Culture

Oakland, Calif. -- New research from Kaiser Permanente finds that post-menopausal women with colorectal cancer were more likely to die from their disease or from any cause if they had low social support before diagnosis. The analysis of 1,429 women in the national long-term health study Women's Health Initiative, which included patients from Kaiser Permanente and other health systems, was published in the journal Cancer January 23.
The study found that women who reported low social support had 52% higher overall mortality than those who reported high levels of support, and 42% higher mortality from colorectal cancer specifically.
The results confirm previous research suggesting a role for social support for patients with serious illness, said lead author Candyce Kroenke, MPH, ScD, a research scientist with the Kaiser Permanente Division of Research. "These findings support the idea that women who have supportive friends and family around them when they are diagnosed do better," Kroenke said.
The researchers delved into the specifics of the women's personal connections, their links with the community, and their living status to better understand the association. They found higher rates of mortality when women lacked:

Emotional support: caring and concern

Informational support: help provided through information

Tangible support: help with tasks, chores, or tangible needs

Positive interaction: someone for the patient to have fun with and take their mind off their illness

In a separate analysis on the impact of social integration, researchers found that having a partner or engaging with their community or in a religious organization was associated with lower risk of death from rectal cancer, but not colon cancer.

Similarly, the analysis found that living alone was associated with higher mortality in patients with rectal cancer. Kroenke said these different findings for rectal and colon cancer need to be replicated.

For patients, the study's message is to lean on others when dealing with a serious diagnosis. "You can and should ask for support instead of going it alone," Kroenke said.

For medical practitioners, the findings are a reminder that social support is an important determinant of outcomes, Kroenke said. "Clinicians can identify patients who are at risk of low social support and provide them with additional resources," she said. Resources might include a therapist to help with the emotional burden of cancer treatment or social services to provide logistical help such as rides to the doctor.

Kaiser Permanente patients in Northern California diagnosed with cancer undergo a 22-point evaluation of their practical, family, emotional, and spiritual support. After treatment cancer patients receive personalized survivorship care including social and emotional support.

Brian Missett, MD, associate executive director of The Permanente Medical Group, said this support is part of Kaiser Permanente's commitment to the total health of its patients. "In viewing our patients as holistic beings with a variety of needs, we provide more comprehensive care that leads to better outcomes," he said.

West Nile virus (WNV) inhibits autophagy -- an essential system that digests or removes cellular constituents such as proteins -- to induce the aggregation of proteins in infected cells, triggering cell death and brain inflammation (encephalitis), according to Hokkaido University researchers. They also discovered that a drug can induce autophagy to remove protein aggregates and thus prevent cell death.

West Nile fever is a zoonosis spread by the bite of an infected mosquito. West Nile fever outbreaks have been reported across the world, mainly in North America and Europe, and caused hundreds of deaths in the past few decades. After a human becomes infected, virus replication temporarily occurs in peripheral tissues. In some patients, the virus enters the brain, infecting neural cells and causing cell death and serious cases of encephalitis.

The team previously found that WNV infection induces the accumulation of proteins in neural cells, but the detailed mechanisms underlying the accumulation and how it triggers neurological diseases remain unclear. There are also no established methods to specifically treat viral encephalitis, which can be caused by various types of viruses.

In the current study published in PLOS Pathogens, the research team including Shintaro Kobayashi and Kentaro Yoshii of Hokkaido University focused on autophagy to clarify how protein aggregates form in cells after WNV infection.

The researchers first identified the viral protein, called capsid protein, that induces accumulation of proteins in neural cells by having viral encoded-proteins expressed in cultured neural cells. The capsid protein induced accumulation and aggregation of proteins in the infected cells by inhibiting autophagy, a cellular digestive system. They also found that the capsid protein does so by disrupting an autophagy-inducing factor called AMP-activated protein kinase (AMPK). When they treated the infected cells with a drug that induces autophagy, protein aggregation and cell death were both suppressed.

Furthermore, a study using a mouse model demonstrated that WNV with mutations in the capsid protein was unable to harm neural cells or cause encephalitis. These findings suggest WNV inhibits autophagy through the capsid protein and the resulting accumulation of protein is involved in the onset of central nervous system disorders.

"Autophagy anomalies are involved in triggering various diseases, including neurodegenerative illnesses such as Alzheimer's disease. So, our finding could help elucidate the pathology of West Nile fever as well as various diseases associated with autophagy anomalies, and to develop treatment methods," said Shintaro Kobayashi of the research team at Hokkaido University.

We live in an increasingly complex world when it comes to chemicals. The number of new chemicals has increased from 20 million in 2002 to 156 million last year. Many of these are ubiquitous in the world around us because of their continuous use. Pesticides, plastics, industrial chemicals and pharmaceuticals are found in nature and in our food chain. And that has consequences. These chemicals can have unwanted side effects and cause disease. The figures are startling: research shows that at least nine million people die each year as a result of air, water and soil pollution.

Getting a hold on who gets sick and who doesn't

When the human genome was unraveled, it brought about a revolution. However, genetic predisposition does not tell everything, external factors may play a more important role. The sum of all the environmental drivers of health and diseases is called the exposome: a combination of external factors such as chemicals in the air, water or food, and of internal components produced by our body in response to these factors. "To fully realize the potential of the human genome, it is necessary to have the complementary information on the environment. The exposome can provide that information", says co-author Gary Miller, Columbia University, U.S.A.

In recent years, scientists have already made significant progress in mapping the exposome. But if we want to safeguard current and future generations from the increasing number of chemicals polluting our environment, another approach is needed, the researchers stress. Thanks to progress in the use of satellites, sensors, modelling and biomedical measurements it is now possible to map the exposome systematically. One of the innovative techniques highlighted by the researchers, is high-resolution mass spectrometry; a technique that can detect tens of thousands of substances in biological and environmental samples.

"This not only means that more chemicals can be studied, but also that previously unrecognized culprits can be found," says Vermeulen. "We are confident that current developments have brought us to the point where we can really understand the effects of exposure to thousands of chemicals." Vermeulen emphasizes that research into the exposome is only truly informative if it takes place on a large scale and systematically. If necessary, based on such research, chemical substances can be removed from our living environment or alternatives can be developed (green chemistry), so that people and the environment are safe.

Vermeulen leads new collaborations

Last summer Vermeulen received a prestigious grant of over seventeen million euros from the Dutch Ministry of Education, Culture and Science to set up a new consortium, Exposome-NL. In this Dutch consortium, a team of epidemiologists, geographers, sociologists, chemists and biomedical scientists are working together to unravel the exposome. Vermeulen and his colleagues are also making progress on a European level. On February 11, the European Commission will launch nine projects on the exposome, together worth 106 million euros. Vermeulen coordinates one of these projects and with his research group is involved in two other projects.

Over the last two decades, the health sciences have been transformed by genomics, which has provided insights into genetic risk factors for human disease. While powerful, the genomics revolution has also revealed the limits of genetic determinants, which account for only a fraction of total disease risk. A new article in the journal Science argues that a similar large-scale effort is needed to ensure a more complete picture of disease risk by accounting for the exposome, defined as our cumulative exposure to environmental agents such as chemical pollutants.

The article by researchers at Columbia University Mailman School of Public Health; Utrecht University, the Netherlands; University of Luxembourg; and Northeastern University reviews progress in assessing the components of the exposome and its implications on human health.

"Our genes are not our destiny, nor do they provide a complete picture of our risk for disease," says senior author Gary Miller, PhD, Vice Dean for Research Strategy and Innovation and professor of environmental health sciences at the Columbia Mailman School. "Our health is also shaped by what we eat and do, our experiences, and where we live and work."

"Less than half of the nongenetic risk burden for disease is accounted for, suggesting the existence of environmental risk factors, exposure to which may largely be preventable," says first author Roel Vermeulen, Professor of Environmental Epidemiology and Exposome Science at Utrecht University. "With growing recognition of the important role nongenetic factors play in disease, we need a coordinated and international effort to characterize the exposome at a scale comparable to that of the human genome."

What Is the Exposome?

The exposome was conceived by the scientist Christopher Wild in 2005 as a way to represent the environmental, nongenetic, drivers of health and disease. These exposures are not restricted to the thousands of chemicals that enter our bodies through the air, water, or food, for example, but also our body's response to our environment, including the built environment and social circumstances, through inflammation, oxidative stress, infections, and gut flora, for example.

Embracing Complexity

Traditionally, our understanding of the health effects of chemicals has come from epidemiological and toxicological studies that analyze one or a small number of pollutants at a time. "However, our exposures are not a simple sum of a handful of chemicals," the authors write. To capture a fuller picture of environmental exposures, scientists are beginning to employ environment-wide association studies (EWAS), the exposome equivalent of genome-wide association studies (GWAS). Complementing GWAS, EWAS studies take advantage of high-resolution mass spectrometry (HRMS) to measure small molecules originating in the environment, such as air pollution, pesticides, plasticizers, and flame retardants, as well as nutrients and biological metabolites.

"A reductionist approach might isolate the role of a single variable, but it will inadequately capture the complexity of the exposome," the authors write. "The challenge in understanding the role of the exposome on our health lies not only in the large number of chemical exposures in our daily lives, but also in the complex ways that they interact with cells."

Scaling Up

Among the challenges to exposome research are that enrollment in studies of nongenetic environmental exposures remains relatively low. Sample sizes in excess of 100,000 are needed to explain a substantial portion of the genomic heritability of common chronic diseases. The authors posit that similar or even greater sample sizes are required for future environmental studies. A step in that direction, efforts are underway to create a Human Exposome Project representing environmental and biological exposures for tens of thousands of people, large enough to identify the most prevalent and strongest chemical risk factors, although larger studies are needed to understand the impact of many exposome factors in combination. In addition to sample size, the authors call for improvements in screening technology and data resources to identify associations; network theory to elucidate the constellation of the chemical environment and its biological consequences; and replication in independent studies and the use of methods to establish causation.

Exposome Research for Policy and Personalized Medicine

Large-scale exposome studies will give regulatory bodies new information on those chemicals that have the largest adverse effects on health. "If systematic analysis reveals major adverse effects on human health from exposure to currently approved or potential replacement chemicals, then those compounds should be removed from the marketplace," the authors write. Moreover, data on the effects of classes of chemicals on specific biological pathways known to be perturbed could help in the design of new compounds with minimal impact on human health and the environment. "Current research approaches and regulatory policies fail to address the chemical complexity of our world," the authors write.

In the realm of medicine, more complete information on the impact of nongenetic factors and chemical exposures would also enable the creation of an exposome risk score (ERS) akin to the polygenic risk score (PRS) which could give individuals and their clinicians a better understanding of their likelihood of developing certain diseases.

"Consolidating knowledge garnered from GWAS [genome-wide association studies] and EWAS [environment-wide association studies]," the authors conclude, "would allow us to map the gene and environment interface, which is where nature meets nurture and chemistry meets biology."

Imagine that you met a charming girl in school. She is an excellent student who concerns about the world welfare and is anti-war and anti-nuclear. Which do you think she is most likely to become in the future, a bank counter clerk, or, a bank counter clerk and feminist? Surveys show that most people think it's easy and choose the latter. Their choice is right. However, according to classical probability theory, the probability of the former is definitely higher than the latter because the former contains the latter. That paradox calls for more modeling to be established to better fit facts.

Prof. ZHANG Xiaochu and his group developed new frameworks to better explain such human decision-making behaviors using the concept of quantum, and their result is published in Nature Human Behaviour in January 2020. They established the quantum reinforcement learning framework for human decision-making applying concepts from quantum probability theory. For example, they chose quantum probability amplitude rather than classical probability to describe the tendency of selecting a specific action. In this way they proposed quantum models that are comparable to the best classical models. Furthermore, they checked the functional magnetic resonance imaging (fMRI) data of human brain playing the Iowa Gambling Task. They were surprised to find that several important internal-state-related variables involved in their models are represented in the medial frontal gyrus (MeFG), which is important for human learning and decision-making. This shows a unique quantum-like neural mechanism for how the internal state is changed due to external information. In other words, this implies that how human brain works is a quantum-like manner, which is worthy of further research.

These models bring people new perspectives on understanding how human brains run. It's inspired by machine learning development and is possible to elevate the efficiency of machine learning. In the meantime, the quantum-like mechanisms in the brain are still not fully understood. This deserves additional studies and is likely to change the history.

Promoting the signalling pathway of reelin -an essential extracellular protein for the neuronal migration and synaptic plasticity- could be an effective therapeutical strategy to counterbalance the main cognitive, biochemical and behavioural alterations seen in Alzheimer's and other pathologies associated with Tau protein, as shown in a new study with animal models -published in the journal Progress in Neurobiology.

The study proves the determining role of reelin in the modulation of pathological processes associated with Alzheimer's and other tauopathies (accumulation of amyloid plaques, aberrant distribution of Tau phosphorylated, synaptic dysfunction and memory loss), and opens a new perspective to design future therapeutical targets and drugs to fight these disorders.

The first author of this study is the researcher Daniela Rossi, and it is led by Eduardo Soriano and Lluís Pujadas, members of the Faculty of Biology and the Institute of Neurosciences (UBNeuro) of the University of Barcelona, the Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) and the Vall d'Hebron Research Institute (VHIR).

Other participants are the experts Agnès Gruart, José M Delgado and Gerardo Contreras-Murillos (University Pablo de Olavide), Jesús Ávila (Center for Molecular Biology Severo Ochoa, CBM), and Ashraf Muhaisen (UB-UBNeuro-CIBERNED-VHIR). This new study on neurosciences counts on the support of the Research Challenges program (Biomedicine) from the Spanish Ministry of Economy and Competitiveness (MINECO) and La Marató de TV3.

Reelin, an essential protein for brain plasticity

Alzheimer's disease is a neurodegenerative disease known for the loss of connection between neurons and neuronal death. It is largely linked to the creation of senile plaques (formed by the amyloid-beta peptide, or Aß), and the presence of neurofibrillary balls (insoluble deposit of Tau).

In the adult brain, the loss of reelin has been related to an increase in the phosphorylation of Tau protein -a factor which is related to the microtubules mainly expressed in neurons- which ends up in neurofibrillary ball form -typical from Alzheimer's.

Therefore, the different states of phosphorylation and dephosphorylation of Tau represent a determining factor in the stability of the cell cytoskeleton and, as a result, of the synaptic and dendritic stability. Hyperphosphorilation and accumulation of Tau causes neuronal death.

In this context, the function of the reelin protein to promote synaptic plasticity and reduce Tau phosphorylation was considered a potential mechanism to reduce the consequences of the neurodegenerative process and protect the brain from neuronal damage.

New beneficial effects of reelin in animal models with tauopahy

In previous studies, experts had affirmed the alteration of reelin in Alzheimer's disease and its role in intracellular signalling pathways related to neuronal survival and the physiology of the adult brain. Researchers had described the active role of reelin in the recovery of cognitive functions and the reduction of fibers of the Aß peptide in vitro and amyloid deposit in the brain in animal models with Alzheimer's (Pujadas et al. Nature Communications, 2014).

The published study in Progress in Neurobiology describes new molecular data on the signalling pathway of reelin and reveals how this protein can reverse the main pathological affectations of Alzheimer's at different levels in animal models affected by tauopathies. In particular, the results reveal that overexpression of reelin is able to modulate levels of phosphorylation of the Tau protein in in vivo models.

Moreover, the in vitro studies confirm the ability of reelin to modulate the anomalous distribution of neurofilaments and Tau protein in dendrites, which is shown in the first phases of these neuropathologies. Last, regarding the cognitive and physiological fields, overexpression of reelin revealed an improvement of deficits that affected a new animal model of tauopathy.

Researchers at the University of Plymouth and Nestlé have revealed new insights into the factors that predispose children to developing type 2 diabetes in adult life.

The findings have emerged from a unique study, EarlyBird, that followed 300 healthy children in Plymouth, UK, for 15 years to determine who would become at risk of developing type 2 diabetes, and why.

The EarlyBird researchers monitored the children from five years of age to early adulthood to explore how the metabolism changes during growth. The findings, appearing in a series of peer-reviewed scientific publications, have shed new light on the biological and physiological factors that are relevant for metabolic health in childhood.

The latest results, published in Diabetes Care (doi: 10.2337/dc19-0806), show that the earliest event leading to pre-diabetes (the earliest signs of diabetes) is dysfunction of the pancreatic beta-cell, independent of body weight. Beta-cells in the pancreas produce insulin, the hormone that regulates blood sugar levels. The study also showed that this beta-cell dysfunction was associated with the presence of genetic factors previously associated with type 2 diabetes in adults.

This discovery could lead to the early identification of children that are at high risk of future type 2 diabetes.

Jon Pinkney, Professor of Endocrinology and Diabetes in the University of Plymouth's Peninsula Medical School and Honorary Consultant Physician in Endocrinology and Diabetes at University Hospitals Plymouth NHS Trust said: "The rapidly rising prevalence of type 2 diabetes is one of the biggest global health challenges, and there is an urgent need to develop effective strategies for early intervention and prevention.

"The research partnership between University of Plymouth and Nestlé has shown how the risks of future type 2 diabetes can be predicted in childhood. This opens up the possibility of individualised advice and early intervention to reduce the risks of future type 2 diabetes".

"In this study we show that beta-cell dysfunction is an early event in the onset of pre-diabetes in children and that this effect is body weight independent", said François-Pierre Martin, an expert in metabolism who led the collaboration at Nestlé Research. "However, we also report in this study that subsequent weight gain during puberty aggravates the progression from pre-diabetes to diabetes. This stresses the importance of lifestyle and nutritional interventions in childhood to reduce the risks to develop diabetes."

Jörg Hager, a genetics expert at Nestlé Research who designed the genetic part of the study said: "Our research has important implications for potentially identifying children at risk of developing pre-diabetes through genetic markers. The new findings will allow us to develop new nutritional approaches that target the insulin response to a meal, and the body's ability to regulate blood sugar level."

Begun in the early 2000s, when the obesity epidemic was still in its infancy and the idea that children could develop type 2 diabetes almost unheard of, EarlyBird was able to develop strong relationships between families and researchers and retain a high proportion of children over the course of the study.

The detailed metabolomic and genetic data collected over such a long period of childhood are unique. As a consequence, researchers have been able to make a number of vital discoveries about the relationships between lifestyle, genetics and health.

New automotive technology that promises enhanced fuel efficiency may have a serious downside, including significant climate and public health impacts, according to research from the University of Georgia College of Engineering.

The gasoline direct injection (GDI) engine is one of the most prominent technologies car manufacturers adopted to achieve the fuel economy and carbon dioxide emission goals established in 2012 by the U.S. Environmental Protection Agency. The market share of GDI-equipped vehicles increased from 2.3% in model year 2008 to 51% in model year 2018. The EPA projects 93% of vehicles in the U.S. will be equipped with GDI engines by 2025.

While this technology is credited with boosting fuel efficiency and reducing CO2 emissions, GDI engines produce more black carbon aerosols than traditional port fuel injection engines. A strong absorber of solar radiation, black carbon exhibits significant climate warming properties.

In a study published this month in the journal Environmental Science and Technology, a team of researchers at UGA predicts the increase in black carbon emissions from GDI-powered vehicles will fuel climate warming in urban areas of the U.S. that significantly exceeds the cooling associated with a reduction in CO2. In addition, they believe the shift will nearly double the premature mortality rate associated with vehicle emissions, from 855 deaths annually to 1,599. The researchers estimate the annual social cost of these premature deaths at $5.95 billion.

"Even though emissions from gasoline vehicles constitute a small fraction of the black carbon in the atmosphere, the vehicle emissions are concentrated in regions with high population densities, which magnifies their effect," said Rawad Saleh, an assistant professor in UGA's School of Environmental, Civil, Agricultural and Mechanical Engineering and the study's principal investigator.

The increase of black carbon is an unintended consequence of the shift to GDI-equipped vehicles that some scientists suspected was based on experimental data, according to Saleh. He says the UGA study is the first to place these experimental findings in a complex modeling framework to investigate the trade-off between CO2 reduction and an increase in black carbon.

While previous research has reported the shift to GDI engines will result in net benefits for the global climate, the UGA researchers say these benefits are rather small and can only be realized on timescales of decades. Meanwhile, the negative impact of black carbon can be felt instantaneously.

"Our research shows the climate trade-off is much different on the regional scale, especially in areas with high vehicle densities. In these regions, the climate burden induced by the increase in black carbon dominates over the climate benefits of the reduction in CO2," said Saleh. "The study concludes the social cost associated with the acute localized climate burden and public health impacts induced by GDI vehicles largely overweigh their marginal global climate benefits."

In a study published in Brain Communications, a new Open Access publication of the well-known journal Brain, the team led by Carlos Barcia, researcher at Institut de Neurociències of the Universitat Autònoma de Barcelona (INc), analysed the role of immune cells in the expansion of glioblastoma, the most aggressive brain tumour. The study is a collaborative effort with the General Hospital in Valencia, and part of Elena Saavedra's doctoral thesis.

The research shows for the first time that microglia and macrophages, cells of the immune system, facilitate the invasive capacity of glioblastoma by clearing the necrotic areas of the tumour while ignoring tumour cells in its niche of invasion.

This invasive niche, which is the part of the tumour that comes into contact with the healthy tissue, is shaped like a pseudopalisade and is poorly irrigated by blood vessels. This results in a lack of oxygen -hypoxia-, which causes, on the one hand, that the tumour cells escape and invade healthy tissue, and on the other, the creation of a necrotic area inside the tumour. Researchers show, in this study, that microglia and macrophages travel to these hypoxic areas and only clean dying tumour cells, facilitating tumour growth and expansion.

"The importance of this work is that we observed for the first time the presence of immune system cells in these particular tumour's invasive areas, and also that the phagocytic capacity of immune cells is not lost and could be trained to facilitate the removal of tumour instead of helping its growth" says Carlos Barcia.

The next step, then, is to study how microglia cells and macrophages could be trained, through immunotherapy or other strategies, to not play in favour of the tumour, but to contribute to its elimination.

Women-only business networks fail to boost female entrepreneurship and instead serve to marginalise further the very people they seek to help.

New research from the University of Edinburgh Business School, Lancaster University Management School and Dublin City University Business School, published in the Journal of Economic Geography, found the networks are unable to overcome bigger societal issues that prevent more women from pursuing their own businesses.

Policy makers see the drive to increase female entrepreneurship as key to helping foster national and regional economic growth. However, women lag behind men in terms of business ownership, growth and access to resources.

The research, carried out in Northern Ireland, a region where female entrepreneurship is low in comparison to the rest of the UK, looked at efforts by regional development agency Invest NI to address the issues.

Regional economic policy has focused on stimulating and supporting women's entrepreneurship through the establishment of formal women-only networks to provide support, role models and access to networks.

The researchers spoke with members and managers of women-only business networks, which have been at the heart of policies in Northern Ireland for nearly two decades, as well as members of mixed networks, and of both.

Policy-makers justify the promotion of women-only networks as providing network opportunities to support women's entrepreneurship and, as a result, boost the economy, but the research, supported by British Academy funding, shows a disconnect between intent and actual impact, as the networks perpetuate women's marginalisation and place them in a niche rather them empowering and encouraging them.

"Entrepreneurship policies targeted at women are contributing little or nothing to their equality, well-being or independence," said co-author Professor Richard Harrison, of the University of Edinburgh. "The outcomes of policy are often limited or contrary to intentions.

"Entrepreneurship is shaped for men, and successful entrepreneurs are male. Women are only deemed successful if they launch businesses in the 'right' (male-dominated) industries and match male-owned businesses for growth. Thus, women-only networks perpetuate the masculinity of entrepreneurship, by reinforcing women as being in the margins."

The research shows policy design ignores inherent structural issues within society and entrepreneurship, where there is still a clear and continuing division of labour between 'men's work' and 'women's work'.

The researchers found that there is a lack of knowledge and information around the sectors women entrepreneurs tend to predominate in. This leads to a shortfall in well-connected and credible contacts and role models to provide information or introductions to suppliers or gatekeepers.

The networks tend to be more geographically restricted and focus more on social support over business development, failing to provide a platform to address issues of gender inequality in entrepreneurship.

The interviews revealed a perception among the network members of having to battle against a male-dominated society, where they had to overcome stereotypes of women as mothers or homemakers, which can affect entrepreneurship being seen as a viable option.

"Strategies and policies focus on addressing failings or limitations unique to women, rather than on systemic, industry or institutional issues, perceiving a deficiency of perceived female underperformance," said co-author Professor Maura McAdam, of Dublin City University.

"By treating women differently to men, treating them a problem that needs to be fixed, and by creating women-only targeted initiatives, women continue to be marginalised. Many business structures are shaped for men, with women restricted in their entrepreneurial ambitions in the lower echelons of the retails and service sector, often referred to as 'pink ghettos'.

"The network managers saw themselves as empowering women, but this was not a sentiment shared by the women entrepreneurs, with the networks instead tending to reaffirm women's secondary place in society and business. The members found it difficult to see themselves as entrepreneurs, undermining their ability and underselling themselves."

The researchers say more needs to be done to combat wider issues around male dominance if female entrepreneurship is to grow.

"Women-only networks have not empowered women entrepreneurs," said co-author Professor Claire Leitch, of Lancaster University. "They do not have the power to overcome issues of male dominance in the area, and it is not a given that other policies would have that ability to achieve the goals of increasing women's entrepreneurial activity, well-being and financial independence either.

"Supporting women-only networks merely pays lip service to women's unequal position and power without addressing the structural issues and inequalities at the heart of the issue. These networks reinforce the masculinity of entrepreneurship and, unfortunately, there is no quick fix for policy design in this area.

"All parties need to identify, address and eliminate the various means by which cultural bias is perpetuated, restructuring the ways social institutions are conceived. If women's entrepreneurship continues to be seen as a gendered niche, aspirations for its impact will never be met."

DALLAS - Jan. 23, 2020 - UT Southwestern Simmons Cancer Center researchers have discovered a two-drug combo that halts the growth of cancer cells that carry HER2 mutations.

The findings, published today in the journal Cancer Cell, were prompted by the observation that, after an initial response, patients with cancers harboring HER2 mutations eventually develop resistance to a promising new cancer drug currently in clinical trials.

The scientists found that another drug, already on the market, counters that resistance and blocks the cancer, thereby providing the basis for a novel drug combination against cancers with mutations in the HER2 gene.

Dhivya Sudhan, Ph.D., a postdoctoral research fellow in the Harold C. Simmons Comprehensive Cancer Center, and collaborators evaluated data from a molecularly guided trial where patients with tumors with HER2 mutations were treated with the HER2 inhibitor neratinib. In this study, patients' cancers were sequenced as the disease progressed during treatment. Based on this analysis, Sudhan discovered in the laboratory that an effective way to offset eventual resistance to neratinib is with everolimus, a TORC1 inhibitor commonly used to treat other types of breast cancer.

"This finding may give clinicians an effective response to neratinib resistance. That could make a real difference for patients with breast, ovarian, lung, and other cancers harboring HER2 mutations," says Carlos L. Arteaga, M.D., Director of the Simmons Cancer Center at UT Southwestern and corresponding author of the study.

HER2 mutations have long been identified as a key driver in breast and other cancers. The authors of this study zeroed in on a signaling network driven by TORC1, which they showed is the pathway through which HER2-mutant cancers become neratinib-resistant.

"We consistently noted activation of TORC1 signaling as a mechanism of resistance to neratinib across different types of HER2-mutant cancers. Different cancer types used different strategies to escape neratinib, but they all converged on TORC1 signaling," Sudhan says.

In addition to studying tumor sequencing data from HER2-mutant cancer patients across the country who are in clinical trials for neratinib, Sudhan also studied neratinib-resistant cells and tumors that continue to live and grow in the laboratory.

The sequencing of the patients' cancer before and during the clinical trial showed that some patients already had a mutation that could activate the TORC1 pathway. Others would develop it eventually, but they could benefit from everolimus which is currently used as a TORC1 inhibitor to address the other roles TORC1 plays in cancer. Everolimus would allow the patient to continue benefiting from neratinib's inhibition of HER2.

Sudhan says the combination of neratinib and everolimus worked in cell lines, organoids established from patient-derived tumors, and in mice harboring HER2 mutant tumors. The next step will be testing this two-drug combo in humans.

Mitochondria are organelles that are found in the eukaryotic cells. A place of cellular respiration, they are the cells' "batteries" and play a major role in energy metabolism and intercellular communication. Their particularity is to possess their own genome, transmitted solely by the mother and separate from the DNA contained in the nucleus. The mitochondria can sometimes be observed outside the cells in the form of fragments encapsulated within microvesicles. Under certain very specific conditions the platelets are also capable of releasing intact mitochondria into the extracellular space.

The work of a team led by Inserm researcher Alain R. Thierry at the Montpellier Cancer Research Institute (Inserm/Université de Montpellier/Montpellier Cancer Institute) has now revolutionized knowledge of this organelle by revealing that whole functioning extracellular mitochondria are in fact found in the bloodstream.

The researchers used previous findings which showed that the plasma of a healthy individual contains up to 50,000 times more mitochondrial DNA than nuclear DNA. They hypothesized that for it to be detectable and quantifiable in the blood in this manner, the mitochondrial DNA had to be protected by a structure of sufficient stability. In order to identify such a structure, plasma samples from around 100 individuals were analyzed.

This analysis revealed the presence in the blood circulation of highly stable structures containing whole mitochondrial genomes. Following examination of their size and density, as well as the integrity of their mitochondrial DNA, these structures observed using electron microscopy (up to 3.7 million per ml of plasma) were revealed to be intact and functional mitochondria.

Throughout the seven-year research period, the scientists used as many technical and methodological approaches as possible to validate this presence of circulating extracellular mitochondria in the blood.

"When we consider the sheer number of extracellular mitochondria found in the blood, we have to ask why such a discovery had not been made before, Thierry says. Our team has built up expertise in the specific and sensitive detection of DNA in the blood, by working on the fragmentation of extracellular DNA derived from the mitochondria in particular", he adds.

But what is the role of these extracellular mitochondria? The answer to that could be linked to the structure of the mitochondrial DNA, similar to that of bacterial DNA, which gives it the ability to induce immune and inflammatory responses. Based on this observation, the researchers hypothesize that these circulating mitochondria could be implicated in many physiological and/or pathological processes requiring communication between the cells (such as the mechanisms of inflammation). Indeed, recent studies have demonstrated the ability of certain cells to transfer mitochondria between themselves, such as the stem cells with damaged cells. "The extracellular mitochondria could perform various tasks as messenger for the entire body", Thierry explains.

In addition to its importance to our knowledge of physiology, this discovery could lead to improvements in the diagnosis, monitoring and treatment of certain diseases. In fact, the research team is now devoting its attention to evaluating the extracellular mitochondria as biomarkers in non-invasive prenatal diagnosis and cancer.

Black and Hispanic borrowers more likely to be rejected when they apply for a loan; more likely to receive a high-cost mortgage

Housing discrimination leads to persistent neighborhood segregation

Discrimination in mortgage market makes it more difficult for minority households to build wealth through housing

EVANSTON, Ill. --- A new Northwestern University analysis finds that racial disparities in the mortgage market suggest that discrimination in loan denial and cost has not declined much over the previous 30 to 40 years, yet discrimination in the housing market has decreased during the same time period.

Northwestern researchers examined how discrimination in housing and mortgage lending against blacks, Latinos and Asians has changed over the last 40 years by performing a meta-analysis of existing studies since the late 1970s to the present.

"We find declines in most forms of discrimination, especially the more extreme forms like falsely claiming an advertised unit is no longer available," said Lincoln Quillian, lead author of the study and professor of sociology in the Weinberg College of Arts and Sciences at Northwestern. "There is less reduction and considerable persisting discrimination in more subtle differences in treatment between whites and minorities.

"For example, in about 10% audits in which a white and an African-American auditor were sent to apply for the same unit after 2005, the white auditor was recommended more units than the African-American auditor. These trends hold in both the large HUD (Housing and Urban Development)-sponsored housing audits, which others have examined with similar findings to us, and in smaller correspondence studies."

In the mortgage market the researchers found that racial gaps in loan denial have declined only slightly, and racial gaps in mortgage cost have not declined at all, suggesting persistent racial discrimination. Black and Hispanic borrowers are more likely to be rejected when they apply for a loan and are more likely to receive a high-cost mortgage.

"It was distressing to find no evidence of reduced discrimination in the mortgage market over the last 35 years," said Quillian, also a faculty fellow with the University's Institute for Policy Research. "Discrimination in the mortgage market makes it more difficult for minority households to build wealth through housing, contributing to racial wealth gaps. Discrimination in the housing market increases housing insecurity for minority households and contributes to persistent neighborhood segregation. These results help account for why black homeownership has not increased over the last 35 years."

The reduction in the most exclusionary forms of housing discrimination suggests that in most cases discrimination will not block persistent efforts by black or Hispanic households to move into white or affluent neighborhoods.

"We believe that more subtle forms of discrimination will steer households with weaker neighborhood preferences toward own-race neighborhoods, helping to maintain residential segregation," Quillian said.

In sum, the researchers say, the results suggest that anti-discrimination enforcement in the housing and mortgage markets should continue, and efforts should be increased to ensure that all home seekers receive equal treatment regardless of their race or ethnic background.

Most research on the mental health of refugees focuses on the first few years after resettlement in the host country, but little is known about their long-term mental health.

A new study of Canadians aged 45-85, released this week, found that refugees were 70% more likely to suffer from depression than those born in Canada when age, sex and marital status were taken into account -- even decades after immigration.

"Our findings indicate that the refugee experience casts a long shadow across an individual's lifespan," says the study's first author Shen (Lamson) Lin, a doctoral student at the University of Toronto's Factor Inwentash Faculty of Social Work (FIFSW).

"While our data did not capture reasons for the high levels of depression among refugees, we believe it may be influenced by exposure to pre-migration traumas such as genocide, forced displacement, human trafficking, sexual assault, famine, and separation from family."

In order to untangle the potential contribution of post-migration challenges, which face all immigrants, from the pre-migration trauma unique to refugees, the research team also investigated depression among immigrants who did not arrive as refugees. Post-migration problems may include downward socioeconomic mobility, racial discrimination, higher levels of unemployment, language barriers, and reduced social networks.

The prevalence of depression among non-refugee immigrants (16.6%) was much closer to that of their Canadian-born peers (15.2%) than to that of refugees (22.1%).

"Our results suggest that post-migration challenges are less important than pre-migration traumas when it comes to depression," says senior author, FIFSW Professor Esme Fuller-Thomson, who is also cross-appointed to U of T's Department of Family & Community Medicine and is is director of the University's Institute for Life Course & Aging.

"The greater prevalence of depression among refugees -- half of whom arrived more than four decades ago -- underlines the importance of providing mental health resources for our refugee community both immediately after arrival, but also in the ensuing decades."

The study investigated factors that may have influenced levels of depression among participants, including age, sex, marital status, income, education, health, chronic pain, health behaviors and the frequency of social contacts. But even when these characteristics were accounted for, refugees still had much higher odds of depression than individuals born in Canada.

The researchers found that social support is a key. A lack of social support was associated with higher levels of depression among refugees -- they were also more likely to have less of it. Refugees were more likely than those born in Canada to report that they lacked: 1) someone who showed them love and affection (17% versus 8%), 2) someone to confide in about their problems (27% vs 16%), and 3) someone to give them good advice about a crisis (27% versus 16%). (The level of social support among immigrants who did not arrive as refugees was relatively similar to the Canadian born group, and much less vulnerable than the refugee group.) When the availability of these three levels of social support was high, the relationship between refugee status and depression significantly diminished.

"Our study indicates that the quality of relationships, rather than the quantity of social connections, matters most for refugees' mental health." says co-author Karen Kobayashi, a professor in the Department of Sociology and a research affiliate at the Institute on Aging & Lifelong Health at the University of Victoria. "This highlights the importance of investigating ways to promote powerful positive social relations among refugees and asylum seekers in their families, neighbourhoods, and communities."

The study's findings also have important policy implications.

In Canada, two different sponsorship programs are currently in place. Government-assisted refugees (GARs) get basic financial aid and assistance offered by professionals to help with the settlement process. Privately sponsored refugees (PSRs) are supported by a network of engaged volunteers, often members of a church, mosque or synagogue who are able to provide extensive assistance with all kinds of settlement issues including housing, health needs and job searches.

According to recent studies on Syrian refugees in Canada, PSRs report having more help in daily errands, fewer unmet needs and a higher employment rate than GARs.

"We anticipate that refugees sponsored under the PSR program may be more likely to thrive post-migration because of a stronger social support network and this may set them on a positive employment and mental health trajectory for decades after their arrival." says co-author Hongmei Tong, Assistant Professor of Social Work at MacEwan University in Edmonton.

Consistent with earlier studies, Canadian adults in this study who were poor, experiencing chronic pain and those with more co-morbid health conditions had a higher prevalence of depression.

"It is not surprising that Canadians who have household incomes under $25,000 per year have double the odds of distress compared to those with incomes above $75,000. Struggling to pay the rent and feed one's family can be extremely distressing," said co-author Simran R Arora, Master of Social Work student at the University of Toronto.

"Mental health professionals must be careful not to neglect physical health concerns such as chronic pain," said co-author Karen Davison, Health Science Program Chair at Kwantlen Polytechnic University in Surrey, B.C. "We really need to be treating the whole person in order to address depression."

Swedish and Japanese researchers have, after ten years, found an explanation to the peculiar emission lines seen in one of the brightest supernovae ever observed - SN 2006gy. At the same time they found an explanation for how the supernova arose.

Superluminous supernovae are the most luminous explosions in cosmos. SN 2006gy is one of the most studied such events, but researchers have been uncertain about its origin. Astrophysicists at Stockholm University have, together with Japanese colleagues, now discovered large amounts of iron in the supernova through spectral lines that have never previously been seen either in supernovae or in other astrophysical objects. That has led to a new explanation for how the supernova arose.

"No-one had tested to compare spectra from neutral iron, i.e. iron which all electrons retained, with the unidentified emission lines in SN 2006gy, because iron is normally ionized (one or more electrons removed). We tried it and saw with excitement how line after line lined up just as in the observed spectrum", says Anders Jerkstrand, Department of Astronomy, Stockholm University.

"It became even more exciting when it quickly turned out that very large amounts of iron was needed to make the lines - at least a third of the Sun's mass - which directly ruled out some old scenarios and instead revealed a new one."

The progenitor to SN 2006gy was, according to the new model, a double star consisting of a white dwarf of the same size as the Earth and a hydrogen-rich massive star as large as our solar system in close orbit. As the hydrogen rich star expanded its envelope, which happens when new fuel is ignited in the late stages of evolution, the white dwarf was caught in the envelope and spiralled in towards the centre of the companion. When it reached the centre the unstable white dwarf exploded and a so-called Type Ia supernova was born. This supernova then collided with the ejected envelope, which is flung out during the inspiral, and this gigantic collision gave rise to the light of SN 2006gy.

"That a Type Ia supernova appears to be behind SN 2006gy turns upside down what most researchers have believed", says Anders Jerkstrand.

"That a white dwarf can be in close orbit with a massive hydrogen-rich star, and quickly explode upon falling to the centre, gives important new information for the theory of double star evolution and the conditions necessary for a white dwarf to explode."

Fact: Superluminous supernovae

Superluminous supernovae are the brightest explosions in the Universe. Over a few months they radiate as much energy as the Sun does over its whole lifetime and reach a peak brightness as high as that of an entire galaxy. The origin of this energy, and what kind of star system that has exploded, are still unclear and debated.

Fact: Emission line

An emission line is a bright feature in the spectrum of a light source. The lines arise as each element in the source emit light at specific wavelengths, and from this one can see which elements are present in the source. Examples of emission line sources are certain astrophysical objects.