Scientists discover pathway that allows cancer to bypass oncology treatments

Researchers at City of Hope have identified a pathway that explains how mutated cancer cells can continue to replicate and become resistant to oncology therapies.
Using whole genome sequencing technology, the scientists discovered a new mechanism for how genetically defective cells mutate to survive stressful situations, such as drug treatment. Understanding this resistance mechanism moves researchers one step closer to developing new strategies to prevent cancer development or to delay and overcome resistance to cancer drugs.
“Targeted cancer therapies have transformed cancer care and prolonged patient lives, but many patients eventually develop resistance to their lifesaving treatments. Our basic research hints at how we might one day be able to increase survival by delaying or even preventing the development of cancer drug resistance,” said Binghui Shen, Ph.D., professor and chair of the Department of Cancer Genetics and Epigenetics at Beckman Research Institute of City of Hope.
Shen has been conducting research on the fundamental mechanisms of DNA replication and the key enzyme called flap endonuclease 1 for the past 25 years at City of Hope. This finding, Shen said, is a milestone moment.
The study, published on Dec. 3 in the journal Science, was conducted in yeast, mouse and human leukemia models. As a next step, Shen’s team will see if they can replicate the discovery in more varied human cancer cells and establish regimens to overcome cancer drug resistance.
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Researchers link new gene variant in Amish population to lower risk of heart disease

University of Maryland School of Medicine (UMSOM) researchers, working with scientists from the Regeneron Genetics Center (RGC), discovered a new gene variant associated with lower levels of heart-damaging LDL cholesterol and a blood clotting protein called fibrinogen that appears to significantly lower a person’s risk of heart disease. While the gene variant is extremely rare in the general population (less than 1 in 10,000), it is found in about 12 percent of those living in the Lancaster county, Pennsylvania Amish community, according to the study published today in the journal Science.
Researchers have long known about gene mutations linked to cholesterol levels. This is the first time, however, they have found a gene variant that can significantly reduce the level of two heart disease risk factors and subsequently reduce a person’s risk of heart disease. The finding could potentially lead to novel treatments that may help prevent clogged arteries, blood clots, and cardiovascular disease.
“Leveraging data from more than 500,000 from the general population, it was found that those who carried this variant had a 35 percent lower risk of heart disease compared to those who did not,” said study leader May Montasser, PhD, Assistant Professor of Medicine at UMSOM and a member of UMSOM’s Program for Personalized and Genomic Medicine. “The genetic variant appears to either control the synthesis of cholesterol and fibrinogen or accelerate their clearance from the blood, which protects the heart. This finding could lead to targeted drugs that mimic the action of this variant to keep arteries free of plaque and clots.”
Genetic sequencing of samples from nearly 7,000 Amish study participants who have been participating in genetic research with UMSOM since 1995 was performed at the RGC. The researchers found a genetic variant in the gene B4GALT1 was associated with a nearly 14 mg/dL lower LDL cholesterol and nearly 30 mg/dL lower fibrinogen. After the variant was identified, they tested its effects in mice that were genetically modified to express the variant.
“The mouse model, encoding for this gene mutation, also showed decreased levels of LDL cholesterol and fibrinogen, confirming the effect of this variant,” said Giusy Della Gatta, PhD, study leader and RGC senior staff scientist. “This model represents an invaluable tool to unravel the molecular mechanisms that help protect against cardiovascular disease.”
The Amish community is ideal for genetic studies due to its common lineage and homogeneous lifestyle that makes finding novel links between genes and health easier for scientists. Study co-author Alan Shuldiner, MD, John L. Whitehurst Professor of Medicine and Associate Dean for Personalized & Genomic Medicine at UMSOM, founded the Amish Research Clinic in Lancaster, PA. The clinic’s research has discovered genes playing a role in type 2 diabetes and heart disease, as well as a gene that plays a role in determining why some people don’t respond to the anticlotting medicine Plavix.
Dr. Shuldiner is also a Vice President at the Regeneron Genetics Center. Other UMSOM co-authors include: Simeon I. Taylor, MD, PhD, Professor of Medicine; Jeffrey O’Connell, PhD, Associate Professor of Medicine; Elizabeth A. Streeten, MD, Professor of Medicine and Braxton Mitchell, PhD, Professor of Medicine. The study was funded by the National Institutes of Health, the American Heart Association, and the Regeneron Genetics Center.
“This is a ground-breaking finding and would not have been possible without the participation and partnership of the Amish community,” 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. “We are so grateful for their continuing commitment to research and advancement of precision medicine.”
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Materials provided by University of Maryland School of Medicine. Original written by Deborah Kotz. Note: Content may be edited for style and length.

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Why Didn’t the U.S. Detect Omicron Cases Sooner?

Genomic surveillance has improved enormously in recent months, but the system has built-in delays, and blind spots remain.Last Friday, just a day after South African scientists first announced the discovery of the Omicron variant, Europe reported its first case: The new coronavirus variant was in Belgium. Before the weekend was out, Australia, Britain, Canada, Denmark, Germany, Israel, Italy and other countries had all found cases.But in the United States, scientists kept searching.“If we start seeing a variant popping up in multiple countries across the world, usually my intuition is that it’s already here,” said Taj Azarian, a genomic epidemiologist at the University of Central Florida.On Wednesday, American officials announced that scientists had found it — in a California patient who had recently returned from South Africa. By then, Canada had already identified six cases; Britain had found more than a dozen.The United States identified two more cases, in Minnesota and Colorado, on Thursday, making it clear that more are almost certainly lurking, scientists said. Why wasn’t the variant detected sooner?Multiple factors may be at play, including travel patterns and stringent entrance requirements that may have delayed the variant’s introduction to the United States. But blind spots and delays in the country’s genomic surveillance system may have been factors, too, experts said. With many labs now conducting a targeted search for the variant, the pace of detection could quickly pick up.Scaling upThe United States’ first case of the Omicron variant was sequenced at the University of California, San Francisco.Mike Kai Chen for The New York TimesSince the beginning of the pandemic, scientists have been sequencing the genetic material from samples of the virus, a process that allows them to spot new mutations and identify specific variants. When done routinely and on a large scale, sequencing also allows researchers and officials to keep tabs on how the virus is evolving and spreading.In the United States, this kind of broad genomic surveillance got off to a very slow start. While Britain quickly harnessed its national health care system to launch an intensive sequencing program, early sequencing efforts in the United States, based primarily out of university laboratories, were more limited and ad hoc.Even after the C.D.C. launched a sequencing consortium in May 2020, sequencing efforts were stymied by a fragmented health care system, a lack of funding and other challenges.In January, when cases were surging, the United States was sequencing fewer than 3,000 samples a week, according to the C.D.C.’s dashboard, far less than 1 percent of reported cases. (Experts recommend sequencing at least 5 percent of cases.)But in recent months, the situation has improved dramatically, thanks to a combination of new federal leadership, an infusion of funding and an increasing concern about the emergence and spread of new variants, experts said.“Genomic surveillance really has caught up in the U.S., and it is very good,” said Dana Crawford, a genetic epidemiologist at Case Western Reserve University.The country is now sequencing approximately 80,000 virus samples a week and 14 percent of all positive P.C.R. tests, Dr. Rochelle P. Walensky, the director of the Centers for Disease Control and Prevention, said at a White House briefing on Tuesday.The problem is that the process takes time, especially when done in volume. The C.D.C.’s own sequencing process typically takes about 10 days to complete after it receives a specimen.“We have really good surveillance in terms of quantity,” said Trevor Bedford, an expert on viral evolution and surveillance at the Fred Hutchinson Cancer Research Center in Seattle. He added, “But by nature, it lags compared to your case reporting. And so we’ll have good eyes on things from two weeks ago.”This kind of delay is not uncommon in countries that have a lot of samples to sequence, Dr. Bedford said.In some states, the timeline is even longer. The Ohio Department of Health notes that, from start to finish, the process of “collecting the sample, testing it, sequencing it and reporting it can take a minimum of 3-4 weeks.”Sorting coronavirus test samples for genomic sequencing at Duke University. Pete Kiehart for The New York TimesBut now that scientists know what they are looking for, they should be able to expedite the process by prioritizing samples that seem most likely to be Omicron, scientists said.In one small bit of luck, Omicron generates a different genetic signal on P.C.R. tests than the Delta variant, which currently accounts for essentially all coronavirus cases in the United States. (In short, mutations in the new variant’s spike gene mean that Omicron samples test negative for the gene, while testing positive for a different telltale gene.)Many labs are now expediting these samples, as well as samples from people who recently returned from abroad, for sequencing.“All of the agencies that are involved with genomic surveillance are prioritizing those recent travel-associated cases,” Dr. Azarian said.That may have been how the California case was flagged so quickly. The patient returned from South Africa on Nov. 22 and began feeling sick on Nov. 25. The person tested positive for the virus on Monday and scientists then sequenced the virus, announcing that they had detected Omicron two days later.“The quick turnaround by the U.S. genomic surveillance system is another example of how much better our system has become over the past few months,” Dr. Crawford said.Blind spotsAs much as surveillance has improved, there are still gaps that could slow the detection of more cases in the United States, including enormous geographic variation.“Some states are lagging behind,” said Massimo Caputi, a molecular virologist at the Florida Atlantic University School of Medicine.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4The Omicron variant.

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Missouri Withheld Data Showing Effectiveness of Mask Mandates

Mask requirements prevented Covid-19 cases and deaths in Missouri, the state found, but data supporting that conclusion was not released until a month later.Mask mandates were effective as the Delta variant of the coronavirus was driving a surge in Covid-19 cases across Missouri, according to an analysis that the state’s Department of Health and Senior Services conducted in early November.But the state did not immediately share that data with the public. Instead, the information was released on Wednesday, a month later, because of a public records request by The Missouri Independent, a nonprofit news organization that reported the findings, and the Documenting Covid-19 project at the Brown Institute for Media Innovation.The records include an email dated Nov. 3 from the director of Missouri’s Health Department to a staff member in the governor’s office. The email included two graphs that compared the rates of reported Covid-19 cases and deaths in parts of Missouri with and without mask mandates.The director, Donald Kauerauf, said in the email that there were many variables to account for when assessing the effects of mask requirements in Missouri this year, but that the analysis ultimately showed that such requirements were effective.“I think we can say with great confidence reviewing the public health literature and then looking at the results in your study that communities where masks were required had a lower positivity rate per 100,000 and experienced lower death rates,” Mr. Kauerauf wrote.The analysis compared the reported case and death rates in the parts of the state without mask requirements to rates in St. Louis, St. Louis County, Kansas City and Jackson County, where mask mandates had been in place.The study looked at the period from April to October, when the Delta variant was driving an increase in coronavirus infections worldwide.During that time frame, there were 15.8 cases per day for every 100,000 residents, on average, in the areas that required masks, compared with 21.7 cases per 100,000 residents in unmasked communities, according to The Missouri Independent’s analysis of the data. Regions without mask requirements recorded one death per 100,000 residents every 3.5 days, compared with one death per 100,000 residents every five days where masks were required, The Missouri Independent said.Gov. Mike Parson, a Republican, has said he supports wearing masks to slow the spread of Covid-19, but he has repeatedly spoken out against mask requirements. In July, he said on Twitter that issuing mask mandates while a vaccine is available eroded public trust. “The vaccine is how we rid ourselves of COVID-19, not mask mandates that ignore common sense,” Mr. Parson wrote.Mr. Parson’s office and the state health department did not immediately respond to requests for comment on Thursday.In Missouri, new cases have risen from a daily average of about 1,000 in early November to more than 2,000 this month, and hospitalizations are up 32 percent over the past 14 days, according to a New York Times database. More than 15,540 people have died from Covid-19 in Missouri, according to the database.In late November, a circuit court judge in Missouri ruled that public health orders issued by local health departments to prevent the spread of the coronavirus violated the state’s constitution.Mask are still required, however, in St. Louis and St. Louis County. Kansas City ended its requirement on Nov. 5, and the Legislature in Jackson County voted to end its mask requirement in early November.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4The Omicron variant.

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Omicron Is Here. Should You Cancel Your Trip?

Most people have become used to making health-risk assessments during the pandemic, but that doesn’t make the decision about whether to travel or cancel easier — especially with a new variant circulating.To cancel or not to cancel. That is the question that travelers are grappling with as the Omicron variant scuttles around the world, reminding people that the pandemic roller-coaster ride is far from over. What’s different this time around is that the holiday travel season is right around the corner, and tourism, in general, has finally started to rebound.Whether the variant, which has been identified in at least 20 countries, is more severe or more transmissible than other forms of the coronavirus will likely remain unknown for at least two weeks. The United States is among the countries that believe that it is a serious enough threat to merit new rules. Soon after researchers in South Africa discovered it, President Biden suspended incoming U.S. travel from eight African nations. On Tuesday, the Centers for Disease Control and Prevention said that the United States would tighten testing requirements, requiring all travelers entering the United States — including returning Americans — to provide negative tests taken within one day of departure instead of the three days now permitted for vaccinated travelers.Though most people are by now experienced with making high-stakes health-risk assessments in the face of incomplete information, that doesn’t make the decision about whether to travel or not easy.Omicron variant pls don’t ruin my 2022 travel plans.— mabintou (@mabintou) November 30, 2021
Courtney Niebrzydowsk, an international travel risk analyst at the University of Denver, said she urges people to ask themselves two primary questions when they consider traveling: 1. Can this travel be postponed? and 2. How flexible can you be?She also urges people to think through all the scenarios that could emerge if they travel — like testing positive, facing a canceled return flight or learning last minute that their destination country has expanded its quarantine requirement — and map out detailed contingency plans, including costs, missed obligations and how to approach health care. Often, she said, after going through this exercise, people have “less appetite for travel.”The C.D.C. advises against international travel until a person is fully vaccinated. The World Health Organization recommends that people who are not fully vaccinated, have not previously been infected, are 60 years or older or have comorbidities such as heart disease, cancer and diabetes should postpone travel to areas with community transmission.Jessica Herzstein, a physician who advises organizations on how to manage the coronavirus and other health risks, including those associated with travel, said that she discourages anyone who is unvaccinated or immune-compromised from traveling. She also advises travelers going to destinations with a particularly high prevalence of cases to consider canceling. For those planning to travel, Dr. Herzstein strongly advises booster shots for those eligible and to take along a supply of at-home rapid antigen tests.David Freedman, the president-elect of the American Society of Tropical Medicine and Hygiene, said that the type of mask one wears while traveling is particularly important. Dr. Freedman discourages people from wearing cloth or homemade masks; N95 or KN95 masks are preferable, he said.It is difficult to assess how likely it is that a traveler will encounter an infected individual while flying to their destination. This is a particularly important to consider when traveling with children too young to be vaccinated or to wear a mask. Domestic flights in the United States do not require testing or proof of vaccination. Some countries and airlines require both. Others don’t.Creating a shorter window for testing — as the United States recently did for everyone flying into the country from abroad, regardless of nationality — makes sense, Dr. Freedman said. Testing three days before a flight can miss those who are incubating the virus and could be contagious and test positive by the time they board their plane. He said that a flight with a P.C.R. test requirement is also lower risk than a flight requiring an antigen test. But, he added, there is potentially more risk of transmission in airports than on planes, with their advanced air filtration systems. So much is out of even a meticulous planner’s control.Part of the challenge that many people are struggling with is how to weigh the other variables — like the mental health benefits of celebrating Christmas with family, or the professional benefits that might come from interacting with co-workers face-to-face. It’s easier for governmentsto define “essential travel” than for individuals, said Ms. Niebrzydowsk, the travel risk analyst.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4The Omicron variant.

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Gene discoveries give new hope to people who stutter

More than 2.5 million Americans have a chronic condition arising in early childhood that can negatively impact their education, job performance and employability well into adulthood.
There is no known cure, and existing treatments are often minimally effective. Yet for those with persistent, developmental stuttering, there is new hope, thanks to groundbreaking research led by scientists at Vanderbilt University Medical Center in Nashville, Tennessee, and Wayne State University in Detroit, Michigan.
In two papers published this week, Jennifer “Piper” Below, PhD, and Shelly Jo Kraft, PhD, describe a “genetic architecture” for developmental stuttering and report the discovery of new genetic variations associated with the condition.
The researchers said that these findings, which were published in The American Journal of Human Genetics and Human Genetics and Genomics Advances, and studies like them have the potential to identify therapeutic directions that could improve outcomes for people who stutter.
“It’s clear that in populations, stuttering is polygenic, meaning that there are multiple different genetic factors contributing to and protecting people from risk,” said Below, associate professor of Medicine at VUMC. “That was something that had not been clearly shown before these studies.”
The new revelations will have a huge impact on people who stutter and on the parents of children affected by the condition, predicted Kraft, associate professor of Communication Sciences and Disorders and director of the Behavior, Speech & Genetics Lab at Wayne State University.

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Why Hasn’t the U.S. Found More Omicron Cases?

Genomic surveillance has improved enormously in recent months, but the system has built-in delays, and blind spots remain.Last Friday, just a day after South African scientists first announced the discovery of the Omicron variant, Europe reported its first case: The new coronavirus variant was in Belgium. Before the weekend was out, Australia, Britain, Canada, Denmark, Germany, Israel, Italy and other countries had all found cases.But in the United States, scientists kept searching.“If we start seeing a variant popping up in multiple countries across the world, usually my intuition is that it’s already here,” said Taj Azarian, a genomic epidemiologist at the University of Central Florida.On Wednesday, American officials announced that scientists had found it — in a California patient who had recently returned from South Africa. By then, Canada had already identified six cases; Britain had found more than a dozen.The United States identified a second case, in Minnesota, on Thursday, and more are almost certainly lurking, scientists said. So why haven’t we found Tthem yet?Multiple factors may be at play, including travel patterns and stringent entrance requirements that may have delayed the variant’s introduction to the United States. But blind spots and delays in the country’s genomic surveillance system may have been factors, too, experts said. With many labs now conducting a targeted search for the variant, the pace of detection could quickly pick up.Scaling upThe United States’s first case of the Omicron variant was sequenced at the University of California, San Francisco.Mike Kai Chen for The New York TimesSince the beginning of the pandemic, scientists have been sequencing the genetic material from samples of the virus, a process that allows them to spot new mutations and identify specific variants. When done routinely and on a large scale, sequencing also allows researchers and officials to keep tabs on how the virus is evolving and spreading.In the United States, this kind of broad genomic surveillance got off to a very slow start. While Britain quickly harnessed its national health care system to launch an intensive sequencing program, early sequencing efforts in the United States, based primarily out of university laboratories, were more limited and ad hoc.Even after the C.D.C. launched a sequencing consortium in May 2020, sequencing efforts were stymied by a fragmented health care system, a lack of funding and other challenges.In January, when cases were surging, the United States was sequencing fewer than 3,000 samples a week, according to the C.D.C.’s dashboard, far less than 1 percent of reported cases. (Experts recommend sequencing at least 5 percent of cases.)But in recent months, the situation has improved dramatically, thanks to a combination of new federal leadership, an infusion of funding and an increasing concern about the emergence and spread of new variants, experts said.“Genomic surveillance really has caught up in the U.S., and it is very good,” said Dana Crawford, a genetic epidemiologist at Case Western Reserve University.The country is now sequencing approximately 80,000 virus samples a week and 14 percent of all positive P.C.R. tests, Dr. Rochelle P. Walensky, the director of the Centers for Disease Control and Prevention, said at a White House briefing on Tuesday.The problem is that the process takes time, especially when done in volume. The C.D.C.’s own sequencing process typically takes about 10 days to complete after it receives a specimen.“We have really good surveillance in terms of quantity,” said Trevor Bedford, an expert on viral evolution and surveillance at the Fred Hutchinson Cancer Research Center in Seattle. He added, “But by nature, it lags compared to your case reporting. And so we’ll have good eyes on things from two weeks ago.”This kind of delay is not uncommon in countries that have a lot of samples to sequence, Dr. Bedford said.In some states, the timeline is even longer. The Ohio Department of Health notes that, from start to finish, the process of “collecting the sample, testing it, sequencing it and reporting it can take a minimum of 3-4 weeks.”Sorting coronavirus test samples for genomic sequencing at Duke University. Pete Kiehart for The New York TimesBut now that scientists know what they are looking for, they should be able to expedite the process by prioritizing samples that seem most likely to be Omicron, scientists said.In one small bit of luck, Omicron generates a different genetic signal on P.C.R. tests than the Delta variant, which currently accounts for essentially all coronavirus cases in the United States. (In short, mutations in the new variant’s spike gene means that Omicron samples test negative for the gene, while testing positive for a different telltale gene.)Many labs are now expediting these samples, as well as samples from people who recently returned from abroad, for sequencing.“All of the agencies that are involved with genomic surveillance are prioritizing those recent travel-associated cases,” Dr. Azarian said.That may have been how the California case was flagged so quickly. The patient returned from South Africa on Nov. 22 and began feeling sick on Nov. 25. The person tested positive for the virus on Monday and scientists then sequenced the virus, announcing that they had detected Omicron two days later.“The quick turnaround by the U.S. genomic surveillance system is another example of how much better our system has become over the past few months,” Dr. Crawford said.Blind spotsAs much as surveillance has improved, there are still gaps that could slow the detection of more cases in the United States, including enormous geographic variation.“Some states are lagging behind,” said Massimo Caputi, a molecular virologist at the Florida Atlantic University School of Medicine.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4The Omicron variant.

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Shining new light on elusive flying bats

How can we understand the activity of wild bats? Mostly soundless, flying in the dark, bats feed at night and evade our senses. Many bats can use echolocation to hunt and can avoid the traditional nets used to capture them; those that do not “echolocate” cannot be detected by ultrasound bat detectors. Now, an international research team led by the University of Göttingen has developed a new method “bat point counts” by combining modern sensing technologies — thermal, ultrasonic and near-infrared — to detect, identify and count all bats flying around in a certain range. This new non-invasive method allows scientists to better understand bat behaviour and populations, which should lead to better informed conservation science. The results were published in the journal Ecology and Evolution.
Traditional methods to sample bats include catching them in nets or recording their ultrasound calls. However, bats that use echolocation can detect and avoid nets even in the dark and some bats do not emit sounds, meaning these methods are prone to errors. Alternatively, non-invasive modern sensing technologies can be used. By combining data from thermal, ultrasonic and near-infrared sensors, researchers created and tested a new method: “bat point counts.” To compare it against the traditional methods, researchers used netting to capture and measure 83 bats, they used sound recorders to analyse dozens of hours of recordings, and they dissected hundreds of near-infrared pictures paired with hours of sound recordings, obtained from bat point counts.
Even though “bat point counts” were only conducted for a third of the sampling time of the other methods, the new technique succeeded in finding similar species numbers. However, only one species could be detected by all three methods — the two traditional methods and the bat point counts — with certainty. First author Dr Kevin Darras, University of Göttingen and Westlake University explains: “This showed that none of the techniques was comprehensive on its own. We needed to combine three modern sensing technologies to get a fuller picture of the flying bat communities around us.”
The researchers found that fruit-eating bats are rare in oil palm plantations (just 7% of bat point count detections). This finding was in stark contrast to previous studies, which used nets and had led researchers to conclude that these bats dominated oil palm plantations. Darras says: “This suggests that fruit-eating bats have a short ‘commute’ through plantations and are easily caught with nets. However, insect-eating bats can easily fly around nets in these open plantations. Our new technique shows that insect-eating bats are actually much more common than previously thought in oil palm and might play a significant role in suppressing insect pests.”
This technique has given researchers new insights into the relative activity and prevalence of different bat species. Darras goes on to say: “We envisage this new method will lead to better conservation measures to protect species as well as new data to understand bat behaviour.”
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Harnessing the organization of the cell surface

Biological cells have multiple functions, and they need to communicate with each other to coordinate them. Molecules on the cell surface are central to this process. For decades, biologists have been studying such surface proteins and it is becoming increasingly clear that not only their presence but also their organisation on the cell’s surface is crucial to the function of a cell.
“Proteins aren’t simply distributed evenly and independently of one another across the cell’s surface; instead, they’re organised into molecular communities. In these communities, proteins often work together to fulfil cellular functions,” explains Bernd Wollscheid, Professor at ETH Zurich’s Institute of Translational Medicine. Together with a large interdisciplinary team that includes further researchers from ETH Zurich and other institutions, Wollscheid’s doctoral student Maik Müller has now developed a technology that can be used to discover the organisation of cell surface molecules.
“Who got a kiss?”
With this technology called LUX-MS, the researchers can determine with nanometer-scale precision how proteins integrate into an organisation on the cell surface — in other words, which proteins are in proximity to each other. So far, scientists were able to measure interactions of individual proteins that have a high affinity for each other, as well as for molecules that reside inside the cell. However, the new method is the first to enable scientists to specifically detect the organisation of the entirety of cell surface molecules. Wollscheid refers to this entirety as the “surfaceome.” The term is composed of the word “surface” and the suffix “-ome,” that is also used in terms such as genome or proteome.
With a twinkle in his eye, Wollscheid explains the principle behind the method as follows: “We specifically modify a particular surface molecule so that it likes to ‘give kisses’ to molecules in its proximity, and then we check the other surface molecules for traces of lipstick.” In more technical terms, a small chemical compound is attached to a protein of interest. When irradiated with light, this compound produces small amounts of what are known as reactive oxygen molecules, that oxidise surface proteins in the immediate vicinity. Using a specific enrichment method and mass spectrometry in combination with statistical data analysis, the scientists can ultimately identify which molecules have been oxidised.
To determine the distance between the protein of interest and the other molecules, the researchers repeat their experiments under slightly modified conditions that affect the amount and survival time of the reactive oxygen molecules. These include the length of irradiation with light and the choice of medium in which the cells are cultured. The more reactive oxygen is locally generated and the longer that process continues, the wider the area in which surface molecules get oxidised.

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Stroke may be triggered by anger, emotional upset and heavy physical exertion

A global study co-led by NUI Galway into causes of stroke has found that one in 11 survivors experienced a period of anger or upset in the one hour leading up to it. One in 20 patients had engaged in heavy physical exertion.
The suspected triggers have been identified as part of the global INTERSTROKE study — the largest research project of its kind, which analysed 13,462 cases of acute stroke, involving patients with a range of ethnic backgrounds in 32 countries, including Ireland.
The research has been published in the European Heart Journal.
Stroke is a leading global cause of death or disability. Each year, approximately 7,500 Irish people have a stroke and around 2,000 of these people die. An estimated 30,000 people are living in Ireland with disabilities as a result of a stroke.
Professor Andrew Smyth, Professor of Clinical Epidemiology at NUI Galway, Director of the HRB-Clinical Research Facility Galway and a Consultant Nephrologist at Galway University Hospitals, was one of the lead researchers.
He said: “Stroke prevention is a priority for physicians, and despite advances it remains difficult to predict when a stroke will occur. Many studies have focused on medium to long-term exposures, such as hypertension, obesity or smoking. Our study aimed to look at acute exposures that may act as triggers.”
The research analysed patterns in patients who suffered ischemic stroke — the most common type of stroke, which occurs when a blood clot blocks or narrows an artery leading to the brain, and also intracerebral haemorrhage — which is less common and involves bleeding within the brain tissue itself.

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