Publisher Health

Increased risk of cancer due to a genetic predisposition in first- and second-degree relatives is long-established but has previously only been studied in white or European populations.
Now, a new study published in eLife is the first to demonstrate that the inherited risk of early-onset cancer is significantly higher among Latino and African American families for solid tumors, and Asian/Pacific Islander families for blood-based cancers, compared to non-Latino white families in California.
“Cancer clustering within families, meaning the devastating diagnosis of more than one early-onset cancer within the same family, usually points to a genetic cause. Interestingly, family cancer clustering has only been examined previously at the population level in white, or European origin population studies,” says study author Joseph Wiemels, PhD, a member of the Cancer Epidemiology Program at the USC Norris Comprehensive Cancer Center, and professor of Preventive Medicine at the Keck School of Medicine of USC. “In this study, we looked at clustering of cancer cases in young family members in California over the past 30 years within non-white populations and compared it, for the first time, to white populations. We found that family-based cancer clustering occurs more frequently among minority populations.”
Researchers used California population-based health registries to evaluate the relative cancer risk among parents, siblings and children of patients diagnosed with cancer by the age of 26. Between 1989 and 2015, they identified 29,632 early-onset cancer patients and then examined cancer incidence in 62,863 healthy family members. They found that overall, mothers and siblings of those cancer patients had a higher relative risk of early onset cancer. But when they looked at the role of race and ethnicity in genetic predisposition, they found that for patients with solid tumors, the familial cancer risk was significantly higher for Latino and non-Latino Black mothers and siblings compared to non-Latino white families. Asian/Pacific Islanders had a higher familial risk for blood-based cancers compared to non-Latino whites.
This study demonstrates the need for increased scrutiny on familial cancer clustering in minority populations. This information could help health care providers and genetic counselors offer more precision-based care and advice, particularly in the multiethnic populations that reside in Los Angeles County.
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Materials provided by Keck School of Medicine of USC. Original written by Hinde R Kast. Note: Content may be edited for style and length.

Genetic mosaic individuals, which contain cells of different genotypes, arise naturally in multicellular organisms. In humans, the development of cancer — where one cell acquires a mutation that allows it to proliferate, while other cells don’t — is a prime example of genetic mosaicism. But inversely, genetic mosaicism can be used to study and understand the development of disease.
A common quirk of nature used to understand genes
One experimental genetic mosaic approach is called Mosaic Analysis with Double Markers (MADM), in which genes are mutated in individual cells while, at the same time, the mutated cells are labelled in fluorescent colors. “MADM is a marking technology, where we can in principle mark cells that could be mutant for any gene of interest, in any organ we are interested in,” lead author Simon Hippenmeyer explains. By altering a gene in a single cell, while keeping the remaining cells “normal,” scientists can follow what happens to the mutated single cell and gain insight into the role and function of the mutated gene. This approach is especially valuable for essential genes: Mutating an essential gene in all cells of an organism would affect the organism’s health and viability. But when mutating the gene in just a few select cells, the organism itself is unaffected, while scientists can follow what happens to the sparse mutated cells — their morphology, development, and function — at the individual cell level.
Up until now, only about 25 percent of mouse genes could be mutated and followed using the MADM technique, as MADM technology was limited to three of the mice chromosomes. Now, Hippenmeyer and his group at IST Austria have dramatically expanded this resource. The group has successfully placed the “MADM marking cassette” required for the MADM technique on all mouse chromosomes (except the sex chromosomes). Now, more than 96% of genes can be mutated and followed on the single-cell level using MADM. “We can now easily manipulate almost every mouse gene, and subject every gene to high-resolution, phenotypic genetic mosaic analysis,” Hippenmeyer explains.
New avenues for cancer research
Hippenmeyer anticipates that this resource will be a boost to the study of disease and general mechanisms of development. “Now, we can study genes associated with diseases that emerge from a single mutated cell, of which cancer is the prime example. With our resource, researchers can systematically study every single known tumor suppressor gene and its role in cancer development and evolution, including in combination with other mutations.” In recent years, researchers have used MADM in several cancer studies, including for screening for drug targets. “Our MADM library is not only a way to analyze disease progression, but also provides a platform for drug and drug target discovery,” Hippenmeyer adds. “This is not limited to cancer, MADM can also be used to study and understand disease in many contexts including neuro-developmental and other brain disorders, which is a prime interest of the Hippenmeyer group.”
In their paper, Hippenmeyer and his group used the novel resources to expand the MADM application spectrum and shed light on an intriguing problem in biology. They found evidence that chromosome segregation during asymmetric cell division follows a non-random pattern. “Our results indicate for the first time in vivo, that the way how parental chromosomes segregate during stem cell division could instruct the cellular fate of resulting daughter cells. In a broader context these findings are relevant for our general understanding of stem cell biology and perhaps the mechanisms of cancer progression” In future, Hippenmeyer, a neuroscientist, will use the expanded capabilities of MADM to study stem cell behavior during brain development and the mechanisms ensuring that brains develop to the correct size. In humans, disorders of brain size, such as micro- and macroencephaly, are associated with epilepsy and intellectual disability. “We can now ask what goes wrong in a stem cell, so that the brain develops to be too large or too small. We anticipate that our future results can also provide a basis of prospective stem cell-based brain repair and regeneration.”
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Materials provided by Institute of Science and Technology Austria. Note: Content may be edited for style and length.

Without an audience, men run slower and women faster: The lack of spectators during the coronavirus pandemic appears to have had a noticeable effect on the performance of athletes at the 2020 Biathlon World Cup, a new study by Martin Luther University Halle-Wittenberg (MLU) in Psychology of Sport and Exercise shows. According to the new analysis, women also performed better in complex tasks, such as shooting, when an audience was present while men did not.
Social facilitation theory states that a person’s performance is impacted if other people watch them. The mere presence of an audience improves the performance of simple tasks, especially those that require stamina. “The studies have been relatively clear so far, but the results are more heterogeneous when it comes to more complex coordinative tasks,” explains Amelie Heinrich from the Institute of Sports Science at MLU. In general, it is assumed that performance tends to deteriorate when there is an audience.
Heinrich is a sports psychology expert who coaches Germany’s junior biathlon squad. In her new study she took advantage of the special situation in sport caused by the coronavirus. “The pandemic offers a unique opportunity to study an audience’s influence outside of experimental conditions in the real world,” says Heinrich. She compared the running times and shooting successes of male and female biathletes from the 2018/2019 season with their performances in the 2020 season in the sprint and mass start events. “The men’s results were as expected: they ran faster with an audience present, but performed more poorly in shooting,” says Heinrich. While cross-country skiing mainly requires stamina, shooting is a coordinative task. “Interestingly, it was the other way around for women.” They ran slower in the presence of spectators, but on average, it took them an entire second less to make their shot and, at least in the sprint, their scoring performance was five per cent higher. The researchers believe the results are not only due to a fluctuation in the athletes’ performance. The study had a good basis of evidence, with 83 (sprint) and 34 (mass start) World Cup biathletes, and the same tendency was shown for both disciplines.
“To our knowledge, this is the first time that a study was able to show a different effect of the audience on men and women,” says Professor Oliver Stoll, head of the sports psychology section at MLU. Most of the previous studies on the topic have been conducted with men mostly. “Our study raises questions about the generalisability of the social facilitation theory and indicates there might be a previously unknown difference between men and women,” says Heinrich. She says, this should be investigated more thoroughly in further studies for other sports that also contain both stamina-related and coordination-related elements.
So far, the researchers can only speculate about the reasons for the possible gender-specific performance differences in response to audiences or the lack of. “It is possible that gender-specific stereotypes play a role,” says Heinrich. For example, men are considered to be physically stronger — a stereotype that could be reinforced by the presence of spectators. Some studies also show that women react more sensitively to feedback. In any case, according to Heinrich, the findings show once again that gender should be taken into account in psychological studies as a possible influencing factor.
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Materials provided by Martin-Luther-Universität Halle-Wittenberg. Note: Content may be edited for style and length.

The venom of a caterpillar, native to South East Queensland, shows promise for use in medicines and pest control, Institute for Molecular Bioscience researchers say.
The Doratifera vulnerans is common to large parts of Queensland’s south-east and is routinely found in Toohey Forest Park on Brisbane’s southside.
Dr Andrew Walker has been researching the striking looking caterpillar since 2017.
“We found one while collecting assassin bugs near Toowoomba and its strange biology and pain-causing venom fascinated me,” Dr Walker said.
Unlike The Very Hungry Caterpillar that charmed generations of children around the world, this caterpillar is far from harmless.
“Its binomial name means ‘bearer of gifts of wounds’,” Dr Walker said.

Researchers from the Turku PET Centre and Technical University of Munich have discovered a new mechanism controlling satiation. According to the recently published study, the hormone secretin induces satiation by activating brown adipose tissue.
Brown adipose tissue is known for its ability to generate heat in response to cold exposure. Its activity has been proven to be connected to normal weight and glucose metabolism as well as lesser risks of cardiovascular diseases. Meals have also been shown to increase the thermogenesis in brown fat, but the significance of this phenomenon has been unclear.
– Secretin is a hormone secreted into blood circulation by the intestines, and it stimulates the production of peptic juices in the pancreas when we have meals. In our research, we discovered secretin receptors in the brown adipose tissue of healthy people, which suggested that secretin also affects brown fat. Secretin infusions not only increased glucose uptake in brown adipose tissue, but also elevated energy expenditure in the whole body, says Doctoral Candidate, Cardiologist Sanna Laurila from the University of Turku.
Using magnetic resonance imaging, the researchers discovered that secretin also decreased the activity of the reward system in the brain when the subjects were looking at delicious photos of food. The subjects’ decreased appetite could also be verified with a questionnaire survey, and the time between their meals grew by 40 minutes.
Brown fat generates great interest from the perspective of weight control because it has the ability to burn fat instead to storing it. However, humans have a relatively small amount of brown fat, which means that the metabolic advantages probably cannot be solely ascribed to increased energy consumption.
“This newly-confirmed message chain affecting satiation in people can be one of the reasons behind the beneficial metabolic effects of brown fat,” sums up Professor Pirjo Nuutila.
“This study underlines the functional relevance of human brown fat in controlling energy balance as it affects both food intake and energy expenditure,” comments Professor Martin Klingenspor from the Technical University of Munich.
The newly-discovered mechanism controlling satiation opens up new opportunities for the research of the development, prevention, and treatment of obesity. Further research is needed to investigate in more detail what kind of role secretin has in metabolic disorders such as metabolic syndrome, obesity, and type 2 diabetes.
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Materials provided by University of Turku. Note: Content may be edited for style and length.

Listening to music while running might be the key to improving people’s performance when they feel mentally fatigued a study suggests.
The performance of runners who listened to a self-selected playlist after completing a demanding thinking task was at the same level as when they were not mentally fatigued, the research found.
The study is the first to investigate the effect of listening to music playlists on endurance running capacity and performance when mentally fatigued.
Researchers at the University of Edinburgh used two tests to study how listening to music affected the running performance of eighteen fitness enthusiasts.
One test looked at the effects on interval running capacity — alternating between high intensity running and lower intensity jogging — with a group of nine physically active exercisers, and the other on a 5km time-trial with a group of nine trained runners.
The groups completed a 30 minute computer based cognitive test which put them in a mentally fatigued state before completing high intensity exercise. The runners were tested with and without self-selected motivational music.

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesGerman Chancellor Angela Merkel has received a dose of Moderna as her second shot of coronavirus vaccine having had Oxford-AstraZeneca as her first, a government spokesman said.The 66-year-old leader was vaccinated a few days ago after getting a dose of AstraZeneca in April.Experts believe mixed dosing of Covid vaccines could be a good idea but it too early to say for sure. Mrs Merkel will be stepping down as leader this year after 16 years.In March, Germany, along with other European countries, halted the rollout of the AstraZeneca vaccine after a number of blood clots cases were reported.Spike in Australians rejecting AstraZeneca vaccineCovid vaccines and rare clots – what do we know?Germany had previously restricted the use of the jab to over-60s, but is now set to offer it to all adults, German broadcaster Deutsche Welle reports.After a slow start, Germany’s vaccination rollout accelerated in recent weeks.More than half of the country’s population has now received their first dose of a vaccine.In April, Mrs Merkel’s spokesman tweeted a photo of her vaccination certificate to show she had received the injection.Kanzlerin #Merkel: „Ich freue mich, dass ich heute die Erstimpfung mit AstraZeneca bekommen habe. Ich danke allen, die sich in der Impfkampagne engagieren – und allen, die sich impfen lassen. Das Impfen ist der Schlüssel, um die Pandemie zu überwinden.“ pic.twitter.com/P4kMJYNrlc— Steffen Seibert (@RegSprecher) April 16, 2021
The BBC is not responsible for the content of external sites.View original tweet on TwitterThere have been some studies conducted on the mixing of different vaccines.One study in the UK found that adults were more likely to report mild and moderate side effects after mixing doses of the AstraZeneca and Pfizer Covid vaccines.Some countries have been looking at mixing vaccines in the face of supply shortages and to improve protection, Reuters news agency reports.The Canadian provinces of Ontario and Quebec have both said they plan to mix vaccines in the near future, amid uncertainty over shipments of the Oxford-AstraZeneca jab and concerns about rare blood clots.Experts believe mixed dosing of Covid vaccines could be a very good idea. It might give broader, longer-lasting immunity against the pandemic virus and new variants of it, and offer more flexibility to vaccine rollout.Studies are under way, but some countries are already allowing it within their national immunisation programs.Germany initially restricted the use of the AstraZeneca (AZ) vaccine to people under 60 because there wasn’t much trial data available on efficacy in older people.It reversed that decision in April, offering it to all adults. Weeks later Mrs Merkel received her first dose. More recently, following reports of rare blood clots in a small number of younger people who had the AZ vaccine, Germany recommended that under-60s who had already received a first dose of should have a different coronavirus vaccine for their booster second jab for safety reasons, as a precaution. Merkel doesn’t fit this age bracket, but, nonetheless, she’s had Moderna rather than AZ for her second dose. It may prove to be a decision that gives her better protection, but until we have the evidence from large trials, it is really too early to say for sure.

Scientists are pursuing a new strategy in the protracted fight against the SARS-CoV-2 virus by engineering nanobodies that can neutralize virus variants in two different ways.
In lab studies, researchers identified two groups of molecules that were effective against virus variants. Using different mechanisms, nanobodies in each group bypassed mutations and disabled the virus’s ability to bind to the receptor that lets it enter host cells.
Though vaccination is enabling the resumption of some pre-pandemic activities in parts of the world, SARS-CoV-2 is rapidly working its way around vaccines by mutating itself. In this study, the nanobodies neutralized three emerging variants: Alpha, Beta and Gamma.
“Companies have already started introducing the variants of concern into the construct of booster shots of the existing vaccines,” said Kai Xu, assistant professor of veterinary biosciences at The Ohio State University and a co-lead author of the research. “But the virus is constantly mutating, and the speed of mutation may be faster than we can capture. Therefore, we need to utilize multiple mechanisms to control the virus spread.”
An accelerated article preview of the study is published online in Nature.
Nanobodies are antibodies derived from immunization of camelid mammals — such as camels, llamas and alpacas — that can be re-designed into tiny molecules that mimic human antibody structures and functions.

Cancer immunotherapy involving drugs that inhibit CTLA-4 also activates an unwanted response that may self-limit its efficacy in fighting tumors, according to a new study led by Francesco Marangoni, Ph.D., assistant professor of physiology & biophysics and member of the Institute for Immunology at the University of California, Irvine. Study results are published online in the journal Cell.
Using a person’s own immune system — immunotherapy — to treat cancer may also stimulate T regulatory cells, which are essential for preventing autoimmunity, in which the body attacks healthy cells and tissue, but limit tumor control. Some anticancer drugs of the checkpoint inhibitor family block the molecule CTLA-4 and activate both the CD8 and CD4 effector T cells, which kill cancer. Using intravital microscopy, a technique that allows imaging of cells within a living organism, researchers found that CTLA-4 blockage also causes the expansion of T regulatory cells, decreasing the effect of immunotherapy.
“Much of our knowledge of the mechanisms by which immunotherapy works is focused on the positive aspects of the body’s reaction, but that treatment targets the whole immune system. In this study, we investigated how Treg cells are activated within the tumor mass. We discovered that Treg cells are continuously activated in cancer. In turn, they use CTLA-4 to instruct dendritic cells to become inefficient activators of the immune system. Upon CTLA-4 inhibition, dendritic cells become more active and promote the function of effector and regulatory T cells at the same time. This has the potential of limiting efficacy and may explain the failure of immunotherapy in some patients,” said Marangoni, corresponding author on the study.
Future research will focus on identifying and removing unwanted immune reactions in other forms of immunotherapy. In particular, new strategies must be developed to decrease the activation of Treg cells in a controlled manner in order to avoid “fatal autoimmunity,” Marangoni said: “The indiscriminate depletion of Treg cells would cause the CD8 and CD4 effector T cells to attack our body and potentially kill us.”
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Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

Researchers have shown why people with mental health disorders, including anorexia and panic disorders, experience physical signals differently.
The researchers, from the University of Cambridge, found that the part of the brain which interprets physical signals from the body behaves differently in people with a range of mental health disorders, suggesting that it could be a target for future treatments.
The researchers studied ‘interoception’ — the ability to sense internal conditions in the body — and whether there were any common brain differences during this process in people with mental health disorders. They found that a region of the brain called the dorsal mid-insula showed different activity during interoception across a range of disorders, including depression, schizophrenia, eating disorders and anxiety disorders.
Many people with mental health disorders experience physical symptoms differently, whether that’s feeling uncomfortably full in anorexia, or feeling like you don’t have enough air in panic disorder.
The results, reported in The American Journal of Psychiatry, show that activity in the dorsal mid-insula could drive these different interpretations of bodily sensations in mental health. Increased awareness of the differences in how people experience physical symptoms could also be useful to those treating mental health disorders.
We all use exteroception — sight, smell, hearing, taste and touch — to navigate daily life. But interoception — the ability to interpret signals from our body — is equally important for survival, even though it often happens subconsciously.