a step forward from the current one size fits all production models. Managers are seeking solutions to their constant struggle to balance getting cows bred while producing highly desirable feeder cattle. Any direction a manager leans, maternal or terminal, tends to leave them in a profitability-strapped state. Have balanced trait idealisms taken us as far as they can? Is it time to consider terminal breeding systems?

Frankly, average cow productivity simply isnt good enough to sustain profitability in most systems long-term. There is a real need for advancements in maternal productivity. Highly functional cows that last longer are simply hard to make while also trying to blend the genetics required for terminal performance.

If we truly believe in sustainable production moving forward, this must be accounted for in the environmental equation that supports progress in all areas. Therefore, is it time to examine the feasibility of focused maternal genetic inputs matched with a terminal genetic line to maximize heterosis and metric specific performance traits?

Moreover, why continue to fight the genetic balancing battle while simultaneously struggling with regional environmental challenges and other competing profit centers? If a tiger stripe is the Cadillac of your area, cultivate internal or external pipelines that will meet annual replacement rates. After that, simply use targeted terminal crosses to maximize value-based marketability. The same can be said for every region from coast to coast.

If large ranching systems coast to coast begin this transition into more defined approaches to production with clear efforts toward highly simplified maternal and terminal genetic lines, is that a step backward? Or, does it represent true progress in system processes that will ultimately drive successful ranching? I think it might be the next logical step. A transition made possible by technologies such as sexed semen and other advancements in genetics and forced by growing challenges to operational efficiencies.

It might represent a form of production that is simply a generation newer. Perhaps the time has come to finally effectively utilize purpose specific lines of genetics to achieve sustainable levels of profit through the right combination of simplicity and precision. Balanced trait genetic approaches have brought the national beef herd to the great place it is today. However, will its overarching effectiveness continue to diminish as our industry progresses?

Jared Wareham is the North American business development manager for ABS NuEra. He has been involved in the cattle industry for over two decades, in business development roles growing genetics-focused companies that service producers along the beef value chain by driving the integration of precision-based production.

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Jared Wareham: Are Balanced Trait Genetics a Long-Term Answer? - Drovers Magazine

Genetics

Turbo Charging the Genetic Stocks Contained in the Worlds Seed Banks – Technology Networks

November 25, 2020 medical

Seed banks across the globe store and preserve the genetic diversity of millions of varieties of crops. This massive collection of genetic material ensures crop breeders access to a wealth of genetics with which to breed crops that yield better or resist stress and disease.

But, with a world of corn genetics at their disposal, how do plant breeders know which varieties are worth studying and which ones aren't? For most of history, that required growing the varieties and studying their performance in the real world. But innovative data analytics and genomics could help plant breeders predict the performance of new varieties without having to go to the effort of growing them.

Jianming Yu, a professor of agronomy at Iowa State University and the Pioneer Distinguished Chair in Maize Breeding, has devoted much of his research to "turbo charging" the seemingly endless amount of genetic stocks contained in the world's seed banks. Yu and his colleagues have published an article in the Plant Biotechnology Journal, a scientific publication, that details their latest efforts to predict traits in corn-based on genomics and data analytics.

Plant breeders searching for varieties to test might feel lost in a sea of genomic material. Yu said applying advanced data analytics to all those genomes can help breeders narrow down the number of varieties they're interested in much faster and more efficiently.

"We're always searching for the best genetic combinations, and we search the various combinations to see what varieties we want to test," said Xiaoqing Yu (no relation), a former postdoctoral research associate in Yu's lab and the first author of the study. "Having these predictions can guide our searching process."

The study focused on predicting eight corn traits based on the shoot apical meristem (SAM), a microscopic stem cell niche that generates all the above-ground organs of the plant. The researchers used their analytical approach to predict traits in 2,687 diverse maize inbred varieties based on a model they developed from studying 369 inbred varieties that had been grown and had their shoot apical meristems pictured and measured under the microscope.

The researchers then validated their predictions with data obtained from 488 inbreds to determine their prediction accuracy ranged from 37% to 57% across the eight traits they studied.

"We wanted to connect the research in foundational biological mechanisms of cell growth and differentiation with agronomic improvement of corn," said Mike Scanlon, a professor of developmental biology at Cornell University and the lead investigator of the multi-institutional team behind the study. "SAM morphometric measurements in corn seedlings allow a quick completion of the study cycle. It not only enables that connection, but also extends the practice of genomic prediction into the microphenotypic space."

Jianming Yu said plant breeders can bump up the accuracy of those genomic predictions by increasing the number of plants per inbred for measurement and findings-improved prediction algorithms. More importantly, plant breeders can finetune their selection process for which inbreds to study closely by leveraging the "U values," a statistical concept that accounts for the reliability of estimates. Yu said the study shows that implementing a selection process that accounts for prediction and statistical reliability can help plant breeders zero in on desirable crop genetics faster.

For instance, analytical models might predict a particular inbred to have modest potential for a given trait, but the U value, or the upper bound for reliability, might indicate a high degree of unreliability in those predictions. So plant breeders might elect to test inbreds that don't do as well in the predictive model simply because of their genetic uniqueness, being less related to those used in building the prediction models.

"We found that there can be a balance between selecting for optimizing short-term gain and mining diversity," Yu said. "It's a tricky balance for plant breeders. Those considerations sometimes go in different directions. Genetic improvement can be viewed as space exploration, either of the vast amount of existing genetic materials in seed banks or of the innumerable breeding progenies constantly being generated. We want to develop better tools to guide those decisions in the process."

Reference: Yu X, Leiboff S, Li X, et al.Genomic prediction of maize microphenotypes provides insights for optimizing selection and mining diversity.Plant Biotechnol. J. 2020. doi:10.1111/pbi.13420

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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Turbo Charging the Genetic Stocks Contained in the Worlds Seed Banks - Technology Networks

Genetics

Forecast: Analysts Think Fulgent Genetics, Inc.’s (NASDAQ:FLGT) Business Prospects Have Improved Drastically – Yahoo Finance

November 25, 2020 medical

TipRanks

Sentiment is on the rise as the annus horribilis 2020 winds to an end. Theres a feeling, after all we have been through over the past ten months, that things just can not get worse. And so, investors are looking forward to 2021.Two big factors in market uncertainty are on their way to resolving themselves. First, COVID-19 vaccines are in the works, and two major drug companies have announced that vaccines will be available in a matter of months. And second, Democrat Joe Biden will take office in the White House, with a strengthened GOP opposition in Congress. The prospect of relief from the coronavirus and a divided government unable to enact extreme or controversial measures promises us a degree of stability that will be welcome.A feeling of optimism and a perception that there are opportunities available, have Wall Streets analysts tagging stocks for success. Weve pulled up theTipRanks dataon three stocks that high-rated analysts have tagged as potentially strong investments. These are buy-rated equities, with double-digit upside potential for the coming year.LendingTree, Inc. (TREE)First up is LendingTree, the online marketplace that connects borrowers and lenders. The company offers borrowers options to shop for competitive rates, loan terms, and various financing products. Among the offerings, from multiple financing sources, are credit cards, deposit accounts, and insurance products. LendingTree is based in North Carolina, with offices in New York, Chicago, and Seattle.In the third quarter, the company showed mixed fiscal results. Revenues were up sequentially, gaining 19% to reach $220 million but earnings were down, both sequentially and year-over-year. At minus $1.33, the EPS was net-negative, and far below the year-ago quarters $1.70.Covering this stock for Needham, 5-star analyst Mayank Tandon rated 66 overall out of more than 7,100 stock pros is upbeat despite the recent turndown after the Q3 results. Tandon noted, [We] remain positive on the shares of TREE LT as we believe that the company is well-positioned to generate strong and consistent revenue Consumer revenue dropped 68% Y/Y as the pandemic constrained consumer credit originations, but trends improved on a sequential basis due to better personal loan volumes and a seasonal boost from the student loan business""TREE's diversified portfolio of personal finance products and the strong secular trends driving the shift of personal finance advertising and shopping to digital channels will help the company achieve its LT growth targets, the analyst concluded. To this end, Tandon rates TREE a Buy, and sets a $375 price target. At current levels, his target suggests a 44% upside for the stock in 2021. (To watch Tandons track record, click here)LendingTree has a unanimous Strong Buy analyst consensus rating, based on 6 Buy reviews set in recent week. The stocks average price target, $362, implies it has room for 39% growth from the current share price of $260.09. (See TREE stock analysis on TipRanks)Allegro MicroSystems (ALGM)Allegro MicroSystems is a semiconductor company and fabless manufacturer of integrated circuits for sensor systems and analyst power technologies. The companys products are used in the automotive and industrial sectors, and include solutions for developing electric vehicle control systems. Allegros circuit chips can also be found in data centers and green energy applications.Allegro is new to the stock markets, having held its IPO just this past October. The stock debuted at $14 per share, and the company put 25 million shares up for offer. In its first day of trading, it closed at more than $17 per share, grossing over $440 million for the IPO. Since then, ALGM has gained 35% in less than four weeks of trading.Vijay Rakesh, 5-star analyst with Mizuho, is clearly bullish on this newly public company.We believe Allegro is leading the early stages of a multi-decade transformation in sensing, automotive electrification, and power distribution, with substantial upside from its industry leadership in magnetic sensors, a differentiated Power IC roadmap, and fabless operating model. Allegro's xMR sensors and power ICs drive technology platform leadership and enable better performance, accuracy, and control for the growing EV market and Industry 4.0 - key for next-generation electrified automotive powertrains, data centers, and factory automation, Rakesh wrote.Along with his upbeat comments, Rakesh gives this stock a Buy rating and a $28 price target. His target implies an upside potential of ~17% for the next 12 months. (To watch Rakeshs track record, click here)Overall, this chip maker is a Wall Street favorite. Out of 6 analysts polled in the last 3 months, all 6 are bullish on ALGM. With a return potential of ~18%, the stock's consensus target price stands at $28.29. (See ALGM stock analysis on TipRanks)American Well (AMWL)American Well, also called AmWell, connects patients, health care providers, and insurers to promote quality care outcomes in a digital world. The company boasts over 55 major insurers and more than 62,000 providers incorporating its service into their networks, giving access to more than 80 million potential patients.AmWell is another newcomer to the markets. This past September, the company held its IPO and raised more than $742 million. Over 41.2 million shares were sold, with the initial price of $18. This compared well to the 35 million shares and $14 to $16 price expected prior to the event. In its first quarter trading as a public company, AmWell reported several gains in key metrics. Revenue was up year-over-year, rising 80% to reach $62.6 million. The active provider total more than 62,000 represents a 930% increase in the past year, and shows strong growth for the company. And the company registered over 1.4 million patient visits during the quarter, a 450% increase from the year-ago quarter.Piper Sandlers 5-star analyst Sean Wieland notes the importance of network growth for AMWL, writing in his note on the stock: 62K providers are using the AMWL Network, up almost 10x from a year ago. The increase was driven primarily by providers employed by, or affiliated with, AMWL's health systems and payor clients As the number of providers on the network grows, so does the value of the network; network expansion makes it easier for patients to find the right provider and for providers to find the right patient.Wieland rates AMWL an Overweight (i.e. Buy), and his $44 price target indicates his confidence in an upside of 78% for the next 12 months. (To watch Wielands track record, click here)All in all, AMWL's Moderate Buy consensus rating is based on 8 reviews, including 5 Buys and 3 Holds. The shares are selling for $24.71 and their average price target, at $35.86, represents a 45% upside potential. (See AMWL stock analysis at 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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Forecast: Analysts Think Fulgent Genetics, Inc.'s (NASDAQ:FLGT) Business Prospects Have Improved Drastically - Yahoo Finance

Genetics

Africa study finds three million new genetic variations – Mail and Guardian

November 25, 2020 medical

Africa is the cradle of humankind. All humans are descendants from this common pool of ancestors. Africa and its multitude of ethnolinguistic groups are therefore fundamental to learning more about humans and our origins.

A genome is the complete set of genetic information in a cell. We inherit our genomes from our parents. Studying the variations in peoples genomes gives clues to how genetic information influences peoples health and tells us about our ancestry.

Very few African individuals have been included in studies looking at genetic variation. Studying African genomes fills a gap in the current understanding of human genetic variation and gives new insights into the history of African populations.

My colleagues and I, who are all members of the Human Heredity and Health (H3Africa) consortium, contributed to a landmark genetics study, which focused on 426 individuals from 13 African countries. More than 50 different ethnolinguistic groups were represented, one of the most diverse groups of Africans ever to be included in such an investigation. We sequenced the whole genome of each of these individuals in other words, we could read every part of the genome to look for variation.

This study contributes a major new source of African genomic data, which shows the complex and vast diversity of African genetic variation.

One of the key outcomes was the discovery of more than three million new genetic variants. This is significant because we are learning about human genetic diversity in general, and discovering more differences that could be linked to disease or traits.

The study also adds details to what is known about the migration and expansion of groups across the continent. We were able to show that Zambia was probably an intermediate site on the likely route of migration from the west of the continent to east and southwards. Evidence supporting movement from east Africa to central Nigeria between 1 500 and 2 000 years ago was also revealed through the identification of east African ancestry in a central Nigerian ethnolinguistic group, the Berom.

The study enabled us to reclassify certain variants that were previously suspected to cause disease. Variants that cause serious genetic diseases are often rare in the general population, mostly because a person with such a variant often does not reach adulthood. The study showed that many of these variants are quite common in the studied populations, something one wouldnt expect in healthy adults. This finding helps to reclassify these variants for clinical interpretation.

Finally, we found a surprising number of regions with signatures of natural selection that have not previously been reported. Selection means that when individuals are exposed to environmental factors like a viral infection, or a drastic new dietary component, some gene variants may confer an added adaptive advantage to the humans that bear them in their genome.

Our best interpretation of these findings is that as humans across Africa were exposed to different environments, sometimes as a result of migration, these variants probably helped them survive in those new conditions. This has left an imprint on the genome and contributes to genomic diversity across the continent.

Our data has also shown that we have not yet found all the variation in the human genome. There is more to learn by looking at unstudied population groups. Less than a quarter of participants in genomics research are of non-European ancestry because most genetic data comes from just three countries the United Kingdom (40%), the United States (19%) and Iceland (12%).

It is essential to keep adding more genomic data from all populations to ensure that everyone can benefit from the advances in health that precision medicine offers. Precision medicine refers to the customisation of healthcare to fit the individual. Including personal genetic information could radically change the nature and scope of healthcare options that would work best for that individual.

The Human Heredity and Health consortium is now in its eighth year of existence and supports more than 51 projects. These include studies focusing on diseases such as diabetes, HIV and tuberculosis. The reference data generated through our study are already being put to use by many of the consortiums studies.

We are planning to take an even deeper look at the data to better understand what other types of genetic variation exist and to add unstudied populations to expand and enrich this data set.

Building capacity for genomics research on the African continent is a key goal of Human Heredity and Health. An important aspect of this study is that it was driven and conducted by researchers and scientists from 24 institutions in Africa participated and led this investigation.

Zan Lombard is principal medical scientist and associate professor at the University of the Witwatersrand. This is an edited version of an article first published by The Conversation. Read the original article here

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Africa study finds three million new genetic variations - Mail and Guardian

Genetics

Fulgent Genetics Announces Increase to Full Year 2020 Guidance to $300 million – Yahoo Finance

November 25, 2020 medical

TEMPLE CITY, Calif., Nov. 23, 2020 (GLOBE NEWSWIRE) -- Fulgent Genetics, Inc. (NASDAQ: FLGT) (Fulgent Genetics or the company), a technology company providing comprehensive testing solutions through its scalable technology platform, today announced that it has updated its revenue guidance for the full year 2020 due to accelerating demand for its COVID-19 testing solutions.

The company now expects to generate at least $300 million in revenue for the full year 2020, an increase of 28% compared to previous guidance of $235 million. This updated guidance represents estimated year-over-year revenue growth of more than 800%.

Since our Q3 earnings call on November 9th, we have seen accelerating demand for our COVID-19 tests and are raising our full year revenue guidance to reflect this significant increase, said Paul Kim, Chief Financial Officer of Fulgent Genetics. As COVID-19 cases continue to rise across the country, we expect to see increasing demand for testing through the balance of the year. We believe we remain well positioned to meet this demand with our ample resources and capacity to run more than 60,000 tests per day.

About Fulgent Genetics

Fulgent Genetics proprietary technology platform has created a broad, flexible test menu and the ability to continually expand and improve its proprietary genetic reference library while maintaining accessible pricing, high accuracy and competitive turnaround times. Combining next generation sequencing (NGS) with its technology platform, the company performs full-gene sequencing with deletion/duplication analysis in an array of panels that can be tailored to meet specific customer needs. In 2019, the company launched its first patient-initiated product, Picture Genetics, a new line of at-home screening tests that combines the companys advanced NGS solutions with actionable results and genetic counseling options for individuals. Since March 2020, the company has commercially launched several tests for the detection of SARS-CoV-2, the virus that causes the novel coronavirus (COVID-19), including NGS and reverse transcription polymerase chain reaction (RT-PCR) - based tests. The company has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for the RT-PCR-based tests for the detection of SARS-CoV-2 using upper respiratory specimens (nasal, nasopharyngeal, and oropharyngeal swabs) and for the at-home testing service through Picture Genetics. A cornerstone of the companys business is its ability to provide expansive options and flexibility for all clients unique testing needs through a comprehensive technology offering including cloud computing, pipeline services, record management, web portal services, clinical workflow, sequencing as a service and automated laboratory services.

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Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements in this press release include statements about, among other things: anticipated future revenue and guidance; evaluations and judgements regarding demand for the companys testing services, including its COVID-19 testing services, evaluations and judgements regarding the companys resources and its ability to meet any increasing demand for testing services and statements regarding the companys ability to continue to grow its business.

Forward-looking statements are statements other than historical facts and relate to future events or circumstances or the companys future performance, and they are based on managements current assumptions, expectations and beliefs concerning future developments and their potential effect on the companys business. These forward-looking statements are subject to a number of risks and uncertainties, which may cause the forward-looking events and circumstances described in this press release to not occur, and actual results to differ materially and adversely from those described in or implied by the forward-looking statements. These risks and uncertainties include, among others: the ongoing impacts of the COVID-19 pandemic, including the preventive public health measures that may continue to impact demand for its tests and the pandemics effects on the global supply chain; the market potential for, and the rate and degree of market adoption of, the companys tests, including its newly-developed tests for COVID-19 and genetic testing generally; the companys ability to capture a sizable share of the developing market for genetic and COVID-19 testing and to compete successfully in these markets, including its ability to continue to develop new tests that are attractive to its various customer markets, its ability to maintain turnaround times and otherwise keep pace with rapidly changing technology; the companys ability to maintain the low internal costs of its business model, particularly as the company makes investments across its business; the companys ability to maintain an acceptable margin on sales of its tests, particularly in light of increasing competitive pressures and other factors that may continue to reduce the companys sale prices for and margins on its tests; risks related to volatility in the companys results, which can fluctuate significantly from period to period; risks associated with the composition of the companys customer base, which can fluctuate from period to period and can be comprised of a small number of customers that account for a significant portion of the companys revenue; the companys ability to grow and diversify its customer base and increase demand from existing and new customers; the companys investments in its infrastructure, including its sales organization and operational capabilities, and the extent to which these investments impact the companys business and performance and enable it to manage any growth it may experience in future periods; the companys level of success in obtaining coverage and adequate reimbursement and collectability levels from third-party payors for its tests; the companys level of success in establishing and obtaining the intended benefits from partnerships, joint ventures or other relationships; the companys compliance with the various evolving and complex laws and regulations applicable to its business and its industry; risks associated with the companys international operations; the companys ability to protect its proprietary technology platform; and general industry, economic, political and market conditions. As a result of these risks and uncertainties, forward-looking statements should not be relied on or viewed as predictions of future events.

The forward-looking statements made in this press release speak only as of the date of this press release, and the company assumes no obligation to update publicly any such forward-looking statements to reflect actual results or to changes in expectations, except as otherwise required by law.

The companys reports filed with the U.S. Securities and Exchange Commission (SEC), including its annual report on Form 10-K for the year ended December 31, 2019 filed with the SEC on March 13, 2020 and the other reports it files from time to time, including subsequently filed quarterly and current reports, are made available on the companys website upon their filing with the SEC. These reports contain more information about the company, its business and the risks affecting its business, as well as its results of operations for the periods covered by the financial results included in this press release.

Investor Relations Contacts:The Blueshirt GroupNicole Borsje, 415-217-2633; nicole@blueshirtgroup.com

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Fulgent Genetics Announces Increase to Full Year 2020 Guidance to $300 million - Yahoo Finance

Genetics

Caveats in Genetic Testing: Reporting in the Media – The Great Courses Daily News

November 25, 2020 medical

By Roy Benaroch, M.D., Emory UniversityPersonal genetic testing is now quite common, but consumers should know about the drawbacks. (Image: Dusan Petkovic/Shutterstock)Are the Example Cases Relevant?

In the October 2017, The New York Times, published an article headlined Personal Genetic Testing is Here. Do We Need It? The tone of the article was set by the subheading: Jody Christ, in her home in Elysberg, PA, says genetic testing saved her life, though experts warn such tests require caution.

This article begins with a personal story, in this case, of a 62-year-old Jody Christ who struggled unsuccessfully for years to control her high cholesterol.

A genetic test revealed she had familial hypercholesterolemia, which put her at high risk for atherosclerotic heart disease, and she underwent a triple-bypass heart surgery. The article quotes Ms. Christ, If I had not taken that test I might be dead by now. Thats a dramatic and unequivocal endorsement of this kind of genetic test.

But this startling example isnt a realistic example of the kind of genetic testing that the rest of this article talks about. Ms. Christ had intractably high cholesterol and testing revealed a definite, causal diagnosis. She needed to have been tested for arterial blockages anyway, even without the genetic test.

This is a transcript from the video series The Skeptics Guide to Health, Medicine, and the Media. Watch it now, on The Great Courses Plus.

The remainder of the article discusses testing on asymptomatic people, or people who dont experience any health problems. And that kind of testing is very different.

Continuing from theTimesarticle:

Experts [] also warn that some consumers may be led astray by genetic findings that are overblown or irrelevant. The Centers for Disease Control and Prevention, for example, takes a cautious approach to personal genomics tests, telling consumers on its website to think before they spit and that evidence on the ability of genetic information to change health behavior has been lacking.

But that cautious sentiment is followed by a paragraph about a company offering testing for genetic variants linked to several kinds of cancer, or another test for heart problems. A medical officer at one of these companies says: This is really for people who dont have any reason to think that theyre at particular riskbut the problem is you really dont know unless you do the genetic test.

Some services, according to the article, claim to predict how well youll respond to different medications or even to different kinds of exercises, or which foods you should eat, or even which types of wine you might prefer.

So, the tests range from things that have at least some scientific support to claims that are just silly. Quoting a professor of genetics, the article says, Theres this mixture of some that have real solid footing and then some that have zero footing.

TheTimesarticle, though beginning with a personal endorsement, did at least superficially present a caveat, by covering the shortcomings inherent in the interpretation of these tests.

Learn more abouthow to better understand and evaluatemedical data.

A 2017Huffington Postarticle focused on a different caveat that ought to be considered before testing. Titled What to Consider Before Taking a 23andMe Test, the thesis was revealed in the subhead, You might not want to know all of your health results. The title refers to testing by a specific company, 23andMe, which is one of the largest direct-to-consumer genetic testing companies.

The article begins in the first person, which is ordinarily taboo in traditional journalism, but gives the article a more personal touch.

I stared at the email announcing Your 23andMe results are ready for several minutes before I had the courage to uncover my genetic health and ancestry secrets.

The article continues, talking about how more and more of these consumer genetic tests are likely to become available. The FDA has announced theyve streamlined approval, and there are several new start-ups that are ready to offer testing for your risk of cancer, genetic diseases, and, quote, an untold number of insights.

A handful of labs are working on offering a very low-cost way to sequence your entire genome, perhaps for as little as $100, in the next few years. Yet experts worry, to quote the article directly again, that consumers might be psychologically unprepared to handle frightening health information.

This is especially true about tests for diseases that currently have no cure, like Alzheimers or Parkinsons disease. In fact, the FDA approval of 23andMes health tests explicitly requires consumers to opt in to testing for these kinds of conditions.

Learn more abouthealth, medicine, and the media.

And, again, theres the crucial importance of understanding that these tests do not make a diagnosis. They can only predict a risk level. The Huffington Post article did say that toward the end, but what it didnt say is that we cannot be sure of the accuracy of these risk estimates.

So what did the authors testing show? The 23andMe material said shed have a 5%-7% chance of having Alzheimers by age 75. But we should take a look at the context the article didnt provide. According to the Alzheimers Association, the risk of having Alzheimers in the 65-74 year age range is between 3% and 9%. The evaluated risk is not much more accurate than the general estimate.

So, the media will often tell you the result of tests but not the complete context. The consumer and the reader should always know the caveats and the pitfalls.

The Centers for Disease Control is cautious about genetic testing because there is generally very little evidence about the ability of genetic information to change health behavior.

Some genetic testing services claim that their tests can predict how well an individual will respond to different medications or even to different kinds of exercise, or which foods you should eat, or even which types of wine you might prefer.

The FDA wants customers to opt in for genetic tests for diseases which have no cure or prevention, such as Alzheimers or Parkinsons disease. This is because consumers might be psychologically unprepared to handle frightening health information.

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Caveats in Genetic Testing: Reporting in the Media - The Great Courses Daily News

Cell Biology

Real Time Spying on the Symphony of Cellular Signals That Drive Biology – SciTechDaily

November 24, 2020 medical

To visualize cellular signals within a neuron, researchers scattered reporters in clusters (green) across the cell. They then identified the signal each cluster represented (multiple colors).Credit: C. Linghu, S. Johnson et al./Cell 2020

A new imaging technology lets scientists spy on the flurry of messages passed within cells as they do . . . potentially everything.

Until now, most scientists could visualize only one or two of these intracellular signals at a time, says Howard Hughes Medical Institute InvestigatorEd Boyden of the Massachusetts Institute of Technology. His teams new approach could make it possible to see as many signals as you want in real time, at once, Boyden says giving researchers a more detailed view of cells internal discussions than ever before.

In tests with neurons, the researchers examined five signals involved in processes such as learning and memory, Boyden and his colleagues report today (November 23, 2020) in the journal Cell. You could apply this technology to all sorts of biological mysteries, he says. Every cell works due to all the signals inside it. Because signaling contributes to all biological processes, a better means to study it could illuminate a host of diseases, from Alzheimers to diabetes and cancer.

The teams new approach is a breakthrough, says Clifford Woolf, a neurobiologist at Harvard Medical School who was not involved with the work. He plans to use it to examine how pain-sensing neurons become more sensitive in injury or illness. With the new imaging technology, he says we can take apart whats happening in cells in a way that just has not been possible before.

Give a computer or a human brain information, and it will crackle with electrical impulses as it prepares a response. Within cells, these impulses result in spurts of multiple molecular signals. Boyden describes this process as a group conversation. Signals within a cell are like a set of people trying to decide what to do for the evening: they take into account many possibilities, and then decide what to collectively do, he says.

These cellular discussions are what prompt, for example, a neuron to encode a memory or a cell to turn cancerous. Despite their importance, scientists still dont have a strong grasp of how these signals work together to guide a cells behavior.

To see cell signaling in action, scientists typically introduce genes encoding sensors connected to fluorescent proteins. These molecular reporters sense a signal and then glow a specific color under the microscope. Researchers can use a different color reporter for each signal to tell the signals apart. But finding sets of reporters with colors that a microscope can differentiate is challenging. And a typical cellular conversation can involve dozens of signals or more.

Changyang Linghu and Shannon Johnson, scientists in Boydens lab, got around this limitation by affixing reporters to small, self-assembling proteins that act like LEGO bricks. These small proteins clicked together, forming clusters that were randomly scattered across the cell like little islands. Each cluster, which appears under the microscope as a luminescent dot, reports only one type of cellular signal. Its like having some islands with thermometers to report temperature and other islands with barometers measuring pressure, Johnson says.

In experiments with neurons, the team created clusters that each glowed upon detection of one of five different signals, including calcium ions and other important signaling molecules. After imaging the live cells, the researchers attached molecular labels to the glowing dots to identify the reporters located there. Using computer analyses, the team turned the dots magenta, yellow, and other colors, depending on whether they represented calcium or another signal. This let them see which signals were switching on and off across a cells interior.

By monitoring so many signals at once, the team was able to figure out how each signal related to one another. Teasing apart such relationships could help scientists understand complex processes like learning, Linghu says.

He likens a cell to an orchestra and its signals to a symphony. Its difficult to fully appreciate a symphony by listening to just a single instrument, he says. Because the new technique lets scientists observe multiple signals at the same time, we can understand the symphony of cellular activities.

Boydens team estimates it may be possible to detect as many as 16 signals with their technology, but improvements in genetic engineering techniques could raise that number significantly. Potentially, you could look at dozens, hundreds, or even more signals, he says. The next challenge, Boyden says, is getting sensors for all of those signals into a cell.

Reference: Spatial multiplexing of fluorescent reporters for dynamic imaging of signal transduction networks by Changyang Linghu, Shannon L. Johnson et al., 23 November 2020, Cell.DOI:: 10.1016/j.cell.2020.10.035

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Real Time Spying on the Symphony of Cellular Signals That Drive Biology - SciTechDaily