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Sophia Antipolis - 12 December 2020: Patients diagnosed with non-cardiac chest pain are reluctant to believe they do not have heart disease. A new study shows that explaining the test results convinces patients and reduces the likelihood of future chest pain. The research is presented at EACVI - Best of Imaging 2020, a scientific congress of the European Society of Cardiology (ESC).1

Chest pain is one of the most frequent causes of consults at the emergency department. This study refers to individuals who sought medical help for chest pain and had a computed tomography (CT) examination of the coronary arteries that showed normal arteries. "Previous studies have reported that these patients do not trust their examination results and still think they have heart disease," said study author Ms. Isabel Krohn, a radiographer at Haukeland University Hospital, Bergen, Norway.2

Patients with chest pain undergo several different types of tests to determine the cause. In 2018, around 600 outpatients with chest pain had CT scans at Haukeland University Hospital to examine the coronary arteries.3 These scans showed that approximately 200 of the 600 patients had healthy arteries - meaning no calcium deposits or narrowing of the arterial lumen. Studies in other centres have reported that chest pain has a non-cardiac origin in two-thirds of patients.4 Typical causes are indigestion or acid reflux, musculoskeletal disorders such as back pain or sore muscles between the ribs, and psychological issues like panic attacks and anxiety.

"I noticed that a number of patients who came for a coronary CT to diagnose their chest pain had previously undergone a coronary CT scan and other heart examinations which found no evidence of coronary disease," said Ms. Krohn. "Given the excellent prognostic value of coronary CT, I thought this information could be beneficial to this patient group."

The study included 92 patients with chest pain and normal results (i.e. no sign of coronary artery disease) on CT examination of the coronary arteries. The average age was 51 years and 63 (68%) were women. Patients were randomly allocated to the intervention or control group. The control group received usual care, meaning that around one week after the scans, their general practitioner or other referring doctor told them the result was normal.

The intervention group went through a three-part explanation with the radiographer. In the first part, participants received extended information about the CT examination they just went through - both orally and in a brochure written in understandable terms. This included the different reasons for chest pain, low probability of inaccurate results, and very low risk of a future heart attack when CT scans show healthy arteries. In the second part, participants were shown their own calcium score images to visually strengthen the message in the brochure. Lastly, the radiographer told patients their results were normal.

Both groups were followed-up at one month. Participants were asked to rate on a scale of 0 to 10 the degree to which they believed that the CT scan of their coronary arteries had found no heart disease (0 = no trust in the results; 10 = fully trust the results). Patients in the intervention group were significantly more likely to believe the test results compared to those in the control group.

Participants were also asked how often they currently experienced chest pain during their most strenuous level of activity compared to one month ago (slightly more often; about the same; slightly less often; much less often). Two-thirds (67%) of patients in the intervention group reported experiencing chest pain much less often compared to 38% of patients in the control group (p=0.042).

Ms. Krohn said it was important to deliver the education as a package and to personalise it. "I explained the information in the brochure and the image, and subtly asked questions to probe if the patient understood. That made it possible to customise the teaching. The sessions took five to 15 minutes depending on how much explanation each patient required. I think discussing the results with patients immediately after the test also helps them to accept the results."

She concluded: "This type of education is likely to become more common in years to come as a way of improving health literacy."

Experts have warned that a 'no deal' Brexit will result in the exclusion of the UK from the 24 European Reference Networks (ERNs) that were established to improve the care of patients bearing the lifelong burden of a rare disease, which require highly specialised diagnosis and treatment.

One in 17 UK citizens lives with a rare disease, which are defined as conditions that affect fewer than one in 2,000 people in the general population. A group of experts has written to The Lancet highlighting their concerns about the detrimental impact a no deal Brexit will have on these individuals.

"Rare diseases are rare, and experts are rarer still," said Dr Marc Tischkowitz from the University of Cambridge, who helped coordinate the letter. "European Reference Networks were set up because no single country has the expertise or resources to cover all of the known rare diseases, which number in the thousands. They've played a pivotal role in harnessing the collective knowledge across the continent and in developing sustainable healthcare to treat those affected."

The UK has been at the forefront of the creation and development of these virtual networks, which involve healthcare providers across Europe. As a result, write the experts, it has been able "to reap the benefits of closer collaboration with experts and patient advocates throughout Europe".

The ERNs have made it much easier to develop guidelines, create disease registries, build research collaborations, and create new education and training programmes. Crucially, they have directly improved patient care by establishing a pan-European platform that brings international experts together to advise on patient-specific complex problem and therapeutic options where insufficient expertise exists in one country alone.

Dr Tischkowitz added: "Leaving the EU without an agreement on UK participation in the Networks means we potentially write off years of progress made by UK clinicians, researchers and patient advocates, while also reducing access to clinical trials and funding. Most importantly, it will diminish our ability to provide the best care for the millions of children and adults with rare diseases and complex conditions in the future."

The letter has a total of 73 signatories, including 20 signatories each representing a patient support group and 53 signatories from senior clinicians and researchers who are currently members of a European Reference Network and who will be removed from the networks as of 1 January if no agreement is reached.

Allison Watson co-founded Ring20, a charity that supports people living with ring chromosome 20 Syndrome, an ultra-rare disease that affects her young adult son. She is also a co-lead for the EpiCARE ERN for rare and complex epilepsies.

"I have been hugely encouraged by the change that being part of an ERN can bring, for people like my son and many others living with ultra-rare diseases," said Watson. "I believe we would not have managed this working with just UK rare disease organisations."

Initiatives already delivered through the EpiCARE ERN include heightened awareness of rare epilepsies (including ring chromosome 20 Syndrome) across the 28 EpiCARE centres, long overdue Orphanet updates, increased information and education to healthcare practitioners and patient families in the form of leaflets and patient journeys, plus updated Clinical Practice Guidelines which aim to simplify and speed up diagnosis and improve care through understanding the unmet needs.

Watson added: "With thousands of rare diseases, many of them ultra-rare where only a handful of people living in the UK are affected, is it cost-effective or even possible that the UK can deliver effective services and research alone for these people alone? I believe only through collaboration with our European partners and others around the world can we truly meet the needs of the affected and ultimately improve their outcomes and quality of life."

Beverley Power, chair of CDH UK, the congenital diaphragmatic hernia support charity, says that one of the main barriers to research within the field of rare diseases is access to patients and patient data.

"Since joining the ERNICA European Reference Network, the access to patients and data has become broader for the UK and the rest of Europe," she explained. "It has enabled charities like CDH UK to better understand other healthcare settings and to be able to signpost newly diagnosed parents and patients with ongoing medical needs in a much better direction. It has also introduced new and innovative ways to collaborate in order to effect better outcomes and quality of life for patients and their families, which ultimately can potentially impact the economic implications of treating rare diseases in the UK and overseas."

According to the results of research led by the Complutense University of Madrid (UCM), one the various strategies deployed by the Leishmania parasite to avoid triggering the human immune system is to activate the SHP-1 protein.

The parasite does this by secreting a molecule capable of interacting with the Mincle receptor expressed by antigen-presenting dendritic cells that help induce T-lymphocytes to trigger an immune response.

"For dendritic cells to be able to present antigens to T-lymphocytes, they must also have been infected by the pathogen, or must acquire 'remains' from another infected cell. This latter process is called 'cross-antigen presentation' and requires specialised enzymatic machinery", explained Salvador Iborra, a researcher in the Department of Immunology, Ophthalmology and ENT at the UCM.

Besides helping to control physiological cell processes such as growth and proliferation, the newly discovered function of SHP-1 presented in Cell Reports is to limit the capacity of dendritic cells to cross-present antigens in order to prevent autoimmune disorders, i.e. to prevent lymphocytes from attacking healthy body tissue. The parasite masks its presence by activating this aspect of immune response control.

SHP-1 inhibitors, key to vaccination

This study, conducted jointly with the Spanish National Centre for Cardiovascular Research (Spanish initials: CNIC) and the Champalimaud Centre for the Unknown in Lisbon, was conducted using genetically modified mice as an experimental model that lacks the Mincle receptor or the SHP-1 enzyme in dendritic cells.

"In addition, we have been able to test the usefulness of chemical compounds that block SHP-1 activation, such as NSC-87877. Among our results, we have shown that vaccination with dendritic cells treated with this inhibitor and loaded with parasite lysates induced a response in cytotoxic lymphocytes that protected the mice against infection", Iborra reported.

The UCM researcher added that SHP-1 not only inhibits cross-presentation of Leishmania antigens, but also of virus-infected and irradiated cells; consequently, "SHP-1 is a potential target that could limit the effectiveness of a vaccine based on inactivated viruses or parasites and intended to induce a cellular response mediated by cytotoxic lymphocytes".

Although vaccines against canine leishmaniasis exist for dogs, which act as reservoirs of the disease, there are still no vaccines against the disease in humans, so "any advance in our knowledge of immunity to the parasite is useful for the development of an effective vaccine", Iborra concluded.

Balancing proliferation and differentiation in a developing organ are a complex act, especially when these two processes occur at the same time in the same space. The retina is an important interface between the body and the external world: it sits at the back of our eyes and receives and encodes all the visual information, so that our brain can continuously process the pictures of what the world has to offer. "For attaining this function, the retina requires a precise balance of different types of neurons organised in several interconnected layers, each receiving, pooling or filtering the visual input", explains Elisa Nerli, first author of the study and researcher at Instituto Gulbenkian de Ciência. "The formation of the different neurons in the correct numbers and proportions is ultimately ensured by balancing cellular proliferation and differentiation during development".

Studying the development of the zebrafish retina, the team led by Caren Norden, principal investigator at the Instituto Gulbenkian de Ciência, discovered that this balancing depends on asymmetric divisions of progenitor cells on their way to making functional neurons. "We further found"- Nerli continues - "that the molecular regulation of this process relies on the Notch signalling pathway, since its inhibition interferes with the division asymmetry. We were able to observe that Notch is asymmetrically distributed during cells division. The cell that inherits Notch signalling will continue to proliferate, whereas the other cell will enter a neurogenic lineage".

Overall, this study adds new perspectives to the fundamental understanding of how cellular decisions of proliferation or differentiation can regulate the development of the nervous system. Understanding how the balance between these processes is determined and maintained is important for a better understanding of brain development, in health and in disease.

Sophia Antipolis - 11 December 2020: Climbing four flights of stairs in less than a minute indicates good heart health, according to research presented at EACVI - Best of Imaging 2020, a scientific congress of the European Society of Cardiology (ESC).1

"The stairs test is an easy way to check your heart health," said study author Dr. Jesús Peteiro, a cardiologist at University Hospital A Coruña, Spain. "If it takes you more than one-and-a-half minutes to ascend four flights of stairs, your health is suboptimal, and it would be a good idea to consult a doctor."

This study was conducted to examine the relationship between a daily activity - i.e. climbing stairs - and the results obtained from exercise testing in a laboratory. "The idea was to find a simple and inexpensive method of assessing heart health," said Dr. Peteiro. "This can help physicians triage patients for more extensive examinations."

The study included 165 symptomatic patients referred for exercise testing because of known or suspected coronary artery disease. Symptoms included chest pain or shortness of breath during exertion. Participants walked or ran on a treadmill, gradually increasing the intensity, and continuing until exhaustion. Exercise capacity was measured as metabolic equivalents (METs).2 After resting for 15 to 20 minutes, patients were asked to climb four flights of stairs (60 stairs) at a fast pace without stopping, but also without running, and the time was recorded.

The researchers analysed the relationship between METs achieved during exercise testing and the time it took to climb four flights of stairs. Patients who climbed the stairs in less than 40-45 seconds achieved more than 9-10 METs. Previous studies have shown that 10 METs during an exercise test is linked with a low mortality rate (1% or less per year, or 10% in 10 years). In contrast, patients who took 1.5 minutes or longer to climb the stairs achieved less than 8 METs, which translates to a mortality rate of 2-4% per year, or 30% in 10 years.

During the treadmill test, the researchers also generated images of the heart to assess its function during exercise - if the heart works normally during exercise this indicates a low likelihood of coronary artery disease. They then compared these findings to the results of the stair climb. Some 58% of patients who completed the stair climb in more than 1.5 minutes had abnormal heart function during the treadmill examination. In contrast, just 32% of those who climbed the stairs in less than one minute had abnormal heart function during the treadmill examination.

Dr. Peteiro noted that the correlation between the stairs time and exercise capacity (i.e. METs) would be similar in the general population. But the corresponding mortality rates and heart function by imaging would be more favourable than for patients with symptoms and suspected or confirmed coronary artery disease.

A deficiency in Vitamin D on the mother's side could explain why Autism spectrum disorder is three times more common in boys, say researchers from The University of Queensland.

In their latest study, Professor Darryl Eyles and Dr Asad Ali from UQ's Queensland Brain Institute found vitamin D deficiency during pregnancy caused an increase in testosterone in the developing brain of male rats.

"The biological cause of Autism spectrum disorder (ASD) is unknown but we have shown that one of the many risk factors--low vitamin D in mothers--causes an increase in testosterone in the brain of the male foetuses, as well as the maternal blood and amniotic fluid," Professor Eyles said.

"In addition to its role in calcium absorption, vitamin D is crucial to many developmental processes.

"Our research also showed that in vitamin D-deficient male foetuses, an enzyme which breaks down testosterone was silenced and could be contributing to the presence of high testosterone levels."

Professor Eyles' previous research has shown that vitamin D plays a critical role in brain development and that that giving vitamin D supplements to mice during pregnancy completely prevented ASD-like traits in their offspring.

Co-author Dr Ali said that excessive exposure of the developing brain to sex hormones like testosterone was thought to be an underlying cause of ASD, but the reasons remained unclear.

"Vitamin D is involved in pathways controlling many sex hormones," Dr Ali said.

"When the rat mothers were fed a low vitamin D diet, it caused male foetal brains to have high levels of exposure to testosterone."

Professor Eyles said the study was the first to show that a known risk factor for ASD alters testosterone in both the foetal brain and the mother's blood -- one possible contributor to why ASD is more prevalent in males.

"We have only studied one risk factor for ASD -- vitamin D deficiency during development -- our next step is to look at other possible risk factors, such as maternal stress and hypoxia - lack of oxygen - and see if they have the same effect," he said.

Photoluminescence (PL) is light emission from a substance after the absorption of photons stimulated by temperature, electricity, pressure, or chemistry doping. An international team of scientists led by Dr. Wenge Yang from Center for High Pressure Science &Technology Advanced Research (HPSTAR) presents a strong tricolor PL achieved in non-PL pyrochlore Ho2Sn2O7 through high pressure treatment. Interestingly the PL can be much enhanced after pressure release and recovered to ambient conditions. Their study is published in the recent issue of Physical Review Letters.

Photoluminescence materials are widely used in the fields of biochemistry and medicine, which can be used as lasers, anti-counterfeiting labels and sensors. Rare earth pyrochlore has attracted extensive attention for its potential optical properties, stable structure and chemical properties. The luminescence character of pyrochlore mainly comes from rare earth ions. It has the potential of application in extreme conditions because the emission of pyrochlore is insensitive to the external environment.

"Pressure has been widely used as a unique tool to tune the PL properties of materials, such as hybride perovskites", said Dr. Wenge Yang. "So what will happen to apply pressure to the non-PL materials like the structural stable pyrochlore Ho2Sn2O7, a typical materials used in nuclear reactor or waste immobilization."

When Ho2Sn2O7 is compressed above ~31 GPa, the non-PL Ho2Sn2O7 shows tricolor PL, spanning from green to red to near infrared range with green PL dominate. More interesting, the tricoloar PL is not only retained but also largely enhanced (two times enhanced in green and near infrared PL and four times in red PL) and with red PL dominant after pressure quench. As reference, the recovered Ho2Sn2O7 with pressure treated below 31 GPa does not show any PL at all.

"Actually pressure has induced PL in a lot of materials, however the pressure-induced PL in most materials will disappear after pressure release," said Dr. Yongsheng Zhao, the leading author of the study. "The tricolor PL in Ho2Sn2O7 can be recovered to ambient condition and largely enhancement with pressure release is really exciting behavior as this materials might have potential application for the pressure threshold sensor on the extreme condition history."

Then what makes the colorful PL in the compressed Ho2Sn2O7?

To further probe the unique PL induced in Ho2Sn2O7, the team carried out X-ray diffraction and X-ray absorption measurements to track the structures during compression in the sample. The X-ray diffractions show that at the pressure where PL emerged, the sample also went through a crystal structure transformation. And upon decompression, the material changed to amorphous state.

"Our further analysis on crystal and electronic structure revealed that the centrosymmetric site symmetry of Ho3+ change to non-centrosymmetric during structural change at high pressure," explained Dr. Yongsheng Zhao. "This enhanced the hybridization of Ho3+ electron orbitals and thus brings in the emerging of tricolor PL. And the enhanced PL in amorphous state comes from the energy-exchange between the two Ho3+, which stimulates one more emission center in the quenched sample."

"Our study highlights the pressure effect on the local ion site symmetry, which largely turns and  enables the new emission center from traditionally less than 1% doping level of RE ion materials to a regular site RE (18% in this case). The new physics principle could be potentially used for many other types of system," added Dr. Yang.

The Last interglacial period was the last warm period before our present Holocene age and dates back some 129,000 to 116,000 years ago. It is more and more in the focus of research interest, as this period could be used as a possible test bed for warmer conditions in the future. A look at the climate evolution during the last interglacial may allow us to draw conclusions about how the present climate will change in a warming world. The last interglacial was significantly warmer and also climatically unstable: Sea level was about 6 to 9 metres higher than today, the Greenland ice sheet was much reduced, and global temperatures were about 2 degrees higher. However, the question of what the Alps looked like at that time remains open. "There are several studies during this timeframe from the foreland of the Alps, based mainly on analyses of organic material such as pollen. But now we add two aspects that were previously not available: On the one hand a continuous record from a mountain site within the Alps with an very precise chronology. And on the other hand a quantitative reconstruction of temperatures over the full duration of the Last Interglacial period," explains Paul Wilcox. The geologist is a post-doc in the Quaternary research group at the University of Innsbruck and is the lead author of the study now published in Nature Research's Open Access journal Communications Earth and Environment.

Alpine region particularly affected

Stalagmites from two caves in the Melchsee-Frutt-region in the Swiss Alps provide the long-awaited data basis for the last interglacial in the Alpine region. "We were really lucky to find dripstones that is so well preserved and allow a continuous reconstruction of the temperatures. You don't often find something like this," says Wilcox. The field work that led to the discovery of these unique samples was a collaborative effort between the Innsbruck team and speleologist Martin Trüssel from the Foundation Naturerbe Karst und Höhlen Obwalden in Switzerland. Most of the analyses were carried out at the Institute of Geology, which has long-term experience in the study of fluid inclusions, a method that is constantly being developed further by researchers like Yuri Dublyansky. "We extract tiny amounts of water that is trapped in the crystals of the cave minerals. We measure the isotopic properties of this old precipitation water that allows us to make quantitative conclusions about the temperature many thousands of years ago. However, this requires sample material containing sufficient trace water - and that is rare", adds Christoph Spötl who leads this project funded by the Austrian Science Fund (FWF). The results show that the last interglacial was much more pronounced for higher altitudes than for lower ones. "Temperatures in the high alpine region were up to 4 degrees higher than today. These are significantly higher values than those known for lower altitudes", says Paul Wilcox. The geologists conclude that the effect of an altitude-dependent warming during the last interglacial was evident, and that stronger warming was therefore observed at high altitudes such as the Alpine region. Moreover, a climatic instability, whose cause is still not completely understood, led to an abrupt cooling event 125,500 years ago: "But even with this development, temperatures in the high alpine region still remained 2 degrees above today's temperatures," adds Wilcox.

The team agrees that this is hardly a good news for the future of the climate in the Alps: "We cannot directly compare the last interglacial with the present Holocene , as orbital parameters were different during these two most recent warm periods. However, these findings are alarming in the light of the acceleration of global-scale warming due to anthropogenic greenhouse gas emissions and mountain regions should be prepared for an even greater temperature increase."

In a new study, researchers at Uppsala University have been able to show differences in how Rituximab, a monoclonal antibody drug, interacts with the blood of healthy individuals compared to patients with chronic lymphocytic leukaemia. This has awakened hopes that this analysis method could pave the way for important breakthroughs in immunotherapy research and treatment.

Immunotherapy - utilising the body's own immune system to combat tumour cells - is an area in which rapid progress is being made. Many new treatments are helping to increase survival rates among cancer patients, but more effective tools are still needed to predict how these drugs will affect an individual's immune system. In a new study at Uppsala University, researchers compared what happens when Rituximab monoclonal antibodies interact with the blood of healthy individuals and of patients with the disease that the monoclonal antibodies are intended to treat. The results showed that the immunological activation markers differ between the groups - an observation that could enable new scientific breakthroughs.

"Rituximab is used to treat a range of diseases in which B cells are malignant or growing out of control. The monoclonal antibody binds to the CD20 protein expressed on the B cell and draws natural killer (NK) cells, a part of the immune system, to the site which then help to kill the B cell. The action of Rituximab is specific with few side effects, but when it binds to B cells it can also activate proteins in our blood that signal danger. This can cause Cytokine Release Syndrome (CSR) - normally with mild symptoms in the form of nausea and fever, but it can also become life-threatening. This unpredictability is a major challenge, but the results from our study show that our analysis method can provide patient-specific information and thus become an important tool for the whole immunotherapy field if we are able to understand the individual's specific response to a given antibody-based therapy," says Sara Mangsbo of the Department of Pharmaceutical Biosciences.

In their study, the researchers used a complete human whole blood model to analyse the immune response, and the efficacy and toxicity of treatment with Rituximab. In healthy individuals, only a reduction in the number of B cells was observed. In patients with chronic lymphocytic leukaemia, however, a variable reduction in the number of B cells as well as CRS were observed - except in one patient who had no NK cells. The results increase our understanding of what happens when Rituximab encounters blood from patients with chronic lymphoid leukaemia.

"Immunotherapy is being used more and more frequently to treat various kinds of cancer, but we need better methods to predict the effect and risk of side effects in individual treatment recipients before the start of treatment. Analysis tools such as this potentially have great value for both the healthcare system and patients," says Mattias Mattsson, consultant physician at the Uppsala University Hospital Haematology Clinic and co-author of the article.

The use of a human whole blood model means that the analysis takes into account all the immune cells circulating in the blood, as well as the many proteins and metabolites present in the blood serum. The method thus adds a new dimension to the analysis results that to date has not been reliably captured by the available methods, which are based on purified cells or serum components.

"Understanding the mechanisms and resistance associated with monoclonal antibody-based drugs requires physiologically relevant tools and methods. Here, in collaboration with Uppsala University, we have studied how the blood loop can be used for the immuno-profiling of blood and drugs. The results show that there is a disease-specific immune response when blood and drugs interact. This indicates that the blood loop can be used for individual treatment and preclinical studies to identify and understand the toxicity risks for monoclonal antibody-based drug candidates," says Mark Cragg, co-author and Professor of Experimental Cancer Research at the University of Southampton.

The method also involves a further step in being able to study monoclonal antibodies without the need for animal studies. The study is based on the group's previous work, which was carried out with financial support from the Swedish Research Council's funding for 3R projects, which aim to replace, reduce and refine animal experiments.

"Our results show a clear way forward. More extensive studies in specific patient groups are needed now to increase our understanding of how individual immune systems will react to both Rituximab and other monoclonal antibodies. In the long term, we hope to take the method all the way to clinical trials as well as to the healthcare system in order to provide a better answer to which patients will respond well to specific immunotherapy treatments," says Sara Mangsbo.

The tail feathers of the peacock, the enormous horn of male rhinoceros beetles, the protruding antlers of some deer: In nature, there are countless examples of features which at first sight may only have disadvantages for their owners. After all, it is more difficult to hide from a predator when one is wearing a colourful plumage, and large antlers do not make escaping in the forest any easier. As a rule, it is the male that has such characteristics.

The evolution of male ornaments has therefore been fascinating to biologists since ever. Already Charles Darwin wondered of how such exaggerated, energy-consuming and in principle harmful structures could have been created by natural selection. Using the example of the swordtail fish (Xiphophorus hellerii), he explained his theory of sexual selection. Darwin's basic idea: If females prefer to mate with the carriers of striking ornamental traits, such traits might become established in the course of evolution even though they are likely to be harmful for their owners.

Publication in Current Biology

Scientists from Würzburg, Constance and the USA have now been successful in finding the genetic bases of this evolutionary model in Xiphophorus, also well known to aquarists as one of their favourite pets. Among all eligible genes, the researchers identified some that are responsible for the development of the corresponding ornamental trait in this species of fish. Their findings also suggest that in the swordtail a gene that is actually important for neuronal processes in the brain has taken on an additional new function during evolution.

The scientists published their findings in the journal Current Biology. Manfred Schartl, a senior professor at the Department of Developmental Biochemistry at the University of Würzburg, is the lead author of the study. The project was co-initiated by the evolutionary biologist Axel Meyer from Constance University with whom the Würzburg researchers have been investigating this phenomenon for many years. For more than two decades, the two laboratories at the Universities of Würzburg and Constance have jointly researched the genetic basis of the sword. The current study has now brought the scientists a big step closer to understanding the genetic basis of the extended caudal fin of swordtails.

"In several species of the genus Xiphophorus, the males carry a so-called 'sword', a striking extension of the lower edge of the tail fin, which is yellow, orange or red in colour and surrounded by a dark black margin," explains Manfred Schartl. The sword develops during puberty and can be as long as the fish itself in some species. This should actually be a disadvantage, because the conspicuous body ornament attracts predators on the one hand and on the other hand makes escaping more difficult as it reduces swimming performance. However, the females of Xiphophorus hellerii and several related species prefer to mate with males that carry a long sword - males with shorter swords literally lose out in this competition.

Gradually excluding the suspects

The genetic bases of this extension of the caudal fin in Xiphophorus have previously been unknown. However, knowledge of this phenomenon is necessary to test hypotheses about the role of sexual selection at the molecular genetic level.

The scientists took a gradual approach to pinpointing the responsible genes. They started by looking for all genes that are specifically active in the sword developing part of the tail fin, but not in fin regions that do not form a sword. "This process resulted in a set of 329 differentially expressed genes in all sword transcriptomes," said Schartl, describing the result. The term transcriptome refers to the entirety of genes that are transcribed in a cell or tissue at a certain point in time, i.e. are active.

The consideration that genes responsible for sword formation are only expressed in males led to a significant reduction in the number of suspects in the next step. The scientists created transcriptomes of cells from specific areas of the caudal fins in both male and female specimens. If the females showed comparable activities to males, it was clear that these genes are not among the sought-after candidates. After this process, 255 of the original 329 genes remained.

"Interestingly, this comparison revealed that a spatial pattern of five transcription factors - Zic1, Hoxb13a, Six2a, Tbx3a and Pax9 - is responsible for organising the preconditions in the caudal fin for the development of a sword, and that this pattern is also present in females," said Schartl.

Backcrossings provide important information

Genetic mapping came next to further reduce the still high number of 255 candidate genes. For this purpose, swordtail males were crossed with females of a related species whose males had lost their sword in the course of evolution. The male descendants from this mating have swords of different lengths due to the mixing of the parental genomes depending on their random genetic make-up. Sequencing those genomes using special high-throughput techniques then made it possible to correlate certain chromosome segments with sword formation, and those with the list of candidate genes. Finally, three genes were left over.

Spotlight on one main suspect

The gene with the scientific name kcnh8 proved to be crucial for the development of the male characteristic. "This gene codes for a potassium channel - a group of channels that play an important role in particular in the transmission and processing of stimuli in the nervous system," said Schartl. The new findings point to a gene with a primary function in neural cells that was recruited during evolution for developing the male sword about three to five million years ago, i.e. early during the diversification of swordtail fishes. The new function is not due to structural changes within the gene and its product, but to changes in gene regulation.

Indeed, experiments show that kcnh8 in the sword during normal development and after treatment with male hormones is highly upregulated in the region where the sword is organised. In all other fin areas of the males and in female caudal fins it is only weakly expressed. In addition, further studies show a direct correlation between the level of gene expression of kcnh8 and the length of swords.

Support of botanists of the JMU

Schartl and Meyer received support for their research on potassium channels from an expected source: botanists from the University of Würzburg. Rainer Hedrich, who heads the Department of Molecular Plant Physiology and Biophysics, and his colleague, Professor Dietmar Geiger, have been studying potassium channels for a long time. The techniques they used - special patch-clamping methods - could be easily transferred from plants to the fish.

Potassium channels transport electrically charged particles and thus cause changes in the membrane potential in cells and tissues. According to the scientists, such channels create tissue-wide bioelectric gradients which affect the overall structure of the cellular microenvironment. Similar phenomena have been observed in the proliferation of cancer cells and have led to hypotheses about the importance of ion gradients for growth control. The role of Kcnh8 in the development of the ventral caudal outgrowth in male swordtails is in good agreement with these models.

Mass extinctions of land-dwelling animals--including amphibians, reptiles, mammals, and birds--follow a cycle of about 27 million years, coinciding with previously reported mass extinctions of ocean life, according to a new analysis published in the journal Historical Biology.

The study also finds that these mass extinctions align with major asteroid impacts and devastating volcanic outpourings of lava called flood-basalt eruptions--providing potential causes for why the extinctions occurred.

"It seems that large-body impacts and the pulses of internal Earth activity that create flood-basalt volcanism may be marching to the same 27-million-year drumbeat as the extinctions, perhaps paced by our orbit in the Galaxy," said Michael Rampino, a professor in New York University's Department of Biology and the study's lead author.

Sixty-six million years ago, 70 percent of all species on land and in the seas, including the dinosaurs, suddenly went extinct, in the disastrous aftermath of the collision of a large asteroid or comet with the Earth. Subsequently, paleontologists discovered that such mass extinctions of marine life, in which up to 90 percent of species disappeared, were not random events, but seemed to come in a 26-million-year cycle.

In their Historical Biology study, Rampino and co-authors Ken Caldeira of the Carnegie Institution for Science and Yuhong Zhu of NYU's Center for Data Science, examined the record of mass extinctions of land-dwelling animals and concluded that they coincided with the extinctions of ocean life. They also performed new statistical analyses of the extinctions of land species and demonstrated that those events followed a similar cycle of about 27.5 million years.

What could be causing the periodic mass extinctions on land and in the seas? Mass extinctions are not the only events occurring in cycles: the ages of impact craters--created by asteroids and comets crashing to the Earth's surface--also follow a cycle aligning with the extinction cycle.

Astrophysicists hypothesize that periodic comet showers occur in the Solar System every 26 to 30 million years, producing cyclical impacts and resulting in periodic mass extinctions. The Sun and planets cycle through the crowded mid-plane of the Milky Way Galaxy about every 30 million years. During those times, comet showers are possible, leading to large impacts on the Earth. The impacts can create conditions that would stress and potentially kill off land and marine life, including widespread dark and cold, wildfires, acid rain, and ozone depletion.

"These new findings of coinciding, sudden mass extinctions on land and in the oceans, and of the common 26- to 27-million-year cycle, lend credence to the idea of periodic global catastrophic events as the triggers for the extinctions," said Rampino. "In fact, three of the mass annihilations of species on land and in the sea are already known to have occurred at the same times as the three largest impacts of the last 250 million years, each capable of causing a global disaster and resulting mass extinctions."

The researchers were surprised to find another possible explanation beyond asteroids for mass extinctions: flood-basalt eruptions, or giant volcanic eruptions that cover vast areas with lava. All eight of the coinciding mass die-offs on land and in the oceans matched times of flood-basalt eruptions. These eruptions also would have created severe conditions for life, including brief periods of intense cold, acid rain, and ozone destruction and increased radiation; longer term, eruptions could lead to lethal greenhouse heating and more acid and less oxygen in the ocean.

"The global mass extinctions were apparently caused by the largest cataclysmic impacts and massive volcanism, perhaps sometimes working in concert," added Rampino.

Sexual health charity Brook has adopted these latest research findings in its teaching methods

A new nuanced way of teaching young people about consent that is based on their real-life experiences helps them develop a better understanding of sexual rights and ethics, a new study suggests.

By teaching consent using this continuum style approach, rather than by the legal definition of 'consent' alone, young people are able to talk more openly and honestly in a way that relates to their own sexual and relationship experiences.

These latest results are published today in the peer-reviewed journal, Sex Education.

Carried out in partnership with Brook, the UK's largest sexual health and wellbeing charity for young people, the findings follow an innovative two-year project which tested the teaching method out during workshops across seven educational institutes including a university, two youth clubs and an all-girls comprehensive school.

The findings were deemed significant enough for resources, including the continuum, to now being used by Brook in its teacher training.

Dr Whittington, who is now based at the Manchester Centre for Youth Studies at Manchester Metropolitan University but was working at the University of Sussex when the study was conducted, led the research.

She says: "We discovered that while young people were able to explain the legal definition of consent, they found this awkward and restrictive when applied to real-world scenarios. It sometimes led to contradictory views and double standards based on gender.

"So, framing consent simply in this 'black and white' way does not match up with young people's sexual and relationship experiences.

"While a legal framework may feel simpler to teach, it does not give young people techniques or ideas for encouraging good communication and feeling informed and empowered."

To encourage the 103 young adults, aged between 13 and 25, who took part in the project, Dr Whittington used various creative methods and activities, including cake decorating, interactive games and scenario-based discussions. These group activities generated various forms of data from which Whittington was able to draw out several common themes. The activities have since been used with hundreds of young people in university and school teaching.

She found that by using a continuum to explore consent, it offered young people a way of viewing sex and consent that is not rigid, and which mirrored their own experiences.

"We found that using continuums and diverse scenarios enabled the young people to think critically about different ways of doing and negotiating consent enabling wider conversations that promote positive sexual ethics," she said.

"Scenarios allowed people to explore gendered double standards, societal expectations and the ways in which age can impact people's ability to negotiate consent.

"The device of the continuum offered a way of speaking about and viewing sex, consent and violation that is not absolute - which mirrored the ways young people spoke about the topic."

Based on a feminist concept to consider the educational possibilities of teaching and talking about sexual consent as a continuum rather than a simple binary between active consent and rape, the sexual consent continuum developed by Whittington, and colleagues at Brook, comprises four sections as defined by young people varying from rape to where consent is explicitly negotiated.

Following the project, Brook has introduced the teaching methodology into its free digital training. The overwhelming majority of participants who have been trained so far have found it useful and said they would plan to use it in their teaching as a result.

A secondary school teacher participant said: "I have solidified my knowledge of 'real-life' consent, particularly by using the Consent Continuum. It's useful to have discussions with young people about situations which are more akin to what they would experience in real life."

A joint research led by City University of Hong Kong (CityU) has built an ultralow-power consumption artificial visual system to mimic the human brain, which successfully performed data-intensive cognitive tasks. Their experiment results could provide a promising device system for the next generation of artificial intelligence (AI) applications.

The research team is led by Professor Johnny Chung-yin Ho, Associate Head and Professor of the Department of Materials Science and Engineering (MSE) at CityU. Their findings have been published in the scientific journal Science Advances, titled "Artificial visual system enabled by quasi-two-dimensional electron gases in oxide superlattice nanowires".

As the advances in semiconductor technologies used in digital computing are showing signs of stagnation, the neuromorphic (brain-like) computing systems have been regarded as one of the alternatives in future. Scientists have been trying to develop the next generation of advanced AI computers which can be as lightweight, energy-efficient and adaptable as the human brain.

"Unfortunately, effectively emulating the brain's neuroplasticity - the ability to change its neural network connections or re-wire itself - in existing artificial synapses through an ultralow-power manner is still challenging," said Professor Ho.

Enhancing energy efficiency of artificial synapses

Artificial synapse is an artificial version of synapse - the gap across which the two neurons pass through electrical signals to communicate with each other in the brain. It is a device that mimics the brain's efficient neural signal transmission and memory formation process.

To enhance the energy efficiency of the artificial synapses, Professor Ho's research team has introduced quasi-two-dimensional electron gases (quasi-2DEGs) into artificial neuromorphic systems for the first time. By utilising oxide superlattice nanowires - a kind of semiconductor with intriguing electrical properties - developed by them, they have designed the quasi-2DEG photonic synaptic devices which have achieved a record-low energy consumption down to sub-femtojoule (0.7fJ) per synaptic event. It means a decrease of 93% energy consumption when compared with synapses in the human brain.

"Our experiments have demonstrated that the artificial visual system based on our photonic synapses could simultaneously perform light detection, brain-like processing and memory functions in an ultralow-power manner. We believe our findings can provide a promising strategy to build artificial neuromorphic systems for applications in bionic devices, electronic eyes, and multifunctional robotics in future," said Professor Ho.

Resembling conductance change in synapses

He explained that a two-dimensional electron gas occurs when electrons are confined to a two-dimensional interface between two different materials. Since there are no electron-electron interactions and electron-ion interactions, the electrons move freely in the interface.

Upon exposure to light pulse, a series of reactions between the oxygen molecules from environment absorbed onto the nanowire surface and the free electrons from the two-dimensional electron gases inside the oxide superlattice nanowires were induced. Hence the conductance of the photonic synapses would change. Given the outstanding charge carrier mobility and sensitivity to light stimuli of superlattice nanowires, the change of conductance in the photonic synapses resembles that in biological synapse. Hence the quasi-2DEG photonic synapses can mimic how the neurons in the human brain transmit and memorise signals.

A combo of photo-detection and memory functions

"The special properties of the superlattice nanowire materials enable our synapses to have both the photo-detecting and memory functions simultaneously. In a simple word, the nanowire superlattice cores can detect the light stimulus in a high-sensitivity way, and the nanowire shells promote the memory functions. So there is no need to construct additional memory modules for charge storage in an image sensing chip. As a result, our device can save energy," explained Professor Ho.

With this quasi-2DEG photonic synapse, they have built an artificial visual system which could accurately and efficiently detect a patterned light stimulus and "memorise" the shape of the stimuli for an hour. "It is just like our brain will remember what we saw for some time," described Professor Ho.

He added that the way the team synthesised the photonic synapses and the artificial visual system did not require complex equipment. And the devices could be made on flexible plastics in a scalable and low-cost manner.

Professor Ho is the corresponding author of the paper. The co-first authors are Meng You and Li Fangzhou, PhD students from MSE at CityU. Other team members include Dr Bu Xiuming, Dr Yip Sen-po, Kang Xiaolin, Wei Renjie, Li Dapan and Wang Fei, who are all from CityU. Other collaborating researchers come from University of Electronic Science and Technology of China, Kyushu University, and University of Tokyo.

The study received funding support from CityU, the Research Grants Council of Hong Kong SAR, the National Natural Science Foundation of China and the Science, Technology and Innovation Commission of Shenzhen Municipality.

https://www.cityu.edu.hk/research/stories/2020/12/10/artificial-visual-system-record-low-energy-consumption-next-generation-ai

Older people who undergo emergency surgeries on their operating surgeon's birthday may be more likely to die within a month than patients who go through similar procedures on other days, a new UCLA-led study suggests.

The study, published today in the peer-reviewed medical journal BMJ, shows that 30-day mortality rates are approximately 23% higher for patients 65 and older who are treated on a surgeon's birthday. While the authors suspect that surgeons may be more distracted on their birthdays than other days, they said more research is needed to explain why this may happen.

There have long been questions about how the work environment impacts a surgeon's performance, said the study's senior author, Dr. Yusuke Tsugawa, an assistant professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. But relevant data has been difficult to collect, so the researchers narrowed their focus to surgeons' birthdays in order to begin exploring this question.

"Our study is the first to show the association between a surgeon's birthday and patient mortality, but further research is needed before we make a conclusion that birthdays indeed have a meaningful impact on surgeons' performance," Tsugawa said. "At this point, given that evidence is still limited, I don't think patients need to avoid a surgical procedure on the surgeon's birthday."

The researchers measured postoperative 30-day mortality for Medicare beneficiaries between the ages of 65 and 99 who underwent one of 17 emergency surgical procedures from 2011 to 2014. They analyzed nearly 981,000 surgeries performed by approximately 48,000 surgeons. Of those, 2,064 procedures, or 0.2 %, were performed on the surgeons' birthdays.

The researchers adjusted for patient characteristics and the surgeon who performed the procedure, effectively comparing their performance on their birthday with other days. They found a 6.9% mortality rate among patients who underwent surgeries on surgeons' birthdays, compared with a 5.6% rate among those who underwent procedures on other days. This gap represents a 23% difference in mortality rates between the two groups.

The researchers note that there are some limitations to their findings. For instance, they were unable to understand the precise mechanisms that led to higher mortality among the patients in question and so could not evaluate the causal link between surgeons' birthdays and patient deaths. In addition, they focused on elderly patients who underwent one of the common emergency procedures, so these findings may not apply to younger people or to elective procedures.

"Our research on rats with heart failure shows that exercise reduces the severity of the disease, improves heart function and increases work capacity. And the intensity of the training is really importance to achieve this effect," says Thomas Stølen, a researcher at the Norwegian University of Science and Technology (NTNU).

Stølen and his colleague Morten Høydal are the main authors of a comprehensive study published in the Journal of Molecular and Cellular Cardiology. The researchers went to great lengths to investigate what happens inside tiny heart muscle cells after regular exercise.

"We found that exercise improves important properties both in the way heart muscle cells handle calcium and in conducting electrical signals in the heart. These improvements enable the heart to beat more vigorously and can counteract life-threatening heart rhythm disorders," says Stølen.

For a heart to be able to beat powerfully, regularly and synchronously, a lot of functions have to work together. Each time the heart beats, the sinus node - the heart's own pacemaker - sends out electrical impulses to the rest of the heart. These electrical impulses are called action potentials.

All the heart muscle cells are enclosed by a membrane. At rest, the electrical voltage on the inside of the cell membrane is negative compared to the voltage on the outside. The difference between the voltage on the outside and the inside of the cell membrane is called the resting membrane potential.

When the action potentials reach the heart muscle cells, they need to overcome the resting membrane potential of each cell to depolarize the cell wall. When this happens, calcium can flow into the cell through channels in the cell membrane.

Calcium initiates the actual contraction of the heart muscle cells. When this process is complete, calcium is transported out of the cell or back to its storage site inside each heart muscle cell. From there, the calcium is ready to contribute to a new contraction the next time an action potential comes rushing by.

If the heart's electrical conduction or calcium management system fails, the risk is that fewer heart muscle cells will contract, the contraction in each cell will be weak, and the electrical signals will become chaotic so that the heart chambers begin to flutter.

"All these processes are dysfunctional when someone has heart failure. The action potentials last too long, the resting potential of the cells is too high, and the transport function of the calcium channels in the cell wall is disturbed. Calcium then constantly leaks from its storage places inside every heart muscle cell," Stølen says.

Before Stølen gives us the rest of the good news, he notes, "Our results show that intensive training can completely or partially reverse all these dysfunctions."

Normally, the sinus node causes a human heart to beat between 50 and 80 beats every minute when at rest. This is enough to supply all the organ systems and cells in the body with as much oxygen-rich blood as they need to function properly.

When we get up to take a walk, our heart automatically starts beating a little faster and pumping a little harder so that the blood supply is adapted to the increased level of activity. The higher the intensity of the activity, the harder the heart has to work.

Exercise strengthens the heart so it can pump more blood out to the rest of the body with each beat. Thus, the sinus node can take it a little easier, and well-trained people have a lower resting heart rate than people who have not done regular endurance training.

At the other end of the continuum are people with heart failure. Here the pumping capacity of the heart is so weak that the organs no longer receive enough blood to maintain good functioning. People with heart failure have a low tolerance for exercise and often get out of breath with minimal effort.

In other words, increasing the pumping power to the heart is absolutely crucial for the quality of life and health of people with heart failure.

Many of the more than 100 000 Norwegians who live with heart failure have developed the condition after suffering a major heart attack - just like the rats in Stølen and Høydal's study.

In the healthy rats, the heart pumped 75 percent of the blood with each contraction. In rats with heart failure, this measure of pump capacity, called ejection fraction, was reduced to 20 per cent, Stølen says.

The ejection fraction increased to 35 percent after six to eight weeks with almost daily interval training sessions on a treadmill. The rats did four-minute intervals at about 90 percent of their maximum capacity, quite similar to the 4 × 4 method that has been advocated by several research groups at NTNU for many years.

"The interval training also significantly improved the rats' conditioning. After the training period, their fitness level was actually better than that of the untrained rats that hadn't had a heart attack," says Stølen.

Impaired calcium handling in a heart muscle cell not only causes the cell to contract with reduced force every time there is an action potential. It also causes the calcium to accumulate inside the fluid-filled area of the cell - the cytosol - where each contraction begins.

The calcium stores inside the cells are only supposed to release calcium when the heart is preparing to beat. Heart failure, however, causes a constant leakage of calcium out of these stores. After each contraction, calcium needs to be efficiently transported back into the calcium stores - or out of the heart muscle cell - via specialized pumps. In heart failure patients, these pumps work poorly.

When a lot of calcium builds up inside the cytosol, the heart muscle cells can initiate new contractions when they're actually supposed to be at rest. An electrical gradient develops which causes the heart to send electrical signals when it shouldn't. This can cause fibrillation in the heart chambers. This ventricular fibrillation is fatal and a common cause of cardiac arrest.

"We found that interval training improves a number of mechanisms that allow calcium to be pumped out of the cells and stored more efficiently inside the cells. The leakage from the calcium stores inside the cells also stopped in the interval-trained rats," says Stølen.

The effect was clear when the researchers tried to induce ventricular fibrillation in the diseased rat hearts: they only succeeded at this in one of nine animals that had completed interval training. By comparison, they had no problems inducing fibrillation in all the rats with heart failure who had not exercised.

So far, the research group had shown that exercise improves calcium management in diseased heart muscle cells in several ways. The training also makes the electrical wiring system of the heart more functional.

In addition, they showed that exercise counteracted processes that cause the heart to become big and stiff.

Taken together, these improvements make each heartbeat more powerful and reduce the severity of heart failure. The risk of dangerous ventricular fibrillation was also reduced.

But Stølen and team still lacked an answer to why exercise corrects slow action potentials and ensures that the heart muscle cells are able to take care of calcium in the right way.

Therefore, they investigated whether the training had altered the genetic activity inside the rat cells. Thousands of different types of micromolecules called micro-RNA probably control most of this activity through direct interaction with genes.

"It turned out that 55 of the micro-RNA variants we examined were altered in rats with heart failure compared to the healthy rats. Interval training changed 18 of these back towards healthy levels. Several of the relevant micromolecules are known to play a role in both calcium management and the electrical conduction system of the heart, but the most interesting thing is that we discovered new micro-RNAs that can play an important role in heart failure," says Stølen.

This article has mostly considered the effects of high-intensity interval training. But the study also includes a group of rats that trained more sedately.

The rats in this group ran the same distance and thus did as much total training work as the rats in the interval training group. However, they had to exercise longer each time since they trained at a lower intensity. Stolen notes that this form of training also resulted in several health improvements.

But, he emphasizes, the vast majority of improvements were greater with interval training. "For example, we were able to induce cardiac fibrillation in five of eight rats after a period of moderate exercise, and their pumping capacity had only improved half as much as in the interval training group."