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Collagen type XII plays a key role in regulating the organisation of the tumour matrix, reveals a new study from the Garvan Institute of Medical Research. A team of scientists led by Associate Professor Thomas Cox, Head of the Matrix and Metastasis lab, also discovered that high levels of collagen XII can trigger breast cancer cells to spread from the tumour to other parts of the body, a process known as metastasis.
The tumour microenvironment is the ecosystem that surrounds a tumour, one component of which is the extracellular matrix. Cancer cells constantly interact with the tumour microenvironment, which affects how a tumour grows. Collagen is an important part of this tumour microenvironment, but just how it influences tumours has not been understood.
“There’s still a lot we don’t know about the role of the extracellular matrix in cancer metastasis. Our study shows that collagen XII plays an important role in breast cancer progression and metastasis,” says senior author Associate Professor Thomas Cox.
“Imagine cancer cells as seeds, and the tumour microenvironment as the soil. By studying the soil — the extracellular matrix — we can begin to understand what makes some tumours more aggressive than others, and by extension, begin to develop new ways to treat cancer,” he says.
The research also suggests that measuring the level of collagen XII in a patient’s tumour biopsy could potentially be used as an additional screening tool to identify aggressive breast cancers with higher rates of metastasis, such as in the triple-negative type of breast cancer. Furthermore, collagen XII might be a possible target for future treatments.
The study is published in the journal Nature Communications.

Tiny smart bed sensors embedded in hospital mattresses could put an end to painful and potentially life-threatening pressure sores, thanks to new technology developed by the University of South Australia.
UniSA scientists have designed minute optical fibre sensors, which can be attached to the upper surface of a mattress to monitor movement and record heart and respiratory rates.
The unobtrusive sensors can detect when a hospital patient turns over, leaves a bed, or just remains motionless, picking up their breathing.
Nurses can therefore be remotely alerted if a patient has not moved within a couple of hours, prompting them to adjust the patient’s position.
Lead UniSA researcher Dr Stephen Warren-Smith says the technology could “significantly relieve” the burden on hospital staff having to constantly monitor patients for pressure sores.
“Each year, millions of older people in hospitals and nursing homes experience pressure injuries, or ulcers, which take a long time to heal and can be fatal,” Dr Warren-Smith says.

Structural or functional abnormalities within the heart’s left atrium, with or without symptoms, may increase a person’s risk of developing dementia later in life by 35%, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association. Dementia risk increased even among those who did not experience atrial fibrillation or stroke, two conditions known to be associated with dementia.
The left atrium is one of four chambers of the heart and is responsible for receiving blood from the lungs and pumping it into the left ventricle, which then pumps the blood to the rest of the body. An abnormality in the structure or functioning of the left atrium, known as atrial cardiopathy, can often serve as a biomarker, or predictor, of a person’s cardiac risk. Atrial cardiopathy is associated with an increased risk of stroke and atrial fibrillation, which are both linked to an enhanced risk of dementia. In a study led by Michelle C. Johansen, M.D., Ph.D., an assistant professor of neurology at The Johns Hopkins University School of Medicine in Baltimore, the research team aimed to determine the relationship between atrial cardiopathy and dementia, and if so, whether it is independent of atrial fibrillation and stroke.
The study results highlight the need to get a better understanding of the relationship and mechanisms between a state of atrial dysfunction, that may be subclinical (not presenting symptoms) and the newly uncovered association with dementia, the researchers noted.
Participants in the current analysis were part of a larger study group of more than 15,000 people originally recruited for the ongoing Atherosclerosis Risk in Communities (ARIC) study, which began in 1987 to research heart health in people living within four diverse communities throughout the U.S. ARIC study participants were ages 45-65 years at the start of the study and from rural areas in the U.S. (Forsyth County, North Carolina, and Washington County, Maryland) and urban areas: Minneapolis and Jackson, Mississippi. All ARIC participants attended clinical visits every three years, and the resulting research and data — including hospital record abstraction, ECG tracings, and physician and coroner questionnaires, as well as death certificate data — have led to discoveries and guidelines surrounding atherosclerosis, heart disease, kidney disease, diabetes, stroke and cognitive decline. This analysis uses data and assessments gathered during participants’ fifth ARIC clinical visit, between 2011 and 2013 as a baseline, and follows the participants through their sixth visit, between 2016 and 2017, and their seventh visit, between 2018 and 2019.
The current analysis included 5,078 of the 5,952 participants who returned for their fifth clinical visit; 59% were female, and 41% were male. The group of 5,078 were an average age of 75 years old, and 21% self-identified as Black adults. During their fifth, sixth and seventh clinical visit, the ARIC participants were evaluated for cognitive decline indicating dementia.
Researchers evaluated cognitive decline in all participants with a comprehensive neuropsychological test battery from the Uniform Data Set of the Alzheimer’s Disease Centers program of the National Institute on Aging, as well an informant interview in a subset of participants. Informant interviews are a screening test of questions, such as the Eight-Item Informant Interview to Differentiate Between Aging and Dementia, given to a spouse, adult child or close friend of the adult being evaluated for cognitive decline. The neuropsychological test battery consists of brief measures of processing speed, episodic memory, language, attention and executive function. A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health.
Hospital discharge codes — obtained as part of the ARIC study either directly from hospital discharge indices or from an indexing service or from an indexing service — and death certificate data, obtained as part of the ARIC study from the Automated Classification of Medical Entities system, were also included to assess participants’ cognitive status. Additionally, cardiac evaluation, including echocardiography, electrocardiography (EKG/ECG) and blood work, was conducted to assess the size and function of the left atrium of the heart to check for signs of atrial cardiopathy.
The analysis of the collective health data found that throughout the more than 30 years of follow-up, 763 people developed dementia, and 1,709 had atrial cardiopathy. The participants with atrial cardiopathy appeared to be 35% more likely to develop dementia. When the researchers adjusted for participants who experienced atrial fibrillation and stroke, even after accounting for other vascular risks, they still observed a respective 31% and 28% increase in dementia risk in patients with atrial cardiopathy. The researchers suggested that a state of atrial cardiopathy leading to dementia s is not a result of atrial fibrillation or stroke alone.
While the researchers note the results do not imply causality, they emphasize the importance of lowering vascular and heart disease risks. Among the study’s limitations was the possibility that asymptomatic atrial fibrillation or silent strokes may have been missed in some study participants. Additionally, dementia develops slowly, therefore, some participants with milder symptoms may have been missed, and some patients in the study may have died before dementia was observed and documented. The study may also not be generalizable among populations with different demographics than the four communities in Forsyth County, North Carolina; Washington County, Maryland; Minneapolis; and Jackson, Mississippi that comprise ARIC.
The study was funded by The National Heart, Lung, and Blood Institute of the National Institutes of Health.

Published6 days agoSharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesScientists are tracking a new, animal-derived virus in eastern China that has infected at least several dozen people.The novel Langya henipavirus (LayV) was found in 35 patients in the Shandong and Henan provinces. Many had symptoms such as fever, fatigue and a cough. They are thought to have contracted the virus from animals. There is no evidence so far LayV can transmit among humans.Researchers detected the virus predominantly in shrews.The discovery was highlighted in a letter written by researchers from China, Singapore and Australia and published in the New England Journal of Medicine this month.One of the researchers, Wang Linfa from the Duke-NUS Medical School in Singapore, told China’s state-run Global Times that the cases of LayV found so far have not been fatal or very serious, so there is “no need to panic”. However, Mr Wang said, there is still a need to be alert as many viruses that exist in nature have unpredictable results when they infect humans.The scientists said LayV was found in 27% of shrews tested, suggesting the mole-like mammals may be “natural reservoirs” for the virus. About 5% of dogs and 2% of goats also tested positive for it. Taiwan’s Center for Disease Control said on Sunday it was paying “close attention” to the development of LayV.Why are we catching more diseases from animals?More outbreaks if we keep exploiting wildlife – UNBat scientists find new coronavirus evidenceLayV is a type of henipavirus, a category of zoonotic viruses which can jump from animals to humans.Zoonotic viruses are very common but have attracted more attention since the start of the Covid pandemic.The US Center for Disease Control and Prevention said scientists estimate that three out of every four new or emerging infectious diseases in people come from animals.The United Nations had previously warned the world will see more of such diseases with increased exploitation of wildlife and climate change.Some zoonotic viruses can be potentially fatal to humans. These include the Nipah virus which has periodic outbreaks among animals and humans in Asia, and the Hendra virus which was first detected in horses in Australia.Other related henipaviruses have also been found in shrews, as well as bats and rodents.You may also be interested in: This video can not be playedTo play this video you need to enable JavaScript in your browser.More on this storyCovid origin studies say evidence points to market26 JulyCoronavirus: This is not the last pandemic6 June 2020

A massive analysis of more than 10,000 different Mycobacterium tuberculosis bacteria isolates from 23 countries has revealed new genes associated with resistance to 13 first- and second-line new and repurposed antibiotics. The work, carried out by Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC), is described in two new papers publishing August 11 in the open-access journal PLOS Biology.
Tuberculosis (TB) is a curable and preventable disease; 85% of those affected can be successfully treated with a six-month regimen of drugs. Despite this, TB has killed more people than other infectious diseases in many recent years, and drug resistant TB is a continual threat. A better understanding of the M. tuberculosis variants that confer antibiotic resistance is important for both better monitoring of resistant strains as well as the development of new drugs.
In the first new paper, the researchers outlined how they assembled an open-access data compendium of 12,289 M. tuberculosis isolates, processed in CRyPTIC partner laboratories around the world. Each isolate was sequenced, and then tested on a high-throughput grid with varying concentrations of 13 antimicrobials. Of the samples included in the compendium, 6,814 were resistant to at least one drug, including 4,685 samples resistant to multiple drugs or to the first-line treatment rifampicin.
In the second paper, the consortium presented their findings from a genome wide association study (GWAS) using the data on 10,228 M. tuberculosis isolates. For all 13 drugs, the group discovered uncatalogued variants associated with significant increases in the minimum inhibitory concentration — the lowest concentration of an antibiotic that stops the growth of M. tuberculosis. Analyzing this concentration, rather than a binary resistant-or-not-resistant result, allowed the identification of variants that cause only subtle changes to antibiotic response that may be overcome by increasing drug dose. The researchers selected the 20 most significant genes that confer resistance to each drug and described the effect size and variations within these specific genes in more depth.
“Our study demonstrates the ability of global partnerships to substantially improve our knowledge of genetic variants associated with antimicrobial resistance in M. tuberculosis,” the authors note.
Together, the papers not only uncover specific genes that can be followed up on to better understand the resistance landscape of M. tuberculosis, but also a framework for future studies on the pathogen.
“The compendium is not designed for measuring prevalence or estimating ‘real-world’ error rates of resistance prediction tools; rather it serves as a resource to accelerate antimicrobial resistance diagnostic development by enriching mutation catalogues for [whole genome sequencing] resistance prediction, improving our understanding of the genetic mechanisms of resistance, and identifying important diagnostic gaps and drug resistance patterns,” the authors say. “The data compendium is fully open-source and it is hoped that it will facilitate and inspire future research for years to come.”
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For the first time, researchers can get a high-resolution view of single blood stem cells thanks to a little help from microscopy and zebrafish.
Researchers at the University of Wisconsin-Madison and the University of California San Diego have developed a method for scientists to track a single blood stem cell in a live organism and then describe the ultrastructure, or architecture, of that same cell using electron microscopy. This new technique will aid researchers as they develop therapies for blood diseases and cancers.
“Currently, we look at stem cells in tissues with a limited number of markers and at low resolution, but we are missing so much information,” says Owen Tamplin, an assistant professor in UW-Madison’s Department of Cell & Regenerative Biology, a member of the Stem Cell & Regenerative Medicine Center, and a co-author on the new study, which was published Aug. 9 in eLife. “Using our new techniques, we can now see not only the stem cell, but also all the surrounding niche cells that are in contact.”
The niche is a microenvironment found within tissues like the bone marrow that contain the blood stem cells that support the blood system. The niche is where specialized interactions between blood stem cells and their neighboring cells occur every second, but these interactions are hard to track and not clearly understood.
As a part of the new study, Tamplin and his co-lead author, Mark Ellisman, a professor of neuroscience at UC San Diego, identified a way to integrate multiple types of microscopic imaging to investigate a cell’s niche. With the newly developed technique that uses confocal microscopy, X-ray microscopy, and serial block-face scanning electron microscopy, researchers will now be able to track the once elusive cell-cell interactions occurring in this space.
“This has allowed us to identify cell types in the microenvironment that we didn’t even know interacted with stem cells, which is opening new research directions,” Tamplin says.

An experimental drug therapy protects mice from sudden death due to the rupture of a major blood vessel in the abdomen, according to a study from researchers at Washington University School of Medicine in St. Louis.
The findings, available online in Biomaterials Advances, may lead to a new strategy in treating abdominal aortic aneurysm, a condition in which the wall of the abdominal aorta — a major vessel that carries blood from the heart to the rest of the body — starts to weaken and bulge outward. The weak spot can start leaking blood or even rupture without warning, triggering a life-threatening emergency that nearly always results in death if not treated promptly. The larger the aneurysm, the more likely it will suddenly burst.
“When people are identified with a medium or small aneurysm, we monitor them,” said senior author Christine T. N. Pham, MD, the Guy and Ella Mae Magness Professor of Medicine and director of the Division of Rheumatology. “Large aneurysms can be repaired surgically, but for smaller aneurysms, there’s no treatment other than waiting for them to get to a size that can be repaired surgically. Our findings in mice illustrate a potentially relevant therapy that could prevent rupture of aneurysm.”
Pham sees patients at the Veterans Affairs Medical Center in St. Louis and Barnes-Jewish Hospital.
About 200,000 people are diagnosed with abdominal aortic aneurysm, or triple A, in the U.S. every year, mostly older men who smoke. Usually, such aneurysms cause no symptoms until they suddenly and catastrophically rupture, causing 15,000 deaths a year in the U.S. alone. The U.S. Preventive Services Task Force — an independent panel of experts in disease prevention and evidence-based medicine supported by the U.S. Department of Health and Human Services — recommends that all men ages 65 to 75 who have ever smoked receive ultrasound scans to screen for triple A.
Scientists have known for decades that inflammation in blood vessels drives the progression of triple A, but attempts to treat the disease using immunosuppressive therapies have not panned out. The immune system is a crucial part of the body’s defenses against infection. It is difficult to find the delicate balance between suppressing inflammation in the aorta enough to stop aneurysms from worsening, while not suppressing the immune system in the rest of the body to the extent that doing so puts a person at risk of serious infections.
In this study, the researchers used nanoparticles to deliver anti-inflammatory payloads directly to inflamed blood vessels. The nanoparticle is based on a fragment of a protein called melittin and optimized to carry the payload: small bits of RNA. The modified protein fragment forms a complex with RNA that, when given to the mice, accumulates primarily in inflamed tissues. There, the protein fragment unloads the bits of RNA and assists their entry into cells’ main compartment, where the RNA suppresses inflammation by interfering with the expression of an important inflammatory protein, NF-kappaB.
Co-author Samuel A. Wickline, MD, formerly of Washington University School of Medicine and now a professor at the University of South Florida and the chief scientific officer at the biotechnology company Altamira Therapeutics, created the basic version of the nanoparticle while at Washington University. This study involves an optimized version of the nanoparticle that was created by Wickline, Pham and their Washington University co-authors Hua Pan, PhD, an associate professor of medicine, and first author Huimin Yan, MD, PhD, a staff scientist.
The researchers used the nanoparticles to carry so-called small interfering RNAs (siRNAs) targeting two subunits of NF-kappaB: p50 and p65. The researchers studied male mice that developed a triple A-like condition that ruptures about half the time. They treated the mice with nanoparticles containing p50 siRNA, p65 siRNA or an irrelevant siRNA for comparison. Suppressing p50 did not halt the progression of the aneurysms, but significantly increased the mice’s chances of survival, from 53% to 85%. Treatment also delayed onset of rupture, from day seven to day 12. In contrast, suppressing p65 did not have significant effect.
“Optimization of the nanoparticle allowed us to use a fraction of the previously established dose of siRNA, which means we can achieve therapeutic effect at a level that is less likely to cause adverse effects,” Pan said. “By targeting p50 and p65 separately, we pieced out the individual contributions of the different subunits and found the one (p50) that we think will be more protective with less potential adverse effects. Altogether, these results are very encouraging. They suggest that it may be possible to develop a therapy to reduce the risk of rupture and death from triple A without unacceptable adverse effects.”
Wickline is the principal investigator and Pham the Washington University site lead on a Small Business Technology Transfer grant from the National Institutes of Health (NIH) involving the original nanoparticle technology created by Wickline and his team at Washington University. The grant supports a project to develop and commercialize the technology as a treatment for inflammatory disease in collaboration with Altamira Therapeutics.
“For that grant, we are looking at rheumatoid arthritis, not triple A,” Pham said. “But once you have the technology approved for one disease, it is a lot easier to apply it to other diseases. I’m hopeful that one day, in the not-too-distant future, we’ll have a treatment to offer people to stabilize the aneurysm, reducing the risk of rupture and sudden death. The technology is still being tested, but there’s more hope now.”

Knowing the structure of a complex biological system isn’t nearly enough to understand how it works. It helps to know how the system moves.
In that light, Rice University researchers have modelled a key mechanism by which DNAreplicates.
Combining structural experiments and computer simulations, bioscientist Yang Gao, theoretical physicist Peter Wolynes, graduate student Shikai Jin and their colleagues have uncovered details about howhelicases, a family of ringlike motor proteins, wrangle DNA during replication. Their work could reveal new targets for disease-fighting drugs.
The synergy between the experiments and large-scale simulations they describe in the Proceedings of the National Academy of Sciences could become a paradigm for modeling of the mechanisms of many complex biological systems.
“These are dynamic processes that cannot be captured well with experimental methods alone,” said Gao, an assistant professor of biosciences and a CPRIT Scholar in Cancer Research. “But it’s important to show the mechanisms of these helicases, because they’re essential for DNA replication, and also possible drug targets.”
Hexameric helicases have six sides that self-assemble from peptides into a washerlike ring that separates the parental double strands of DNA into daughter single strands. Until now, researchers have been unable to pin down how the helicase steps along as it unzips the double strand.

Tendencies toward impulsivity in early adolescence are linked with a variety of poor outcomes in later adolescence, including antisocial personality disorder and alcohol use disorder. However, by the time teenagers reach mid-adolescence, it may be too late to target impulsivity to prevent the development of these behavioral disorders.
Past research has shown the link between impulsivity and these disorders, but not how it unfolds. Now, a new study based on data tracking hundreds of Philadelphia youth over more than a half-dozen years details the complex pathway connecting impulsivity, alcohol use, and antisocial behavior.
The findings suggest that targeting adolescents who exhibit high levels of impulsivity in early adolescence could halt a cascading chain of events that leads to late-adolescence antisocial personality disorder (APD) and alcohol use disorder (AUD).
“Kids with impulse control problems are at risk for a variety of adverse outcomes, such as drug use, acting-out behavior, and antisocial behavior,” said study co-author Dan Romer, research director of the Annenberg Public Policy Center of the University of Pennsylvania. “What we’ve found is that you’ve got to start mitigating impulsivity before it starts influencing behaviors that lead to substance use and antisocial behavior disorders. Once adolescents are on a trajectory of engaging in those behaviors, it may become more difficult to prevent disorders later in adolescence than it is to treat impulsivity itself.”
The open-access study, published this week in the Journal of Adolescent Health, was conducted by researchers from the Annenberg Public Policy Center (APPC), University of Amsterdam, University of Oregon, and Children’s Hospital of Philadelphia.
The Philadelphia Trajectory Study
The study is based on data from the Philadelphia Trajectory Study, a six-wave study during which participants ages 10 to 12 were interviewed annually from 2004 to 2010, with a final two-year follow-up in 2012. The current study relies on five years of self-reported data, from waves 3 through 6. During the final wave the participants were 18 to 21 years old. The study was based on data from 364 adolescents (at wave 3) of diverse ethnic backgrounds.

When male and female fruit flies age, their brains become desexualized. Age-related changes take place in both sexes, but the male brain becomes feminized to a larger extent than the female brain becomes masculinized. This is the conclusion of a study performed by a research group at Linköping University. The findings are published in the journal Proceedings of the Royal Society of London B.
It is a well-known fact that weaker individuals cannot afford to “invest” in sexual behaviours to the same extent as their healthier conspecifics. However, it is not clear if ageing, which weakens individuals, also leads to a reduced investment in sexual activities. You might think that for individuals close to the end of their lives, going “all in” on reproduction, in order to pass on their genes before it is too late, would be best. Sexual behaviours are directed from the brain, and to find out what happens to sex differences in this tissue when fruit flies age the researchers have investigated how genes expressed to different degrees in young males and females change over time.
“Our results show that gene expression in male and female brains become more similar with age, and that both sexes contribute to this pattern,” says Dr Antonino Malacrinò, one of the study’s main authors who now works at the University of Reggio Calabria in Italy.
What the study shows is that if the expression of a certain gene is higher in the brains of young females than in young males, the gene’s expressions is reduced in older females and increased in old males — and vice versa for genes with higher expression in young males.
“The results also show that the changes are larger in males than in females,” says Antonino Malacrinò.
The fact that females change less with age than males is presumably the result of that the connection between investment in sexual traits and reproductive success is not as strong in females as in males. While a male fruit fly, in order to reproduce, must out-compete other males in quickly finding females and encouraging them to mate through an intricate and taxing dance performance, a female only needs to decide how much energy she has available for reproduction. Ageing implies that reduced amounts of resources are available to invest in reproduction and other activities for both sexes, but stiff competition between males means that the cost of increased investment is greater for them than for females.
“If you keep investing as much as before in reproduction when you get old, you don’t have energy left for survival,” says Urban Friberg, who has led the study and is senior associate professor at the Department of Physics, Chemistry and Biology (IFM) at Linköping University.
Studies on other animals, including humans, which have mainly focused on age-related changes in gene expressions in one sex, have given results pointing in the same direction. This indicates that the results shown in fruit flies may also apply to many other animals.
“We get the same general results in both the populations of fruit flies that we have examined, even if they differ quite a bit with respect to which genes are involved,” says Urban Friberg.
The results of the study are reminiscent of those obtained by the group in a previous investigation. In that study, sex differences in gene expression were compared between male and female flies of high and low genetic quality. Similarly to how ageing reduces sex differences, the earlier study show that reduced genetic quality makes gene expression more similar in male and female flies, and again it was males that changed their gene expression more than females.
The study provides no answer to what molecular signal associated with ageing lies behind the reduced sex differences in the brain. Further exploration on this topic could be rewarding, especially if the signalling molecule would turn out to be shared with other species.
The study was funded with support from the Längmanska Foundation Culture Fund, the Swedish Research Council, the Sven and Lilly Lawkis Fund, the Olle Engqvist Foundation and the Knut and Alice Wallenberg Foundation via National Bioinformatics Infrastructure Sweden.
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