Tag Archives: proteins

A Cannabis Molecule Reduces Plaque, Improves Cognition in Alzheimer’s

A two-week course of high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improves cognition in an experimental model of early onset familial Alzheimer’s, investigators report. The proteins TREM2 and IL-33 are important to the ability of the brain’s immune cells to literally consume dead cells and other debris like the beta-amyloid plaque that piles up in patients’ brains, and levels of both are decreased in Alzheimer’s.

The investigators report for the first time that CBD normalizes levels and function, improving cognition as it also reduces levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer’s, says Dr. Babak Baban, immunologist and associate dean for research in the Dental College of Georgia (DCG) and the study’s corresponding author. There is a dire need for novel therapies to improve outcomes for patients with this condition, which is considered one of the fastest-growing health threats in the United States, DCG and Medical College of Georgia (MCG) investigators write in the Journal of Alzheimer’s Disease.

Right now we have two classes of drugs to treat Alzheimer’s,” says Dr. John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology. “One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer’s, and another works through the NMDA receptors involved in communication between neurons and important to memory. But we have nothing that gets to the pathophysiology of the disease,” says Morgan, a study coauthor.

The DCG and MCG investigators decided to look at CBD’s ability to address some of the key brain systems that go awry in Alzheimer’s.

They found CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally in the brain, where it helps sound the alarm that there is an invader like the beta-amyloid accumulation. There is emerging evidence of its role as a regulatory protein as well, whose function of either turning up or down the immune response depends on the environment, Baban says. In Alzheimer’s, that includes turning down inflammation and trying to restore balance to the immune system, he says.

CBD also improved expression of triggering receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is on the microglial cells, a special population of immune cells found only in the brain where they are key to eliminating invaders like a virus and irrevocably damaged neurons.

Source: https://jagwire.augusta.edu/

Soon a Vaccine to Prevent Melanoma

A personalized “cancer vaccine” may help keep a deadly form of skin cancer from growing for years, a small new study in humans suggests. Unlike vaccines that prevent infections, such as measles and influenza, cancer vaccines are a form of immunotherapy that take down cancer cells that already exist. The vaccines train immune cells, called T cells, to better recognize cancer and target it for destruction, while sparing healthy cells in the body. For example, the new experimental vaccine works by training T cells to spot specific proteins on melanoma cells, a type of skin cancer. In the study, scientists found that the T cells continue to “remember” these proteins for at least four years after the vaccination — and they even learn to recognize more melanoma-related proteins over time.

The only way that could have happened is if there was actually killing of the tumor cells. And presumably it was the T cells induced by the vaccine that did that killing,” said study author Dr. Catherine Wu, a physician-scientist with the Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Broad Institute in Cambridge, Massachusetts. That’s because, once killed, tumor cells fall apart and spill their contents; T cells then swoop in to examine these remains and log that information away for future attacks, Wu said.

While the results are promising, the new study only included eight patients, and more trials need to be conducted to pin down exactly how effective the vaccine is, she added. But as of now, the limited data hint that the vaccine triggers a persistent immune response and can help keep cancer under control, especially when combined with other immunotherapies, the authors noted. The new study, published Jan. 21 in the journal Nature Medicine, included patients with advanced melanoma who had recently undergone surgery for the cancer. The researchers took samples of the patients’ removed tumors and used them to craft personalized vaccines for each of the eight participants.

Source: https://www.realclearscience.com/

Immune System Killer Cells Controlled By Circadian Rhythms

An analysis of an exhaustive dataset on cells essential to the mammalian immune system shows that our ability to fight disease may rely more heavily on daily circadian cycles than previously assumed.

Malfunctions in , the process that keeps our bodies in tune with the day/night cycles, are increasingly associated with diabetes, cancer, Alzheimer’s, and many other diseases. An investigation published today in Genome Research shows that the activity of macrophagescells within us that seek and destroy intruders like bacteria—may time daily changes in their responses to pathogens and stress through the circadian control of metabolism. In this study, Jennifer Hurley, the Richard Baruch M.D. Career Development Assistant Professor of Biological Sciences at Rensselaer Polytechnic Institute and senior author on this study, and her team investigated how the levels of RNA and proteins in macrophages change over two days.

We have shown there is an incredible amount of circadian timing of macrophage behavior, but the clock is timing macrophages in unexpected ways” said Hurley.

The circadian system is comprised of a set of core clock proteins that anticipate the day/night cycle by causing daily oscillations in levels of enzymes and hormones, and ultimately affecting physiological parameters such as body temperature and the immune response. This molecular clock marks time through a self-regulating cycle of  production and decay. The “positive” element proteins of the clock trigger production of the “negative” element proteins, which in turn block production of positive element proteins until the negative element proteins decay, thus creating a negative feedback cycle that occurs once every 24 hours.

Positive element proteins also regulate fluctuations in a substantial number of gene products, known as messenger RNA or mRNA. Genetic instructions are transcribed from DNA to mRNA, which are then used as a recipe for assembling proteins, the functional building blocks of the cell. It has long been assumed that the levels of each subsequent step could be predicted from the previous. If that were the case, oscillating mRNA would correspond with oscillating levels of cellular proteins, and therefore, if one could track mRNA, they would know what proteins the circadian clock controlled in the cell.

However, this investigation showed that this paradigm may not always be true. The analysis of the macrophage dataset revealed that there was a substantial mismatch between the proteins and mRNAs that are controlled by the circadian clock. This data paralleled research published in Cell Systems in 2018 by the Hurley lab, showing that about 40% of oscillating proteins in the fungus and circadian model system, Neurospora crassa, had no corresponding oscillating mRNA.

But the scale of the difference in macrophages really surprised us,” Hurley said. “Eighty percent of the proteins that oscillate don’t have associated oscillating mRNA in macrophages. That means we were really missing how the clock was timing immunity.”

Source: https://medicalxpress.com/

How To Fine-Tune Bacterial Metabolism To Boost Longevity

Studies have shown that gut microbes can influence several aspects of the host’s life, including aging. Given the complexity and heterogeneity of the human gut environment, elucidating how a specific microbial species contributes to longevity has been challenging.

To explore the influence of bacterial products on the aging process, scientists at Baylor College of Medicine and Rice University developed a method that uses light to directly control gene expression and metabolite production from bacteria residing in the gut of the laboratory worm Caenorhabditis elegans.

The team reports (“Optogenetic control of gut bacterial metabolism to promote longevity”) in eLife that green-light-induced production of colanic acid by resident Escherichia coli bacteria protected gut cells against stress-induced cellular damage and extended the worm’s lifespan. The researchers indicate that this method can be applied to study other bacteria and propose that it also might provide in the future a new way to fine-tune bacterial metabolism in the host gut to deliver health benefits with minimal side effects.

Illustration of bacteria in the intestine.

Gut microbial metabolism is associated with host longevity. However, because it requires direct manipulation of microbial metabolism in situ, establishing a causal link between these two processes remains challenging. We demonstrate an optogenetic method to control gene expression and metabolite production from bacteria residing in the host gut. We genetically engineer an E. coli strain that secretes colanic acid (CA) under the quantitative control of light,” the investigators wrote.

Using this optogenetically-controlled strain to induce CA production directly in the C. elegans gut, we reveal the local effect of CA in protecting intestinal mitochondria from stress-induced hyper-fragmentation. We also demonstrate that the lifespan-extending effect of this strain is positively correlated with the intensity of green light, indicating a dose-dependent CA benefit on the host.

“Thus, optogenetics can be used to achieve quantitative and temporal control of [the microbiome] metabolism in order to reveal its local and systemic effects on host health and aging. “We used optogenetics, a method that combines light and genetically engineered light-sensitive proteins to regulate molecular events in a targeted manner in living cells or organisms,” said co-corresponding author Meng Wang, PhD, professor of molecular and human genetics at the Huffington Center on Aging at Baylor.

Source: https://www.genengnews.com/

New Variant Of Coronavirus Identified In England

Health Secretary Matt Hancock said at least 60 different local authorities had recorded Covid infections caused by the new variantHe said the World Health Organization had been notified and UK scientists were doing detailed studies.“Nothing to suggest” it caused worse disease or that vaccines would no longer work, he added. Over the last week, there had been sharp, exponential rises in coronavirus infections across London, Kent, parts of Essex and Hertfordshire.

We’ve currently identified over 1,000 cases with this variant predominantly in the South of England although cases have been identified in nearly 60 different local authority areas.“We do not know the extent to which this is because of the new variant but no matter its cause we have to take swift and decisive action which unfortunately is absolutely essential to control this deadly disease while the vaccine is rolled out”, he explained.

England’s Chief Medical Officer Prof Chris Whitty said current coronavirus swab tests would detect the new variant that has been found predominantly in Kent and neighbouring areas in recent weeks. The changes or mutations involve the spike protein of the virus – the part that helps it infect cells, and the target Covid vaccines are designed around.

It is too soon to know exactly what this will do to the behaviour of the virus.

Source: https://www.bbc.com/

How The Coronavirus Infects Human Cells

Tiny artificial lungs grown in a lab from adult stem cells have allowed scientists to watch how coronavirus infects the lungs in a new ‘major breakthrough‘. Researchers from Duke University and Cambridge University produced artificial lungs in two independent and separate studies to examine the spread of Covid-19. The ‘living lung‘ models minimic the tiny air sacs that take up the oxygen we breathe, known to be where most serious lung damage from the deadly virus takes place.   Having access to the models to test the spread of SAS-CoV-2, the virus responsible for Covid-19, will allow researchers to test potential drugs and gain a better understanding of why some people suffer from the disease worse than others.

In both studies the 3D min-lung models were grown from stem cells that repair the deepest portions of the lungs when SARS-CoV-2 attacks – known as alveolar cells. To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, especially in patients that develop pneumonia, appear to be alveoli, according to the Cambridge team. They extracted the alveoli cells from donated tissue and reprogrammed them back to their earlierstem cell‘ stage and forced them to grow into self-organising alveolar-like 3D structures that mimic the behaviour of key lung tissue. Dr Joo-Hyeon Lee, co-senior author of the Cambridge paper, said we still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease.

Representative image of three – dimensional human lung alveolar organoid produced by the Cambridge and Korean researchers to better understand SARS-CoV-2

Our approach has allowed us to grow 3D models of key lung tissue – in a sense, “mini-lungs” – in the lab and study what happens when they become infected.’

Duke researchers took a similar approach. The team, led by Duke cell biologist Purushothama Rao Tata, say their model will allow for hundreds of experiments to be run simultaneously to screen for new drug candidates. ‘This is a versatile model system that allows us to study not only SARS-CoV-2, but any respiratory virus that targets these cells, including influenza,‘ Tata said.

Both teams infected models with a strain of SARS-CoV-2 to better understand who the virus spreads and what happens in the lung cells in response to the disease. The Cambridge team worked with researchers from South Korea to take a sample of the virus from a patient who was infected in January after travelling to Wuhan. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.

When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infectionReplication enables the virus to spread throughout the body, infecting other cells and tissue, explained the Cambridge research team. Around the same time, the cells began to produce interferonsproteins that act as warning signals to neighbouring cells, telling them to activate their defences. After 48 hours, the interferons triggered the innate immune response – its first line of defence – and the cells started fighting back against infectionSixty hours after infection, a subset of alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.

Source: https://today.duke.edu/

Covid-19: Type O blood Divides By 2 The Risk Of Intubation

Research is coalescing around the idea that people with Type O blood may have a slight advantage during this pandemicTwo studies published this week suggest that people with Type O have a lower risk of getting the coronavirus, as well as a reduced likelihood of getting severely sick if they do get infected. One of the new studies specifically found that COVID-19 patients with Type O or B blood spent less time in an intensive-care unit than their counterparts with Type A or AB. They were also less likely to require ventilation and less likely to experience kidney failure.

These new findings echo similar findings about Type O blood seen in previous research, creating a clearer picture of one particular coronavirus risk factor. Both new studies came out Wednesday in the journal Blood AdvancesOne looked at 95 critically ill COVID-19 patients at hospitals in Vancouver, Canada, between February and April. They found that patients with Type O or B blood spent, on average, 4.5 fewer days in the intensive-care unit than those with Type A or AB blood. The latter group stayed, on average, 13.5 days in the ICU. The researchers did not see any link between blood type and the patient’s total hospital stay, however. They did, however, find that only 61 percent of the patients with Type O or B blood required a ventilator, compared to 84 percent of patients with Type A or AB.

Patients with Type A or AB, meanwhile, were also more likely to need dialysis, a procedure that helps the kidneys filter toxins from the blood.

“Patients in these two blood groups may have an increased risk of organ dysfunction or failure due to COVID-19 than people with blood types O or B,” the study authors concluded.

A June study found a similar link: Patients in Italy and Spain with Type O blood had a 50 percent reduced risk of severe coronavirus infection (meaning they needed intubation or supplemental oxygen) compared to patients with other blood types.

The second new study found that people with Type O blood may be at a lower risk of getting he coronavirus in the first place relative to people with other blood types. The team examined nearly half a million people in the Netherlands who were tested for COVID-19 between late February and late July. Of the roughly 4,600 people who tested positive and reported their blood type, 38.4 percent had Type O blood. That’s lower than the prevalence of Type O in a population of 2.2 million Danish people, 41.7 percent, so the researchers determined that people with Type O blood had disproportionately avoided infection. “Blood group O is significantly associated with reduced susceptibility,” the authors wrote.

In general, your blood type depends on the presence or absence of proteins called A and B antigens on the surface of red blood cells – a genetic trait inherited from your parents. People with O blood have neither antigen. It’s the most common blood type: About 48 percent of Americans have Type O bloodaccording to the Oklahoma Blood Institute.

The new studies about blood type and coronavirus risk align with prior research on the topic. A study published in July found that people with Type O were less likely to test positive for COVID-19 than those with other blood types. An April study, too, (though it has yet to be peer-reviewed) found that among 1,559 coronavirus patients in New York City, a lower proportion than would be expected had Type O blood.

And in March, a study of more than 2,100 coronavirus patients in the Chinese cities of Wuhan and Shenzhen also found that people with Type O blood had a lower risk of infection.

Past research has also suggested that people with Type O blood were less susceptible to SARS, which shares 80 percent of its genetic code with the new coronavirusA 2005 study in Hong Kong found that most individuals infected with SARS had non-O blood types. Despite this growing body of evidence, however, Mypinder Sekhon, a co-author of the Vancouver study, said the link is still tenuous.

I don’t think this supersedes other risk factors of severity like age and comorbidities and so forth,” he told CNN, adding, “if one is blood group A, you don’t need to start panicking. And if you’re blood group O, you’re not free to go to the pubs and bars.”

Source: https://www.businessinsider.com/

How To Protect Cells From Premature Aging

Molecules that accumulate at the tip of chromosomes are known to play a key role in preventing damage to our DNA. Now, researchers at EPFL (Ecole Polytechnique Fédérale de Lausanne in Switzerland) have unraveled how these molecules home in on specific sections of chromosomes—a finding that could help to better understand the processes that regulate cell survival in aging and cancer.

Much like an aglet of a shoelace prevents the end of the lace from fraying, stretches of DNA called telomeres form protective caps at the ends of chromosomes. But as cells divide, telomeres become shorter, making the protective cap less effective. Once telomeres get too short, the cell stops dividing. Telomere shortening and malfunction have been linked to cell aging and age-related diseases, including cancer.

A new study by EPFL researchers shows how RNA species called TERRA muster at the tip of chromosomes, where they help to prevent telomere shortening and premature cell aging

Scientists have known that RNA species called TERRA help to regulate the length and function of telomeres. Discovered in 2007 by postdoc Claus Azzalin in the team of EPFL Professor Joachim Lingner, TERRA belongs to a class of molecules called noncoding RNAs, which are not translated into proteins but function as structural components of chromosomes. TERRA accumulates at chromosome ends, signaling that telomeres should be elongated or repaired.

However, it was unclear how TERRA got to the tip of chromosomes and remained there. “The telomere makes up only a tiny bit of the total chromosomal DNA, so the question is ‘how does this RNA find its home?’”, Lingner says. To address this question, postdoc Marianna Feretzaki and others in the teams of Joachim Lingner at EPFL and Lumir Krejci at Masaryk University set out to analyze the mechanism through which TERRA accumulates at telomeres, as well as the proteins involved in this process. The findings are published in Nature.

By visualizing TERRA molecules under a microscope, the researchers found that a short stretch of the RNA is crucial to bring it to telomeres. Further experiments showed that once TERRA reaches the tip of chromosomes, several proteins regulate its association with telomeres. Among these proteins, one called RAD51 plays a particularly important role, Lingner says.

RAD51 is a well-known enzyme that is involved in the repair of broken DNA molecules. The protein also seems to help TERRA stick to telomeric DNA to form a so-called “RNA-DNA hybrid molecule”. Scientists thought this type of reaction, which leads to the formation of a three-stranded nucleic acid structure, mainly happened during DNA repair. The new study shows that it can also happen at chromosome ends when TERRA binds to telomeres. “This is paradigm-shifting,” Lingner says.

The researchers also found that short telomeres recruit TERRA much more efficiently than long telomeres. Although the mechanism behind this phenomenon is unclear, the researchers hypothesize that when telomeres get too short, either due to DNA damage or because the cell has divided too many times, they recruit TERRA molecules. This recruitment is mediated by RAD51, which also promotes the elongation and repair of telomeres. “TERRA and RAD51 help to prevent accidental loss or shortening of telomeres,” Lingner says. “That’s an important function.”

Source: https://actu.epfl.ch/

‘Game Changing’ 15-Minute Covid-19 Test Cleared in Europe

Becton Dickinson and Co.’s Covid-19 test that returns results in 15 minutes has been cleared for use in countries that accept Europe’s CE marking, the diagnostics maker said Wednesday. The test is part of a new class of quicker screening tools named for the identifying proteins called antigens they detect on the surface of SARS-CoV-2. Becton Dickinson expects to begin selling the test, which runs on the company’s cellphone-sized BD Veritor Plus System, in European markets at the end of October. It will likely be used by emergency departments, general practitioners and pediatricians.

Becton Dickinson said its antigen assay is 93.5% sensitive, a measure of how often it correctly identifies infections, and 99.3% specific, the rate of correct negative tests. The data, which differ from the U.S. label’s 84% sensitivity and 100% specificity, come from a new clinical study that was recently submitted to the U.S.  , spokesman Troy Kirkpatrick said.

https://www.bloomberg.com/

How To Eradicate (Again) Tuberculosis

Scientists find new way to kill tuberculosis (TB). A toxin called MenT can block the use of important amino acids required by the bacteria to produce essential proteins needed for survival. An international team of researchers, led by Durham University, UK, and the Laboratory of Molecular Microbiology and Genetics/Centre Integrative Biology in Toulouse, France, are aiming to exploit this  to develop new anti-TB drugs.

Surface electrostatic representation of toxin MenT (blue, positive; red, negative), showing where target tRNA would bind and the enzymatic active site.

TB is the world’s deadliest infectious disease with nearly 1.5 million deaths each year. Whilst most cases can be cured with , the number of antibiotic-resistant infections are steadily increasing. It is spread by breathing in tiny droplets from the coughs or sneezes of an infected person and mainly affects the lungs though it can affect any part of the body, including the glands, bones and  .

Bacteria, such as the germs that cause TB, produce toxins to help them adapt to stress in the environment. These toxins are normally counteracted by a matching antidote, but when they are active they can potentially slow bacterial growth and even lead to cell death. The research team found a new toxin, called MenT, produced by the TB bacterium Mycobacterium tuberculosis. The researchers built an extremely detailed 3-D picture of MenT which, combined with genetic and biochemical data, showed that the toxin inhibits the use of amino acids needed by the bacteria to produce protein.

If it is not neutralised by its MenA anti-toxin, MenT stalls the growth of Mycobacterium tuberculosis, causing the bacteria to die.

Co-Senior author Dr. Tim Blower, Associate Professor in the Department of Biosciences, and Lister Institute Prize Fellow at Durham University, said: “Effectively the tuberculosis is actively poisoning itself. “Through the forced activation of MenT, or by destabilising the relationship between the toxin and its anti-toxin MenA, we could kill the  that cause TB”  The remarkable anti-bacterial properties of such toxins make them of huge therapeutic interest.”

Their findings are published in the journal Science Advances.

Source: https://www.dur.ac.uk/
AND
https://phys.org/