Dos and don’ts for constipation relief, as explained by Ayurvedic practitioners

Don't allow constipation to cause other lifestyle issues

Do you know constipation is not just a problem related to your stomach or bowel system, but can also often be a cause for dry skin, dry hair and even sleep issues? “So many of our issues can be attributed to the gut! Problems such as eczema, psoriasis, dry hair, attention disorders, insomnia are all aggravated by constipation. Ayurveda places so much importance on eliminating at least once a day,” holistic health practitioners Suchi Kothari and Hansa Melvani mentioned on their Instagram page Something Holistic.

Much like immunity, good gut health can also be developed over a period of time with proper dietary measures.

https://www.instagram.com/p/CDMND-PJw7c/

A post shared by Suchi & Hansa (@somethingholistic)

According to the duo, one needs to take adequate precautions to prevent the lifestyle-induced issue of constipation.

Here are some simple tips to relieve constipation.

What to have?

*Warm and moist foods: Soups, khichdi, stews, and poached apples

*Okra or bhindi: This slimy vegetable is perfect to clean the colon

*Flax oil added to room temperature smoothies helps lubrication.

*Overnight soaked prunes, figs, and raisins.

*Warm milk, ghee, saffron and turmeric.

*Lots of warm water or water kept at room temperature

What not to have?

*Dry snacks like popcorn or crackers

*Don’t drink carbonated drinks including sparkling water

*Avoid cold foods like ice-cream. Avoid cold water, too.

Yoga poses that could help

Vajrasana (diamond pose)

Vakrasana (seated twisting pose)

Pawanmuktasana (wind relieving pose)

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A Patchwork: Europe and COVID-19 Vaccination Passports

(Reuters) – European Union leaders moved closer on Thursday to an agreement on certificates showing that citizens have been vaccinated against COVID-19, a move that could revive international travel and save this summer’s holiday season.

Some countries want an EU-wide approach instead of a patchwork of national schemes that in many cases are not intended to serve as travel documents. Halfway through a summit of leaders on the pandemic, officials said “convergence on a harmonised approach” to certificates was emerging.

Here’s where several EU member states and other European countries stand on vaccination certificates:

BETTER TOGETHER

GREECE has led calls for an EU-wide vaccine certificate to open up summer tourism. It has reached an agreement with Israel, which has launched a digital “Green Pass”, to ease travel for those with proof of vaccination. It issues certificates for people who have had twin shots.

Athens is in talks with Britain about a similar agreement, but its tourism minister was quoted as saying on Thursday that even unvaccinated Britons could visit the country.

SPAIN, AUSTRIA and BULGARIA also support a common EU approach. The government in Vienna says that, if there is no agreement at EU level by the spring, it will implement its own plan.

DOING THEIR OWN THING

DENMARK plans to launch a digital passport to document a traveller’s vaccination status, designed to be compatible with any future EU-wide scheme. SWEDEN plans a similar digital passport by summer, assuming an international standard is in place by then, as does FINLAND.

HUNGARY has announced that from March 1 it will issue a vaccination passport in the form of a card to citizens who have had the vaccine or have immunity after recovering from COVID-19. A decision about possible waivers from coronavirus restrictions will be taken later. People carrying the immunity passport will not have to go into quarantine.

RUSSIAN President Vladimir Putin ordered his government in January to consider issuing certificates to those who had been inoculated with domestic vaccines against COVID-19 for overseas travels.

THINKING ABOUT IT

BRITAIN is reviewing how COVID-19 status certificates could help reopen the economy. It will consider a system allowing vaccinated individuals to travel abroad more freely once more is known about the efficacy of vaccines against COVID-19 variants. The UK is working with the World Health Organization and other countries on an international framework for travel.

PORTUGAL is considering various options to resurrect the travel sector, but has cautioned that an EU-wide passport could lead to “some constraints” given delays in vaccinations.

WE HAVE OUR DOUBTS

GERMANY, which has restricted travel from neighbours with high rates of infection, is still in the early stages of debating the idea of vaccination certificates. There are widespread concerns that these could result in discrimination against those who choose not to be vaccinated.

ROMANIAN President Klaus Iohannis has said an EU vaccination passport would be divisive, splitting Europe between those who have been vaccinated and those who have not.

NO PLANS YET

POLAND has introduced a special QR code via its mObywatel app that can be scanned to confirm a user has been fully vaccinated, meaning they have received two doses. It has not yet said if it will introduce a specific vaccination “passport”.

FRANCE has not revealed any plans for a vaccination passport of its own, though travel industry lobbies and some opposition politicians have been pressing for such a scheme. ITALY does not have a national vaccination passport scheme.

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LOL! How Pregnant Bindi Irwin Reacted to Robert Calling Her 'Massive'

Whoops! Robert Irwin has been kicking himself ever since he called his pregnant sister, Bindi Irwin, “massive.”

Family Photo! See Bindi Irwin’s Pregnancy Pics Ahead of 1st Child

“I have a knack for always putting my foot in it on live television,” the Crikey! It’s the Irwins star, 17, said during a Thursday, February 25, Access Hollywood appearance. “Hopefully I won’t do that today, but I called Bindi massive because I think it’s a point of pride. She is, like, pretty big. I thought it was pretty cool. She took it pretty well, but I’m really measuring my words now.”

As for his mom Terri Irwin’s reaction, Robert said that he “got a nice little pinch on the arm from” the My Steve author, 56.

See Tiffany Thornton, More Celeb Moms’ Most Creative Sex Reveals: Pics

Mario Lopez advised the teenager to never call a woman “massive,” and he replied, “I’m finding that out.”

Robert was on Australia’s Sunrise morning show on February 9 when Terri said that Bindi, 22, had reached “that sweet spot where you really miss being able to see your shoes.”

The Robert’s Real Life Adventures host chimed in, “She’s massive now!” When his mom nudged him, he added, “Like, in a good way! No, like, it’s special! I’m in so much trouble. I’m in so much trouble. Don’t tell her about this please.”

The Robert Irwin: Dinosaur Hunter author went on to tweet about the misstep. “Haha … whoops [sic],” he wrote at the time. His sister replied, “‘Don’t tell her about this.’ … Thanks, Robert!”

https://www.instagram.com/p/CKCitgRhRAL/

A post shared by Bindi Irwin (@bindisueirwin)

The Bindi the Jungle Girl alum announced in August 2020 that she and husband Chandler Powell are expecting their first child. The following month, they used pink flowers to reveal their upcoming arrival’s sex.

Budding Bellies! Cassie and More Pregnant Stars’ 2021 Bump Pics

She and the Florida native, 24, are calling their little one their “Baby Wildlife Warrior” for now — a nickname inspired by her late dad, Steve Irwin.

“My dad was the first person to create the term ‘Wildlife Warrior,’” the pregnant star explained to The Bump earlier this month. “Being a Wildlife Warrior means to stand up and speak for those who cannot speak for themselves. … I know in my heart that she will forge her own path to make our planet a better place.”

The mom-to-be added at the time: “My dad would have been the best grandfather. I always joke that if he was still here, we’d never see our baby because he’d take her on all kinds of adventures! I want to make sure our baby girl gets to know my dad and thankfully, we have many documentaries and photos we can share with her. I think she’ll love getting to watch footage of Dad working with all kinds of animals and learning about his legacy.”

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3 Syllables! Prince Harry Shares Son Archie's Surprising 1st Word

One smart cookie! Prince Harry and Meghan Markle’s son Archie’s first word was a big one.

Everything Prince Harry, Meghan Markle Have Said About Raising Archie

The 21-month-old said “crocodile,” the former military pilot, 36, told James Corden on Thursday, February 25. “Three syllables,” he bragged.

The toddler also says “waffles” every morning when he wakes up, the duke added, explaining, “My grandmother [Queen Elizabeth II] asked us what Archie wanted for Christmas and Meg said a waffle maker. She sent us a waffle maker for Archie, so for breakfast now, Meg makes a beautiful organic mix, [puts it] in the waffle maker and out it comes. He loves it.”

Archie’s Photo Album: Prince Harry, Meghan Markle’s Royal Baby

He and the Suits alum, 39, often Zoom with the monarch, 94, and her husband, Prince Philip. “They’ve seen Archie running around,” he said during the Late Late Show With James Corden appearance.

Harry went on to tell Corden, 42, about his “hysterical” son. “He’s got the most amazing personality,” he gushed. “He’s already putting three, four words together, already singing songs.”

Markle gave birth to Archie in May 2019. In January of the following year, the former actress and Harry announced their decision to step back from their duties as senior royal family members. The pair then moved to Canada before living in Tyler Perry’s Los Angeles mansion. In June 2020, news broke that they had purchased a home in Montecito, California.

Us Weekly confirmed earlier this month that Archie is going to be a big brother. “The Duke and Duchess of Sussex are overjoyed to be expecting their second child,” the couple’s rep told Us on February 14.

How Meghan Markle Hid Her Baby Bump Ahead of 2nd Pregnancy Announcement

Later that same week, Harry and Markle revealed that they will not return as working members of the royal family. “Following conversations with the duke, the queen has written confirming that in stepping away from the work of the royal family it is not possible to continue with the responsibilities and duties that come with a life of public service,” the February 19 Buckingham Palace statement read. “The honorary military appointments and royal patronages held by the duke and duchess will therefore be returned to Her Majesty before being redistributed among working members of the royal family. While we are all saddened by their decision, the duke and duchess remain much-loved members of the family.”

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Retroviruses invading the koala germline contribute to high cancer rates

Koalas are facing multiple environmental and health issues which threaten their survival. Along with habitat loss – accelerated by last year’s devastating bush fires – domestic dog attacks and road accidents, they suffer from deadly chlamydial infections and extremely high frequency of cancer.

An international team of scientists led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) now demonstrate that a retrovirus invading the koala germline explains the high frequency of koala cancer. The results are reported in the journal Nature Communications.

The koala retrovirus (KoRV) is a virus that, like other retroviruses such as HIV, inserts itself into the DNA of an infected cell. At some point in the past 50,000 years, KoRV has infected the egg or sperm cells of koalas, leading to offspring that carry the retrovirus in every cell in their body.

The entire koala population of Queensland and New South Wales in Australia now carry copies of KoRV in their genome. All animals, including humans, have gone through similar "germline" infections by retroviruses at some point in their evolutionary history and contain many ancient retroviruses in their genomes.

These retroviruses have, over millions of years, mutated into degraded, inactive forms that are no longer harmful to the host. Since in most animal species this process occurred millions of years ago, the immediate health effects on the host at that time are unknown but it has been suspected for some time that the invasion of a genome by a retrovirus may have considerable detrimental health effects.

The koala is at a very early stage of this process when the retrovirus is still active and these health effects can be studied.

Since retroviruses can cause cancer, it was thought that there is a link between KoRV and the high frequency of lymphoma, leukaemia and other cancers in koalas from northern Australia. To investigate this link, scientists at the Leibniz-IZW sequenced DNA from wild koalas suffering from cancer.

This allowed them to accurately detect the number of copies of KoRV in the koala genomes and identify the precise locations where the retrovirus had inserted its DNA. By comparing this information between healthy and tumour tissues in single koalas, and by comparing insertion sites between koala individuals, they found multiple links between KoRV and genes known to be involved in the kind of cancers to which koalas are prone.

"Each koala carries around 80 – 100 inherited copies of KoRV in its genome. The genomic locations of most of these are not shared between koalas, indicating a rapid expansion and accumulation of KoRV copies in the population. Each time a retrovirus copies and re-inserts itself into the genome, it causes a mutation, potentially disrupting gene expression, which could be detrimental to the host," says Prof Alex Greenwood, Head of Department of Wildlife Diseases at the Leibniz-IZW.

This means that by frequently copying itself to new locations in the genome, KoRV is currently conferring a high mutational load on the koala population. Tumour tissues contain many new copies of KoRV, indicating that KoRV is more active in tumour cells.

These copies generally were located close to genes associated with cancer. New KoRV insertions in tumour tissues affected the expression of genes in their vicinity. Such changes in gene expression associated with cancer can cause increased cell growth and proliferation, which leads to tumours.

Although other factors may also contribute to cancer in koalas, the mutational burden from KoRV likely increases the frequency of cells becoming cancerous and may shorten the time for cancer to develop.

In one koala, a copy of KoRV was found that had incorporated an entire cancer-related gene from the koala genome into its DNA sequence. This greatly increased the expression of this gene and most likely caused cancer in this particular koala.

If this mutated virus is transmissible, it would be of grave concern for koala conservation efforts. Comparing the genomic location of KoRVs between koalas also suggests that KoRV may predispose related koalas to particular tumours, with koalas sharing KoRV insertions in specific cancer-related genes suffering from similar types of cancer which they can pass on to their offspring.

Across all koalas studied, there were "hot spots" in the genome where KoRV frequently inserts itself. These hot spots were also located in proximity to genes associated with cancer.

In summary then, we find multiple links at the genomic level between cancer-related genes and KoRV, revealing ways in which KoRV underlies the high frequency of cancer in koalas."

Gayle McEwen, Scientist, Leibniz Institute for Zoo and Wildlife Research (IZW)

The results highlight the detrimental health consequences that wildlife species can suffer following germline infection by retroviruses.

Germline invasions have been repeatedly experienced during vertebrate evolution and have shaped vertebrate genomes, including the lineage leading to modern humans. These were most likely associated with severe detrimental health effects, which must be endured and overcome to ensure species survival.

The scientists at the Leibniz-IZW have previously shown that old retroviruses present in the koala genome aid the rapid degradation of KoRV. The koala finds itself in a race to survive the effects of KoRV long enough for the virus to be degraded. Considering the many threats to koalas, it is a race they need to win.

Source:

Leibniz Institute for Zoo and Wildlife Research (IZW)

Journal reference:

McEwen, G. K., et al. (2021) Retroviral integrations contribute to elevated host cancer rates during germline invasion. Nature Communications. doi.org/10.1038/s41467-021-21612-7.

Posted in: Genomics | Life Sciences News

Tags: Cancer, Cell, DNA, Evolution, Frequency, Gene, Gene Expression, Genes, Genome, Genomic, Germline, HIV, Leukemia, Lymphoma, Mutation, Proliferation, Research, Retrovirus, Sperm, Virus

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Study describes the sequencing of 64 full human genomes

Researchers at the University of Maryland School of Medicine (UMSOM) co-authored a study, published today in the journal Science, that details the sequencing of 64 full human genomes. This reference data includes individuals from around the world and better captures the genetic diversity of the human species.

Among other applications, the work will enable population-specific studies on genetic predispositions to human diseases as well as the discovery of more complex forms of genetic variation.

Twenty years ago this month, the International Human Genome Sequencing Consortium announced the first draft of the human genome reference sequence.

The Human Genome Project, as it was called, required 11 years of work and involved more than 1000 scientists from 40 countries. This reference, however, did not represent a single individual, but instead was a composite of humans that could not accurately capture the complexity of human genetic variation.

Building on this, scientists have conducted several sequencing projects over the last 20 years to identify and catalog genetic differences between an individual and the reference genome. Those differences usually focused on small single base changes and missed larger genetic alterations.

Current technologies now are beginning to detect and characterize larger differences – called structural variants – such as insertions of new genetic material. Structural variants are more likely than smaller genetic differences to interfere with gene function.

The new finding in Science announced a new and significantly more comprehensive reference dataset that was obtained using a combination of advanced sequencing and mapping technologies.

The new reference dataset reflects 64 assembled human genomes, representing 25 different human populations from across the globe. Importantly, each of the genomes was assembled without guidance from the first human genome composite. As a result, the new dataset better captures genetic differences from different human populations.

We've entered a new era in genomics where whole human genomes can be sequenced with exciting new technologies that provide more substantial and accurate reads of the DNA bases. This is allowing researchers to study areas of the genome that previously were not accessible but are relevant to human traits and diseases."

Scott Devine, PhD, Study Co-Author and Associate Professor, Medicine, University of Maryland School of Medicine

Scott Devine is also the Faculty Member of IGS. Institute of Genome Science (IGS)'s Genome Resource Center (GRC) was one of three sequencing centers, along with Jackson Labs and the University of Washington, that generated the data using a new sequencing technology that was developed recently by Pacific Biosciences. The GRC was one of only five early access centers that was asked to test the new platform.

Dr. Devine helped to lead the sequencing efforts for this study and also led the sub-group of authors who discovered the presence of "mobile elements" (i.e., pieces of DNA that can move around and get inserted into other areas of the genome).

Other members of the Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine are among the 65 co-authors. Luke Tallon, PhD, Scientific Director of the Genomic Resource Center, worked with Dr. Devine to generate one of the first human genome sequences on the Pacific Bioscences platform that was contributed to this study. Nelson Chuang, a graduate student in Dr. Devine's lab also contributed to the project.

"The landmark new research demonstrates a giant step forward in our understanding of the underpinnings of genetically-driven health conditions," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "This advance will hopefully fuel future studies aimed at understanding the impact of human genome variation on human diseases."

Source:

University of Maryland School of Medicine

Journal reference:

Ebert, P., et al. (2021) Haplotype-resolved diverse human genomes and integrated analysis of structural variation. Science. doi.org/10.1126/science.abf7117.

Posted in: Molecular & Structural Biology | Genomics

Tags: Bases, DNA, Gene, Genetic, Genome, Genomic, Genomics, Medical Research, Medical School, Medicine, Research

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CRISPR screen identifies clinically approved immunosuppressants that could treat coronavirus infections

Researchers in Switzerland and Germany have identified host cell factors required for coronavirus replication that could serve as targets for treatment with clinically-approved drugs.

The team found that several autophagy-related genes were common host defense factors required for the replication of both endemic and emerging coronaviruses.

These coronaviruses include the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic.

Autophagy – cellular response to stressors such as hypoxia or infection – involves the recycling of proteins and organelles to maintain homeostasis. Various trafficking pathways enable the transportation of cytoplasmic material to the lysosome, where it is destroyed.

Among the autophagy-related genes were three immunophilins – high affinity-receptor proteins that specifically bind to certain immunosuppressive agents.

Furthermore, inhibition of the immunophilins with the clinically-approved drugs Cyclosporin A and Alisporivir resulted in dose-dependent reduction of coronavirus replication in primary human nasal epithelial cells.

The study was conducted by a team from the Institute of Virology and Immunology in Bern and Mittelhäusern, Switzerland and Ruhr-Universität Bochum in Germany

“Overall, we identified host factors that are crucial for coronavirus replication and demonstrate that these factors constitute potential targets for therapeutic intervention by clinically approved drugs,” writes Volker Thiel and the team.

A pre-print version of the paper is available on the bioRxiv* server, while the article undergoes peer review.

Study: A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets. Image Credit: Meletios Verras / Shutterstock

Three highly pathogenic coronaviruses have emerged over the last two decades

The last two decades have seen the emergence of three highly pathogenic coronaviruses, including the SARS-CoV virus responsible for the 2002-2004 SARS outbreaks, the Middle Eastern respiratory syndrome coronavirus (MERS-CoV) that emerged in 2012 and, most recently, the SARS-CoV-2 virus that causes COVID-19.

The severe risk these outbreaks have posed to human health over a relatively short period has highlighted the importance of developing effective approaches to treating both current coronavirus infections and those that could emerge in the future.

Coronaviruses rely on host dependency factors

Coronaviruses rely on cellular host factors – termed host dependency factors (HDFs) – for viral entry, replication and survival.

“The identification of HDFs is therefore important for understanding essential host-virus interactions required for successful viral replication and providing a framework to guide the development of new pharmacological strategies for the treatment of coronavirus infections,” says Thiel and colleagues.

One hallmark process that occurs during coronavirus replication is extensive virus-induced remodeling of host endomembranes to form double-membrane vesicles (DMVs) that are targeted by viral replication and transcription complexes.

“However, the host factors that are required for the formation of these structures remain elusive,” says the team.

What did the researchers do?

The researchers conducted two independent genome-wide loss-of-function CRISPR screens to identify HDFs required for the replication of both endemic and emerging coronaviruses.

The knockout screens were performed in Huh7 cells infected with the highly pathogenic MERS-CoV and with human coronavirus 229E (HCoV-229E) – a less pathogenic endemic coronavirus that generally only causes mild respiratory symptoms.

Enrichment analysis uncovers host biological networks crucial for CoV replication. (A) Enrichment map summarizing major host biological networks co-opted by CoVs during infection. Gene Ontology (GO) enrichment analysis was performed using hits from both MERS-CoV and HCoV-229E CRISPR screens and filtered to contain conserved representative GO terms and genes. Each node represents an individual GO term and nodes that are functionally related cluster together into a larger network. Node size reflects number of significantly enriched genes in the node and color indicates the CoV screen for which the node was significant.

What did the study find?

The team identified multiple virus-specific and conserved HDFs, including several that are required for replication of SARS-CoV-2.

The study revealed that several autophagy-related genes, including the immunophilins FK506 binding protein 8 (FKBP8), transmembrane protein 41B (TMEM41B), and membrane integral NOTCH2-associated receptor 1 (MINAR1) were common HDFs.

The researchers say that the interaction between autophagy components and coronaviruses in the context of replication has been considered for some time because parts of the autophagy process share similarities with the process of DMV formation.

However, “studies investigating the possible involvement of the early autophagy machinery in the conversion of host membranes into DMVs reached conflicting conclusions,” says Thiel and colleagues.

“Another possibility is that single components of the autophagic machinery may be hijacked by coronaviruses independently of their activity in autophagic processing,” they add.

The team says that irrespective of the precise underlying mechanism, the results suggest that FKBP8, TMEM41B, and MINAR1 represent potential therapeutic targets.

CoV HDFs are interactors of the autophagy pathway but do not depend on autophagy for replication. (A) Upon starvation, the mTORC1 complex is blocked and activation of the PI3K complex, as well as the ULK1 complex leads to the initiation of phagophore formation, as an initial step in the autophagy pathway. MERS-CoV and HCoV503 229E top scoring CRISPR knockout screen hits FKBP8, MINAR1, TMEM41B and VMP1 are involved in this early pathway. Furthermore, the ATG8 system containing among others LC3, which is recruited by VPM1 or FBKP8 is necessary for targeting cellular cargo to the autophagosome. PPP3R1 is upregulated and initiates TFEB translocalization to the nucleus, where it catalyzes transcription of ATGs. MERS-CoV or conserved host dependency factors (HDFs) are indicated in respective colors. Inhibitor intervention in this pathway is shown in red.

Targeting the immunophilins with clinically-approved drugs

Next, the researchers showed that inhibition of the immunophilin family with the clinically-approved and well-tolerated drugs Tacrolimus, Cyclosporin A and Alisporivir reduced the replication of MERS-CoV, SARS-CoV, and SARS-CoV-2 in a dose-dependent manner.  

However, the team noted that while Huh7 cells are valuable for studying coronaviruses, they are likely less effective at capturing important aspects of infection than primary human airway epithelial cells.

To address this limitation, the researchers also tested the drugs in primary human nasal epithelial cell cultures.

This revealed that Cyclosporin A and Alisporivir potently inhibited SARS-CoV-2 replication at concentrations known to be achievable and efficacious in patients.

“Overall, the genes and pathways identified in our coronavirus screens expand the current repertoire of essential HDFs required for replication that can be exploited to identify novel therapeutic targets for host-directed therapies against both existing and future emerging CoVs,” writes Thiel and colleagues.

“Together these findings depict a promising path towards the repurposing of Cyclosporin A and Alisporivir as COVID-19 treatment options,” concludes the team.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Thiel V, et al. A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets. bioRxiv, 2021. doi: https://doi.org/10.1101/2021.02.24.432634, https://www.biorxiv.org/content/10.1101/2021.02.24.432634v1

Posted in: Device / Technology News | Medical Research News | Disease/Infection News

Tags: Autophagy, Cell, Coronavirus, Coronavirus Disease COVID-19, CRISPR, Drugs, Gene, Genes, Genome, Hypoxia, Immunology, Knockout, MERS-CoV, Pandemic, Protein, Receptor, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Tacrolimus, Transcription, Virology, Virus

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Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.

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In Boost for COVID-19 Battle, Pfizer Vaccine Found 94% Effective in Real World

JERUSALEM (Reuters) – The first big real-world study of the Pfizer/BioNTech vaccine to be independently reviewed shows the shot is highly effective at preventing COVID-19, in a potentially landmark moment for countries desperate to end lockdowns and reopen economies.

Up until now, most data on the efficacy of COVID-19 vaccines has come under controlled conditions in clinical trials, leaving an element of uncertainty over how results would translate into the real world.

The research in Israel – two months into one of the world’s fastest rollouts, providing a rich source of data – showed two doses of the Pfizer shot cut symptomatic COVID-19 cases by 94% across all age groups, and severe illnesses by nearly as much.

The study of about 1.2 million people also showed a single shot was 57% effective in protecting against symptomatic infections after two weeks, according to the report published in the New England Journal of Medicine on Wednesday.

The results of the study for the Clalit Research Institute were close to those in clinical trials last year which found two doses were found to be 95% effective.

“We were surprised because we expected that in the real-world setting, where cold chain is not maintained perfectly and the population is older and sicker, that you will not get as good results as you got in the controlled clinical trials,” senior study author Ran Balicer told Reuters. “But we did and the vaccine worked as well in the real world.”

“We have shown the vaccine to be as effective in very different sub-groups, in the young and in the old in those with no co-morbidities and in those with few co-morbidities,” he added.

The study also suggests the vaccine, developed by U.S drugmaker Pfizer and Germany’s BioNTech, is effective against the coronavirus variant first identified in the UK. Researchers said they could not provide a specific level of efficacy, but the variant was the dominant version of the virus in Israel at the time of the study.

The research did not shed light on how the Pfizer shot will fare against another variant, now dominant in South Africa, that has been shown in lab experiments and trials to reduce the efficacy of current vaccines.

‘THIS IS MORE GREAT NEWS’

Of the nine million people in Israel, a nation with universal healthcare, nearly half have received a first dose, and a third have received both doses since the rollout began on Dec. 19.

This made the country a prime location for a real-world study into the vaccine’s ability to stem the pandemic, along with its advanced data capabilities.

The study examined about 600,000 vaccinated people against the same sized control group of unvaccinated people. Researchers at Harvard T.H. Chan School of Public Health, Harvard Medical School and Boston Children’s Hospital also collaborated.

“This is more great news, confirming that the vaccine is around 90% effective at preventing documented infection of any degree of severity from 7 days after the second dose,” said Peter English, a British government consultant in communicable disease control.

“Previous recently studied papers from Israel were observational studies. This one used an experimental design known as a case-control study … giving greater confidence that differences between the groups are due to their vaccination status, and not to some other factor.”

The study published on Wednesday was the first analysis of a national COVID-19 vaccination strategy to be peer-reviewed. It also offered a more detailed look at how the vaccine was faring at weekly intervals, while matching people who received the shot to unvaccinated individuals with similar medical histories, sex, age and geographical characteristics.

Other research centres in Israel, including the Weizmann Institute of Science and the Israel Institute of Technology have shared several studies in recent weeks that show the vaccine to be effective.

At least three studies out of Israel have also suggested the vaccine can reduce coronavirus transmission, but the researchers have cautioned that wider studies must be conducted in order to establish clear-cut conclusions.

GOT YOUR IMMUNITY PASS?

The Weizmann Institute’s latest data shows a dramatic drop in illness – which began this month with the first age group vaccinated, the over-60s – has now extended to the two subsequent groups to have completed both doses.

As infections have fallen in Israel, the country has eased its third national lockdown and reopened swathes of its economy including malls, shops, schools and many workplaces in the past two weeks.

Recreational venues such as theatres, gyms and hotels opened on Sunday, but are open only to those deemed immune – holders of a “Green Pass”, a health ministry document available for download only by people seven days after their second dose or people who have recovered from COVID-19.

On Wednesday, Tel Aviv held one of the country’s first live concerts after months of gatherings being banned under coronavirus restrictions.

“This is so exciting, we are really so happy to be here today. It’s unbelievable after one year of staying at home, it’s great to be out to see some culture,” said 60-year-old Gabi Shamir as she took her seat at the open-air show.

Still, the vaccine’s efficacy does not mean the country will be pandemic free any time soon. Like elsewhere in the world, a large proportion of the population are under 16 – about a third in Israel – meaning that they cannot yet get vaccinated as there have not been clinical trial results for children.

“This is definitely not the end of the pandemic,” said Eran Kopel, an epidemiologist at Tel Aviv University. “Once there is a safe vaccine for the children in Israel and all over the world we can then start to say that we could be approaching herd immunity.”

SOUREC: https://bit.ly/3utMHLJ The New England Journal of Medicine, online February 24, 2021.

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Scientists identify cells responsible for liver tissue maintenance and regeneration

Scientists identify cells responsible for liver tissue maintenance and regeneration

While the amazing regenerative power of the liver has been known since ancient times, the cells responsible for maintaining and replenishing the liver have remained a mystery. Now, research from the Children’s Medical Center Research Institute at UT Southwestern (CRI) has identified the cells responsible for liver maintenance and regeneration while also pinpointing where they reside in the liver.

These findings, reported today in Science, could help scientists answer important questions about liver maintenance, liver damage (such as from fatty liver or alcoholic liver disease), and liver cancer.

The liver performs vital functions, including chemical detoxification, blood protein production, bile excretion, and regulation of energy metabolism. Structurally, the liver is comprised of tissue units called lobules that, when cross-sectioned, resemble honeycombs. Individual lobules are organized in concentric zones in which hepatocytes, the primary liver cell type, carry out diverse functions. Over the past 10 years, there has been debate about whether all hepatocytes across the lobule contribute to the production of new cells or if a certain subset of hepatocytes or stem cells is responsible.

Previous efforts to identify the cells most responsible for liver regeneration were hindered by a lack of markers to distinguish and compare the functions of distinct types of hepatocytes in different regions of the liver. Scientists in the Zhu lab addressed this issue by comparing the genes that mark hepatocytes throughout the liver. Using this approach, they identified genes that were only turned on by specific subsets of hepatocytes, and then used these genes as markers to distinguish the identities and functions of different hepatocyte subsets. They created 11 new mouse strains, each of which carries a marker for a specific subset of hepatocytes. Along with three previously established mouse strains, researchers observed how the labeled cells multiplied or disappeared over time, and which were responsible for liver regeneration after damage. These experiments allowed researchers to directly compare how different subsets of hepatocytes contributed to liver maintenance and regeneration.

Members of the Zhu lab discovered that cells in zone 2 gave rise to new hepatocytes that populated all three zones of liver lobules while cells from zones 1 and 3 disappeared. These unexpected observations suggested that there is not a rare population of stem cells responsible for liver maintenance, but instead, a common set of mature hepatocytes within a specific region of the liver that regularly divide to make new hepatocytes throughout the liver. The Zhu lab also exposed mice to chemicals that mimicked common forms of liver damage, showing that cells in zone 2 were most able to evade death, regenerate hepatocytes, and sustain liver function.

“In humans, cells in zones 1 and 3 are most often harmed by alcohol, acetaminophen, and viral hepatitis. So it makes sense that cells in zone 2, which are sheltered from toxic injuries affecting either end of the lobule, would be in a prime position to regenerate the liver. However, more investigation is needed to understand the different cell types in the human liver,” says Hao Zhu, M.D., an associate professor at CRI and lead author of the study.

To learn more about mechanisms that hepatocytes in zone 2 use to regenerate liver function, members of the Zhu lab performed genetic screens to look for genes important for growth and regeneration. They discovered a pathway known as the IGFBP2-mTOR-CCND1 axis that was active in zone 2 but less so in zones 1 and 3. When they deleted components of this pathway from mice, the cells in zone 2 no longer gave rise to new hepatocytes, establishing that this was the mechanism responsible for the regenerative capacity of zone 2 cells.

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