Culture

Sex chromosomes are presumed to originate from a pair of identical ancestral chromosomes by acquiring a male- or a female-determining gene on one chromosome. To prevent the sex-determining gene from appearing in the opposite sex, recombination is suppressed on sex chromosomes. This leads to the degeneration of Y chromosome (or the W chromosome in case of birds) and the morphological difference of sex chromosomes between sexes. For example, the human Y chromosome bears only less than 50 genes, while the human X chromosome still maintains over 1500 genes from the autosomal ancestor. This process occurred independently in birds, in monotremes (the Australian platypus and echidnas), and in the other mammals (therians, e.g., kangaroo, mouse and human etc.).

Platypus has ten sex chromosomes

With its venom, duck-bill, egg, and milk, platypus features an extraordinary combination of reptiles, birds and mammals. Previous work showed that platypus, although undoubtedly a mammalian species, have sex chromosomes that do not share the same origin with those of human. It turns out that male platypus has five pairs of XY chromosomes (named as X1Y1, X2Y2, etc.), and none of them are homologous to the XY of human or mouse. These ten sex chromosomes pair with each other in a head-to-tail manner and form a chain during meiosis when sperm cells develop. The genetic makeup and the evolution process of such a complex and unique sex chromosome system remained unclear, because the previously published platypus genome is was from a female, and only a quarter of the sequences is was mapped onto chromosomes.

Cutting-edge sequencing techniques

An international team of researchers adopted a new sequencing technique (called PacBio, or third-generation sequencing) that can "read" the genome information for over 300-fold longer in length than the last-generation technique, and the new chromatin conformation capture technique that can connect and map the genomic sequences into the chromosome level.

"With further laborious cytogenetic experiments, we improved the genome quality and mapped over 98% of the sequences into 21 autosomes, and 5X and 5Y chromosomes of platypus" says Guojie Zhang from BGI-Shenzhen and University of Copenhagen. "The new genomes are a hugely valuable public resource for research in mammalian biology and evolution, with applications in wildlife conservation and even human health," says Frank Grützner at University of Adelaide in Australia.

From a ring to a chain

"What surprised us is that, from the new sex chromosome sequences, we found the last Y chromosome, Y5 does not share many sequences with its pairing X5 chromosome, but with the first X chromosome of the chain, X1", says Qi Zhou. "This suggested that the 10 platypus sex chromosomes used to be in a ring shape. Maybe the acquisition of a male-determining gene and suppression of recombination broke the ancestral chromosome ring into a chain". This part of the sex chromosome work provides an entirely new perspective on the evolution of this extraordinary sex chromosome system, along with other new discoveries of platypus genes related to milk production, loss of teeth and so on, were published in Nature as a research article.

Different sex systems of birds and mammals

With similar new techniques used for the platypus genome, the Zhou group simultaneously decoded the sex chromosome sequences of emu and Pekin duck, which represent the different phase of sex chromosome evolution. Most mammalian and bird species' sex chromosomes have evolved into their terminal stage of evolution like that of human or chicken. A key difference between mammals and birds is that instead of the XY sex system, birds have so-called ZW sex chromosomes. That is, male birds have a pair of ZZ chromosomes, female birds have a Z and a W sex chromosomes.

Slow-evolving sex chromosomes of emu and duck

The Y or W chromosomes usually have lost most functional genes, and become a "gene desert" full of repetitive sequences. Emu is an exception: its sex chromosomes are largely like a pair of autosomes, with over two-thirds of the sequences and active genes still shared between the Z and W chromosomes. "This may be related to the slower evolution rate of the emu compared to other birds'', says Jing Liu, a Ph.D. student in the Zhou group. "By comparing the genomes of emu and 11 other bird species, we found that large-bodied birds like emu and ostrich tend to have much less chromosome rearrangements than other birds".

Another possible reason is that these flightless large birds may undergo much weaker sexual selection, a potential driver for sex chromosome evolution, compared to other birds, given that male and female emus are largely monomorphic. This provides a great system to understand how sex chromosomes evolve in their early phase - and in the case of Pekin duck, in the middle phase. Another project from the Zhou group generated the high-quality genome sequence of Pekin duck, a very popular poultry species. Emu, duck and chicken together mark the different time phase of sex chromosome evolution.

In this work we found that the W chromosomes of emu and duck have retained many more functional genes on their W chromosomes compared to the chicken. Such a large variation in the tempo of sex chromosome evolution is not observed in mammals, and reflects the different evolutionary modes of the XY and ZW sex systems. These novel sex chromosome sequences of emu and duck will also provide important resources for poultry studies.

The Covid-19 pandemic is impacting people's mental health. But what helps and hinders people in getting through a lockdown? A new study led by researchers at the University of Basel addressed this question using data from 78 countries across the world. The results hint at the pivots and hinges on which the individual's psyche rests in the pandemic.

At the outset of the Covid-19 pandemic, little was known about the impact of population-wide governmental lockdowns. What was known was taken from restricted quarantines of small groups of people. "On the one hand, such drastic changes to daily routines can be detrimental to mental health," explains Professor Andrew Gloster from the University of Basel, co-leader of the study now published in PLOS One. "On the other hand, because the entire population was more or less equally affected during the lockdown, it remained unclear whether this impact would occur."

To address this question, Gloster and his international colleagues conducted an online survey in 18 languages. Almost 10,000 people from 78 countries participated, giving information about their mental health and overall situation during the Covid-19 lockdown.

One in ten respondents reported low levels of mental health - including negative affect, stress, depressive behaviors and a pessimistic view of society. Another 50% had only moderate mental health, which has previously been found to be a risk factor for further complications. These figures are consistent with other studies addressing the impact of the pandemic on mental health.

Lowest levels of well-being in Hong Kong and Italy

Overall, the responses in the different surveyed countries were largely similar. However, although no country emerged as either consistently better or worse across all outcomes, there were some differences. Hong Kong and Turkey reported more stress than other countries; the USA reported more depressive symptoms; and well-being was lowest in Hong Kong and Italy. Participants in Austria, Germany and Switzerland, on the other hand, reported significantly fewer negative emotions (negative affect) than the average level across all countries.

These differences are likely due to a combination of chance, nation-specific responses to the pandemic, cultural differences and factors such as political unrest. Beyond that, they may in part be explained by factors the researchers found to be connected to outcomes. Loss of financial income compared to pre-lockdown levels and not having access to basic supplies were consistently associated with worse outcomes. Factors that consistently improved outcomes were having social support, higher education levels, and being able to respond and adapt flexibly to the situation.

"Public health initiatives should target people without social support and those whose finances worsen as a result of the lockdown. Based on these results, interventions that promote psychological flexibility like acceptance and commitment therapy hold promise when it comes to mitigating the impact of the pandemic and lockdowns," says Gloster. Given the continued fluid development of the pandemic and its economic consequences, attention to people's mental health remains important.

Northeastern Asia has a complex history of migrations and plague outbursts. That is the essence of an international archaeogenetic study published in Science Advances and lead from the Department of Archaeology and Classical Studies at Stockholm University. Genomic data from archaeological remains from 40 individuals excavated in northeastern Asia were explored in the study.

"It is striking that we find everything here, continuity as well as recurrent migrations and also disease-related bacteria", says Anders Götherström, professor at the Center for Palaeogenetics at Stockholm University and one of the Principal investigators of the study.

The scientists discovered that there were demographic events in the past common for the whole Lake Baikal region. For example, around 8300 years ago there was a migratory event discernible both east and west of Lake Baikal. But there were also events specific for each of the two areas. While the areas west of Lake Baikal provides evidence for recurrent migrations and intense mobility, the areas east of Lake Baikal preserved a long-term continuity for thousands of years, apparently with limited mobility from other areas.

"It is intriguing that our data reveals complex and contrasting patterns of demographic change in one of the least populated regions on earth; including notable gene flow and at the same time a genetic continuity without major demographic changes in the two areas around Lake Baikal", says lead-author Gulsah Merve Kilinc, former postdoctoral researcher at the Department of Archaeology and Classical Studies at Stockholm University and currently Lecturer at Department of Bioinformatics at Hacettepe University in Ankara.

The study also provides some new clues to the history of the Paleo-Inuit groups, the people who inhabited northern Greenland and Canada. While it has been suspected that the so called Belkachi-complex, a cultural group in the Baikal area, played a part in the early history of Paleo-Inuits, it has not been possible to evaluate this in detail. The analyses of remains of an individual associated with the Belkachi cultural-complex, dated to more than 6000 years before present now show that there is an association to a previously published Paleo Inuit (Saqqaq) individual (dated c.4000 yrs BP) on Greenland.

"This is the first genetic evidence of a link between a Neolithic period human group in Yakutia and the later Palaeo-Inuit groups, and this will inspire to new of research on the demographic development", says Jan Storå, Professor at Osteoarchaeological Research Laboratory at the Department of Archaeology and Classical Studies at Stockholm University.

Finally, the study provides new data on the most eastern occurrences of the bacteria Yersinia pestis, the plague. One individual from the Lena basin, dated to c. 3800 years ago, and buried with individuals that proved to be close kin genetically, carried DNA from Yersinia pestis. Also, an individual dated to c. 4400 years ago from the area west of Lake Baikal hosted Yersinia pestis. Interestingly, the population west of Lake Baikal seems to have decreased in size around 4400 years ago, judging from the genomic data.

"Despite a need for more data, our discovery of the decrease in effective population size that coincided with the appearance of Yersinia pestis points to a possible presence of a prehistoric plague - possibly a pandemic. However, this is just as an educated guess which needs to wait for confirmation", says Emrah K?rdök, former postdoctoral researcher at the Department of Archaeology and Classical Studies at Stockholm University and currently Lecturer at Mersin University in Turkey.

In a study to examine a Mediterranean diet in relation to prostate cancer progression in men on active surveillance, researchers from The University of Texas MD Anderson Cancer Center found that men with localized prostate cancer who reported a baseline dietary pattern that more closely follows the key principles of a Mediterranean-style diet fared better over the course of their disease.

"Men with prostate cancer are motivated to find a way to impact the advancement of their disease and improve their quality of life," said Justin Gregg, M.D., assistant professor of Urology and lead author of the study, published today in Cancer. "A Mediterranean diet is non-invasive, good for overall health and, as shown by this study, has the potential to effect the progression of their cancer."

After adjusting for factors known to increase risk of cancer getting worse over time, such as age, prostate-specific antigen (PSA) and tumor volume, men with a diet that contained more fruits, vegetables, legumes, cereals and fish had a reduced risk of their prostate cancer growing or advancing to a point where many would consider active treatment. The researchers also examined the effect of diabetes and statin use and found a similar risk reduction in these patient groups.

The study, whose largest number of participants were white, also found that the effect of a Mediterranean diet was more pronounced in African American participants and others who self-identified as non-white. These findings are significant as the rate of prostate cancer diagnosis is more than 50% higher in African American men, who also have a higher risk of prostate cancer death and disease progression.

"The Mediterranean diet consistently has been linked to lower risk of cancer, cardiovascular disease and mortality. This study in men with early stage prostate cancer gets us another step closer to providing evidence-based dietary recommendations to optimize outcomes in cancer patients, who along with their families, have many questions in this area," said Carrie Daniel-MacDougall, Ph.D., associate professor of Epidemiology and senior author of the study.

After skin cancer, prostate cancer is the most common cancer in men in the United States. Since most cases are low-risk disease, localized to the prostate and have favorable outcomes, many men do not need immediate treatment and opt for active surveillance by their doctor. Treatments for prostate cancer can cause changes in quality of life and declines in urinary and sexual function, therefore there is interest in finding modifiable factors for men managed by active surveillance.

The study followed 410 men on an active surveillance protocol with Gleason grade group 1 or 2 localized prostate cancer. All study participants underwent a confirmatory biopsy at the beginning of the study and were evaluated every six months through clinical exam and laboratory studies of serum antigen PSA and testosterone.

Trial participants were 82.9% Caucasian, 8.1% Black and 9% other or unknown. The median age was 64, 15% of the men were diabetic and 44% used statins.

The men completed a 170-item baseline food frequency questionnaire, and Mediterranean diet score was calculated for each participant across 9 energy-adjusted food groups. The participants were then divided into three groups of high, medium and low adherence to the diet.

After adjustments for age and clinical characteristics, researchers saw a significant association between high baseline diet score and lower risk of cancer grade progression. For every one-point increase in the Mediterranean diet score, researchers observed a >10% lower risk of progression. After a median follow-up of 36 months, 76 men saw their cancer progress.

The study was limited by the low number of events in these men with mostly low risk disease monitored at MD Anderson. Future research is needed to see if the same effects are seen for larger and more diverse patient groups and men with higher-risk prostate cancer.

"Our findings suggest that consistently following a diet rich in plant foods, fish and a healthy balance of monounsaturated fats may be beneficial for men diagnosed with early-stage prostate cancer," Gregg said. "We are hopeful that these results, paired with additional research and future validation, will encourage patients to adapt a healthy lifestyle."

Scientists who publish in Cell Press research journals (e.g., Cell, Joule, Current Biology, etc.) will now have the option to include a short statement that highlights elements of the study design and/or author characteristics that are relevant to inclusion and diversity. The statement is generated based on information provided on a dedicated inclusion and diversity form that study authors complete as part of the acceptance process. This pilot initiative will also allow Cell Press to better collect, analyze, and share back data about research teams' general inclusion and diversity efforts.

"In an ideal world, science would cover and be conducted by as broad a range of individuals as exist in global society, with everyone who wants to participate both being and feeling welcomed as part of the overall scientific community. Currently, however, the scientific enterprise is a long way from such inclusion and diversity," says Anne Kitson, Managing Director, Cell Press and The Lancet. "We want to find ways to push for positive change through the platform of our journals. As part of that, we see an opportunity to give authors the ability to share efforts that that they are making too."

The concept underlying this initiative is similar to existing statements about declarations of interests, author contributions, and data and code availability but focuses on highlighting aspects of the paper that are relevant to inclusion and diversity. It is purposely multifunctional and designed to give authors a venue to express ways in which their work, their research group, or both are contributing to helping science become more inclusive and diverse. It also reflects the focus of Elsevier's Inclusion and Diversity Board and a broader commitment to promoting women in science as well as racial, ethnic and geographic diversity in editorial boards, peer review and scientific conferences while supporting publication and inclusive participation in research.

Researchers can include information about efforts to ensure diversity in cell lines or genomic datasets used for a study, efforts to ensure sex/gender balance in research subjects, efforts to ensure that any study questionnaires are prepared in an inclusive way, efforts to avoid "helicopter science," self-identification of authors as members minority groups, support that any authors have received from programs designed to support minority scientists, and efforts made to promote gender balance in citation lists.

For example, one paper's inclusion and diversity statement could read: "We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in science." Cell Press will run this program as a pilot during the course of 2021 and then decide whether to continue, adapt, or build on it towards the end of the year. The first iteration will focus on research articles only.

"Any research group that doesn't want to publish a statement will not be required, but Cell Press will keep the data submitted via the inclusion and diversity forms for aggregated reporting. "We need to have data to help us monitor progress. We hope to be able to use it to benchmark and set goals for the types of inclusion and diversity efforts that Cell Press and our authors are making," says John Pham, Editor-in-Chief of Cell. "For example, we would like to be able to report how many of our papers have at least one minority scientist among the author group or made efforts to consider diversity in the selection of experimental materials or samples. We can then develop ways to challenge ourselves and the community to increase diversity and monitor outcomes."

"We hope that this new inclusion and diversity initiative will give our authors a powerful opportunity to share their contributions in a visible way within the context of their article," says Deborah Sweet, Cell Press Vice President of Editorial. "We see it as a way to acknowledge current authors who have worked to improve inclusion and diversity in science and encourage others to do more going forward. We also hope it will be a source of inspiration and confidence within the scientific community and beyond."

HOUSTON - (Jan. 7, 2021) - Rice University and Baylor College of Medicine researchers have found a way to mimic conditions in intestines, giving them a mechanical model for the real-time growth of bacterial infections.

In a new study, they demonstrate a lab tool that simplifies simulations of the human intestine, making it more practical to find treatments for diseases like infectious diarrhea.

The team led by bioengineer Jane Grande-Allen of Rice's Brown School of Engineering developed transparent millifluidic perfusion cassettes (mPCs) that are easy to fabricate and operate and compatible with common microscopic and biochemical analysis.

The cassettes allow even non-bioengineers to perform the kind of studies typically done with a 96-well petri dish, with the added benefit of fluid flow over seeded epithelial cells infected with bacteria. The cassettes also have micro-scale ports for input and output, allowing not only for fluid flow but also for sampling of the environment.

The study led by Grande-Allen, Rice's Isabel C. Cameron Professor of Bioengineering, and lead author and Rice and Baylor M.D./Ph.D. alumnus Reid Wilson, currently a resident at Oregon Health and Science University, appears in the Annals of Biomedical Engineering.

Replicating the complicated human gut is a challenge for researchers, said co-author Anthony Maresso, an associate professor of molecular virology and microbiology at Baylor. "Devices like these are often not user-friendly and practical for biologists like myself," he said. "This one was designed to be easy to use by scientists with less engineering know-how. The hope is it will lower barriers between engineers and medical researchers."

Grande-Allen said making a microfluidic system that doesn't leak can be technically challenging. "In this case, we needed to mimic the rate of fluid throughout the intestine that, especially compared to blood, is really slow," she said.

Molds of the devices, about the size of standard 96-well plates, were created with a 3D printer and used to form the clear polymer cassettes. The mPCs were seeded with human intestinal enteroids (HIEs), cultures that contain the major cell types native to the intestinal epithelium. When fluid containing bacteria flowed through, it formed a biofilm on the cells, a phenomenon not seen in static platforms.

Researchers can easily evaluate how well bacteria adhere to and infect the cells, both visually and by sampling through the ports on either end. Static plates allow bacteria to overgrow the cells and limit experiments to a few hours, but the slow flow through mPCs allows extended observation and more realistic results, Grande-Allen said.

Testing the device led the researchers to find the first direct evidence that aggregative adherence fimbriae, sticky appendages found on most infectious enteroaggregative Escherichia coli (EAEC), are necessary for the bacteria to form a biofilm.

"Our intention was to slowly flush the bacterial toxins to keep them from harming the cells," Grande-Allen said. "That allowed more cells to survive so we could watch the process of infection. We were completely surprised to see that it also dramatically changed the nature of the film that formed."

The devices also keep HIE cultures alive by replenishing oxygen and nutrients in the mPC chamber, allowing for better evaluation of realistic interactions between the cells and invading pathogens, Grande-Allen said.

She said mPCs will facilitate research on many such interactions. "This will allow the systematic examination of a lot of different combinations, good and bad, and how flow changes the dynamics of this environment," she said.

The COVID-19 pandemic has seen hardware developers clamouring to make 'open source' technology to support our frontline services. Their intentions have been honourable - an invitation to teams across the world to collaborate in developing essential equipment such as ventilators, thereby making the process of producing critical instruments more effective, both in time and cost.

In practice, however, most developers of hardware have shown little 'openness' in their sharing of designs, a fact lamented by a group of physicists from the University of Bath in the UK, in a paper published this week in The Design Journal.

According to the group, the pandemic has highlighted serious flaws in a system that forces research groups around the world to start from scratch every time a tweak needs to be made to an existing instrument, simply because they can't get their hands on the original designs.

"The term 'open source' is being applied to the final design of an instrument - and I'm pleased to say there has been a willingness during the pandemic to share these final designs - but the design process itself also needs to be open, something it isn't now," explains physics researcher Dr Julian Stirling.

Dr Stirling uses a fictional scenario to describe the problem with the current model of open design: "Alice, a university researcher, gets public funding to create a new type of microscope, the NewScope. She spends two years developing this instrument and eventually gets it working.

A paper is published describing the principles behind her microscope, but the designs themselves are sold to a company. From these designs, the company produces the Fab NewScope. The instrument is popular with scientists and they are happy to buy it.

"Then Bob, another researcher, has an idea that will improve the Fab NewScope, and he gets public funding to make these improvements. But he doesn't have access to the designs for the NewScope, so he has to start from scratch. Bob spends two years creating his improved NewScope, 18 months of which are spent redesigning the original microscope. He makes most of the same mistakes as Alice and goes down many of the same dead ends.

"Eventually, the NewScope+ is complete and a paper describing the principles behind it is published, but the designs themselves are sold to a company. Some time later, Charlie has a great idea for improving NewScope+ and so the whole process of reinventing the NewScope starts again."

Dr Stirling believes complete openness is needed at every point in the design process, not least because hardware designs are generally generated by academics from public funds.

"If the public is funding a generation of knowledge, they should have access to it," he says. "For a company to collect the data that comes from this public-funded knowledge and then patent it seems a bit perverse to me."

During the pandemic, many large tech companies - including Amazon, Microsoft and IBM - have signed the Open COVID pledge in recognition of the need for them to apply every tool at their disposal to halt the pandemic and treat those affected. The pledge is to make intellectual property available free of charge where it can be put to use in the fight against Covid-19. Dr Stirling welcomes this gesture of goodwill but he points out that the pledge is time-limited.

"So when the next pandemic hits, we'll be back in the same situation."

This year has seen a surge in the development of ventilators to treat those most severely affected by the Covid virus, and participants of the open-source pledge have showed willing in sharing their ventilator designs. However, as Dr Stirling explains, for legitimate legal and liability reasons, many pledge signatories have adopted an open-when-finished model, meaning their final design plans are open for others to use but their engineering efforts happen behind closed doors, so remote teams aren't able to collaborate in real time.

"There has been a proliferation of projects with teams across the world independently designing over a hundred mutually incompatible ventilators," said Dr Stirling. "This a huge amount of duplicated effort."

Dr Stirling believes the way forward is for universities to give more support to staff who wish to engage in open design. He also calls on governments to clarify the liability of individual teams contributing to open design, so researchers are more willing to share their ideas throughout the design process without fearing they could face a lawsuit if a manufacturer produces a malfunctioning product from their prototype design. He also highlights that the regulatory process may be a barrier for open-source designs, as a manufacturer is required to understand and explain why a device has been designed the way it has.

"Ultimately, it is a device not a design that gets certified. It has to be this way as you don't want anyone manufacturing a ventilator - you want accredited trained professionals," said Dr Stirling. "If a manufacturer only sees your final design, how can they understand it enough to take legal responsibility? With an open design process, transferring this knowledge should be possible."

For the past five years the same research group has worked on the design for an open-source microscope that is now being adapted by individuals and organisations around the world. The 3D printed OpenFlexure Microscope is highly customisable, meaning it be can adapted for laboratory, school and home use. The project has evolved such that every step of the design process is openly available.

"The more we work in the open, the less time we waste re-explaining the same issues to collaborators. This body of knowledge about the design is so important for our Tanzanian collaborators as they work to develop the design into a certified medical diagnostic device."

Whenever an organism develops and forms organs, a tumour creates metastases or the immune system becomes active in inflammation, cells migrate within the body. As they do, they interact with surrounding tissues which influence their function. The migrating cells react to biochemical signals, as well as to biophysical properties of their environment, for example whether a tissue is soft or stiff. Gaining detailed knowledge about such processes provides scientists with a basis for understanding medical conditions and developing treatment approaches.

A team of biologists and mathematicians at the Universities of Münster and Erlangen-Nürnberg has now developed a new method for analysing cell migration processes in living organisms. The researchers investigated how primordial germ cells whose mode of locomotion is similar to other migrating cell types, including cancer cells, behave in zebrafish embryos when deprived of their biochemical guidance cue. The team developed new software that makes it possible to merge three-dimensional microscopic images of multiple embryos in order to recognise patterns in the distribution of cells and thus highlight tissues that influence cell migration. With the help of the software, researchers determined domains that the cells either avoided, to which they responded by clustering, or in which they maintained their normal distribution. In this way, they identified a physical barrier at the border of the organism's future backbone where the cells changed their path. "We expect that our experimental approach and the newly developed tools will be of great benefit in research on developmental biology, cell biology and biomedicine," explains Prof Dr Erez Raz, a cell biologist and project director at the Center for Molecular Biology of Inflammation at Münster University. The study has been published in the journal "Science Advances".

Details on methods and results

For their investigations, the researchers made use of primordial germ cells in zebrafish embryos. Primordial germ cells are the precursors of sperm and egg cells and, during the development of many organisms, they migrate to the place where the reproductive organs form. Normally, these cells are guided by chemokines - i.e. attractants produced by surrounding cells that initiate signalling pathways by binding to receptors on the primordial germ cells. By genetically modifying the cells, the scientists deactivated the chemokine receptor Cxcr4b so that the cells remained motile but no longer migrated in a directional manner. "Our idea was that the distribution of the cells within the organism - when not being controlled by guidance cues - can provide clues as to which tissues influence cell migration, and then we can analyse the properties of these tissues," explains ?ukasz Truszkowski, one of the three lead authors of the study.

"To obtain statistically significant data on the spatial distribution of the migrating cells, we needed to study several hundred zebrafish embryos, because at the developmental stage at which the cells are actively migrating, a single embryo has only around 20 primordial germ cells," says Sargon Groß-Thebing, also a first author and, like his colleague, a PhD student in the graduate programme of the Cells in Motion Interfaculty Centre at the University of Münster. In order to digitally merge the three-dimensional data of multiple embryos, the biology researchers joined forces with a team led by the mathematician Prof Dr Martin Burger, who was also conducting research at the University of Münster at that time and is now continuing the collaboration from the University of Erlangen-Nürnberg. The team developed a new software tool that pools the data automatically and recognises patterns in the distribution of primordial germ cells. The challenge was to account for the varying sizes and shapes of the individual zebrafish embryos and their precise three-dimensional orientation in the microscope images.

The software named "Landscape" aligns the images captured from all the embryos with each other. "Based on a segmentation of the cell nuclei, we can estimate the shape of the embryos and correct for their size. Afterwards, we adjust the orientation of the organisms", says mathematician Dr Daniel Tenbrinck, the third lead author of the study. In doing so, a tissue in the midline of the embryos serves as a reference structure which is marked by a tissue-specific expression of the so-called green fluorescent protein (GFP). In technical jargon the whole process is called image registration. The scientists verified the reliability of their algorithms by capturing several images of the same embryo, manipulating them with respect to size and image orientation, and testing the ability of the software to correct for the manipulations. To evaluate the ability of the software to recognise cell-accumulation patterns, they used microscopic images of normally developing embryos, in which the migrating cells accumulate at a known specific location in the embryo. The researchers also demonstrated that the software can be applied to embryos of another experimental model, embryos of the fruit fly Drosophila, which have a shape that is different from that of zebrafish embryos.

Using the new method, the researchers analysed the distribution of 21,000 primordial germ cells in 900 zebrafish embryos. As expected, the cells lacking a chemokine receptor were distributed in a pattern that differs from that observed in normal embryos. However, the cells were distributed in a distinct pattern that could not be recognised by monitoring single embryos. For example, in the midline of the embryo, the cells were absent. The researchers investigated that region more closely and found it to function as a physical barrier for the cells. When the cells came in contact with this border, they changed the distribution of actin protein within them, which in turn led to a change of cell migration direction and movement away from the barrier. A deeper understanding of how cells respond to physical barriers may be relevant in metastatic cancer cells that invade neighbouring tissues and where this process may be disrupted.

Impaired intelligence, movement disorders and developmental delays are typical for a group of rare diseases that belong to GPI anchor deficiencies. Researchers from the University of Bonn and the Max Planck Institute for Molecular Genetics used genetic engineering methods to create a mouse that mimics these patients very well. Studies in this animal model suggest that in GPI anchor deficiencies, a gene mutation impairs the transmission of stimuli at the synapses in the brain. This may explain the impairments associated with the disease. The results are now published in the journal "Proceedings of the National Academy of Sciences of the United States of America (PNAS)".

Just as ships anchor to the seabed in storms and waves, GPI anchors (GPI = glycosylphosphatidylinositol) ensure that special proteins can hold on to the outside of living cells. If the GPI anchor does not function properly due to a gene mutation, the signal transmission and transport between cells are disrupted. "GPI anchor deficiencies comprise a group of rare diseases that primarily cause intellectual deficits and developmental delays," explains Prof. Dr. Peter Krawitz from the Institute for Genomic Statistics and Bioinformatics at the University Hospital Bonn, who started his research at the Charité - Universitätsmedizin Berlin and continued it at the University Hospital Bonn. About 20 to 30 genes can be altered in GPI anchor deficiency.

A mutation in the PIGV gene was found in most European patients. It encodes an enzyme that is of great importance for the synthesis of the GPI anchor. Using the CRISPR-Cas9 gene scissors, the researchers and their colleagues from the Max-Planck-Institute for Molecular Genetics in Berlin modified the PIGV gene in mice based on a model of the patients. "Extensive behavioral tests have shown that this mouse model very closely reflects the disease observed in humans," says Miguel Rodríguez de los Santos from the Institute for Medical Genetics and Human Genetics at the Charité. He has been working with Prof. Krawitz for years and is now continuing his research at the University Hospital Bonn.

How similar is the mouse to human patients?

The behavioral tests on the genetically modified mice were carried out in cooperation with scientists from the "Animal Outcome Core Facility" of the NeuroCure Cluster of Excellence at the Charité. The animals exhibited cognitive deficits, just like the patients. For example, they showed significantly worse spatial orientation than mice without this mutation and displayed altered social behavior. "They were particularly sociable, which is something we did not expect," reports Rodríguez de los Santos.

Research revealed that patients with GPI anchor deficiencies also exhibit this sociability in some cases. The PIGV-altered mice also displayed deviations in the day-night rhythm. "This symptom has so far not appeared to be relevant, but it is certainly described in patients," says Krawitz. "We now have the rare case that the large similarity of a mouse model allows us to infer and re-evaluate the symptoms of patients in reverse."

Dysregulations in the hippocampus

The researchers knew from preliminary studies that the hippocampus plays a major role in GPI anchor deficiencies. This brain structure, which resembles the shape of a seahorse, enables access to memories. The researchers studied microglia cells and subicular neurons from the hippocampus of genetically modified mice. Microglia cells are immune cells of the brain that fend off intruders. The subicular neurons are also responsible for memory retrieval. "Many genes in these two cell types were misregulated," says Rodríguez de los Santos. This could explain why the mice showed orientation problems in the tests.

Researchers at the Neuroscience Research Center of the Charité studied the electric fields in the hippocampus of genetically modified mice. "This showed that the transmission of stimuli at the synapses was impaired," says Krawitz. The results in the animal model suggest that the intellectual deficits found in the patients may be related to this synapse defect. Together with colleagues involved in translational epilepsy research at the University Hospital Bonn under Prof. Dr. Albert Becker, the researchers also discovered that the transgenic mice have an increased susceptibility to epilepsy. A further similarity with humans: Approximately 70 percent of patients with GPI anchor deficiencies develop epilepsy, again possibly caused by a synapse defect. Krawitz: "These observations and our mouse model open up completely new possibilities for further research in this direction."

CHAMPAIGN, Ill. -- In almost all successful advertising campaigns, an appeal to emotion sparks a call-to-action that motivates viewers to become consumers. But according to research from a University of Illinois Urbana-Champaign expert who studies consumer information-processing and memory, emotionally arousing advertisements may not always help improve consumers' immediate memory.

A new paper co-written by Hayden Noel, a clinical associate professor of business administration at the Gies College of Business at Illinois, finds that an ad's emotional arousal can have a negative effect on immediate memory but a positive effect on delayed memory - but only if the level of emotional arousal elicited by the ad is congruent with the ad's claims.

"Emotionally arousing appeals have long been used in advertising, but the impact of those appeals on consumers' memory has always been a bit unclear," Noel said. "So we examined the impact of different aspects of emotionally arousing ads on memory. Why did we focus on emotion? Well, in the majority of business-to-consumer ads that are crafted to drive sales, eliciting emotional activation, or arousal, plays a critical role."

In three experiments using print and video ads from different English-speaking countries, Noel and co-author Hila Riemer of Ben Gurion University of the Negev tested the moderating roles of retention time and the fit between the emotional arousal communicated in the ad and the ad claim. All experiments used combinations of low- and high-emotionally arousing ads.

The researchers found that when the level of emotional activation elicited by the ad doesn't fit the ad's claim, then the message conveyed ultimately doesn't stick in the consumer's mind.

"It's an examination of boundary conditions under which you can maximize the use of emotional appeals," Noel said. "And the role of retention time shows that low-arousal stimuli are better remembered in the short term, but high-arousal stimuli are better in the long term. But if the emotional arousal doesn't match with the ad's claim - if you're trying to promote the idea of a relaxing vacation with images of activity - then there's no effect. Ultimately, advertisers should use emotionally arousing messages only if they are interested in improving consumers' long-term memory of the ad, and avoid such messages if the goal is to enhance their short-term memory of the ad and its claims."

Emotional appeals continue to be essential tools for marketers, and emotionally arousing ads are generally the most successful type of advertisement, "leading to higher levels of profit relative to other ads that may appeal to intellect or rational thought," Noel said.

"Ads that pump up the emotional content really move the needle," he said. "Advertisers know that for an ad to be effective, it needs to be memorable, which accounts for how often they use high-intensity appeals. But over time, that's problematic. Creatives tend to fall in love with the quirky and funny ads that otherwise have little to do with the claims the ad is making. So emotionally arousing advertisements may not always be helpful or provide an advantage in remembering the ad's content.

"You don't want creatives to ignore fit or relevance at the expense of the emotion."

Noel said the research has practical implications for advertisers and marketers interested in developing suitable message strategies under various circumstances.

"In 2019, $239 billion was spent on advertising," he said. "In election years, we typically see an increase in advertising, but COVID-19 will put a damper on 2020's final tally. However, advertising will continue to be a very large and important industry in the U.S., which is home to some of the largest advertising spenders on the planet, as well as consumers who are routinely exposed to extensive advertising campaigns.

"All of those factors make it even more critical now to ensure advertising effectiveness, given that the market and budgets have shrunk so much because of the pandemic."

If you've ever been in an operating room where tools are used to simultaneously cut and cauterize human flesh, you know what surgical smoke is. The heat generated by these surgical tools produces vapors made up of aerosolized chemicals and substances that can be hazardous to health.

Two new papers led by researchers in the University of Illinois Chicago College of Nursing suggest that policies and laws mandating the evacuation of surgical smoke from operating rooms are the best way to reduce the negative health impacts on perioperative staff as well as surgical patients.

Surgical smoke poses a health risk to everyone in the operating room. The smoke can sometimes be thick enough to obscure vision, especially during longer operations where cauterizing tools are heavily used. Perioperative teams exposed to surgical smoke report twice as many respiratory health issues as the general public. The smoke can even contain viruses.

Definitively defining surgical smoke is the first step toward facilitating laws and policies to manage it, explained Rebecca Vortman, clinical assistant professor of population health nursing science in the UIC College of Nursing, and an author on both papers.

"Surgical smoke hasn't yet been clearly defined in the literature and is sometimes known by other names like 'plume,' 'bioaerosols' and 'lung-damaging dust,'" said Vortman. "While any member of the perioperative team knows exactly what surgical smoke is, it's important to have a definition so clinicians, leaders, researchers, and lawmakers can be on the same page."

Vortman and her colleagues identified research papers that used the term surgical smoke. They discovered 36 papers that met their search criteria. "We found that smoke was already a mature concept with relatively little variation in its definition among the papers we looked at," Vortman said.

In a paper in January in AORN Journal, Vortman and colleagues define surgical smoke as "a visible plume of aerosolized combustion byproducts produced by heat-generating surgical instruments. It consists of water vapor and gaseous substances; can carry toxic chemicals such as benzene, toluene and hydrogen cyanide; bacteria, viruses, and tumors; can obscure the surgical field; and can be inhaled. Surgical smoke has a distinctive noxious odor and can cause physical symptoms such as watery eyes and throat irritation."

In a November 2020 paper published in the journal, Nurse Leader focused on taking action to mitigate the harmful effects of surgical smoke, Vortman and co-author Janet Thorlton, clinical associate professor of population health nursing science at UIC note that perioperative professionals -- surgeons, anesthesiologists, nurses, scrub techs and others -- are exposed to the hazardous byproducts of surgical smoke each year, but precautions to evacuate the smoke from operating rooms are inconsistent. Only Rhode Island and Colorado have laws that mandate the evacuation of surgical smoke. Eight more states have recently introduced legislation, including Illinois.

"We hope to see Illinois be the next state to pass surgical smoke evacuation laws," Vortman said.

In the paper, the authors note that the cost of evacuation technology is relatively low. "These systems aren't super expensive and will vary depending on the size of the facility," Vortman said.

According to Vortman and Thorlton, the best chance for reducing the harmful effects of surgical smoke lie in getting states to pass legislation; otherwise, individual hospitals and centers are left to draft their own policies, and not all facilities in Illinois are evacuating surgical smoke.

"Laws that mandate the use of surgical smoke evacuations systems are the best way we can address the issue of surgical smoke; otherwise, perioperative teams and their patients will remain at risk," Vortman said.

A University of Arizona-led research team has found bands and stripes on the brown dwarf closest to Earth, hinting at the processes churning the brown dwarf's atmosphere from within.

Brown dwarfs are mysterious celestial objects that are not quite stars and not quite planets. They are about the size of Jupiter but typically dozens of times more massive. Still, they are less massive than the smallest stars, so their cores do not have enough pressure to fuse atoms the way stars do. They are hot when they form and gradually cool, glowing faintly and dimming slowly throughout their lives, making them hard to find. No telescope can clearly see the atmospheres of these objects.

"We wondered, do brown dwarfs look like Jupiter, with its regular belts and bands shaped by large, parallel, longitudinal jets, or will they be dominated by an ever-changing pattern of gigantic storms known as vortices like those found on Jupiter's poles?" said UArizona researcher Daniel Apai, an associate professor in the Department of Astronomy and Steward Observatory and the Lunar and Planetary Laboratory.

Apai is lead author of a new study published today in The Astrophysical Journal that seeks to answer that question using a novel technique.

He and his team found that brown dwarfs look strikingly similar to Jupiter. The patterns in the atmospheres reveal high-speed winds running parallel to to the brown drawfs' equators. These winds are mixing the atmospheres, redistributing heat that emerges from the brown dwarfs' hot interiors. Also, like Jupiter, vortices dominate the polar regions.

Some atmospheric models predicted this atmospheric pattern, Apai said, including models by the late Adam Showman, a UArizona Lunar and Planetary Laboratory professor and a leader in brown dwarf atmosphere models.

"Wind patterns and large-scale atmospheric circulation often have profound effects on planetary atmospheres, from Earth's climate to Jupiter's appearance, and now we know that such large-scale atmospheric jets also shape brown dwarf atmospheres," said Apai, whose co-authors on the paper include the Astronomical Observatory of Padua's Luigi Bedin and Domenico Nardiello, who is also affiliated with Laboratoire d'Astrophysique de Marseille in France.

"Knowing how the winds blow and redistribute heat in one of the best-studied and closest brown dwarfs helps us to understand the climates, temperature extremes and evolution of brown dwarfs in general," Apai said.

Apai's group at UArizona is a world leader in mapping the atmospheres of brown dwarfs and planets outside of our solar system using space telescopes and a new method.

The team used NASA's Transiting Exoplanet Survey Satellite, or TESS, space telescope to study the two brown dwarfs closest to Earth. At only 6 1/2 light-years away, the brown dwarfs are called Luhman 16 A and B. While both are about the same size as Jupiter, they are both more dense and therefore contain more mass. Luhman 16 A is about 34 times more massive than Jupiter, and Luhman 16 B - which was the main subject of Apai's study - is about 28 times more massive than Jupiter and about 1,500 degrees Fahrenheit hotter.

"The TESS space telescope, although designed to hunt for extrasolar planets, also provided this incredibly rich and exciting dataset on the closest brown dwarf to us," Apai said. "With advanced algorithms developed by members of our team, we were able to obtain very precise measurements of the brightness changes as the two brown dwarfs rotated. The brown dwarfs get brighter whenever brighter atmospheric regions turn into the visible hemisphere and darker when these rotate out of view."

Since the space telescope provides extremely precise measurements and it is not interrupted by daylight, the team collected more rotations than ever before, providing the most detailed view of a brown dwarf's atmospheric circulation.

"No telescope is large enough to provide detailed images of planets or brown dwarfs," Apai said. "But by measuring how the brightness of these rotating objects changes over time, it is possible to create crude maps of their atmospheres - a technique that, in the future, could also be used to map Earthlike planets in other solar systems that might otherwise be hard to see."

The researchers' results show that there is a lot of similarity between the atmospheric circulation of solar system planets and brown dwarfs. As a result, brown dwarfs can serve as more massive analogs of giant planets existing outside of our solar system in future studies.

"Our study provides a template for future studies of similar objects on how to explore - and even map - the atmospheres of brown dwarfs and giant extrasolar planets without the need for telescopes powerful enough to resolve them visually," Apai said.

Apai's team hopes to further explore the clouds, storm systems and circulation zones present in brown dwarfs and extrasolar planets to deepen our understanding of atmospheres beyond the solar system.

People taking immunosuppressive drugs to prevent organ transplant rejection or to treat inflammatory or autoimmune diseases do not fare worse than others on average when they are hospitalized with COVID-19, according to a study from researchers at the Johns Hopkins Bloomberg School of Public Health.

Estimates suggest that there are approximately 10 million immunocompromised people in the U.S. alone. Suppression of the immune system has been considered a potentially major risk factor for severe and fatal COVID-19 because it could allow the SARS-CoV-2 virus to spread unchecked in the body. At the same time, there have been anecdotal reports of immunosuppressed people who experienced only mild COVID-19 or even no symptoms at all--suggesting that immunosuppressive drugs might have a protective effect by preventing the inflammatory storm sometimes associated with severe COVID-19.

For their study, the researchers analyzed the anonymized records of 2,121 hospitalized COVID-19 patients seen at the Johns Hopkins Medicine medical system in Baltimore, MD, and Washington, D.C., from March 4 to August 29, 2020. They found that the COVID-19 patients who were immunosuppressed prior to their COVID-19 hospitalization did not, on average, have worse COVID-19 outcomes--such as longer length of stay in the hospital, death in hospital, or use of a ventilator--compared to their counterparts who were not immunosuppressed.

The study was published January 5 in Clinical Infectious Diseases.

"The COVID pandemic has released a wave of scientific investigations that examine who fares better and who fares worse with this new virus. We examined one important group of individuals, those on chronic immunosuppressive medicines such as people with a history of organ transplantation or rheumatologic disease and found some good news," says senior author G. Caleb Alexander, MD, a professor in the Bloomberg School's Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health and a practicing internist.

"There has been concern that immunosuppression might be an important risk factor for severe COVID-19, but reassuringly we found no sign of that," says study first author Kayte Andersen, a PhD candidate in the Bloomberg School's Department of Epidemiology.

To date, there have been 83 million COVID-19 cases confirmed around the world, and the Northern Hemisphere's recent shift to cold weather has brought the largest surge in new cases. Many health care systems are struggling to cope with this surge and are trying to allocate limited resources. Knowing which incoming patients are more likely to progress to severe COVID-19 helps them do that. But whether patients who are "immunocompromised" due to immune-suppressing drug treatment belong in the highest risk category has been a mystery.

The Johns Hopkins researchers found that 108, or about 5 percent, of the total COVID-19 cases hospitalized in the Baltimore/Washington Johns Hopkins medical network during the study period could be classified as immunosuppressed because they were taking an anti-inflammatory drug such as prednisone or an anti-rejection drug such as tacrolimus after organ transplant.

These results were obtained after using statistical methods to account for differences between the groups in factors such as age, sex, and non-COVID-19 disease burden that might have skewed the analysis. But even the researchers' raw, unadjusted analysis found no statistical association between worse COVID-19 outcomes and immunosuppression status.

The researchers are now following up with an analysis of a much larger set of data of nationwide COVID-19 cases, which should allow for more precise estimates, potentially including findings of different risks for different types of immunosuppression medications. However, they note, the findings in this smaller study suggest at the very least that immunosuppression does not appear to be associated with a major worsening of COVID-19 outcomes.

"At this point, there is no indication that people taking immunosuppressive drugs for other diagnosed conditions should be concerned that their medication increases their risk for severe COVID-19," Andersen says.

New research indicates adolescent offspring of the menacing sabre-toothed predator, Smilodon fatalis, were more momma's cubs than independent warriors.

A new study by scientists at the Royal Ontario Museum (ROM) and University of Toronto, published January 7, 2021 in iScience¸ documents a family group of the sabre-toothed cats whose remains were discovered in present-day Ecuador. By studying the fossils, collected for the ROM in the early 1960s, the scientists were able to show that while the supersized Ice Age cats grew quite quickly, they also appeared to stay with their mother for longer than some other large cats before forging their own path.

"This study started out as a simple description of previously unpublished fossils," says Ashley Reynolds, a graduate student based at the Royal Ontario Museum who led the study while completing her PhD research in Ecology & Evolutionary Biology at the University of Toronto. "But when we noticed the two lower jaws we were working on shared a type of tooth only found in about five percent of the Smilodon fatalis population, we knew the work was about to become much more interesting."

Encouraged by this new discovery, the researchers dug deeper and found that they were likely looking at three related individuals: one adult and two "teenaged" cats. What's more, they were able to determine that the younger cats were at least two years old at the time of their death, an age at which some living big cats, such as tigers, are already independent.

To support this conclusion, the team studied the preservation and formation of the Ecuadorian site (an area of study called taphonomy), based on historic collecting records and the suite of clues on the fossil bones themselves.

Historically, Smilodon specimens that have largely been collected from "predator trap" deposits, such as the famous La Brea Tar Pits in Los Angeles, California. But the Ecuador deposit, which formed on an ancient coastal plain, is likely derived from a catastrophic mass death event. This means that, unlike the "traps," all the fossils in the deposit died at the same time. As this preserves a snapshot of an ecosystem, fossils like these can provide new and unique insights into the behaviour of extinct species.

"The social lives of these iconic predators have been mysterious, in part because their concentration in tar seeps leaves so much room for interpretation" says Dr. Kevin Seymour, Assistant Curator of Vertebrate Paleontology at the ROM and a co-author of this study, "This historic assemblage of sabre-cat fossils from Ecuador was formed in a different way, allowing us to determine the two juveniles likely lived, and died, together--and were therefore probably siblings"

The fossils were collected from Coralito, Ecuador in 1961 by A. Gordon Edmund, who was curator of Vertebrate Palaeontology at the ROM from 1954-1990, and Roy R. Lemon, who was curator of Invertebrate Palaeontology from 1957-1969. Together, Edmund and Lemon collected tonnes of tar-soaked sediment which was later prepared at the ROM.

"These world-famous collections made 60 years ago have been studied for years, but a measure of their importance is that they continue to produce new insights into the lives of these extinct animals" says Dr. David Evans, Temerty Chair of Vertebrate Palaeontology at the Royal Ontario Museum and Reynolds's thesis supervisor.

Wearing cooling vests during a COVID-19 shift ensures that nurses experience less heat during their work. During their shifts, nurses wear protective clothing for three hours in a row, during which the temperature can rise to as much as 36 degrees. The cooling vests offer such effective cooling that they are now part of the standard work clothing for nurses in the COVID nursing departments at Radboud university medical center.

Due to the high level of contagiousness present with COVID-19, health care personnel have to work in protective clothing that is not or is barely ventilated. Good protective clothing is essential for their work, but the temperature under these suits can reach up to 36 degrees, leading to reduced comfort. The cooling vests - originally developed for elite athletes competing at the Tokyo Summer Olympic Games - were modified and prepared for use in COVID-related health care.

Cooling vests for top athletes

Thijs Eijsvogels, exercise physiologist and principal investigator, explains: "The elite-athlete cooling vests were not immediately suitable for this use because they were designed to cool aggressively before or after physical exertion. COVID care involves long-term use in which the vests are worn during the health care activities. The cooling power of the modified vest is lower, but it works longer."

Although the cooling vests were already in use, a study of their effects was being carried out at the same time. The Cooling for COVID-19 healthcare workers (COOLVID) study followed 17 nurses working in COVID care for two days: one day with and one day without a cooling vest. They wore the vest over their medical clothing but under their protective clothing. Study measurements included core temperature and heart rate, as well as subjective measurements such as comfort and heat sensation.

Less heat stress during a shift

The results, now published in Temperature, show that the participants' core temperature increased slightly but not enormously, even while the temperature under their protective clothing did. Therefore, the cooling vest had little effect on core temperature. However, the participants' heart rates were a few beats per minute lower on the days they wore the cooling vests. The biggest difference was in the subjective perceptions of the health care providers. Co-research Yannick de Korte: "Without a cooling vest, almost 90% of the nurses experienced discomfort and warmth. With a cooling vest, only 20-30% of the participants experienced this. They therefore perceived the conditions under which they have to do their work as more pleasant and comfortable. Virtually everyone said: 'With a cooling vest, I can work like I normally do without protective clothing'."