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Genetics

A $140,000 lesson in the economics of bovine genetics and breeding – CBC.ca

A black Anguscow from Coaldale, Alta.sold for a record $140,000 earlier this month, setting a record for a southern Alberta auction house and the industry as a whole.

Listed as U2 Erelite 109z in the auction catalogue, the salewas part of U2 Ranch Ltd.'s complete herd dispersal, held atthe Perlich Bros.Auction Marketin Lethbridge, Alta.

It was standing room only at the auction,with buyers from Canada, the United States, Mexico and Europe all hoping to get the chance to own the prized animal.

"The sale started on Monday, Nov. 12," recalls Ken Perlich,one of the five family partners who own and operate the auction.

"We sold all through the red [Angus] andthe top seller there was $65,000. That was very impressive. Then the next day when the black [Angus] came in, theytopped-out the the two-day sale at at $140,000. That was truly amazing," Perlich said.

"I think the [seller's] family was surprised. We were surprised," Perlich said.

"I don't think there was anybody there that expected that kind of price range."

The auction catalogue included a detailed description of the $140,000 cow.

"109z is the most influential cow to walk our pastures," itreads.

"She is admired by all with her unique blend of massive power and exquisite femininity. She and her daughters are beyond compare for teat spacing and udder quality."

Every rancher is lookingfor different traits in a bred cowto improve the quality of theirherd. The Canadian Angus Association evaluates about 25 different traits.

That's why there's so much detail in the auction catalogue descriptions like those listed above.

"[109z]ranks in the top one percent for Weaning Weight, Yearling Weight and Total Maternal Value. Since 2015 she has had a perfect production record and turned into a very productive donor," read the catalogue.

$140,000 seems like a lot of money for one cowto many outside thecattle industry.

But insiders say that a price for bovine that's higher than a Buick shouldn't be a surprise.

"It's not uncommon for an Angus female to sell for $25,000up to $50,000," saidMylesImmerkar,Chief Executive Officer of the Canadian Angus Association.

ManyAngus bred cows will sell for $1,000 to $2,500 each.

When it comes to 109zspecifically, Immerkar says the value of that cow came down to her total maternal value.

If you're buying 109z, you're not buying her for meat. You're buying her for her production record and her pedigree.

When it comes to her breeding potential, 109zis a pregnant 8-year old cow. She's no spring chicken, but in those years she's proven herself.

All three of her sonshave sold to purebred herds.One bull, named Coalition, sold for $32,000. Anothercalled Temptation soldfor over $47,000.

While 109z is entering her twilight years, she's not done producing yet.

She's likely got another two to sevenbreeding years left in her.

Every year she'll give birth to a single calf and produce another 25 to 30 embryos, which can be transplanted into surrogate cows or sold for hundreds of dollars each.

If all goes well, 109z could produce over two dozen calves every yearfor the rest of her fertile life, which could mean hundreds of thousands of dollars.

So what does all this mean for the average Canadian beef eater?

Nothing directly. You're never going to find cuts from a $140,000dollar animal on sale at Safeway or Loblaws.

However, the meat from her lineagewilleventually end up on your kitchen table because 109z'sprogeny will pass her expensive genetics to the greater North American Angus herd.

Some of those genes will end up in the commercial sector, which provides meat for fine butchers, steak houses even on the menuat mass-market burger chains such asMcDonalds or Harvey's.

Genes matter because producers are always striving to breed better beef.

Sciencecan't help usgrow a better burger, so instead it helps the herd through selective breeding.

"Well, certainly [109z] isa recordwithin our association in Canada for a female selling," saidMylesImmerkar,Chief Executive Officer of the Canadian Angus Association.

"Earlier this year we did have another record where a bull sold for$200,000," he said.

At the Perlich Bros. Auction, the sale of 109z will stand as an important day in the market's 52-year history.

"It was a historic thing fornot just the cattle industry or the Angus industry but for our family business," saidMaureen Perlich-Kasko, whowas on the block during the historic sale.

"I don't think we'll ever be a part of anything so momentous. It's something we're very proud of, that it got to happen here and that we werea part of that day."

Written and produced by Tracy Fuller.

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A $140,000 lesson in the economics of bovine genetics and breeding - CBC.ca

Genetics

Genetic Databases Are Leaving Marginalised People out of Their Data – The Wire

Imagine this: you are a cash-strapped early-career health scientist, looking for your next big project. One day, you get your big break the chance to study half a million people, and the freedom to focus on virtually any topic you like, from DNA mutations to blue cheese intake.Best of all, this study will cost you virtually nothing.

Its easy to imagine that organisations like the UK Biobank make anything possible. Biobanks are huge repositories containing health, genetic, and demographic information from volunteers. Researchers look through the vast amount of data to find new health patterns and trends. There are few limits: you can analyse scans of volunteers hearts, infer their sexual behaviours, or study their reasoning skills.

Over 850 UK Biobank papers have been published, with new studies appearing in journals constantly. Studies so far have found results which could improve global health, such as a study showing that anyone, regardless of their genetic background, can reduce their risk of dementia with a change in lifestyle.

Criticisms of the project include that the research coming out of the UK Biobank will only benefit certain people, and even then, the usefulness of the health associations found are under question.

Compared to the 2011 UK census, Black, Indian, Pakistani and Chinese participants are all underrepresented in the Biobank by at least one third. David Curtis, at University College London, tested whether this under-representation of ethnic minority groups has any impact on schizophrenia genetics research.

Also read:How Do We Stop Genetic Medicine From Perpetuating Inequality?

He found that calculating the risk for schizophrenia when using Biobank data is only accurate for white European populations. This means that in the future, white people could be offered genetic tests for certain health conditions, while other people could be offered incorrect or no testing at all.

This is because of the complex evolutionary history of humans. While humans who migrated out of Africa and settled in Europe faced bottlenecks where their genetic diversity was reduced dramatically, Africans have maintained large and diverse populations, and so have a more unique genetic makeup.

Other researchers are investigating the Biobanks data as well. Na Cai, a statistical geneticist at the Wellcome Trust Sanger Institute and European Bioinformatics Institute, began thinking about howwhat gets putinto the Biobank affects what conclusions come out of it, similar to Curtis study on schizophrenia.

In herstudy, currently a pre-print posted on bioRxiv, Cai and colleagues decided to focus on major depressive disorder. Depression is one of the most common mental health disorders, and has been a major topic of investigation in genetic association studies.

Because of this, Cai was concerned that researchers might not be investigating depression specifically, but instead looking at the genetics of poor mental health in general.

Cai defined depression in five different ways, using both strict and loose criteria. For example, some people might tell their doctor that they feel depressed, but not meet the specific psychiatric definition of major depressive disorder. She looked to see if the same genetic variants were associated with each different definition of depression.

The results were surprising. She found less of a genetic contribution towards all the looser definitions of depression compared to the full assessment used by psychiatrists.

Also read:DNA Sequencing Is Inadvertently Exacerbating Social Biases and Inequalities

First, it shows that researchers do not have the power in their studies that they assume they do. Previously, it was assumed that it didnt matter too much if researchers defined depression loosely. It could be that these broader definitions are just milder cases of depression, or show less of a genetic association because more people in these groups are misdiagnosed, which dilutes the signal.

However, when the researchers controlled for these factors, nothing changed. The strict psychiatric definition of depression was still genetically distinct from these other versions, meaning that it had more genes associated with it, and there wasnt much overlap in the genes which all the definitions did share.

A technician works at a genetic testing laboratory in China. Photo: Reuters

This throws into question whether papers which have found links between depression and genes are coming to the right conclusions. Are they finding a genetic basis for major depressive disorder, or are they showing something else like the less specific genetic basis for poor mental health in general?

Both Cai and Curtis conclude that we need to rethink how we collect biobank data. Both issues are the result of design flaws present since the UK Biobanks inception. Cai does not necessarily think all participants need to be assessed by a psychiatrist. She suggests that we use new technologies, such as computer assessments and smartphone behavioral tracking, to diagnose people with clinical depression.

But tackling the lack of diversity in biobank data requires those in charge to recognise that the current design excludes marginalised and hard-to-reach groups.

John Savill, the Chief Executive of the UK Medical Research Council, the organisation which provided major funding for the Biobank, was reported by the Guardian to say in response to Curtis research that I do not think it is helpful to cast concerns over experimental design as equalities issues.

Also read:Widely-Available Genetic Risk Tests Arent Always Useful and Could Even be Harmful

However, David Heel, who is the Chief Investigator of the East London Genes & Health Project, which aims to improve the health of South Asian people in the UK, thinks that the UK Biobanks recruitment tactic of mailing a letter meantBritish-Bangladeshi and British-Pakistani people missed out. When reached via email, Heelsaid that, in regards to volunteers in the project, A much better response rate comes from a face to face discussion, or a trusted setting such as talking at a doctors office.

Curtis also thinks more can be done, but is not optimistic that we can save the UK Biobank from this bias. He saidIt may be too late to try to make the UK Biobank more representative. We may need to look to other initiativesand to look to samples recruited in other countries.

The article was originally published onMassive Science.You can read ithere.

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Genetic Databases Are Leaving Marginalised People out of Their Data - The Wire

Genetics

Genetics and Weather in NL Producing Highest Incidence of Arthritis in Canada – VOCM

Genetics and weather are coming against Newfoundlanders and Labradorians who have the highest incidence of arthritis in Canada.

One in four Newfoundlanders and Labradorians suffer from one form of arthritis or another.

That from the Arthritis Societys Jennifer Henning. She says arthritis is an inflammation of the joint, but there are some 100 different types of the disease which is split into two major categories, inflammatory and degenerative.

Rheumatoid arthritis is an autoimmune attack on the joints by the bodys own immune system. It can happen at any time, and affect the entire body.

Osteoarthritis is the most common form and comes as the result of wear and tear, injury or the general aging process. It involves a degeneration of the cartilage between the bones of the joint.

Both types of arthritis result in significant pain and loss of mobility.

Henning says unfortunately, weather doesnt help.

She says in laymans terms, the body is tighter because its cold, and when its wet the tissues swell, causing a greater amount of pain and inflammation.

She says genetics also play a strong role especially in the inflammatory type of arthritis.

Rheumatoid arthritis is more common in women and is often triggered by a traumatic event like childbirth, injury or illness.

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Genetics and Weather in NL Producing Highest Incidence of Arthritis in Canada - VOCM

Genetics

Alzheimer’s and Autism: Researchers Pinpoint Genetic Mutations Overlapping in Both Diseases – Being Patient

As the quest to understand the complexities of Alzheimers continues, researchers have now identified genetic mutations related to autism that may play a role in the neurodegenerative disease as well.

The study, out of Tel Aviv University, pinpointed thousands of genetic mutations in aging human brains that overlapped with mutations involved in autism and intellectual disability. They also found that many of these mutations occurred in the cell skeleton/transport system, a network of proteins that help organize cells.

We were surprised to find a significant overlap in Alzheimers genes undergoing mutations with genes that impact autism, intellectual disability and mechanisms associated with the cell skeleton/transport system health, Illana Gozes, lead author of the study, said in a news release. Importantly, the cell skeleton/transport system includes the protein Tau, one of the major proteins affected in Alzheimers disease, which form the toxic neurofibrillary tangles

Two decades ago, Gozes and the team at the laboratory discovered a protein known as ADNP. ADNP is mainly known for its connection to ADNP syndrome, a neurodevelopmental disorder that includes intellectual disability and autism spectrum disorder. But the team of researchers identified that ADNP also experiences mutations in the brains of people with Alzheimers.

Gozes built on that in the latest study, which aimed to create a paradigm shift in how people understand Alzheimers. That viewpoint focuses on how genetic alterations that are not inherited, known as mosaic somatic mutations, lead to brain pathology and disease.

The researchers hope the research will help lead to new therapeutic channels down the road.

We found in cell cultures that the ADNP-derived snippet, the drug candidate NAP, inhibited mutated-ADNP toxicity and enhanced the healthy function of Tau, Gozes said. We hope that new diagnostics and treatment modes will be developed based on our discoveries.

Genetics continues to be a large area of research around Alzheimers and dementia. Recently, researchers discovered that a genetic mutation known as APOE3ch delayed a womans high risk of developing Alzheimers by three decades.

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Alzheimer's and Autism: Researchers Pinpoint Genetic Mutations Overlapping in Both Diseases - Being Patient

Genetics

Collection of genetic data leads to privacy concerns – The New Economy

A DNA test can reveal surprising facts about us certain genes make us more inclined to have dry earwax, for example, and others make us more likely to sneeze when we see a bright light. Some genes even result in people being more attractive targets for mosquitoes, so if youve ever felt personally singled out by the insect during the summer months, its not a cruel conspiracy its your DNA.

Innocuous facts like these were what DNA kits were used for finding out when they first became commercially available. However, as the tests have become more sophisticated, the companies behind them have shifted their marketing focus. Users of at-home DNA tests have been known to uncover deep-rooted facts about themselves, from discovering long-lost relatives to learning of their ancestors origins and their susceptibility to genetic diseases.

Finding out that you have a pre-existing health condition might not seem like the best idea for a Christmas present, but that hasnt stopped the test kits from enjoying a surge in popularity. MIT Technology Review estimates that by the start of 2019, more than 26 million people had taken an at-home ancestry test. The market is expected to be worth $45bn by 2024.

Nevertheless, despite the emerging industrys rampant growth, there have been mounting concerns that its practices could infringe on consumers rights. Whenever people fork out $100 to $200 for a DNA test, the hidden cost of that transaction is their personal data which, from then on, is held in the databases of a private company. Once these companies obtain genetic information, its very difficult for users to get it back.

By taking DNA tests at home, many have unwittingly stumbled upon long-kept family secrets. Some have seen their parents go through a bitter divorce after their test revealed they were actually conceived through an affair

Ignorance is blissLong before people were able to take DNA tests from the comfort of their own home, psychologists worried about their possible impact on peoples mental health. Ever since the Human Genome Project was started in 1990, many scholars have maintained that DNA tests should be used with caution, on the grounds that understanding ones own health risks could lead to anxiety or depression.

Conversely, a study by the Hastings Centre found that discovering an increased risk of developing Alzheimers disease did not make people more depressed or anxious. And in the event that people discover a particularly urgent health risk like a mutation of the BRCA1 or BRCA2 genes, which puts individuals at a high risk of developing cancer at a young age any adverse psychological effects are presumably worth it to obtain this life-saving information.

However, at-home DNA tests could still pose a risk to mental health, in part because they remove medical professionals from the equation. Adrian Mark Thorogood, Academic Associate at the Centre of Genomics and Policy, warned that this is far from best practice for receiving a DNA test result. Results should be communicated through a medical professional who can interpret the result in the individuals specific context, and offer a clear description of the tests limits, he told The New Economy.

Without a professionals assistance, users could be left alone to battle with a troubling revelation about their health. There is also a danger that without guidance, some people could misinterpret their test result, placing undue stress on their mental health.

There is another unpleasant discovery that people can make through a DNA test one they may be even less prepared for. By taking DNA tests at home, many have unwittingly stumbled upon long-kept family secrets. Some have seen their parents go through a bitter divorce after their test revealed they were actually conceived through an affair. Others have discovered they were conceived by rape and that their mother decided to never tell them. What began as a seemingly harmless urge to find out more about their heritage ends in psychological trauma and family breakdown.

Brianne Kirkpatrick, a genetics counsellor, is part of a growing sector of therapy specifically tailored towards helping people come to terms with receiving unexpected DNA results. One cant help but wonder whether her patients end up wishing theyd never taken the test at all.

I dont recall anyone saying they wish they could go back and not learn the truth, Kirkpatrick said. But I have had a number of people say to me they wish they had found out their shocking information from a person, rather than a computer.

While we might think wed prefer to suffer a DNA leak than a leak of our credit card details, genetic data has its own unique set of complications

The fact that virtually anyone can now find out their real parentage through a simple DNA test has wide-reaching repercussions for the accountability of paternity. Historically, men have always had a much greater ability to conceal their status as a parent, as they dont have to bear the child. The world of direct-to-consumer DNA testing blows this capacity for anonymity out of the water.

This is particularly problematic when it comes to sperm donation. Anonymity is a key selling point for many potential donors, but now all their future biological offspring has to do is swab the inside of their cheek to completely compromise that anonymity. Research suggests that we could see a drop in donor rates as a result. A 2016 study in the Journal of Law and the Biosciences found that 29 percent of potential donors would actually refuse to donate if their name was put on a registry.

The wave of parental discoveries made through direct-to-consumer DNA tests raises questions about where the responsibility of the seller sits in all this. Most health professionals recommend that individuals seek out genetics counselling once they receive DNA results. Some, like Invitae, offer counselling services but arent direct-to-consumer companies. Many of those that are including 23andMe do not offer such a service. It could be argued that this shows a certain disregard for the consequences of using their product. Unfortunately, irresponsible decisions like this have tended to characterise the industrys path to success.

Genetic Wild WestIn September 2019, 17 former employees from the Boston-based genetic testing company Orig3n accused the firm of giving consumers inaccurate results. Allegedly, if a customer took the same test twice, their results could be extremely different each time. A former lab technician produced a leaked report to Bloomberg Businessweek that revealed 407 errors like this hadoccurred over a period of three months.

Part of Orig3ns USP was that it offered advice supposedly calculated based on a consumers genetic profile. Former employees have cast doubt over the companys modus operandi by claiming that the advice they gave was in fact routinely lifted from the internet. The advice given ranged from the technically correct but uninspired to the broadly unhelpful such as telling people to eat more kale and the utterly bogus, like advising clients to eat more sugar to eliminate stretch marks.

Although Orig3n is a relatively small player in the sector, news of this scam nonetheless illustrates how little protection consumers have in this nascent market. Analysts say we are currently witnessing a Wild West period in the consumer genetics space thanks to a lack of regulation, raising concerns over whether we can trust these companies with our genetic data. While we might think wed prefer to suffer a DNA leak than a leak of our credit card details, genetic data has its own unique set of complications.

In the United States, if my social security number is stolen, that is difficult, but not impossible, to get frozen, changed, etc, said Natalie Ram, an associate professor at the University of Maryland Francis King Carey School of Law and a specialist in bioethics and criminal justice. But theres literally no way to change your genetic code.

Genetics platforms like 23andMe, AncestryDNA and FamilyTreeDNA are now sitting on a goldmine of very personal data. In 2013, a 23andMe board member told Fast Company that it wanted to become the Google of personalised healthcare. If this statement makes anything clear, its that the company wasnt planning on making its millions simply by selling DNA test kits: its mission was always to amass significant amounts of data on its users, which it could then monetise.

There is a wide range of reasons why companies might want to buy genetic data. Perhaps the most benign is medical research, which genetics platforms allow users to opt in or out of. But other companies might use your genetic data to better sell you products or, conversely, deny them to you for instance, one sector that would see a clear monetary value in obtaining genetic data is insurance. In the US, the Genetic Information Nondiscrimination Act of 2008 prevents employers and health insurers from using a persons genetic information when making decisions about hiring, firing or raising rates. However, this does not include life insurance or short or long-term disability insurance.

At first glance, it seems as if theres a simple solution: if users are concerned about these risks, they should just choose for their data to be kept anonymous. However, choosing this option is not as foolproof as it once was. As long ago as 2009, researchers demonstrated that they could correctly identify between 40 and 60 percent of all participants in supposedly anonymous DNA databases by comparing large sets of that data with public datasets from censuses or voter lists. Since that experiment, DNA databases have grown massively.

With access to four to five million DNA profiles, upwards of 90 percent of Americans of European descent will be identifiable, said Ram. Its verging on a comprehensive DNA database that no US state or jurisdiction has suggested would be appropriate.

Shaping the lawWith comforting statements like your privacy is very important to us (ancestry.co.uk) and we wont share your DNA (familytreedna.com) emblazoned on their websites, some genetics platforms seem to be making privacy their number one priority. In the US, 23andMe and Ancestry are part of the Coalition for Genetic Data Protection, which lobbies for privacy protection in the DNA space. However, while the coalition advocates genetic data privacy in a specific context, it argues for a one-size-fits-all policy concerning all data. By comparison, the EUs General Data Protection Regulation regards genetic information as personal data, which makes DNA unique from other kinds of data.

There is a fundamental legal problem with boxing genetic data in with all other varieties, including the data that social media websites collect about us. In most cases, what a person does on the internet implicates them alone genetic data is different. We share our DNA with members of our family, which means that sharing it without their consent can be problematic.

Even if I can consent to using my DNA to identify me, that should not extend to my ability to consent to using my DNA to identify my relatives, said Ram. The reason I think thats a really critical distinction is because genetic relatedness is almost always involuntarily foisted upon us. So we dont choose our parents, we dont choose how many siblings we have. Its a product of biology, not a product of choice.

The legal issues surrounding genetic relatedness were put to the test in 2018 when police discovered the true identity of the Golden State Killer, who terrorised California in the 1970s and 1980s in a homicidal spree. Law enforcement officials were able to convict him only because they had succeeded in connecting the DNA of the suspect with that of a family relative on GEDmatch, a genetic database in the public domain. Across the US and around the world, people celebrated the arrest of a notorious criminal. The only problem was that the means of capturing him was not necessarily legal.

Prior to the case, GEDmatchs site policy made no explicit reference to the potential use of consumers data by law enforcement. However, the company defended itself by saying that users should have assumed it could be put to that use.

While the database was created for genealogical research, it is important that GEDmatch participants understand the possible uses of their DNA, including identification of relatives that have committed crimes or were victims of crimes, said GEDmatch operator Curtis Rogers in a statement.

Some genes even result in people being more attractive targets for mosquitoes, so if youve ever felt personally singled out by the insect during the summer months, its not a cruel conspiracy its your DNA

However, privacy advocates like Ram argue that users consent for law enforcement to look at their data should not have been assumed. At least from a constitutional perspective in the United States, individuals ought to be recognised to have whats called an expectation of privacy in their genetic data, even if they use one of these services, she told The New Economy.

After the case, genetics platforms updated their policies to clarify their position on law enforcements use of peoples data. Interestingly, they took very different stances. While 23andMe and Ancestry said they would not allow law enforcement to search through their genetic genealogy databases, FamilyTreeDNA updated its policy to say it would give up data to officials, but only in the investigation of violent crimes. Users didnt know it at the time, but FamilyTreeDNAs policy update was already too little too late: in January 2019, it was revealed that the company had been secretly working with the FBI for nearly a year to solve serious crimes, without informing its users.

The Golden State Killer case exposed how little protection consumers really had in the direct-to-consumer genetics market. It showed that genetics platforms were capable of suddenly changing or contradicting their own policies and even, in the case of FamilyTreeDNA, betraying the trust of consumers.

Some might argue that this infringement on genetic privacy is simply the price we must pay to catch dangerous criminals. Of course, without the use of a genealogy database, the Golden State Killer may never have been caught. But the fact that genetic data can be harnessed to solve very serious crimes should not justify law enforcements unbridled access to such databases. Abuses of power do happen and, in the context of direct-to-consumer DNA tests, they already have: in 2018, for example, Canadian immigration officials compelled a man to take a DNA test and upload his results to FamilyTreeDNAs website. They then used the website to find and contact some of his relatives in the UK to gather more evidence in order to deport him.

Todays consumers are continually adjusting to shrinking levels of privacy. From the introduction of video surveillance and the mapping of residential areas on Google Earth to the revelation that Facebook harvests vast amounts of user data, we have seen the public react in the same way again and again: there is an initial public outcry, and then consumers simply adjust to the new level of diminished privacy. Our response to the rise of genetics platforms risks the issue being consigned to the same fate.

It is up to regulators to protect individuals right to privacy. While our genetic data may be something of a genie out of the bottle, that should not give the companies that collect it free rein over who sees it and what they choose to do with it.

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Collection of genetic data leads to privacy concerns - The New Economy

Cell Biology

Aquatic microorganisms offer important window on the history of life – Arizona State University

November 25, 2019

The air, earth and water of our planet are pulsating with living things. Within it, a vast and diverse web of life exists, about which almost nothing is known. This is the world of flagellates, tiny organisms that persist in staggering numbers in many diverse ecosystems around the world.

According to Jeremy Wideman, a researcher at theBiodesign Center for Mechanisms in Evolutionat Arizona State University, we have a great deal to learn from these delicate and wildly varied creatures. Among other surprises, flagellates could provide valuable clues about a shadowy event that may have occurred 1.5-2 billion years ago (no one is really sure of the timing) with the arrival of a new type of cell. The graphic shows a tree of life for complex forms known as Eukaryotes that arose mysteriously around 1.2-2 billion years ago from a progenitor known as LECA (for Last Eukaryote Common Ancestor.) ASU researcher Jeremy Wideman and his colleagues used a new method to sequence mitochondrial DNA for around 100 species of flagellates tiny aquatic organisms that populate many branches of the tree. These are seen on the graphic as red dots marking the particular lineages these flagellates belong to. Graphic by Shireen Dooling Download Full Image

Known as LECALast Eukaryote Common Ancestor, it was a sort of primal egg out of which the astonishing profusion of complex life from flagellate organisms, fungi and plants, to insects, zebra and humans exploded and spread over the Earth.

In new research appearing today in the journalNature Microbiology, Wideman and his many international colleagues, including Proferssor Thomas Richards at the University of Exeter, describe a new method for investigating the genomes of eukaryotic flagellate organisms, which have been notoriously tricky to pinpoint and sequence.

Specifically, they explored samples of mitochondrial DNA, sequencing around 100 such genomes for previously undocumented flagellates. The new technique could help scientists like Wideman begin to fill in the largely blank region of the eukaryotic puzzle, where flagellate life flourishes.

Wideman, originally a traditional cell biologist, became frustrated with the many unaddressed questions in the field, recently joining the emerging discipline of evolutionary cell biology. This rapidly advancing research area uses cells as fundamental units for the study of evolutionary processes and imports concepts from evolutionary biology to better understand how cells work.

I'm literally a cell biologist that wants to know more about things we know nothing about, he said.

Evolutionary cell biology is a profoundly transdisciplinary endeavor, fusing evolutionary theory, genomics and cell biology with quantitative branches of biochemistry, biophysics and population genetics.

Jeremy Wideman is a researcher in the Biodesign Center for Mechanisms in Evolution and the School of Life Sciences at Arizona State University.

Flagellates include many parasites implicated in human disease, from the intestinal bug Giardia to more damaging trypanosomes and leishmania. Flagellates also perform more benevolent tasks. As the major consumers of bacteria and other protists in aquatic ecosystems, they help ensure the recycling of limiting nutrients.

Single-celled eukaryotic organisms, which include flagellates, constitute the overwhelming majority of eukaryotic diversity, vastly outpacing the more familiar multicellular plants, animals and fungi. Despite their importance and ubiquity across the globe, flagellates are, as Wideman stresses, an almost entirely unknown inhabitant of the living world and one of the most enigmatic. When viewed under a microscope, their often science fiction-like appearance is markedly distinct from the kinds of eukaryotic cells commonly described in biology textbooks. Their emergence from comparatively rudimentary prokaryotes marks the most momentous transition in the history of life on earth.

Novel lineages of heterotrophic flagellates are being discovered at an alarming rate, Wideman said. In the last two years, two kingdom level lineages have been discovered, meaning lineages that have been evolving independently of animals and fungi for over a billion years.

Nevertheless, researchers have barely scratched the surface of this astonishing diversity and new methods must be brought to bear to speed up the quest.

Any drop of pond, lake or ocean water is likely to contain many flagellates, but separating them from a multitude of nonflagellates and accurately reading their genomes by conventional means has been slow and painstaking work. Only a minute fraction of extant flagellates have known genomic sequences and its even possible that the overwhelming majority have never actually been seen. According to Wideman, flagellate life forms represent the "dark matter" of the eukaryotic universe.

HeterotrophicHeterotrophs are organisms that cannot synthesize their own food, relying instead on other organisms for nutrition. flagellates are the target, Wideman said. They're not a lineage. They're many, many lineages that are from all over the tree of life. LECA, the Last Eukaryotic Common Ancestor, was a heterotrophic flagellate, which means that every major lineage (of eukaryotes) evolved from some sort of heterotrophic flagellate.

To access the elusive flagellate mitochondrial DNA, the researchers exploited a feature common to all flagellates and from which they take their name the existence of flagella, which, unlike in animal sperm are on the front of cells and are often used to pull them forward like a microscopic breast stroke but are also involved in sensation, feeding, and perhaps other as-yet unknown functions.

Flagella are rich in a particular protein known as tubulin. The new method for identifying flagellates and distinguishing them from their aquatic neighbors primarily algae and bacteria capitalizes on this fact by applying a selective stain to flagella-bearing organisms, activated by their high tubulin content. (Algal cells are naturally marked by their chloroplasts, which the flagellates of interest in the new study lack.)

Samples of sea water collected in 2014 off the coast of California provided a test case. Using the technique, the researchers gathered a windfall of mitochondrial sequence data, significantly expanding the catalog of flagellates identified by molecular means. Indeed, they doubled the existing mitochondrial DNA library for flagellate organisms.

We got many, many different kinds of organisms. So it was a very rich sample and very few were identical, Wideman said.

Apart from the mystery of lifes origin, the puzzle of where eukaryotes came from and how the LECA event transpired is the most important and vexing unanswered question in all of biology. (It has been dubbed theblack holeat the heart of the living world.)

Correctly establishing the sequence of events underlying the crucial innovations within eukaryotes, from whence all complex life sprang, will take much more research in unexplored regions of the existing eukaryotic domain, particularly, the flagellates. Wideman believes the rapid advance of techniques for identifying and sequencing these organisms, such as the one outlined in the new study, offer hope such questions may one day find answers.

This project was supported by a Gordon and Betty Moore foundation grant (GBMF3307) to 597 TAR, AES, AZW and PJK, and a Philip Leverhulme Award (PLP-2014-147) to TAR. Field sampling was 598 supported by the David and Lucile Packard Foundation and GBMF3788 to AZW. TAR and AM are 599 supported by Royal Society University Research Fellowships. JGW was supported by the European 600 Molecular Biology Organization Long-term Fellowship (ALTF 761-2014) co-funded by European 601 Commission (EMBOCOFUND2012, GA-2012-600394) support from Marie Curie Actions and a College for 602 Life Sciences Fellowship at the Wissenschaftskolleg zu Berlin. RRM is supported by CONICYT FONDECYT 603 11170748. FM is supported by Genome Canada.

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Aquatic microorganisms offer important window on the history of life - Arizona State University

Cell Biology

UpNano: Forging Ahead in Microfabrication With Two-Photon Polymerization – 3DPrint.com

Cell biology has very particular characteristics. During the last decade, researchers and scientists have astounded us with their discoveries in bioprinting and regenerative medicine, proving that a great deal of what happens at the lab is basically knowing and understanding cells. These microscopic structures are the foundation of most projects where cells are patterned to grow into mature tissues, interacting with other cells and non-cellular components of their local environment, such as the extracellular matrix and nutrient sources.

But there have been a few challenges along the way, basically: how to keep the cells alive, what materials to use for cells to live in, and keeping up with the requirements of micro parts in the production sector as well as in academic and industrial research. And that is a big part of bioprinting. Tissue growth and the behavior of cells can be controlled and investigated particularly well by embedding the cells in a delicate 3D framework, yet some methods are very imprecise or only allow a very short time window in which the cells can be processed without being damaged. Moreover, the materials used must be cell-friendly during and after the process, restricting the variety of possible materials, which includes biocompatible synthetic and natural polymers. Now a new high-resolution bioprinting process developed at Vienna University of Technology (TU Wien), in Austria, ensures living cells can be integrated into fine structures created in a 3D printer extremely fast.

Thanks to a special bioink and 3D printing system, cells can be embedded in a 3D matrix printed with micrometer precision, at a printing speed of one meter per second. This high-resolution bioprinting process with completely new materials allows the fabrication of structures and surface textures mimicking the microenvironment of cells.

The behavior of a cell depends crucially on the mechanical, chemical and geometric properties of its environment, said Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at the Institute of Materials Science and Technology at TU Wien. The structures in which the cells are embedded must be permeable to nutrients so that the cells can survive and multiply. But it is also important whether the structures are stiff or flexible and whether they are stable or degrade over time.

The high-resolution 3D printing technology and the materials are being commercialized by UpNano GmbH, a spin-off company of TU Wien. The ultrafast high-resolution 3D printing system called NanoOne is based on multiphoton lithography and combines the precision of two-photon polymerization. UpNano claims that their patented process enables the batch production of microparts with the highest resolution and complexity in the market, enabling the economic production of polymer parts from micro to mesoscale. The biocompatible process in combination with optimized materials facilitates cell, tissue, and biofabrication. Meaning that the living cells of choice can be mixed into the material and printed directly or seeded on sterile, pre-fabricated scaffold structures.

NanoOne 3D printing system

In order to achieve an extremely high resolution, two-photon polymerization methods have been used at TU Wien for years. This method uses a chemical reaction that is only initiated when a molecule of the material simultaneously absorbs two photons of the laser beam. According to the institute, this is only possible where the laser beam has a particularly high intensity. At these points, the substance hardens, while it remains liquid everywhere else. Therefore, this two-photon method is best suited to produce extremely fine structures with high precision.

However, these high-resolution techniques usually have the disadvantage of being very slowoften in the range of micrometers or a few millimeters per second. At TU Wien, however, cell-friendly materials can be processed at a speed of more than one meter per second, and they claim that only if the entire process can be completed within a few hours there is a good chance of the cells surviving and developing further.

Aleksandr Ovsianikov

According to Ovsianikov, printing microscopically fine 3D objects is no longer a problem today, however, the use of living cells presents science with completely new challenges: until now, there has simply been a lack of suitable chemical substances. You need liquids or gels that solidify precisely where you illuminate them with a focused laser beam. However, these materials must not be harmful to the cells, and the whole process has to happen extremely quickly.

UpNanos high-performance two-photon materials are engineered and optimized to utilize the full potential of the NanoOne printing system. In addition to UpBio, the hydrogel material for biological applications and bioprinting, UpNano offers photopolymers (UpPhoto) and sol-gel hybrid materials (UpSol). Living cells of choice can be mixed into the material and printed directly, and cells embedded in an UpBio matrix can be used for 3D in vitro cell tests, which gain increasing importance in cell culture, tissue regeneration and pharmaceutical research.

Our method provides many possibilities to adapt to the environment of the cells. Depending on how the structure is built, it can be made stiffer or softer. Even fine, continuous gradients are possible. In this way, we can define exactly how the structure should look in order to allow the desired kind of cell growth and cell migration. The laser intensity can also be used to determine how easily the structure will be degraded over time.

Ovsianikov is convinced that this is an important step forward for cell research: Using these 3D scaffolds, it is possible to investigate the behavior of cells with previously unattainable accuracy. It is possible to study the spread of diseases, and if stem cells are used, it is even possible to produce tailor-made tissue in this way.

The research project is an international and interdisciplinary cooperation in which three different institutes of the TU Vienna were involved: Ovsianikovs research group was responsible for the printing technology itself, the Institute of Applied Synthetic Chemistry at TU Wien developed fast and cell-friendly photoinitiators (the substances that initiate the hardening process when illuminated) and TU Wiens Institute of Lightweight Structures and Structural Biomechanics analyzed the mechanical properties of the printed structures.

Cells spreading in a 3D scaffold. From left to right: week 1, week 3 week 5. Top: 3D setup, bottom: one layer only.

The advantages of the NanoOne high-resolution printing system enable the additive manufacturing of polymeric microparts in research, science, and industry, with achievable part sizes, ranging from micro to mesoscale, with structure details in a submicrometer range and throughput of the system that opens up a universe of application possibilities. Considering that UpNano is a very new company, founded in 2018, we can expect researchers to come up with some very interesting solutions in a universe of applications.

Join the discussion of this and other 3D printing topics at3DPrintBoard.com.

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UpNano: Forging Ahead in Microfabrication With Two-Photon Polymerization - 3DPrint.com

Cell Biology

Combination therapy using malaria drug quickly clears TB – The Hindu

Researchers from Bengaluru have made an important discovery of the mechanism used by TB bacteria to tolerate TB drugs, which necessitates longer treatment of six-nine months. They have also demonstrated that a drug combination that prevents the bacteria from inducing this mechanism leads to almost complete clearance of the bacteria from the mice lungs in just two months of therapy. If further studies and trials show similar results, a shorter treatment regimen might be sufficient to treat drug-sensitive TB.

The common notion is that only the non-replicating or slowly metabolising TB bacteria become tolerant to anti-TB drugs. But the team led by Amit Singh from the Department of Microbiology and Cell Biology, and Centre for Infectious Disease Research at the Indian Institute of Science (IISc) found a fraction of the bacteria inside the macrophages was able to tolerate anti-TB drugs even when actively multiplying.

The researchers found that using an already approved anti-malaria drug chloroquine in combination with a TB drug isoniazid can almost clear all the bacteria from the lungs of mice and guinea pigs in just eight weeks. In addition, the drug combination also reduces the chances of TB relapse. The results were published in the journal Science Translational Medicine.

Reducing the pH to make it acidic is the first-line of defence by macrophages when infected with pathogens. But the researchers found that instead of controlling the TB bacteria, the mildly acidic pH was actually facilitating a fraction of the bacteria to continue multiplying and develop drug tolerance.

We used a biosensor which we had developed a few years ago to see the amount of oxidative stress inside the TB bacteria during infection. We found that anti-TB drugs induce oxidative stress to kill bacteria inside macrophages. However, the drug tolerant bacteria have a remarkable ability to counter oxidative stress, says Prof. Singh. The bacteria used the acidic pH of macrophages as a cue to specifically increase its capacity to deal with oxidative stress. Also, the drug-tolerant bacteria induce efflux pumps to expel antibiotics as an additional mechanism to reduce antibiotic efficacy.

The drug-tolerant bacteria were found in macrophages that were more acidic (pH 5.8) while the drug-sensitive bacteria were seen in macrophages that were less acidic (pH 6.6).

We hypothesised that reverting the pH within macrophages to its normal state could probably make the bacteria sensitive to antibiotics, Prof. Singh says. The chloroquine drug does just that it neutralises the pH within the macrophages. This prevented the bacteria from inducing the mechanism to protect themselves from oxidative stress. So no drug-tolerant TB bacteria emerged. Once the pH is neutralised, the isoniazid drug was able to eradicate TB from animals.

While the two-month treatment was able to completely sterilise mouse lungs, a near-complete eradication was observed from the lungs of guinea pigs. The combination was shown to reduce TB bacteria load in both mice and guinea pigs, says Richa Mishra from IISc and the first author of the paper.

In the case of in vitro studies using cell lines and mice macrophages, the ability of the combination drug therapy to reduce TB load was found to be three- to fivefold higher than when treated only with TB drugs. Reduction in bacteria load was more when we combined chloroquine with isoniazid, says Mishra. We observed threefold reduction when we combined chloroquine with rifampicin and fivefold reduction when we used chloroquine-isoniazid combination.

To determine TB relapse following treatment, mice infected with TB were completely rid of bacteria using the drug combination. Eight weeks later, the immune system of mice was suppressed using a drug. While all the five mice treated with only isoniazid relapsed with high bacterial load, three of the five mice treated with the combination drug showed very little presence of bacteria. This shows that the drug combination reduces the chances of TB relapse, says Mishra.

The work was carried out in collaboration with researchers from Bengalurus National Centre for Biological Sciences and Foundation for Neglected Disease Research.

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Combination therapy using malaria drug quickly clears TB - The Hindu

Cell Biology

How Flight Feathers Evolved: Study of Chickens, Ostriches, Penguins, Ducks and Eagles – SciTechDaily

This picture shows a spirited flying Taiwan Blue Magpie displaying a full array of flight feathers in action. Credit: Shao Huan Lang

If you took a careful look at the feathers on a chicken, youd find many different forms within the same birdeven within a single feather. The diversity of feather shapes and functions expands vastly when you consider the feathers of birds ranging from ostriches to penguins to hummingbirds. Now, researchers reporting in the journal Cell on November 27, 2019, have taken a multidisciplinary approach to understanding how all those feathers get made.

We always wonder how birds can fly and in different ways, says corresponding author Cheng-Ming Chuong of the University of Southern California, Los Angeles. Some soar like eagles, while others require rapid flapping of wings like hummingbirds. Some birds, including ostriches and penguins, dont fly at all.

This picture shows a the asymmetric vane and tapering main shaft of a single flight feather from a goshawk. Credit: Hao Howard Wu and Wen Tau Juan

Such differences in flight styles are largely due to the characteristics of their flight feathers, Chuong adds. We wanted to learn how flight feathers are made so we can understand nature better and learn principles of bioinspired architecture.

In the new study, the researchers put together a multidisciplinary team to look at feathers in many different ways, from their biophysical properties to the underlying molecular biology that allows their formation from stem cells in the skin. They examined the feathers of flightless ostriches, short-distance flying chickens, soaring ducks and eagles, and high-frequency flying sparrows. They studied the extremes by including hummingbirds and penguins. To better understand how feathers have evolved and changed over evolutionary time, the team also looked to feathers that are nearly 100 million years old, found embedded and preserved in amber in Myanmar.

Based on their findings, the researchers explain that feathers modular structure allowed birds to adapt over evolutionary time, helping them to succeed in the many different environments in which birds live today. Their structure also allows for the specialization of feathers in different parts of an individual birds body.

The flight feather is made of two highly adaptable architectural modules: the central shaft, or rachis, and the peripheral vane. The rachis is a composite beam made of a porous medulla that keeps feathers light surrounded by a rigid cortex that adds strength. Their studies show that these two components of the rachis allow for highly flexible designs that enabled to fly or otherwise get around in different ways. The researchers also revealed the underlying molecular signals, including Bmp and Ski, that guide the development of those design features.

Attached to the rachis is the feather vane. The vane is the part of the feather made up of many soft barbs that zip together. The researchers report that the vane develops using principles akin to paper cutting. As such, a single epithelial sheet produces a series of diverse, branched designs with individual barbs, each bearing many tiny hooklets that hold the vane together into a plane using a Velcro-like mechanism. Their studies show that gradients in another signaling pathway (Wnt2b) play an important role in the formation of those barbs.

To look back in time, the researchers studied recently discovered amber fossils, allowing them to explore delicate, three-dimensional feather structures. Their studies show that ancient feathers had the same basic architecture but with more primitive characteristics. For instance, adjacent barbs formed the vane with overlapping barbules, without the Velcro-like, hooklet mechanism found in living birds.

Weve learned how a simple skin can be transformed into a feather, how a prototypic feather structure can be transformed into downy, contour, or flight feathers, and how a flight feather can be modulated to adapt to different flight modes required for different living environments, Chuong says. In every corner and at different morphological scales, we were amazed at how the elegant adaption of the prototype architecture can help different birds to adapt to different new environments.

The researchers say that, in addition to helping to understand how birds have adapted over time, they hope these bioinspired architectural principles theyve uncovered can be useful in future technology design. They note that composite materials of the future could contribute toward the construction of light but robust flying drones, durable and resilient wind turbines, or better medical implants and prosthetic devices.

Team co-leader and biophysicist Wen Tau Juan of the Integrative Stem Cell Center of China Medical University Hospital, Taiwan, has already begun to explore the application of feather-inspired architectural principles in bio-material design. The team also hopes to learn even more about the molecular signals that allow the formation of such complex feather structures from epidermal stem cells that all start out the same.

###

Reference: The Making of a Flight Feather: Bio-architectural Principles and Adaptation by Wei-Ling Chang, Hao Wu, Yu-Kun Chiu, Shuo Wang, Ting-Xin Jiang, Zhong-Lai Luo, Yen-Cheng Lin, Ang Li, Jui-Ting Hsu, Heng-Li Huang, How-Jen Gu, Tse-Yu Lin, Shun-Min Yang, Tsung-Tse Lee, Yung-Chi Lai, Mingxing Lei, Ming-You Shie, Cheng-Te Yao, Yi-Wen Chen, J.C. Tsai, Shyh-Jou Shieh, Yeu-Kuang Hwu, Hsu-Chen Cheng, Pin-Chi Tang, Shih-Chieh Hung, Chih-Feng Chen, Michael Habib, Randall B. Widelitz, Ping Wu, Wen-Tau Juan and Cheng-Ming Chuong, 27 November 2019, Cell.DOI: 10.1016/j.cell.2019.11.008

This work was supported by the ISCC, CMUH, Taiwan, the Drug Development Center, CMU, Higher Education Sprout Project, Ministry of Education (HESP-MOE), and grants from the National Institutes of Health, Ministry of Science and Technology, Taiwan, iEGG/Avian Genetic Resource/ABC supported by HESP-MOE, the Human Frontier Science Program, the National Natural Science Foundation of China, NSFC, Academia Sinica Research Program on Nanoscience and Nanotechnology, Top Notch Project, NCKU, and a University Advancement grant by MOE, Taiwan.

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How Flight Feathers Evolved: Study of Chickens, Ostriches, Penguins, Ducks and Eagles - SciTechDaily

Cell Biology

UC Scientists Say Babies In The Womb May See More Than We Thought – Sierra Sun Times

An intrinsically photosensitive retinal ganglion cell (ipRGC) as it would appear if you looked at a mouses retina through the pupil. The white arrows point to the many different types of cells it networks with: other subtypes of ipRGC cell (red, blue and green) and retinal cells that are not ipRGCs (red). The white bar is 50 micrometers long, approximately the diameter of a human hair. (Image by Franklin Caval-Holme)

November 30, 2019 - ByRobert Sanders- By the second trimester, long before a babys eyes can see images, they can detect light.

But the light-sensitive cells in the developing retina the thin sheet of brain-like tissue at the back of the eye were thought to be simple on-off switches, presumably there to set up the 24-hour, day-night rhythms parents hope their baby will follow.

University of California, Berkeley, scientists have now found evidence that these simple cells actually talk to one another as part of an interconnected network that gives the retina more light sensitivity than once thought, and that may enhance the influence of light on behavior and brain development in unsuspected ways.

In the developing eye, perhaps 3% of ganglion cells the cells in the retina that send messages through the optic nerve into the brain are sensitive to light and, to date, researchers have found about six different subtypes that communicate with various places in the brain. Some talk to the suprachiasmatic nucleus to tune our internal clock to the day-night cycle. Others send signals to the area that makes our pupils constrict in bright light.

But others connect with surprising areas: the perihabenula, which regulates mood, and the amygdala, which deals with emotions.

In mice and monkeys, recent evidence suggests that these ganglion cells also talk with one another through electrical connections called gap junctions, implying much more complexity in immature rodent and primate eyes than imagined.

Given the variety of these ganglion cells and that they project to many different parts of the brain, it makes me wonder whether they play a role in how the retina connects up to the brain, said Marla Feller, a UC Berkeley professor of molecular and cell biology and senior author of a paper that appeared this month in the journalCurrent Biology. Maybe not for visual circuits, but for non-vision behaviors. Not only the pupillary light reflex and circadian rhythms, but possibly explaining problems like light-induced migraines, or why light therapy works for depression.

The cells, called intrinsically photosensitive retinal ganglion cells (ipRGCs), were discovered only 10 years ago, surprising those like Feller who had been studying the developing retina for nearly 20 years. She played a major role, along with her mentor, Carla Shatz of Stanford University, in showing that spontaneous electrical activity in the eye during development so-called retinal waves is critical for setting up the correct brain networks to process images later on.

Hence her interest in the ipRGCs that seemed to function in parallel with spontaneous retinal waves in the developing retina.

We thought they (mouse pups and the human fetus) were blind at this point in development, said Feller, the Paul Licht Distinguished Professor in Biological Sciences and a member of UC Berkeleys Helen Wills Neuroscience Institute. We thought that the ganglion cells were there in the developing eye, that they are connected to the brain, but that they were not really connected to much of the rest of the retina, at that point. Now, it turns out they are connected to each other, which was a surprising thing.

UC Berkeley graduate student Franklin Caval-Holme combined two-photon calcium imaging, whole-cell electrical recording, pharmacology and anatomical techniques to show that the six types of ipRGCs in the newborn mouse retina link up electrically, via gap junctions, to form a retinal network that the researchers found not only detects light, but responds to the intensity of the light, which can vary nearly a billionfold.

Gap junction circuits were critical for light sensitivity in some ipRGC subtypes, but not others, providing a potential avenue to determine which ipRGC subtypes provide the signal for specific non-visual behaviors that light evokes.

Aversion to light, which pups develop very early, is intensity-dependent, suggesting that these neural circuits could be involved in light-aversion behavior, Caval-Holme said. We dont know which of these ipRGC subtypes in the neonatal retina actually contributes to the behavior, so it will be very interesting to see what role all these different subtypes have.

The researchers also found evidence that the circuit tunes itself in a way that could adapt to the intensity of light, which probably has an important role in development, Feller said.

In the past, people demonstrated that these light-sensitive cells are important for things like the development of the blood vessels in the retina and light entrainment of circadian rhythms, but those were kind of a light on/light off response, where you need some light or no light, she said. This seems to argue that they are actually trying to code for many different intensities of light, encoding much more information than people had previously thought.

The research was supported by the National Institutes of Health.

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UC Scientists Say Babies In The Womb May See More Than We Thought - Sierra Sun Times