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Category Archives: Genome
A Woman May Have Been Cured of H.I.V. Without Medical Treatment – The New York Times
Posted: August 31, 2020 at 8:09 pm
A woman who was infected with H.I.V. in 1992 may be the first person cured of the virus without a risky bone-marrow transplant or even medications, researchers reported on Wednesday.
In an additional 63 people in their study who controlled the infection without drugs, H.I.V. apparently was sequestered in the body in such a way that it could not reproduce, the scientists also reported. The finding suggested that these people may have achieved a functional cure.
The research, published in the journal Nature, outlines a new mechanism by which the body may suppress H.I.V., visible only now because of advances in genetics. The study also offers hope that some small number of infected people who have taken antiretroviral therapy for many years may similarly be able to suppress the virus and stop taking the drugs, which can exact a toll on the body.
It does suggest that treatment itself can cure people, which goes against all the dogma, said Dr. Steve Deeks, an AIDS expert at the University of California, San Francisco, and an author of the new study.
The woman is Loreen Willenberg, 66, of California, already famous among researchers because her body has suppressed the virus for decades after verified infection. Only two other people Timothy Brown of Palm Springs, Calif., and Adam Castillejo of London have been declared cured of H.I.V. Both men underwent grueling bone-marrow transplants for cancer that left them with immune systems resistant to the virus.
Bone-marrow transplants are too risky to be an option for most people infected with H.I.V., but the recoveries raised hopes that a cure was possible. In May, researchers in Brazil reported that a combination of H.I.V. treatments may have led to another cure, but other experts said more tests were needed to confirm that finding.
I think that is a novel, an important discovery, Dr. Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity in Melbourne, said of the new study. The real challenge, of course, is how you can intervene to make this relevant to the 37 million people living with H.I.V.
Even among viruses, H.I.V. is particularly wily and difficult to eradicate. It inserts itself into the human genome and tricks the cells machinery into making copies. H.I.V. naturally prefers to lurk within genes, the most active targets of the cells copiers.
In some people, the immune system over time hunts down cells in which the virus has occupied the genome. But intensive scrutiny of the participants in this study showed that viral genes may be marooned in certain blocked and locked regions of the genome, where reproduction cannot occur, said Dr. Xu Yu, the studys senior author and a researcher at the Ragon Institute in Boston.
The participants in the research were so-called elite controllers, the 1 percent of people with H.I.V. who can keep the virus in check without antiretroviral drugs.
It is possible that some people who take antiretroviral therapy for years may also arrive at the same outcome, especially if given treatments that can boost the immune system, the researchers speculated.
This unique group of individuals provided to me sort of a proof of concept that it is possible with the host immune response to achieve what is really, clinically, a cure, Dr. Deeks said.
Elite controllers have been exhaustively studied for clues to how to control H.I.V. Ms. Willenberg has been enrolled in such studies for more than 15 years. With the exception of one test years ago that indicated a small amount of virus, researchers were never able to identify H.I.V. in her tissues.
In the new study, Dr. Yu and her colleagues analyzed 1.5 billion blood cells from Ms. Willenberg and found no trace of the virus, even using sophisticated new techniques that can pinpoint the viruss location within the genome.
Millions of cells from the gut, rectum and intestine also turned up no signs of the virus.
She could be added to the list of what I think is a cure, through a very different path, Dr. Lewin said.
Other researchers were more circumspect. Its certainly encouraging, but speculative, said Dr. Una ODoherty, a virologist at the University of Pennsylvania. I need to see more before I would say, Oh, shes cured.
But Dr. ODoherty, an expert in analyzing large volumes of cells, said she was impressed by the results overall.
Another 11 people in the study, whom the researchers referred to as exceptional controllers, have the virus only in a part of the genome so dense and remote that the cells machinery cannot replicate it.
Some people who suppress the virus without drugs dont have detectable antibodies or immune cells that rapidly respond to H.I.V. But their immune systems carry a potent memory of the virus, the team found.
Powerful T cells, a constituent of the immune system, eliminated cells in which the viral genes had lodged in more accessible parts of the genome. The infected cells that remained held the virus only in remote regions of the genome where it could not be copied.
Thats really the only explanation for the findings we have, said Dr. Bruce Walker, a researcher at the Ragon Institute who has studied elite controllers for 30 years.
About 10 percent of people who take antiretroviral treatments, especially those who start doing so soon after being infected, also successfully suppress the virus even after they stop taking the drugs. Perhaps something similar is at work in those people as well, experts suggested.
H.I.V. cure studies have focused on rooting out all of the virus thats hidden in the genome. The new study offers a more attainable solution: If the virus remains in only parts of the genome where it cannot be reproduced, the patient may still achieve a functional cure.
The part thats in the gene deserts just doesnt matter, Dr. Walker said. It suggests that as were doing these studies, we need to not just be looking at quantity of the reservoir, but we really need to look at quality.
Since the researchers completed the study, they have analyzed samples from 40 elite controllers and have found a couple more that could qualify as cures, Dr. Yu said: We believe theres definitely many of them out there.
With help from Dr. Deeks, they are contacting people with H.I.V. who have taken antiretroviral drugs for 20 years or more and who may have managed to banish the virus to the deserts of their genomes.
Antiretroviral drugs can have harsh side effects, including heart disease and organ damage, especially when taken over many years. A functional cure, if it is borne out by further research, would transform patients lives, Dr. Yu said: They can stop their treatment and can be just cured, to be healthy for the rest of their life.
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Australia can take the lead in biotechnology revolution | The Strategist – The Strategist
Posted: at 8:09 pm
The Australian government needs to develop a bold vision and strategic plan to create the data-driven healthcare system and bioeconomy of the future.
In my new report for ASPI, Biodata and biotechnology: Opportunity and challenges for Australia, I explain how the extraordinary developments in genome sequencing and genetic engineering will transform all biological enterprises, especially healthcare, and create new ones, like the electronic revolution. I explain why Australia should harness and capitalise on our high-quality biomedical science, agricultural research and development, and healthcare systems to realise a once-in-a-generation opportunity to play a leading role in a major economic revolution.
Biotechnology dates back over 6,000years to the domestication of wheat and the use of yeast for fermentation, but has entered the province of human design and invention as a consequence of the gene-cloning, gene-manipulation and genome-sequencing revolutions of the past 50years.
While often thought of in terms of drug development and genetic engineering, biotechnology is fundamentally becoming an information industry with a universe of applications.
Humans have acquired the ability to read the genetic programming and analyse the structure of the molecules of lifehow cells work, how were different from each other, and what makes a lime different from a lemon. Life has evolved the most exquisite nanomachinesprotein machines that can bind oxygen and almost any other type of molecule; trap photons to turn carbon dioxide and water into carbohydrates; detect electric fields or sound waves and turn them into visual images; pump ions; facilitate the entry of viruses, bacteria and parasites into cells; and make molecular motors that spin or contract to trap prey, exert force and move.
The extraordinary advances in DNA sequencing are leading to an avalanche of genomic information. Genetic engineering can now be done with high speed and precision. The pace of change is accelerating, and biological technologies are intersecting with optical technologies, nanotechnologies, advanced computing and artificial intelligence to create possibilities that were, if not beyond imagination, well beyond feasibility just a few years ago.
The advent of population-scale genomic and smart sensor data will transform health care, health economics, medical research and drug development. It will also transform the national economy and create digital products that can be exported to the world. To achieve this, the Australian government needs a strategic plan for acquiring genomic, clinical, pharmaceutical, sensor and patient self-reporting data and for providing trusted online evidence-based analysis of that information and advice to healthcare practitioners and citizens.
Governments also need to convince citizens of the personal and national value of big data in health care, and the privacy and security of that data, using a model that combines political leadership with subject-matter expertise.
The Australian government should establish a secure national repository for genomic and phenotypic data for research and healthcare use. This de-identified data should be made available to Australian researchers and health system managers. It could be provided to external parties, such as pharmaceutical companies, under appropriate conditions in exchange for early access to expensive treatments or shared benefits.
The Australian government should establish a central unit to assemble and supply evidence-based, well-curated and continuously updated genomic analysis, integrated with clinical and other data, and linked to national treatment guidelines, for decision support at the point of care.
The cost of doing this will be trivial compared with other costs in the healthcare system, and trivial in relation to the cost reductions and healthcare improvements that it will enable. This work could be funded from the Medical Research Future Fund and publicprivate partnerships.
Smart sensors should be made available through Medicare and routinely installed in hospitals, clinics and other healthcare settings, such as aged-care homes.
Conversion to electronic health records should be mandatory for all healthcare providers receiving government support or reimbursement in Australia, as recommended by the Australian Academy of Technology and Engineering.
Genetic tests should be progressively upgraded to whole-genome sequencing to build the national genomic estate. That would convert diagnostic expenses into an enduring strategic asset.
All suitably accredited health professionals, including general practitioners, should be able to obtain a genomic report, pharmacogenomic advice, early warning of an incipient disease, or any combination of that information, about a patient (with patient approval) upon request, and bulletins issued where relevant. Citizens should also be entitled to access such information in the interests of caring for their own health, provided it is conservative and actionable.
Security and police agencies should establish internal expertise in biotechnology and biodata analysis. They should have access to national genomic information under defined circumstances and subject to judicial approval and oversight.
Major investment funds and relevant government departments should consider establishing bio-intelligence units to keep abreast of opportunities and incorporate those opportunities into their strategic planning. Australian research funding agencies and the CSIRO should continue to invest in advanced genetic engineering and vaccine and drug development. Superannuation funds should be encouraged to invest at least 1% of their resources into domestic start-up and early-phase high-tech and digital enterprises, especially in health and biotechnologies.
Universities should provide training in computer programming and big-data analysis as a core component of all science and engineering degrees.
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Human DNA alone does not produce a positive result on the RT-PCR test for SARS-CoV-2 – Health Feedback
Posted: at 8:09 pm
CLAIM
WHO coronavirus PCR test primer sequence is found in all human DNA; this means that the WHO test kits should find a positive result in all humans
DETAILS
Fails to grasp significance of observation: In order for the PCR amplification process to begin, it is essential for both primers to flank the same target sequence. Having only a single primer that binds to a sequence does not lead to amplification and produces a negative test result.Flawed reasoning: If the SARS-CoV-2 RT-PCR test detected human DNA, then all tests would return a positive result. This is clearly contradicted by the fact that only about 9% of all tests administered in the U.S. have been positive.
KEY TAKE AWAY
The reverse-transcription PCR (RT-PCR) test is the method of choice for detecting SARS-CoV-2 in samples and is highly specific for the virus. For a PCR test to successfully amplify nucleic acids (DNA or RNA) in a sample, it is necessary for a pair of primers, which are short sequences of single-stranded nucleic acids that recognize and bind to a specific region of the genome, to flank the same target sequence. If only one primer in the pair is able to do so, amplification does not take place and the test would produce a negative result. Therefore, an RT-PCR test for SARS-CoV-2 which uses a primer that matches a human gene sequence would produce a negative result if only human DNA alone were present.
REVIEW A blog post claiming that the SARS-CoV-2 nucleic acid test would give positive results for every test because it also identifies human DNA was published in April 2020 and has received more than 13,000 interactions on Facebook and other social media platforms like Reddit, according to social media analytics tool CrowdTangle. While it was published several months ago, the article has seen a resurgence of interest on social media in August 2020.
Claims calling into question the nucleic acid tests used to detect SARS-CoV-2 are not new; Health Feedback also reviewed a related claim that the PCR test would detect other coronaviruses and found it to be false, as the test is highly specific and does not detect genetic material from other coronaviruses.
The Piece of Mindful blog post takes a different tack from the earlier claim by citing the protocol of a SARS-CoV-2 nucleic acid test developed at the Pasteur Institute in Paris, which is available on the website of the World Health Organization. The protocol lists the nucleotide sequences of various primers used in the test. According to the blog post, the sequence of one primer matches that of a sequence found on the human chromosome 8 and because of this, the post claims that the test would also detect human DNA, thereby giving false-positive results. As we explain below, this claim stems from a fundamental misunderstanding of how PCR works.
The laboratory technique known as PCR, or polymerase chain reaction, is a widely-used technique in laboratories worldwide that was invented by Kary Mullis, who received the 1993 Nobel Prize in Chemistry for this work. PCR is used to make many copies of a particular segment of nucleic acid (DNA/RNA), a process known as amplification, which enables scientists to detect tiny amounts of nucleic acid in a sample (see animation video by Cold Spring Harbor Laboratorys DNA Learning Center below).
The method of choice for detecting SARS-CoV-2 in most countries is a variant of PCR which detects RNA, called reverse transcription PCR (RT-PCR) (SARS-CoV-2 is an RNA virus).
Our knowledge of the SARS-CoV-2 genetic sequence allows us to design primers that specifically bind to sequences that are unique to the virus, based on the principle of complementary base pairing. These primers are required to start the amplification process. In the protocol, the primers in question detect the presence of the gene sequence for RNA-dependent RNA polymerase (RdRp), which encodes an enzyme that is needed to make more copies of the viral genome[1].
However, primers act in pairs. In order to begin the amplification process, it is essential for both the forward and reverse primers to bind/anneal and flank the same target sequence. Although the sequence CTCCCTTTGTTGTGTTGT which matches the reverse primer also exists on the human chromosome 8, the forward primer listed in the protocol (ATGAGCTTAGTCCTGTTG) does not bind to any sequence on chromosome 8. We demonstrate this below by using the Basic Local Alignment Search Tool (BLAST), developed by the U.S. National Center for Biotechnology Information, to align the forward primer listed in the protocol with the human genome.
As we can see from the alignment results, none of the sequences among the top matches in the list, which are partial matches, can be found on chromosome 8:
In summary, although the sequence CTCCCTTTGTTGTGTTGT is present in the human chromosome 8, only one of the primers is able to recognize this sequence, which would produce a negative result if only human DNA was present. Therefore the claim that the PCR test would produce a false-positive result due to human DNAand the implication that the number of positive SARS-CoV-2 test results is artificially inflatedis incorrect and misleading. Furthermore, it is evident from testing statistics that not all tests produce positive results; according to the U.S. Centers for Disease Control and Preventions COVID Data Tracker, only 9% of all tests conducted in the U.S. are positive as of 30 August 2020, as Lead Stories pointed out in their fact-check of the same blog post:
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A Man Was Reinfected with Coronavirus After RecoveryWhat Does This Mean for Immunity? – UPJ Athletics
Posted: at 8:09 pm
This article was written by Megan Culler Freeman, a pediatric infectious disease fellow at Pitt,for The Conversation. Faculty members and researchers who want to learn more about publishing in The Conversation canread about the process here.
A 33-year old man was found to have a second SARS-CoV-2 infection some four-and-a-half months after he was diagnosed with his first, from which he recovered. The man, who showed no symptoms, was diagnosed when he returned to Hong Kong after a trip to Spain.
I am a virologist with expertise in coronaviruses and enteroviruses, and Ive been curious about reinfections since the beginning of the pandemic. Because people infected with SARS-CoV-2 can often test positive for the virus for weeks to months, likely due to the sensitivity of the test and leftover RNA fragments, the only way to really answer the question of reinfection is by sequencing the viral genome at the time of each infection and looking for differences in the genetic code.
There is no published peer-review report on this manonly a press release from the University of Hong Kongalthough reports say the work will be published in the journal Clinical Infectious Diseases. Here I address some questions raised by the current news reports.
Immunity to endemic coronavirusesthose that cause symptoms of the common coldis relatively short-lived, with reinfections occurring even within the same season. So it isnt completely surprising that reinfection with SARS-CoV-2, the virus that causes COVID-19, might be possible.
Immunity is complex and involves multiple mechanisms in the body. That includes the generation of antibodiesthrough whats known as the adaptive immune responseand through the actions of T-cells, which can help to educate the immune system and to specifically eliminate virus-infected cells. However, researchers around the world are still learning about immunity to this virus and so cant say for sure, based on this one case, whether reinfection will be a cause for broad concern.
Strain has a particular definition when referring to viruses. Often a different strain is a virus that behaves differently in some way. The coronavirus that infected this man in Europe is likely not a new strain.
A STAT News article reports that the genetic make up of the sequenced virus from the patients second infection had 24 nucleotidesbuilding blocks of the viruss RNA genomethat differed from the SARS-CoV-2 isolate that infected him the first time.
SARS-CoV-2 has a genome that is made up of about 30,000 nucleotides, so the virus from the mans second infection was roughly 0.08% different than the original in genome sequence. That shows that the virus that caused the second infection was new; not a recurrence of the first virus.
The man wasnt suffering any of the hallmark COVID-19 symptoms which might mean he had some degree of protective immunity to the second infection because he didnt seem sick. But this is difficult to prove.
I see three possible explanations. The first is that the immunity he gained from the first infection protected him and allowed for a mild second infection. Another possibility is that the infection was mild because he was presymptomatic, and went on to develop symptoms in the coming days. Finally, sometimes infections with SARS-CoV-2 are asymptomaticat the moment it is difficult to determine whether this was due to the differences in the virus or in the host.
Only that it seems to be possible after enough time has elapsed. We do not know how likely or often it is to occur.
As we are still learning about how humans develop immunity to SARS-CoV-2 after infection, my recommendation is for continued masking, hand hygiene and distancing practices, even after recovery from COVID-19, to protect against the potential for reinfection.
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Genomic Study Has Discovered Which Animals Can Get Coronavirus – The National Interest
Posted: at 8:09 pm
There already have been plenty of reports detailing that dogs and cats can be infected by the novel coronavirus.
Chimpanzees and gorillas? Not a huge surprise that theyre susceptible. But what about giant anteaters, bottlenose dolphins, sheep, minks, and Siberian tigers?
Its an emphatic yes to those animals, too, according to a team of researchers at the University of California, Davis.
The new study, which was published in the Proceedings of the National Academy of Sciences, has found that any animal that has the same enzyme that SARS-CoV-2 uses to infect human beings is also at risk of infection from coronavirus.
That particular enzyme is called ACE2, which can be found in a number of different cells in the human body, including the epithelial cells on the lungs, nose, and mouth. When infecting humans, the coronavirus binds itself to twenty-five amino acids of the ACE2 enzyme.
We identified a large number of mammals that can potentially be infected by SARS-CoV-2 via their ACE2 proteins, the studys authors wrote.
This can assist the identification of intermediate hosts for SARS-CoV-2 and hence reduce the opportunity for a future outbreak of COVID-19.
In other words, the animals that have the same twenty-five amino acids in those ACE2 enzymes have the highest risk of contracting the virus.
In addition to discovering some surprises as to which animals were susceptible to coronavirus, the researchers are hoping that their efforts might help protect vulnerable endangered speciesespecially great apes, which were shown to be nearly as susceptible as humans, according to the study.
Among the species we found with the highest risk for SARS-CoV-2 infection are wildlife and endangered species, the study stated.
These species represent an opportunity for spillover of SARS-CoV-2 from humans to other susceptible animals.
In the United States, more than twenty-five dogs and cats have been confirmed to be infected with coronavirus, according to the United States Department of Agriculture.
But the Centers for Disease Control and Prevention has stated that owners of pets do not have to worry about the potential for transmission.
The virus that causes COVID-19 spreads mostly from person to person through respiratory droplets from coughing, sneezing, and talking, the CDC states.
Recent studies indicate that people who are infected but do not have symptoms likely also play a role in the spread of COVID-19. At this time, there is no evidence that companion animals, including pets, can spread COVID-19 to people or that they might be a source of infection in the United States.
The agency is recommending that owners prevent their pets from interacting with people or animals outside their homes. If they are outside, the pets should maintain at least a six-foot distance.
Treat pets as you would other human family members, the CDC said.
If a pet owner tests positive for the virus or believes he or she is sick, all contact with the animal should be immediately cut off, the agency added.
Ethen Kim Lieser is a Minneapolis-based Science and Tech Editor who has held posts at Google, The Korea Herald, Lincoln Journal Star, AsianWeek and Arirang TV. Follow or contact him on LinkedIn.
Image: Reuters.
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Broad Researchers Identify February Biogen Conference as Source of Tens of Thousands of COVID-19 Cases | News – Harvard Crimson
Posted: at 8:09 pm
Broad Institute researchers identified a conference held by the Cambridge-based company Biogen in February as a superspreading event for COVID-19 that caused tens of thousands subsequent cases in the Boston area.
The study, which tracked occurrences of unique COVID-19 genomes from a dataset of the earliest known cases of the virus in Massachusetts, was led by researchers from the Broad Institute and various universities. The team used viral genome sequencing a process of decoding the nucleotides within a given genome to find over 80 separate introductions of COVID-19 into Massachusetts.
The team marked the Biogen conference as a COVID-19 superspreading event after discovering that a specific variation of the virus containing the C2416T allele had contributed to 35.1 percent of COVID-19 cases studied in the dataset. Using the frequency of the allele in four Massachusetts counties, the study estimated that around 20,000 cases in the counties could be attributed to the event.
Samples from the Boston Health Care for the Homeless Program also revealed that the COVID-19 variation introduced at the conference spread into Boston homeless shelters.
In a statement provided by a Broad spokesperson, Broad scientists Bronwyn MacInnis and Stephen Schaffner members of the team wrote that the event most likely led to even more COVID-19 cases outside the Boston area.
This back-of-the-envelope calculation does not include other counties in MA or any other US states or any other countries, they wrote. It thus seems likely that this is an event whose impact is measured in tens of thousands of individuals, but a precise estimate of the total number involved is not possible with current data.
The study also found that effective isolation processes had resulted in lower rates of COVID-19 spread. Schaffner wrote in a Broad website post that a skilled nursing facility studied by the group had a lesser impact on the general Massachusetts population than the Biogen conference.
The outbreak in the nursing facility was devastating for those involved, but it occurred in a fairly isolated population, Schaffner wrote. As a result, it caused little transmission outside the facility. The outbreak in the conference, by contrast, occurred in a highly mobile population in late February and spilled out into the larger community.
Although the study accounted for almost all early confirmed COVID-19 cases, Lydia A. Krasilnikova, a Harvard graduate student and member of the team, wrote in an emailed that asymptomatic cases were not a focus of this study.
It is entirely possible that there were additional asymptomatic cases in Massachusetts, even in the Boston area, that were not captured in our samplingindeed, I would be very surprised if we captured all cases from early in the Massachusetts outbreak, she wrote.
Krasilnikova wrote that the team plans to continue its collaborations with the Massachusetts Department of Public Health and Massachusetts General Hospital while continuing to use genomic sequencing to better understand the virus.
Genomic epidemiology, especially combined with traditional epidemiology, can show us if cases or clusters of cases are connected: this can, with enough sampling, determine whether disease is being continually reintroduced into a community or is spreading within it, she wrote. These scenarios require different responses; genomic epidemiology can equip leaders with the information they need to make difficult and urgent decisions.
Staff writer Ethan Lee can be reached at ethan.lee@thecrimson.com.
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Microbes Living Deep Below Earth’s Surface Could Be Remnants of Ancient Life Forms – ScienceAlert
Posted: at 8:09 pm
There's an enormous variety of life thriving deep beneath Earth's surface. A new analysis of two major groups of subsurface microbes has now revealed that their evolutionary path to life in the dark has been more curious than we expected.
In our planet's first 2 billion years of existence, there was no oxygen in the atmosphere. Once the air on our blue planet changed, not all life forms adapted, with many microbes retreating into less oxygenated parts of the planet.
Patescibacteria and DPANN are two ubiquitous groups of such subsurface microbes - bacteria and archaea, respectively - that appear to have very simple genomes. This has led many to suspect that without the ability to breathe oxygen, these microbes might need to rely on complex interactions with other organisms to supplement their simple lifestyles.
Now, it seems we may not be giving them enough credit. New research indicates that instead of having a symbiotic dependency on other major groups of organisms, most Patescibacteria and DPANN live as completely free cells.
"These microbes [..] are really special, really exciting examples of the early evolution of life,"saysRamunas Stepanauskas, who studies microbial biology and evolution at the Bigelow Laboratory for Ocean Sciences.
"They may be remnants of ancient forms of life that had been hiding and thriving in the Earth's subsurface for billions of years."
Previous work on Patescibacteria and DPANN has gathered a small number of examples near the surface of the Earth, and mainly in North America, but this new study goes deeper and wider than ever before, analysing nearly 5,000 individual microbial cells from 46 locations around the globe, including a mud volcano on the bottom of the Mediterranean Sea, hydrothermal vents in the Pacific, and gold mines in South Africa.
"Our single cell genomic and biophysical observations do not support the prevailing view that Patescibacteria and DPANN are dominated by symbionts," the authors write.
"Their divergent coding potential, small genomes, and small cell sizes may be a result of an ancestral, primitive energy metabolism that relies solely on [fermentation]."
Fermentation is one of the metabolic options living organisms have for breaking down glucose without the help of oxygen, and many life forms use fermentation for energy production, especially the microbes that don't breathe air at all.
However, using fermentation is less efficient than breathing - it produces only 2 ATP per glucose compared to 38 ATP per glucose with aerobic respiration - so this type of metabolism comes with the cost of putting organisms in the metabolic slow lane.
Patescibacteria and DPANN are just fine with that, however. Based on the new analysis, the two groupscontain no trace of what's known as an electron transport chain, a metabolic process that makes energy by dumping electrons onto oxygen. Their relatively simple, potentially ancient survival tricks simply don't need it.
Genomic research and direct experimental tests on samples representing the two groups showed no evidence of respiration, and close examination of cell-to-cell links revealed most were on their own, not attached to hostslike some of their surface cousins.
The authors can't deny that some symbiotic relationships could have been shaken apart by human handling, but gentle mixing was attempted when sorting the cells.
Even if the team is underestimating cell-to-cell interactions, genomic analysis found no evidence of evolutionary enrichment from symbiotic relationships compared to other phyla.
Rather, genome content and lab analysis of cell physiology suggests these microbial groups contain few, if any, other ways of producing energy than fermentation.
"Our findings indicate that Patescibacteria and DPANN are ancient forms of life that may have never learned how to breathe,"saysStepanauskas.
"These two major branches of the evolutionary tree of life constitute a large portion of the total microbial diversity on the planet - and yet they lack some capabilities that are typically expected in every form of life."
The study was published in Frontiers in Microbiology.
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Microbes Living Deep Below Earth's Surface Could Be Remnants of Ancient Life Forms - ScienceAlert
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Researchers announce likely case of coronavirus reinfection in Reno – KTNV Las Vegas
Posted: at 8:09 pm
Scientists at the University of Nevada, Reno School of Medicine (UNR Med), led by its Nevada State Public Health Laboratory (NSPHL) are studying a likely case of COVID-19 reinfection.
Forty-eight days after testing positive for SARS-CoV-2 in April 2020 and after testing negative consecutively twice, a Washoe County, Nevada patient tested positive again, in June.
The patient had tested negative on two separate occasions in the interim. The genomes of the patients virus samples were sequenced in April and June, displaying significant genetic discordance between the two cases, implying the patient was infected twice.
We examined the genomic material of the viruses and samples to investigate this, says NSPHL Director Mark Pandori. It is just one finding, but it shows that a person can possibly become infected with SARS-CoV-2 a second time.
To solidify confidence in the case, Pandori and the research team partnered with the Washoe County Sheriffs Office Biology Unit to conduct identity testing on the specimens and lab samples evaluated in the study to verify the specimens were from the same person.
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Embedded in the genomic material of SARS-CoV-2 is a detailed code that Pandori says may provide insight to better understanding of this virus.
A virus has a biological genome like all living things. Since March, the NSPHL has analyzed the genomic RNA of approximately 200 positive COVID-19 samples from Nevadans who have tested positive for COVID-19, said Pandori. The power of genomic information could turn the tables in the fight against the coronavirus. The information is shared to a world-wide database known as GISAID, alongside the work of thousands of researchers.
According to Pandori and the NSPHL-led research team, reinfection cases are a potential warning sign that it is possible to catch COVID-19 more than once, and with unpredictable severity.
If reinfection is possible on such a short timeline, there may be implications for the efficacy of vaccines developed to fight the disease. It may also have implications for herd immunity, says Pandori. It is important to note, that this is a singular finding. It does not provide any information to us with regard to the generalizability of this phenomenon.
Herd immunity depends on the theory that after natural infection, our immune systems will collectively protect us as a community from reinfection and further spread.There are currently many more unknowns than knowns about immune responses to COVID-19. After one recovers from COVID-19, we still do not know how much immunity is built up, how long it may last, or how well antibodies play a role in protection against a reinfection, says Pandori.
While research and scientific advancements continue to build, Pandori says the hard work of fighting this pandemic together will continue through the use of facial coverings, hand-washing, social distancing, as well as wide-scale testing, contact tracing, and isolation of new cases.
This is a novel disease. We still have a steep learning curve ahead and lots of work to do, especially as inconvenient truths arise, says Pandori.
The NSPHL team are publishing their COVID-19 reinfection findings. Their report is publicly accessible on the SSRN preprint server, at https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3681489.
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Revealing the intrinsic functioning of human and mouse genomes – Tech Explorist
Posted: July 31, 2020 at 6:51 pm
The Encyclopedia of DNA Elements (ENCODE) Consortium is a universal coordinated effort of research groups funded by the National Human Genome Research Institute (NHGRI). The objective of ENCODE is to make a comprehensive parts list of functional elements in the human genome, including elements that work at the protein and RNA levels, and regulatory elements that control the cells and conditions where a gene is active.
The project will detail how the human genome functions. Recently, the project completed its latest phase- scientists have added millions of candidate DNA switches from the human and mouse genomes. These genomes appear to control when and where genes are turned on, and a new registry that assigns a portion of these DNA switches to useful biological categories.
It also provides the latest visualization tools to help in the use of ENCODEs large datasets.
NHGRI Director Eric Green, M.D., Ph.D. said,A major priority of ENCODE 3 was to develop means to share data from the thousands of ENCODE experiments with the broader research community to help expand our understanding of genome function. ENCODE 3 search and visualization tools make these data accessible, thereby advancing efforts in open science.
To evaluate the potential functions of various DNA locales, ENCODE specialists considered biochemical procedures that are normally connected with the switches that regulate genes. This biochemical methodology is an effective method to investigate the whole genome wholly and quickly.
This strategy assists with finding regions in the DNA that are candidate functional elements DNA regions that are anticipated to be practical components dependent on these biochemical properties. Candidates would then be able to be tested in further experiments to distinguish and portray their useful roles in gene regulation.
Elise Feingold, Ph.D., scientific advisor for strategic implementation in the Division of Genome Sciences at NHGRI and a lead on ENCODE for the institute, said,A key challenge in ENCODE is that different genes and functional regions are active in different cell types. This means that we need to test a large and diverse number of biological samples to work towards a catalog of candidate functional elements in the genome.
During the recently completed third phase of ENCODE, scientists performed almost 6000 experiments in several biological contexts- 4,834 in humans and 1,158 in mice- to enlight details of the genes and their potential regulators in their respective genomes.
Scientists studied developing embryonic mouse tissues to comprehend the timeline of various genomic and biochemical changes that occur during mouse development.
Scientists analyzed how chemical modifications of DNA, proteins that bind to DNA, and RNA (a sister molecule to DNA) interact to regulate genes. Results from ENCODE 3 also help explain how variations in DNA sequences outside of protein-coding regions can influence the expression of genes, even genes located far away from a specific variant itself.
Brenton Graveley, Ph.D., professor and chair of the Department of Genetics and Genome Sciences at UCONN Health, said,The data generated in ENCODE 3 dramatically increase our understanding of the human genome. The project has added tremendous resolution and clarity for previous data types, such as DNA-binding proteins and chromatin marks, and new data types, such as long-range DNA interactions and protein-RNA interactions.
As a new feature, ENCODE 3 scientists created a resource detailing different kinds of DNA regions and their corresponding candidate functions. A web-based tool called SCREEN(link is external) allows users to visualize the data supporting these interpretations.
The projects latest results were published in Nature, accompanied by 13 additional in-depth studies published in other major journals.
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Revealing the intrinsic functioning of human and mouse genomes - Tech Explorist
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California and Zuckerberg lab team up to map coronavirus genome, one of the largest efforts to discover how it spreads – San Francisco Chronicle
Posted: at 6:51 pm
Health officials and scientists believe genome sequencing of the coronavirus could hold great promise. The technique today helps trace where infections began, and perhaps one day it could help shape the way doctors treat COVID-19 patients.
A new initiative between California and the San Francisco research institution funded by Facebook CEO Mark Zuckerbergs philanthropic organization could bring them one step closer.
The Chan Zuckerberg Biohub will offer free genome sequencing for lab samples that have tested positive for the coronavirus from all California counties, the institution is slated to announce Thursday.
It is one of the largest statewide, coordinated efforts to do genome sequencing for COVID-19, said Dr. Joe DeRisi, co-president of the Chan Zuckerberg Biohub. Genome sequencing helps determine what strain of the virus people have, which helps public health officials trace how transmission occurred and where it came from.
The Biohub had already been doing genome sequencing on samples from many California county public health departments on a smaller scale since March. Now, it is formally partnering with the state Department of Public Health to expand the work.
Sequencing is not necessary for all samples, but can be useful to determine the source of an outbreak in some settings or to rule out a suspected pattern of transmission. For example, if sequencing found that similar strains of the virus are rampant at two different nursing homes, and the two facilities share staff, that may indicate a staffer brought the virus from one home to the other. Or if one factory employee has a strain that is similar to that of a coworker, it may indicate the virus spread at work; but if strains found in one workplace are vastly different, it indicates the employees likely got sick from interactions outside of work.
Where its the most helpful is understanding the number of circulating strains in a given community, to understand if theres been a new introduction of a strain to a particular geographic area or facility, DeRisi said. That establishes whether youre looking at ongoing, in-community transmission, or whether theres been an outside introduction that was unbeknownst to you.
Sequencing involves putting a sample that has tested positive for the coronavirus into a lab machine that analyzes the viral genetic material and identifies where mutations occur.
A strain is a group of viruses with similar mutations. SARS-CoV-2, the virus that causes COVID-19, has 30,000 letters of RNA, genetic material that includes instructions on how to make new copies of the virus. When the virus spreads from cell to cell and person to person, it passes on small changes, or mutations, in the viral information. Some of those mutations are then passed on to the next person. A strain is a product of a long chain of transmission, and the cumulative changes that occurred over time.
The Biohub will not sequence every single sample. But it will sequence samples when the work can help answer critical questions about some outbreaks and how they started. Biohub has sequenced about 1,600 samples from nursing homes, packing plants and prisons from 20 California counties. It is sequencing samples from San Quentin State Prison to determine whether the outbreak there came in from one source and then spread, or if it came in from multiple sources carrying different strains.
Sequencing has helped scientists determine that the East Coast has largely been hit with a European strain of the virus, while California has been hit by many strains, including from Europe and China.
One of the potential promises of genome sequencing is that it could eventually help scientists learn whether certain strains of the coronavirus are resistant to certain drugs. That could help doctors pick which drugs, or cocktail of drugs, to administer to patients. With HIV, for instance, sequencing helped researchers glean that some strains of the virus respond well to certain drugs while other strains are resistant to the same drugs.
Ultimately, we might be able to use this data for things like susceptibility to drugs or a vaccine, said Dr. Robert Siegel, a Stanford infectious disease expert. Were not there yet.
It is too early with the coronavirus to know whether some strains are resistant to drugs. There have not been many drugs that have successfully treated COVID-19. But a few, including remdesivir, appear to help some very sick patients.
Imagine that you took all the patients on remdesivir, and you had good clinical data on them, and it turns out some people responded to remdesivir and some didnt, Siegel said. Its possible that is either a function of the viral strain or of the genetic makeup of the host, or a combination of the two. Or it could be luck. ... If we started seeing remdesivir resistance, almost certainly wed be able to tell what mutations gave rise to remdesivir resistance.
It costs about $15 to $20 to sequence each sample, DeRisi said.
The sequencing will be done at a lab at the Biohub, which is financed by the philanthropic organization Chan Zuckerberg Initiative in San Franciscos Mission Bay. The initiative was created in 2015 by Zuckerberg and his wife Dr. Priscilla Chan, who pledged $600 million over 10 years to help advance medical research.
The initiative has also committed $13.6 million to fund large, long-term COVID-19 studies in the Bay Area and a $4 million UCSF lab to process coronavirus tests.
Catherine Ho is a San Francisco Chronicle staff writer. Email: cho@sfchronicle.com Twitter: @Cat_Ho
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California and Zuckerberg lab team up to map coronavirus genome, one of the largest efforts to discover how it spreads - San Francisco Chronicle
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