Category Archives: Human Genetics

Patented CRISPRclean Technology is a Foundational Tool that Improves the Performance of Next-Generation Sequencing and Other Molecular Workflows by Increasing Sensitivity, Reducing Costs and Enabling Novel Discovery

CARLSBAD, CA, UNITED STATES - Sep 17, 2020 - Jumpcode Genomics - a genome technology company founded by industry veterans in 2016 focused on improving the understanding of human disease - today exited stealth mode and announced the commercial launch of its CRISPRclean technology. Initially available via three kits, CRISPRclean unlocks the power of next generation sequencing (NGS) by improving sensitivity, reducing costs and simplifying workflows. The company also announced that it has strengthened its leadership team with the addition of Yaron Hakak, Ph.D., as CEO. In addition, the company has added new advisors, including Dr. Stanley Nelson, vice chairman of Human Genetics at UCLA as consulting chief scientist, and Gary Schroth, Ph.D., vice president and distinguished scientist at Illumina, as a member of the companys scientific advisory board.

CRISPRclean technology is based on the in-vitro utilization of the CRISPR/Cas system to cleave and physically remove nucleic acid sequences pre- or post-NGS library preparation. This enables researchers to remove overabundant and uninformative sequences to allow discovery and detection of molecules previously undetectable (the needles). Like polymerase chain reaction (PCR), the technology broadly applies to many molecular biology techniques, particularly sequencing technologies.

Initial research applications focus on ribosomal RNA depletion, single cell analysis and repeat removal for whole genome sequencing. Additionally, Jumpcode Genomics is pursuing clinical applications, including the removal of human host molecules for a universal pathogen test and depletion of wild type alleles for somatic mutation detection in oncology. The technology seamlessly integrates into existing workflows and is agnostic to library preparation methods and sequencing platforms.

We aim to revolutionize the practice of molecular biology with our technology and to drive better results for researchers today and ultimately patients tomorrow, said Dr. Hakak, CEO of Jumpcode Genomics. When researchers perform NGS on biological samples, most molecules sequenced are uninformative, which results in a needle in a haystack problem. CRISPRclean solves this problem by simply removing the haystack.

The expansion of the leadership team and scientific advisory board enables Jumpcode Genomics to commercialize its technology and strengthen direct access to thought leaders in the scientific community.

About Jumpcode Genomics: Founded in 2016, Jumpcode Genomics aims to improve the understanding of human biology and the contribution to disease. The companys proprietary CRISPRclean technology utilizes the CRISPR/Cas system to deplete unwanted nucleic acid molecules from sequencing libraries. The process fits seamlessly within standard next generation sequencing workflows and works with most commercially available library preparation solutions. For more information, please visit: http://www.jumpcodegenomics.com

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Jumpcode Genomics Exits Stealth Mode, Unveils Technology that Addresses the 'Needle in the Haystack' Problem of Molecular Biology - Bio-IT World

Its uncontroversial among biologists that many species have two, distinct biological sexes. Theyre distinguished by the way that they package their DNA into gametes, the sex cells that merge to make a new organism. Males produce small gametes, and females produce large gametes. Male and female gametes are very different in structure, as well as in size. This is familiar from human sperm and eggs, and the same is true in worms, flies, fish, molluscs, trees, grasses and so forth.

Different species, though, manifest the two sexes in different ways. The nematode worm Caenorhabditis elegans, a common laboratory organism, has two forms not male and female, but male and hermaphrodite. Hermaphroditic individuals are male as larvae, when they make and store sperm. Later they become female, losing the ability to make sperm but acquiring the ability to make eggs, which they can fertilise with the stored sperm.

This biological definition of sex has been swept up into debates over the status of transgender people in society. Some philosophers and gender theorists define a woman as a biologically female human being. Others strongly disagree. Im addressing those who reject the very idea that there are two biological sexes. Instead, they argue, there are many biological sexes, or a continuum of biological sexes.

Theres no need to reject how biologists define the sexes to defend the view that trans women are women. When we look across the diversity of life, sex takes stranger forms than anyone has dreamt of for humans. The biological definition of sex takes all this in its stride. It does so despite the fact that there are no more than two biological sexes in any species youre likely to have heard of. To many people, that might seem to have conservative implications, or to fly in the face of the diversity we see in actual human beings. I will make clear why it does not.

I call this the biological definition of sex because its the one biologists use when studying sex that is, the process by which organisms use their DNA to make offspring. Many philosophers and gender theorists will protest at making the creation of offspring foundational to how we define sex or distinguish different sexes. Theyre surely right that sex as a social phenomenon is much richer than that. But the use of DNA to make offspring is a central topic in biology, and understanding and explaining the diversity of reproductive systems is an important scientific task. Gender theorists are understandably worried about how the biology of sex will be applied or misapplied to humans. What they might not appreciate is why biologists use this definition when classifying the mind-stretching forms of reproduction observed in limpets, worms, fish, lizards, voles and other organisms and they might not understand the difficulties that arise if you try to use another definition.

Many people assume that if there are only two sexes, that means everyone must fall into one of them. But the biological definition of sex doesnt imply that at all. As well as simultaneous hermaphrodites, which are both male and female, sequential hermaphrodites are first one sex and then the other. There are also individual organisms that are neither male nor female. The biological definition of sex is not based on an essential quality that every organism is born with, but on two distinct strategies that organisms use to propagate their genes. They are not born with the ability to use these strategies they acquire that ability as they grow up, a process which produces endless variation between individuals. The biology of sex tries to classify and explain these many systems for combining DNA to make new organisms. That can be done without assigning every individual to a sex, and we will see that trying to do so quickly leads to asking questions that have no biological meaning.

While the biological definition of sex is needed to understand the diversity of life, that doesnt mean its the best definition for ensuring fair competition in sport or adequate access to healthcare. We cant expect sporting codes, medical systems and family law to adopt a definition simply because biologists find it useful. Conversely, most institutional definitions of sex break down immediately in biology, because other species contradict human assumptions about sex. The United States National Institutes of Health (NIH) uses a chromosomal definition of sex XY for males and XX for females. Many reptiles, such as the terrifying saltwater crocodiles of northern Australia, dont have any sex chromosomes, but a male saltie has no trouble telling if the crocodile that has entered his territory is a male. Even among mammals, at least five species are known that dont have male sex chromosomes, but they develop into males just fine. Gender theorists have extensively criticised the chromosomal definition of human sexes. But however well or badly that definition works for humans, its an abject failure when you look at sex across the diversity of life.

The same is true of phenotypic sex, the familiar idea that sex is defined by the typical physical characteristics (phenotypes) of males and females. Obviously, this approach will produce completely different definitions of male and female for humans, for worms, for trees and so forth. Incubating eggs inside your body, for example, is a female characteristic in humans but a male one in seahorses. That doesnt mean that human institutions cant use the phenotypic definition. But it isnt useful when studying the common patterns in the genetics, evolution and so forth of female humans, female seahorses and female worms.

Understanding the complex ways in which chromosomes and phenotypes relate to biological sex will make clear why the biological definition of sex shouldnt be the battleground for philosophers and gender theorists who disagree about the definition of woman. There might be very good reasons not to define woman in this way, but not because the definition itself is poor biology.

Why did sexes evolve in the first place? Biologists define sex as a step towards answering this question. Not all species have biological sexes, and biology seeks to explain why some do and others dont. The fact that no species has evolved more than two biological sexes is also a puzzle. It would be quite straightforward to engineer a species that has three, but none has evolved naturally.

Many species reproduce asexually, with each individual using its own DNA to create offspring. But other species, including our own, combine DNA from more than one organism. Thats sexual reproduction, where two sex cells gametes merge to make a new individual. In some species, these two gametes are identical; many species of yeast, for example, make new individuals from two, identical gametes. They reproduce sexually, but they have no sexes, or, if you prefer, they have only one sex. But in species that make two different kinds of gamete and where one gamete of each kind is needed to make a new organism there are two sexes. Each sex makes one of the two kinds of gamete.

In complex multicellular organisms, such as plants and animals, these two kinds of gamete are very different. One is a large, complex cell, what wed typically call an egg. Its similar to the eggs produced by asexual species, which can develop into a new organism all on their own. Many species of insect and some lizards, snakes and sharks can reproduce using just an egg cell. The other kind of gamete is a much smaller cell that contains very little beyond some DNA and some machinery to get that DNA to the larger gamete. We are familiar with these two kinds of gametes from human eggs and sperm.

Theres no obvious reason why complex multicellular organisms need to have two kinds of gamete, or why these two kinds are so different in size and structure. Its perfectly possible to make three or more different kinds of gamete, or gametes that vary continuously, just as people vary continuously in height. One question that biologists seek to answer, then, is why those forms of sexual reproduction arent observed in complex organisms such as animals and plants.

Earthworms are hermaphrodites: one part of the worm produces sperm and another part produces eggs

When a species produces two different kinds of gamete, biologists call this anisogamy, meaning not-equal-gametes. Some anisogamic species have separate sexes, like humans do, where each individual can produce only one kind of gamete. Other anisogamic species are hermaphrodites, where each individual produces both kinds of gamete. Because they produce two kinds of gametes, hermaphroditic species still have two biological sexes they simply combine them in one organism. When a biologist tells you that earthworms are hermaphrodites, they mean that one part of the worm produces sperm and another part produces eggs.

Some single-celled and very simple multicellular organisms have evolved something called mating types. These are gametes that are identical in size and structure, but in which the genome of each gamete contains genetic markers that affect which other gametes it can combine with. Typically, gametes with the same genetic marker cant recombine with one another. Some species have many hundreds of these mating types, and newspapers often report research into this phenomenon under headlines such as: Scientists discover species with hundreds of sexes! But, formally, biologists refer to these as mating types, and reserve the term sexes for gametes that are different in size and structure.

Why distinguish between these two phenomena? One reason is that the evolution of anisogamy gametes that differ in size and structure explains the later evolution of sex chromosomes, sex-associated physical characteristics and much more. But the existence of mating types doesnt have these dramatic knock-on evolutionary effects. Another reason to keep the distinction is that anisogamy and mating types are thought to have evolved via different evolutionary processes. One theory is that anisogamy appeared when mating-type genome markers somehow became linked to genes that controlled the size of the gamete, or mutated in some way that affected gamete size. These differences in gamete size would then kickstart the evolution of sexes.

The evolution of sex seems to be strongly associated with multicellularity, so the obvious place to look for a shift from mating types to sexes is in organisms that sit at the multicellular boundary such as algae, which sometimes exist as single-celled organisms, and sometimes as colonies of cells. And indeed, there are species of algae where gametes are just a little bit anisogamous, blurring the distinction between mating types and sexes. Theres much we dont know about how sex evolved, and how it might have evolved differently across species. But the point is that sexes and mating types are very different phenomena, with different causes and consequences.

The fact that sex evolved in some species but not others tells us something important about how biologists think about sex. Many cultures take the difference between male and female to be something fundamental, and label other natural phenomena such as the Sun and the Moon as male or female. But for biologists, the separation between male and female is no more fundamental or universal than photosynthesis or being warm-blooded. Some species have evolved these things, and some havent. They exist when they do only because of the local advantages they afforded in evolutionary competition.

So why did some species evolve two, distinct sexes? To answer this question, we need to forget about creatures with complex sex organs and mating behaviours. These evolved later. Instead, think of an organism that releases its gametes into the sea, such as coral, or into the air, such as fungal spores. Next, consider that there are two goals that any gamete must achieve if its to reproduce sexually. The first is finding and recombining with another gamete. The second is producing a new individual with enough resources to survive. One widely accepted idea, then, is that the evolution of sexes reflects a trade-off between these goals. Because no organism has infinite resources, organisms can either produce many small gametes, making it more likely that some of them will find a partner, or produce fewer but larger gametes, making it more likely that the resulting individual will have what it needs to survive and thrive.

Since the 1970s, this idea has been used to model how anisogamic species might have evolved from species with only one kind of gamete. As mutations introduce differences in gamete size, two winning strategies emerge. One is to produce a large number of small gametes too small to create viable offspring unless they recombine with a larger, well-provisioned gamete. The other winning strategy is to produce a few, large, well-resourced gametes that can create viable offspring, no matter how small the recombinant they end up merging with. Intermediate approaches, such as producing a moderate number of moderately well-provisioned gametes, dont do well. Organisms that try to follow the middle way end up with gametes less likely to find a partner than smaller gametes, and more likely to have insufficient resources than larger gametes. When the two successful complementary strategies have evolved, fresh evolutionary pressures make the gametes even more distinct from one another. For example, it can be advantageous for the small gametes to become more mobile, or for the large, immobile gametes to send signals to the mobile ones.

Once anisogamy has evolved, it shapes many other aspects of reproductive biology. Most species of limpet shellfish that you see on rocks at the beach are sequential hermaphrodites. When young and small they are male, and when mature and large they become female. This is believed to be because small limpets dont have sufficient resources to produce large female gametes, but theyre capable of producing the smaller male ones. In some other species, successful males can arrest their growth and remain small (and male) for their entire life.

Chromosomes arent male or female because these bits of DNA define biological sex. Its the other way around

Sequential hermaphroditism occurs in the opposite direction too. Australian snorkellers love to spot the large blue males of the eastern blue groper, but its rare to see more than one. Most groper are smaller, brown females. They are all born female and become sexually mature after a few years, when 20 or 30 cm in length. At around 50 cm, they change sex and acquire other male characteristics, such as being blue. Unlike the limpet, the main problem facing a male groper is controlling a territory on the reef, so becoming male when youre small is a losing strategy.

Biology aims to understand the extraordinary diversity of ways in which organisms reproduce themselves, as well as to identify common patterns, and to explain why they occur. In general, organisms become sexually mature when they reach an optimal size for reproduction. This optimal size is often different for the two sexes, because the two sexes represent divergent strategies for reproduction. The limpet and the groper are two of many examples. In constructing these explanations, biological sex is defined as the production of one type of viable anisogamous gamete. If we defined sex in some other way, it would be hard to see the common patterns across the diversity of life, and hard to explain them.

So-called sex chromosomes, such as the XX and XY chromosome pairs seen in humans, are often brandished as something thats fundamental to sex. Its partly the inadequacy of this definition that drives scepticism about the existence of two, discrete biological sexes. Molecular genetics is likely to require a shift from binary sex to quantum sex, with a dozen or more genes each conferring a small percentage likelihood of male or female sex that is still further dependent on micro- and macroenvironmental interactions, writes the gender scholar Vernon Rosario.

But any biologist already knows that theres more to sex determination than chromosomes and genes, and that male and female sex chromosomes are neither necessary nor sufficient to make organisms male and female. Several species of mammal, all rodents of one kind or another, have completely lost the male Y chromosome, but these rats and voles all produce perfectly normal, fertile males. Other groups of species, such as crocodiles and many fish, have neither sex chromosomes nor any other genes that determine sex. Yet they still have two, discrete biological sexes. The Australian saltwater crocodile, whom we met before, lays eggs that are very likely to develop into gigantic, highly territorial males if incubated between 30 and 33 degrees Celsius. At other temperatures, genetically identical eggs develop into much smaller females.

The reality is that chromosomes arent called male or female because these bits of DNA define biological sex. Its the other way around in some species that reproduce using two discrete sexes, those sexes are associated with different bits of DNA. But in other species this association is either absent or unreliable. Medical institutions use a chromosomal definition of sex because they judge, rightly or wrongly, that this is a reliable way of categorising humans. But humans really arent the best place to start when trying to understand sex across the diversity of life.

So much for genes. But perhaps sex could be defined by the physical characteristics that organisms develop, which then add up to constitute an organisms sex? An organism with more female than male characteristics would be more female than male and vice-versa. Thats a reasonable way to think about sex, and this idea of phenotypic sex is widely used. But if we apply the biological definition of sex, some of the individuals who are in the middle as far as sex-associated characteristics go are bona fide members of one biological sex. Others are not clearly members of either biological sex.

Nothing in the biological definition of sex requires that every organism be a member of one sex or the other. That might seem surprising, but it follows naturally from defining each sex by the ability to do one thing: to make eggs or to make sperm. Some organisms can do both, while some cant do either. Consider the sex-switching species described above: what sex are they when theyre halfway through switching? What sex are they if something goes wrong, perhaps due to hormone-mimicking chemicals from decaying plastic waste? Once we see the development of sex as a process and one that can be disrupted it is inevitable that there will be many individual organisms that arent clearly of either sex. But that doesnt mean that there are many biological sexes, or that biological sex is a continuum. There remain just two, distinct ways in which organisms contribute genetic material to their offspring.

Whats more, the physical characteristics of an organism can be labelled as male or female only if there is already a definition of sex. Whats so male about a groper being blue as opposed to brown? Many male organisms are brown. Whats so female about incubating eggs in a womb? After all, in many pipefish and seahorse species the male incubates the eggs in his brood pouch. What makes this part of the hermaphroditic earthworm male and that part female? Gender studies scholars have noticed this logical discrepancy, and some have gone on to argue that the sexes must therefore be defined in terms of gender. But from a biological perspective, what makes an observable physical characteristic male or female is not its association with gender, but its association with something more tangible: the production of one or other of the two kinds of gamete.

This explains why the existence of individuals with combinations of male and female characteristics doesnt show that biological sex is a continuum. These organisms have a combination of characteristics associated with one biological sex and characteristics associated with the other biological sex. They do not have some part of the ability to make small gametes combined with some part of the ability to make large gametes. Their phenotypic sex might be intermediate, but their biological sex is not. Being fully biologically male and fully biologically female hermaphroditic can be an effective evolutionary strategy, and we have encountered several hermaphroditic species already. But making both kinds of gametes incompletely would be an evolutionary dead-end.

Like phenotypic characteristics, sex chromosomes can be more or less reliably associated with biological sex. The eastern three-lined skink, an Australian lizard, has sex chromosomes, and under some circumstances XY skinks become male and XX skinks become female, just as in humans. But in cold nests, every skink becomes male, whatever their chromosomes. By becomes male, biologists mean that they grow up to produce small gametes sperm.

No animal is conceived with the ability to make sperm or eggs (or both). This ability has to grow

This effect of temperature on sex is not surprising, as many reptile species produce genetically identical offspring whose sex is determined by incubation temperature. Whats more surprising is that varying the size of the egg yolk in this species of skink can produce both sexes with the wrong sex chromosomes: XX males and XY females. The skink seems to have three mechanisms for determining sex chromosomes, temperature and hormones in the yolk. This is not a mere quirk of nature. The skink is one of many species that actively control the sex of their offspring, responding to environmental cues that predict whether male or female offspring have better chances of surviving and reproducing.

If all species were like the skink, we probably wouldnt label sex chromosomes as male or female. After all, we dont think of extreme nest temperatures as female and intermediate temperatures as male, merely because they produce male and female crocodiles or male and female geckos. We think of sex chromosomes as male or female because we focus on species where they are reliably associated with the production of male or female gametes.

Sex chromosomes play much the same role in sex determination as nest temperatures and hormones. Theyre simply mechanisms that organisms use to turn genes on and off in offspring so that they develop a biological sex. No animal is conceived with the ability to make sperm or eggs (or both). This ability has to grow, through a cascade of interactions between genes and environments. In some species, once an individual acquires a sex, it remains that sex for the rest of its life. In others, individuals can switch sex one or more times. But in every case, the underlying mechanisms are designed to grow organisms that make either male or female gametes (or both). The other changes the body undergoes as it becomes male, female or hermaphroditic are designed to fit the reproductive strategies that this species has evolved.

These mechanisms by which organisms develop or switch biological sex are complex, and many factors can interfere with them. So they produce a lot of phenotypic diversity. Sometimes, organisms grow up able to make fertile gametes, but otherwise atypical for their biological sex. Sometimes, they grow up unable to make fertile gametes of either kind. This is usually an accident, but sometimes by design. In bees, eggs that arent fertilised develop into males, so male bees have half as many chromosomes as female bees. Meanwhile, all fertilised eggs start to develop into females, but most of them never complete their sexual development. The queen sends chemical signals that block the development of the worker bees ovaries at an early stage. So worker bees are female in the extended sense that they would develop into fertile females if they werent actively prevented from doing so. Occasionally, worker bees manage to evade these controls and lay their own eggs. They are not popular with beekeepers, who select against these mutant strains.

The diversity of outcomes in individual sexual development doesnt mean that there are many biological sexes or that biological sex is a continuum. Whatever the merits of those views for chromosomal sex or phenotypic sex, they are not true of biological sex. A good way to grasp this is to imagine a species that really does have three biological sexes. Biotechnologists have proposed curing mitochondrial diseases by removing the nucleus from an egg with healthy mitochondrial DNA, and inserting a new nucleus containing the nuclear DNA from an unhealthy egg and the nuclear DNA from a sperm. The resulting child would have three genetic parents.

Now imagine if there was a whole species like this, where three different kinds of gametes combined to make a new individual a sperm, an egg and a third, mitochondrial gamete. This species would have three biological sexes. Something like this has actually been observed in slime moulds, an amoeba that can, but need not, get its mitochondria from a third parent. The novelist Kurt Vonnegut imagined an even more complex system in Slaughterhouse-Five (1969): There were five sexes on Tralfamadore, each of them performing a step necessary in the creation of a new individual. But the first question a biologist would ask is: why havent these organisms been replaced by mutants that dispense with some of the sexes? Having even two sexes imposes many extra costs the simplest is just finding a mate and these costs increase as the number of sexes required for mating rises. Mutants with fewer sexes would leave more offspring and would rapidly replace the existing Tralfamadorians. Something like this likely explains why two-sex systems predominate on Earth.

We can also imagine a species where biological sex really does form a continuum. Recall that some algae have slightly anisogamous gametes, much closer together than sperm and eggs. We can imagine a more complex organism using this system, with some slightly smaller gametes and some slightly larger ones. Successful reproduction might require two gametes that, when added together, are big enough but not too big. But the sexually reproducing plants and animals that actually exist all have just two, very different kinds of gamete male and female. Theyre not merely different in size, theyre fundamentally different in structure. This is the result of competition between organisms to leave the greatest number of genetic descendants. In complex multicellular organisms such as plants and animals, we know of only three successful reproductive strategies: two biological sexes in different individuals, two biological sexes combined in hermaphroditic individuals, and asexual reproduction. Some species use one of these strategies, some use more than one.

Human beings have come up with many ways to classify the diversity of individual outcomes from human sexual development. People who want to apply the biological definition of sex to humans should recognise that its ill-suited to do what many human institutions want, which is to sort every individual into one category or another. What sex are worker bees? They are sterile workers whose genome was designed by natural selection to terminate ovary development on receipt of a signal from the queen bee. They share much of the biology of fertile female bees but if someone wants to know Are worker bees really female?, theyre asking a question that biology simply cant answer.

Nor is being a sterile worker a third biological sex alongside male and female. This is easier to see in ants, where there is more than one sterile caste. Workers, soldiers, queens and male flying ants each have specialised bodies and behaviour, but there are not four biological sexes of ant. Workers and soldiers are both female in an extended sense, but not in the full-blown sense that queen ants are female. There is a human imperative to give everything a sex, as mentioned above, but biology doesnt share it.

The biological definition of sex wasnt designed to ensure fair sporting competition, or settle healthcare disputes

Juvenile organisms and postmenopausal human females also cant produce either kind of gamete. Juveniles are assigned to the sex they have started to grow into. But once again, this is more complicated than it seems when we focus only on humans. In almost all mammals, sexual differentiation is initiated by a region of the Y chromosome, so a mammalian egg can become either male or female. In birds, its the other way around the egg carries the sex-determining W chromosome, so sperm can become either male or female. After fertilisation, therefore, we can say that an individual mammal or bird has a sex in the sense that it has started to grow the ability to produce either male or female gametes. With a crocodile or a turtle, though, wed have to wait until nest temperature had its sex-determining effect. But that doesnt mean that we need to create a third biological sex for crocodile eggs!

More importantly, nothing guarantees that any of these organisms, including those with sex chromosomes, will continue to grow to the point where they can actually produce male or female gametes. Any number of things can interfere. From a biological point of view, there is nothing mysterious about the fact that organisms have to grow into a biological sex, that it takes them a while to get there, and that some individuals develop in unusual or idiosyncratic ways. This is a problem only if a definition of sex must sort every individual organism into one sex or another. Biology doesnt need to do that.

In human populations, there are plenty of individuals whose sex is hard to determine. Biologists arent blind to this. The definition of biological sex is designed to classify the human reproductive system and all the others in a way that helps us to understand and explain the diversity of life. Its not designed to exhaustively classify every human being, or every living thing. Trying to do so quickly leads to questions that have no biological meaning.

Human societies cant delegate to biology the job of defining sex as a social institution. The biological definition of sex wasnt designed to ensure fair sporting competition, or to settle disputes about access to healthcare. Theorists who want to use the biological definition of sex in those ways need to show that it will do a good job at the Olympics or in Medicare. The fact that its needed in biology isnt good enough. On the other hand, whatever its shortcomings as an institutional definition, the concept of biological sex remains essential to understand the diversity of life. It shouldnt be discarded or distorted because of arguments about its use in law, sport or medicine. That would be a tragic mistake.

The authors research is supported by the Australian Research Council and the John Templeton Foundation. He would also like to thank Nicole Vincent, Jussi Lehtonen, Stefan Gawronski and Joshua Christie for their feedback on earlier drafts.

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Sex is real - aeon.co

In early January, the first genome sequence of Sars-CoV-2 the virus that causes COVID-19 was released under the moniker Wuhan-1. This string of 30,000 letters (the A, T, C and Gs of the genetic code) marked day one in the race to understand the genetics of this newly discovered coronavirus. Now, a further 100,000 coronavirus genomes sampled from COVID-19 patients in over 100 countries have joined Wuhan-1. Geneticists around the world are mining the data for answers. Where did Sars-CoV-2 come from? When did it start infecting humans? How is the virus mutating and does it matter? Sars-CoV-2 genomics, much like the virus itself, went big and went global.

The term mutation tends to conjure up images of dangerous new viruses with enhanced abilities sweeping across the planet. And while mutations constantly emerge and sometimes sweep early mutations in Sars-CoV-2 have made their way around the world as the virus spread almost unnoticed mutations are a perfectly natural part of any organism, including viruses. The vast majority have no impact on a viruss ability to transmit or cause disease.

A mutation just means a difference; a letter change in the genome. While the Sars-CoV-2 population was genetically essentially invariant when it jumped into its first human host in late 2019, over 13,000 of these changes are now found in the 100,000 Sars-CoV-2 sequenced to date. Yet any two viruses from any two patients anywhere in the world differ on average by only ten letters. This is a tiny fraction of the total 30,000 characters in the viruss genetic code and means that all Sars-CoV-2 in circulation can be considered part of a single clonal lineage.

It will take some time for the virus to acquire substantial genetic diversity. Sars-CoV-2 mutates fairly slowly for a virus, with any lineage acquiring a couple of changes every month; two to six-fold lower than the number of mutations acquired by influenza viruses over the same period.

Still, mutations are the bedrock on which natural selection can act. Most commonly mutations will render a virus non-functional or have no effect whatsoever. Yet the potential for mutations to affect transmissibility of Sars-CoV-2 in its new human hosts exists. As a result, there have been intense efforts to determine which, if any, of the mutations identifiable since the first Sars-CoV-2 genome was sequenced in Wuhan may significantly alter viral function.

An infamous mutation in this context is an amino acid change in the Sars-CoV-2 spike protein, the protein that gives coronaviruses their characteristic crown-like projections and allows it to attach to host cells. This single character change in the viral genome termed D614G has been shown to increase virus infectivity in cells grown in the lab, though with no measurable impact on disease severity. Although this mutation is also near systematically found with three other mutations, and all four are now found in about 80% of sequenced Sars-CoV-2 making it the most frequent set of mutations in circulation.

The challenge with D614G, as with other mutations, is disentangling whether they have risen in frequency because they happened to be present in viruses responsible for seeding early successful outbreaks, or whether they truly confer an advantage to their carriers. While genomics work on a UK dataset suggests a subtle role of D614G in increasing the growth rate of lineages carrying it, our own work could find no measurable impact on transmission.

D614G is not the only mutation found at high frequency. A string of three mutations in the protein shell of Sars-CoV-2 are also increasingly appearing in sequencing data and are now found in a third of viruses. A single change at position 57 of the Orf3a protein, a known immunogenic region, occurs in a quarter. Other mutations exist in the spike protein while myriad others seem induced by the activity of our own immune response. At the same time, there remains no consensus that these, or any others, are significantly changing virus transmissibility or virulence. Most mutations are simply carried along as Sars-CoV-2 continues to successfully spread.

But replacements are not the only small edits that may affect Sars-CoV-2. Deletions in the Sars-CoV-2 accessory genes Orf7b/Orf8 have been shown to reduce the virulence of Sars-CoV-2, potentially eliciting milder infections in patients. A similar deletion may have behaved in the same way in Sars-CoV-1, the related coronavirus responsible for the Sars outbreak in 2002-04. Progression towards a less virulent Sars-CoV-2 would be welcome news, though deletions in Orf8 have been present from the early days of the pandemic and do not seem to be increasing in frequency.

While adaptive changes may yet occur, all the available data at this stage suggests were facing the same virus since the start of the pandemic. Chris Whitty, chief medical officer for England, was right to pour cold water on the idea that the virus has mutated into something milder than the one that caused the UK to impose a lockdown in March. Possible decreases in symptom severity seen over the summer are probably a result of younger people being infected, containment measures (such as social distancing) and improved treatment rather than changes in the virus itself. However, while Sars-CoV-2 has not significantly changed to date, we continue to expand our tools to track and trace its evolution, ready to keep pace.

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Coronavirus mutations: what we've learned so far - The Conversation UK

FILE PHOTO: The offices of gene sequencing company Illumina Inc are shown in San Diego, California

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(Reuters) Illumina Inc said on Monday it would buy cancer screening startup Grail Inc in a cash-and-stock deal worth $8 billion, buying out investors including Jeff Bezos and snatching back a business it spun out four years ago.

Grail is developing a liquid biopsy, a blood test intended to diagnose cancers at early stages when the disease is easier to treat. The company has said it expects to launch its flagship test Galleri in 2021, betting on a market expected to grow rapidly in coming years.

Grail was founded by Illumina as a separate company in 2016 and had since raised about $2 billion, with investors including the founders of Amazon.com Inc and Microsoft . Illumina remained its largest shareholder, owning about 14.5% of its outstanding shares. Illumina Chief Executive Francis deSouza said in an interview that he began speaking to his board early this year about acquiring Grail after the start-up released promising data on its experimental diagnostic. From our perspective, early detection of cancer is the largest application of genomics for the next decade, decade and a half, he said. Many cancers, like ovarian cancer, are difficult to diagnose and often only caught when the disease has spread to other areas of the body, when it is far deadlier. If a blood test can effectively detect these cancers earlier, it could significantly improve the prognosis for many patients.

Analysts have forecast a future market for liquid biopsies as high as $130 billion in the United States alone.However, the technology is still experimental and must demonstrate efficacy in clinical trials before being approved by regulators.

Illumina shares fell 8.3% to $271.07, as some analysts questioned the deals rationale.

We dont see the clear fit for acquiring a company that is still at a stage where clinical studies and clinical product development are still critical and will be for years, Cowen analyst Doug Schenkel said in a research note.DeSouza attributed the stock reaction to the deals cost. Its just a big deal. The numbers are large and so investors want to process what this means, he said. DeSouza said the deal fits into Illuminas long-term strategy of developing next generation technology that uses human genetics to improve patients lives.

(Reporting by Manojna Maddipatla in Bengaluru; Editing by Bernard Orr and Bill Berkrot)

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Illumina to buy Jeff Bezos-backed cancer testing firm Grail in $8 billion deal - Metro US

Thirty-eight McGill research projects have received federal grants through the CFI's John R. Evans Leaders Fund, which will provide them with state-of-the art research infrastructure needed to foster innovation.

The Government of Canada through the Canada Foundation for Innovation (CFI) recently announced their funding investment of more than $96 million to support 377 new research infrastructure projects at 55 institutions from coast to coast. The CFI also announced the funding of projects through the John R. Evans Leaders Fund (JELF) in partnership with the Canada Research Chairs (CRC) Program, investing $4.6 million in 21 Chairs at 16 institutions to provide them with the innovative tools they need to pursue their valuable work.

Thirty-eight McGill research projects have received a combined total of $9.3M in federal grants through this round of JELF. The fund helps universities attract top talent in diverse fields of research by providing them with the highly specialized research infrastructure they need to be leaders in their field. The recipients will also receive matching funds from the Quebec government for their research endeavours.

ProfessorsJrg Hermann FritzandCorinne Mauriceof the Department of Microbiology and Immunology, andBastien Castagnerof the Department of Pharmacology and Therapeutics, received $352,778 in JELF funding for their project on harnessing microbiota metabolism for human health benefits. The project will focus on the ill-defined relationship between bacteria in the human gut, metabolism and the immune system. The research will help design new, more effective drugs to treat inflammatory bowel diseases, obesity, asthma and other chronic diseases.

One McGill project received $520,000 in JELF funding, in partnership with the Canada Research Chairs (CRC) program. ProfessorStephen Lomberof the Department of Physiology and Canada Research Chair in Brain Plasticity and Development, received $520,000 from the JELF and CRC partnership to establish an internationally recognized laboratory with state-of-the-art facilities for the study of brain plasticity and auditory neuroscience. The laboratory will help researchers understand how the brain processes sound, and how to best design therapeutic strategies for the 300,000 Canadians burdened with profound hearing loss.

McGill CRC-JELF recipient:

Hearing Loss and Restoration LaboratoryProfessorStephen Lomberof the Department of Physiology, Faculty of Medicine and Health Sciences, is the principal investigator.$520,000 from the CRC-JELF partnership; $520,000 matching provincial funds.

List of McGill JELF recipients:Creation of a Multidisciplinary Sleep Laboratory at the NeuroProfessorsJulien DoyonandBirgit Frauscherof the Department of Neurology and Neurosurgery, Faculty of Medicine and Health Sciences, are the principal investigators.$254, 296 from JELF; $254, 296 matching provincial funds.

Harnessing Microbiota Metabolism for Human Health BenefitsProfessorsJrg Hermann FritzandCorinne Mauriceof the Department of Microbiology and Immunology, andBastien Castagnerof the Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, are the principal investigators.$352,778 from JELF; $352,778 matching provincial funds.

Multi-scale in Vivo Imaging of Biological SystemsProfessorAbigail Gerholdof the Department of Biology, Faculty of Science, is the principal investigator.$271,990 from JELF; $271,990 matching provincial funds.

MAP-PRO: An Electronic Database and Learning Hub for Canadian Early Psychosis ServicesProfessorsSrividya IyerandManuela Ferrariof the Department of Psychiatry, Medicine and Health Sciences, are the principal investigators.$80,000 from JELF; $80,000 matching provincial funds.

McGill Soil Biogeochemistry and Ecology LaboratoryProfessorCynthia Kallenbachof the Department of Natural Resource Sciences, Faculty of Agricultural and Environmental Sciences, is the principal investigator.$150,000 from JELF; $150,000 matching provincial funds.

Subsurface Hydrogeochemistry and Fluid FlowProfessorMary Kangof the Department of Civil Engineering and Applied Mechanics, Faculty of Engineering, is the principal investigator.$475,360 from JELF; $475,360 matching provincial funds.

Combined Microreactor Mass Spectrometry Infrastructure for Catalyst CharacterizationProfessorJan Kopyscinskiof the Department of Chemical Engineering, Faculty of Engineering, is the principal investigator.$120,000 from JELF; $120,000 matching provincial funds.

Fast Scalable Deep Learning for Sensitive Big Data in Healthcare and Social ContextsProfessorsYue Li,William HamiltonandReihaneh Rabbanyof the School of Computer Science, Faculty of Science, are the principal investigators.$120,000 from JELF; $120,000 matching provincial funds.

Click Chemistry for Precision MedicineProfessorNathan Luedtkeof the Department of Chemistry, Faculty of Science, is the principal investigator.$285,000 from JELF; $285,000 matching provincial funds.

Conformational Dynamics of Complex Proteins in Health and DiseasesProfessorGergely Lukacsof the Department of Physiology, ProfessorKalle Gehringof the Department of Biochemistry, andJean-Francois Trempeof the Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, are the principal investigators.$592,636 from JELF; $592,636 matching provincial funds.

Antagonistic Inter-bacterial InteractionsProfessorJennifer Ronholmof the Department of Food Science and Agricultural Chemistry, Faculty of Agricultural and Environmental Sciences, is the principal investigator.$143,180 from JELF; $143,180 matching provincial funds.

Blood-based Biomarkers for Ageing-related Brain DiseasesProfessorsPedro Rosa-Netoof the Department of Psychiatry,Gerhard Multhaupof the Department of Pharmacology and Therapeutics, andAngela Gengeof the Department of Neurology and Neurosurgery, are the principal investigators.$417,175 from JELF; $417,175 matching provincial funds.

Infrastructure for Advanced Arctic and Urban Climate Modelling in Support of Climate-resilient Engineering SystemsProfessorLaxmi Sushamaof the Department of Civil Engineering and Applied Mechanics, Faculty of Engineering, is the principal investigator.$135,180 from JELF; $135,180 matching provincial funds.

CoDEx: Computational Design ExploratoryProfessorTheodora Vardouliof the Peter Guo-hua Fu School of Architecture, Faculty of Engineering, is the principal investigator.$78,807 from JELF; $78,807 matching provincial funds.

Metabolism of Stress-regulated Genes in Health and Disease using Single Molecule ImagingProfessorMaria Vera Ugaldeof the Department of Biochemistry, Faculty of Medicine, is the principal investigator.$200,000 from JELF; $200,000 matching provincial funds.

Drivers of Breast Cancer Progression Identified within Arm-level Somatic Copy Number AlterationsProfessorLogan Walshof the Department of Human Genetics, Faculty of Medicine and Health Sciences, is the principal investigator.$109,179 from JELF; $109,179 matching provincial funds.

Development of Biodegradable Functional Materials from Low-value Biomass for Food and Agricultural ApplicationsProfessorYixiang Wangof the Department of Food Science and Agricultural Chemistry, Faculty of Agricultural and Environmental Sciences, is the principal investigator.$121,500 from JELF; $121,500 matching provincial funds.

The Role of Lipoma Preferred Partner (LPP) in Regulating Breast Cancer ProgressionProfessorsClaire Brownof the Department of Physiology andPeter Siegelof the Departments of Medicine, Biochemistry, and Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, are the principal investigators.$744,304 from JELF; $744,304 matching provincial funds.

Muscle Stem Cell Biology in Health and DiseaseProfessorNatasha Changof the Department of Biochemistry, Faculty of Medicine and Health Sciences, is the principal investigator.$149,582 from JELF; $149,582 matching provincial funds.

NIR Imaging Platform for Biophotonic Technologies Relying on New Dormant Sensors/SensitizersProfessorGonzalo Cosaof the Department of Chemistry, Faculty of Science, is the principal investigator.$172,875 from JELF; $172,875 matching provincial funds.

A Path to Anti-aging DrugsProfessorSiegfried Hekimiof the Department of Biology, Faculty of Science, is the principal investigator.$179,196 from JELF; $179,196 matching provincial funds.

Markers to Market: A Platform to Translate Quantitative Genomics Data into Field-ready, Value-added Commodity CultivarsProfessorValerio Hoyos-Villegasof the Department of Plant Science, Faculty of Agricultural and Environmental Sciences, is the principal investigator.$152,062 from JELF; $152,062 matching provincial funds.

Mechanism and Therapy for Autism Spectrum Disorders Associated with Copy Number VariantsProfessorWei-Hsiang Huangof the Department of Neurology and Neurosurgery, Faculty of Medicine and Health Sciences, is the principal investigator.$169,634 from JELF; $169,634 matching provincial funds.

Development of Strategies to Better Understand and Control the Long-term Side Effects of RadiotherapyProfessorJohn Kildeaof the Department of Oncology, Faculty of Medicine and Health Sciences, is the principal investigator.$87,579 from JELF; $87,579 matching provincial funds.

4D Immersive Scene Capture and ProcessingProfessorDerek Nowrouzezahraiof the Department of Electrical and Computer Engineering, Faculty of Engineering, is the principal investigator.$78,020 from JELF; $78,020 matching provincial funds.

Mapping Dopamine Circuits in the Healthy and Diseased BrainProfessorJean-Francois Poulinof the Department of Neurology and Neurosurgery, Faculty of Medicine and Health Sciences, is the principal investigator.$294,592 from JELF; $294,592 matching provincial funds.

UHPLC-MS to Develop Technologies to Control the Presence and Fate of Contaminants in Natural & Engineered Water SystemsProfessorViviane Yargeauof the Department of Chemical Engineering, Faculty of Engineering, is the principal investigator.$406,300 from JELF; $406,300 matching provincial funds.

Integrated Facility for Research on Large Animals SpeciesProfessorsVilceu Bordignonof the Department of Animal Science andLuis B Agellon, of the Department of School of Human Nutrition, Faculty of Agricultural and Environmental Sciences, are the principal investigators.$800,000 from JELF; $800,000 matching provincial funds.

Exercise and Nutrition to Support Skeletal Muscle Heath Across the LifespanProfessorTyler Churchward-Venneof the Department of Kinesiology and Physical Education, Faculty of Education, is the principal investigators.$344,957 from JELF; $344,957 matching provincial funds.

Neuroecology of Spatial Behaviour LabProfessorMlanie Guiguenoof the Department of Biology, Faculty of Science, is the principal investigator.$165,000 from JELF; $165,000 matching provincial funds.

Biotechnological Production of High-value CompoundsProfessorCodruta Igneaof the Department of Bioengineering, Faculty of Engineering, is the principal investigator.$140,000 from JELF; $140,000 matching provincial funds.

Atomic Layer Deposition of Electrochemical Energy Storage DevicesProfessorEmmeline Kaoof the Department of Mechanical Engineering, Faculty of Engineering, is the principal investigator.$260,101 from JELF; $260,101 matching provincial funds.

High Throughput Monitoring of Cell Metabolism using a Modernized Tissue Culture FacilityProfessorRyan Maillouxof the School of Human Nutrition, Faculty of Agricultural and Environmental Sciences, is the principal investigator.$234,500 from JELF; $234,500 matching provincial funds.

Anishinaabe Stories DatabaseProfessorAaron Millsof the Faculty of Law, is the principal investigator.$46,961 from JELF; $46,961 matching provincial funds.

New Computational Techniques for Modeling of Disordered Molecular Systems for Applications in Nano- and Bio- engineeringProfessorYelena Simineof the Department of Chemistry, Faculty of Science, is the principal investigator.$80,000 from JELF; $80,000 matching provincial funds.

Circulating Immune Cells and Interactions in the Nervous SystemProfessorJo Anne Strattonof the Department of Neurology and Neurosurgery, Faculty of Medicine and Health Sciences, is the principal investigator.$141,863 from JELF; $141,863 matching provincial funds.

Heat Transfer in Thermal Energy TechnologiesProfessorMlanie Ttreault-Friendof the Department of Mechanical Engineering, Faculty of Engineering, is the principal investigator.$233,308 from JELF; $233,308 matching provincial funds.

Read CFIs official press release.

This article was first published on 25 August by McGill University.

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Canada Foundation for Innovation invests $9.3M in McGill highly-specialized research infrastructures - Science Business

SAN FRANCISCO, CA / ACCESSWIRE / August 24, 2020 / Tribe Public announced today that Dietrich Stephan, Chief Executive Officer of NeuBase Therapeutics, Inc. (NASDAQ:NBSE), a biotechnology company developing next-generation antisense oligonucleotide (ASO) therapies using its scalable PATrOL platform to address genetic diseases, will present at Tribe Public's Presentation and Q&A Webinar Event at 8 am pacific/11 am eastern on Wednesday, August 26th, 2020. During this complimentary, 30-minute event, Dr. Stephan will introduce the NeuBase's next-generation gene silencing technology and discuss the company's progress with treatment candidates in Huntington's Disease (HD) and Myotonic Dystrophy (DM1). A question and answer session will follow the presentation. To register to join the complimentary event, please visit the Tribe Public LLC website: http://www.tribepublic.com, or send a message to Tribe's management at research@tribepublic.com to request your seat for this limited capacity Zoom-based event.

Dietrich A. Stephan, Ph.D. is an industry veteran who is considered one of the fathers of the field of precision medicine, having trained with the leadership of the Human Genome Project at the NIH and then going on to lead discovery research at the Translational Genomics Research Institute and serve as professor and chairman of the Department of Human Genetics at the University of Pittsburgh. Dr. Stephan has identified the molecular basis of dozens of genetic diseases and published extensively in journals such as Science, the New England Journal of Medicine, Nature Genetics, PNAS, and Cell. In parallel, Dr. Stephan has founded or co-founded more than ten biotechnology companies and has advised numerous other companies. These companies are backed by top-tier investors such as Sequoia Capital, KPCB, Thiel Capital, and Khosla Ventures as well as corporate partners such as Life Technologies, Pfizer, and Mayo Clinic. Notably, Dr. Stephan founded NeuBase Therapeutics in August 2018, took it public in 2019, and has since grown the company to market capitalization to the tune of hundreds of millions of dollars. Dr. Stephan received his Ph.D. from the University of Pittsburgh and his B.S. from Carnegie Mellon University.

ABOUT TRIBE PUBLIC LLCTribe Public LLC is a San Francisco, CA-based organization that hosts complimentary worldwide webinar & meeting events in the U.S. Tribe's events focus on issues that the Tribe members care about with an emphasis on hosting management teams from publicly traded companies from all sectors & financial organizations that are seeking to increase awareness of their products, progress, and plans. Tribe members primarily include Institutions, Family Offices, Portfolio Managers, Registered Investment Advisors, & Accredited Investors. Website: http://www.tribepublic.com.

ABOUT NEUBASE THERAPEUTICSNeuBase Therapeutics, Inc. is developing the next generation of gene silencing therapies with its flexible, highly specific synthetic antisense oligonucleotides. The proprietary NeuBase peptide-nucleic acid (PNA) antisense oligonucleotide (PATrOL) platform allows for the rapid development of targeted drugs, increasing the treatment opportunities for the hundreds of millions of people affected by rare genetic diseases, including those that can only be treated through accessing of secondary RNA structures. Using PATrOL technology, NeuBase aims to first tackle rare, genetic neurological disorders. NeuBase is continuing its progress towards developing treatment candidates in Huntington's Disease (HD) and Myotonic Dystrophy (DM1.)

CONTACT:

Tribe Public, LLC.John F. Heerdink, Jr.Managing Partnerjohn@tribepublic.com

SOURCE: NeuBase Therapeutics, Inc.

View source version on accesswire.com:https://www.accesswire.com/603092/NeuBase-Therapeutics-CEO-Dietrich-A-Stephan-PhD-to-Present-at-Tribe-Publics-Presentation-and-QA-Webinar-Event-on-August-26-2020

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NeuBase Therapeutic's CEO, Dietrich A. Stephan, Ph.D., to Present at Tribe Public's Presentation and Q&A Webinar Event on August 26, 2020 - BioSpace

According to the CDC, patients at any age who have cancer are at an increased risk of severe illness due to coronavirus disease 2019 (COVID-19), and this may be aggravated by aspects such as race, ethnicity, and socioeconomic factors.1 Discrepancies in patient outcomes were explored in a virtual symposium on health inequities in the COVID-19 pandemic at the COVID-19 and Cancer meeting, hosted by the American Association for Cancer Research.

The United States has the highest number of reported cases of COVID-19 cases in the world, with deaths occurring more often in patients with advanced age and comorbidities. The disparity for COVID-19 deaths is seen for all age groups, with African Americans showing the highest death rates at any age. Compared with non-Hispanic whites, both African American and Hispanic COVID-19 deaths outpace those of non-Hispanic whites, even at younger ages.

In my own state of Michigan, African Americans share of cases, as well as deaths, greatly outstrip the proportion of African Americans in the state population, John M. Carethers, MD, professor and chair of the Department of Internal Medicine and professor of human genetics at the University of Michigan Medical School in Ann Arbor, said during his presentation.2 Overall, African Americans make up 13% of the population but make up 23% of COVID-19 deaths. If you assess this per 100,000 population, [deaths in] non-Hispanic whites occur at a rate of 27 per 100,000, [whereas] African Americans are at a whopping 62 per 100,000.

In one cross-sectional study evaluating the association between COVID-19 infection and mortality rate from 369 counties of 7 states, African Americans were observed to be more vulnerable to the virus than any other ethnic group. Variables irrespective of race that were most closely associated with death rates in the study were medical disabilities, lack of grocery mobility, and poverty.3

In a cohort of patients hospitalized with laboratory-confirmed COVID-19, cancer status, race and ethnicity, and descriptive statistics for baseline characteristics were collected to analyze the cumulative effects in patient mortality.

The findings showed that patients in the COVID-19positive cancer population were more likely to be African American, present at an older age, and have an increased risk of intensive care stay and intubation, as well as a longer duration of hospital and intensive care time, compared with the COVID-19positive population without cancer. There was a trend toward higher rates of death in African Americans, men, and patients on Medicare/Medicaid in the COVID-19positive cancer population, but those associations were not found to be statistically significant.4

There was a disproportionate number of men and specifically, African American men, who were coming in and requiring hospitalization, Steven S. Chang, MD, director of the Head and Neck Cancer Program at the Henry Ford Cancer Institute in Detroit, Michigan, said while presenting the data. Once they are in the hospital, their outcomes were similar regardless of race, but the factors that led to the emergency room door were probably the drivers of morbidity.

It has been surmised that higher mortality and infection rates among racial minorities may be due to disproportionally increased nonCOVID-19 comorbidities seen in stratified patient subgroups.

African Americans in particular carry more health conditions making them more susceptible to COVID-19, with a higher vulnerability index in the middle and older ages and higher numbers of comorbid risk factorscompared with non-Hispanic whites, Carethers said.

However, recent studies suggest that this may not represent the full scope of the issue. In one study, the risk of testing positive for the virus by race and ethnicity compared with the non-Hispanic white population carried higher odds ratios (ORs) in patients who identified as Hispanic/Latino (age-adjusted OR, 2.69; 95% CI, 2.14-3.39), African American (age-adjusted OR, 3.69; 95% CI, 2.83-4.81), and Asian (age-adjusted OR, 1.87; 95% CI, 1.36-2.58). When adjusted for sex, history of diabetes, heart disease, lung disease, kidney disease, current smoker status, and body mass index, corresponding ORs in the same patient subgroups did not change drastically (multivariate OR, Hispanic/Latino [2.68; 95% CI, 2.13-3.38], African American [3.51; 95% CI, 2.68-4.60], and Asian [1.97; 95% CI, 1.43-2.73]).5

Hydroxychloroquine, a drug used to prevent and treat COVID-19 in the early days of the pandemic, was since found to offer no benefit to infected patients.6 In patients who have a sodium channel variant known as p.Ser1103Tyr-SCN5A, seen in 1 in 13 African Americans, there is a higher risk of heart arrythmia and sudden cardiac death, which can be exacerbated by COVID-19related conditions such as hypoxia, myocardial injury, cytokine storm, and use of QTc-prolonging drugs.7

The coalescing of these 3 items puts the patient at extremely high risk for sudden cardiac death, said Carethers, although he noted that there arent any study findings to confirm this association.

Sexual dimorphic responses to COVID-19 may be due to expression of the receptor ACE2 and serine protease TMPRSS2 for S protein priming, which both are necessary cellular factors for virus entry to human cells.8 Preexisting conditions may explain why these have upregulated expression in certain patients. In patients with asthma, those who were men, African American, and/or had diabetes all had increased ACE2 and/or TMPRSS2 from collected sputum cells, providing rationale for monitoring these subgroups for COVID-19 outcomes.9 Patients with lung diseases, including cancer, also have increased expression of TMPRSS2.10

Carethers also pointed out that a societal picture could provide the greatest rationale for disparities in infection rates and outcomes in patients infected with COVID-19

It starts with socioeconomic inequality, where you have lower status, lower level of education, and difficult access to health care that causes downstream consequences [FIGURE], Carethers said.2,11 This in turn causes changes to physiology, which include alterations to the lung and gut microbiome, increased localized inflammation, and compromised immunity. That affects the pathophysiologic health morbidities of cancer, obesity, diabetes, COPD [chronic obstructive pulmonary disorder] and asthma, hypertension, and cardiovascular and chronic kidney disease.

The high unemployment rate, in large part caused by the pandemic, worsens inequities in health care. According to the Bureau of Labor and Statistics, the rate of unemployment in May was at 13.3, the highest since level since the Great Depression. Importantly, job loss for many patients also leads to loss of medical insurance and in turn reduces access to cancer screening.

In one study that used data from the National Health Interview Survey, the relationship between unemployment, health insurance status, and cancer screening was examined to inform the potential lasting effects of COVID-19. Forty percent of patients who were unemployed were also uninsured versus roughly 10% of those who were currently working, with unemployed individuals more likely to have Medicaid. Racial minority groups were also more likely to be unemployed than employed, including Hispanic and African American respondents.12

Controlling for nonmodifiable risk factors, unemployed individuals were less likely to be up-to-date on breast and colorectal cancer screenings, leading the investigators to conclude that unemployment is adversely associated with guideline-recommended care.

This is concerning because we know that cancer screening can potentially save lives, Stacey A. Fedewa, PhD, an epidemiologist and senior principal scientist in the Surveillance and Health Services Research Program at the American Cancer Society, said while presenting the study data. Because a growing number of people are losing their jobs and several racial and ethnic minority groups are more likely to be unemployed, this could drive disparities even further than what is seen now.

Carethers concluded by reflecting on how socioeconomic and biological factors together explain why these differences in outcome may exist. In many ways, the disparities observed with COVID-19 may start from socioeconomic vulnerabilities that enter a vicious cycle of comorbidities, increased ACE2 and TMPRESS2 expression that [boosts] ones susceptibility to COVID-19, and lead to severe illness and death, he said. If one survives, they become more vulnerable from the aftereffects of COVID-19 and more socioeconomically disadvantaged with loss of jobs.

Although Carethers acknowledged that there is no quick fix for these issues, he is optimistic that bringing these data to the surface will help undermine some of the structural issues that are responsible for aggravating health disparities. COVID-19 has enhanced the visibility of some of the [structural inequalities] that we have in the United States, and most people are seeing that, he said.

This is the first article in a series related to health disparities and their effects on patients with cancer. In the next issue, inequities seen in conducting clinical trials will be reviewed.

References:

1. People with certain medical conditions. CDC. Updated July 17, 2020. Accessed July 23, 2020. https://bit.ly/2WOVvN0

2. Carethers JM. Potential insights into COVID-19 disparities from the science of cancer health disparities. Presented at: American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer; July 20-22, 2020.

3. Abedi V, Olulana O, Avula V, et al. Racial, economic and health inequality and COVID-19 infection in the United States. medRxiv. Published online May 1, 2020. doi:10.1101/2020.04.26.20079756

4. Chang SS, Hwang C, Elshaikh MA, et al. Outcomes by race for cancer patients hospitalized with SARS-CoV-2 infection. Presented at: American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer; July 20-22, 2020.

5. Lo CH, Nguyen LH, Drew DA, et al. Racial and ethnic determinants of Covid-19 risk. medRxiv. Published online June 20, 2020. doi:10.1101/2020.06.18.20134742 6. Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;382(25):24112418. doi:10.1056/NEJMoa2012410

7. Giudicessi JR, Roden DM, Wilde AAM, Ackerman MJ. Genetic susceptibility for COVID-19-associated sudden cardiac death in African Americans. Heart Rhythm. Published online May 5, 2020. doi:10.1016/j. hrthm.2020.04.045

8. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8. doi:10.1016/j. cell.2020.02.052

9. Peters MC, Sajuthi S, Deford P, et al. COVID-19-related genes in sputum cells in asthma. relationship to demographic features and corticosteroids. Am J Respir Crit Care Med. 2020;202(1):83-90. doi:10.1164/ rccm.202003-0821OC

10. Pinto BGG, Oliveira AER, Singh Y, et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. medRxiv. Published online March 27, 2020. doi:10.1101/2020.03.21.20040261

11. Carethers JM, Doubeni CA. Causes of socioeconomic disparities in colorectal cancer and intervention framework and strategies. Gastroenterology. 2020;158(2):354-367. doi:10.1053/j.gastro.2019.10.029

12. Fedewa SA, Yabroff KR, Zheng Z, et al. Unemployment and cancer screening: baseline estimates to inform healthcare provision in the context of COVID-19 economic distress. Presented at: American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer; July 20-22, 2020.

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Closing Gaps in Care: COVID-19 in Patients With Cancer Bring Health Inequities to the Surface - Targeted Oncology

Dairy cows could be genetically selected to produce "niche milk to improve human health, including a component that provides some benefits of human breast milk, according to an Agriculture Victoria scientist.

And this technology could deliver the dairy industry a step-change in terms of what it could produce with infant formula.

Agriculture Victoria principal research scientist Jennie Pryce said there was great science behind the opportunity to breed cows to produce human milk oligosaccharides.

They are the same as you would find in the milk of human breast milk and give children or babies protection against pathogenic infections, she said.

They also promote development of the intestine and help the gut microbiome to get going, obviously thats one of the reasons why breast milk is promoted.

Professor Pryce was speaking at a presentation about breeding the socially acceptable cow at the 2020 Genetics Australia online conference.

She said a genetic marker explained about 80 per cent of the genetic variation in the oligosaccharide, which meant it would be simple to aggressively select for these niche milks.

Breeding a socially acceptable cow should also consider the cows impact on the environment, its welfare and sustainability, she said.

Sharing preliminary research data, Prof Pryce showed how selecting for bulls with both a high Balanced Performance Index (BPI) and lower methane emissions was possible without too much compromise in profitability.

Prof Pryce plotted the BPI the dairy industry herd improvement organisation DataGenes economic index against a greenhouse gas index.

It showed if a dairy farmer only selected high BPI bulls with the most favourable greenhouse gas emissions, they would compromise their BPI by about 20 units.

This is down from a mean of 333 BPI if they selected the top 30 BPI bulls without a consideration of emissions.

It doesnt seem like a huge comprise to be able to get that advance in terms of reduced emissions, Prof Pryce said.

She also highlighted how Australia led the world with research on heat tolerance and feed saved both traits with contributed to a socially acceptable cow.

The former Australian Breeding Value enables cows to better handle warming temperatures, the latter ABV increasing their feed-to-milk efficiency.

Prof Pryce said a lot of what the dairy industry was already doing was hugely progressive.

Consumers need to know that we are already breeding for more environmentally friendly, resource efficient cows.

If we focus on profit, welfare and social acceptability we will be more successful in the long term.

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Gains for humans, cows and the environment in breeding a socially acceptable cow - Dairy News Australia

Published Aug 22, 2020 at 8:00 am(Updated Aug 22, 2020 at 6:51 am)

Coming back: Carika Weldon (File photograph by Blaire Simmons)

An expanded government laboratory will be set up at Bermuda College to help train scientists in an amazing achievement for the island, the Premier said.

David Burt revealed that Carika Weldon, a geneticist, will move back home from Britain to set up the enhanced site, which is expected to help tackle the increased number of Covid-19 tests. He said that he was elated that she decided to relocate.

Mr Burt said at the regular Covid-19 briefing on Thursday: We will be establishing and moving the government lab from its temporary facility, which is at an undisclosed location, to a new and expanded facility at the Bermuda College.

That facility at the Bermuda College will not only enable Dr Carika Weldon to establish the lab a government laboratory there but also to expand what is being done there because some of the capacity issues which we are having with the increase of testing is due to the temporary nature of the small space where Dr Weldon and the Molecular Diagnostic Lab is located.

He added: It will enable us to start teaching laboratory science in Bermuda and so this is an amazing accomplishment.

Mr Burt denied a suggestion that Dr Weldon had resigned her post at the MDL.

Dr Weldon was a researcher at the Oxford Genomics Centre, part of Oxford University Hospitals, before she returned to Bermuda to boost the islands coronavirus test capabilities in April.

Lieutenant-Colonel David Burch, the public works minister, said earlier that Dr Weldon spent her 14-day quarantine period co-ordinating the set-up of the MDL.

She led the work at the laboratory when it launched later that month.

The Premier added: We are moving the lab from its undisclosed location to the Bermuda College, expanding the service which we will offer and making sure that we can expand the training opportunities that are there at the Bermuda College.

I think that this is something that is amazing and Bermuda is very fortunate and Im myself pleased that a doctor who has taught overseas has decided to come back home and to assist us in the work which we are doing.

Dr Weldon told The Royal Gazette in March that she would like to be able to help with Covid-19 testing in Bermuda.

She added then: All the steps of how the test is conducted are what I teach in my science outreach.

This whole situation has really brought to light how urgently Bermuda needs human genetics research on island.

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Returning Weldon to head up full-time lab - Royal Gazette

Babies who are born prematurely have to fight through days, weeks, or even months of stressful existence.

University of Connecticut School of Nursing professor Xiaomei Cong saw this struggle firsthand working as a registered nurse in a neonatal intensive care unit (NICU) early in her career. She watched as these vulnerable newborns underwent up to 20 painful procedures a day. She had always been a practitioner, but these experiences pointed her towards providing support through research and innovation.

These stressful events can have long-term neurobehavioral effects. These effects are one of the focuses of Congs research.

One of Congs earlier studies focused on how Kangaroo Care a method of holding newborns can alleviate NICU procedural pain. Kangaroo Care involves skin-to-skin contact, an important aspect for any babys development. Cong found for neonates undergoing painful procedures, this has an added benefit of alleviating some of the pain and stress that those procedures induce.

Cong also studies longer-term effects of these stressful events early in life. Focusing on children from birth to three years old, Cong looks at their language development, weight, height, emotional development, cognition and how these children respond to stressful events.

Much of Congs current research focuses on using biomarkers to measure stress in babies. Neonates cannot express when they are experiencing stress or pain in the same way older children can. Cong has thus looked to biomarkers like cortisol, a stress hormone and oxytocin, a love hormone or cuddle chemical in neonates saliva. These chemicals can tell researchers and clinicians a lot about how a baby is handling stress without words.

Whats in the gut

Congs research has recently pivoted to look at neonates microbiome. The microbiome is a dynamic system of bacteria, microbes, and other organisms that live in and on the human body. The organisms in the microbiome outnumber cells in a human body by approximately 10 to one.

The microbiome supports important digestion, immunity, and nutrition functions. A person accumulates their unique microbiome over their lifetime. Babies are born as a clean slate and begin growing their biome right from birth. The first few months of life are key to developing a healthy biome for the rest of a persons life.

They undergo big changes in those first few weeks of life, Cong says.

When babies are in the NICU, they are not exposed to the normal bacteria and microbes because their health is so fragile.

One of Congs current studies looks at mothers who are unable to breastfeed their infants in the NICU. Often, these babies will be tube-fed pasteurized breastmilk from donors. Compared to mothers own milk, this milk may have disadvantages, because pasteurization kills many of the helpful bacteria and microbes along with those which may endanger the babies nascent immune systems.

It has the same nutritional value, but hampers the development of the microbiome, Cong says.

Cong has found that milk from the babys own mother, even if it has to be through tube-feeding for the very premature infant, is better for the babys microbiome development than that of pasteurized donor milk.

This finding helps inform clinical practice, as doctors and nurses can encourage mothers to send their own milk to the NICU even when they cannot breastfeed directly.

Cong also studies stool samples from neonates to look for additional biomarkers that reveal the development and health of their microbiome, as well as the microbiome of people with Irritable Bowel Syndrome (IBS). Cong is studying the manifestations of emotional stress in patients with IBS using many of the same concepts she uses to study neonates in the NICU.

Keeping up with tech

More recently, Cong has also used genetic markers to study this aspect of neonates experience in the NICU. The emergence of genomic science has provided a new avenue for Cong to expand her research.

We always have these new technologies, Cong says. Especially in recent years with genetics and genome science, we really have to catch up with whats going on there.

These advancements have shown Cong how important fruitful collaborations with other researchers can be. Cong works with researchers at Connecticut Childrens Medical Center and The Jackson Laboratory for Genomic Medicine, who have expertise in areas that can inform her research.

You always have to learn some new thing, Cong says. And that often means you have to build up your team and work together.

Cong also works closely with the Microbial Analysis, Resources and Services (MARS) center, which is part of UConns Center for Open Research Resources and Equipment (COR2E), which conducts microbiome sequencing. Cong is also the director of the UConn School of Nursings Biobehavioral Research Lab.

All the collaborations are so important to our studies, Cong says. We get amazing results.

Not just on paper

One of the most rewarding aspects of her work for Cong is how directly it can be applied and have real-life impacts.

It goes into clinical practice, Cong says. Its not just on the paper.

The goal of Congs research is to improve the short- and long-term neurodevelopment and quality of life for babies who start their lives in the NICU.

Cong says she sees her research continuing in new directions facilitated by technological developments which support new avenues for her work.

Definitely we want to see all these babies have an improved quality of life and better health later in life, Cong says.

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Excerpt from:
Meet the Researcher: Xiaomei Cong, School of Nursing - UConn Today