Culture

Together with their multifaceted action mechanisms, activation-induced cytidine deaminase (AID) and so-called APOBEC proteins are important factors in the body's immune response and offer fast and effective protection against a large number of DNA and RNA viruses. The task of AID is to strengthen the human immune response, while APOBECs are able to block the virus. A MedUni Vienna research team comprising Anastasia Meshcheryakova, Diana Mechtcheriakova and Peter Pietschmann from the Institute of Pathophysiology and Allergy Research has now addressed the potential interrelations between AID/APOBECs and the SARS-CoV-2 virus, particularly in connection with the course of COVID-19 in different patients. This could provide a starting point for future clinical strategies to improve and strengthen individual antiviral response.

The defence mechanisms associated with AID/APOBECs in response to the coronavirus were assessed on the basis of integrative data mining and gene expression analyses, as part of a study conducted with international partners. It was found that members of the APOBEC family are preferentially expressed in a particular type of cell or tissue: "However, this does not mean that a particular cell type only expresses a particular member of the APOBEC family but that each cell type exhibits its own characteristic APOBEC repertoire," explains Diana Mechtcheriakova.

What is completely new is that the researchers found that APOBEC4 is highly expressed in cells and tissues that are points of attack for SARS-CoV-2. These include epithelial cells in the bronchi, in the lungs, in the trachea and in the nose. It was also found that there is an extremely high level of expression of both molecules (one of the members of the APOBEC family and ACE2, the entry receptor for SARS-CoV-2), in the gastrointestinal tract, in the heart and in the testis.

"Based on this knowledge, the clinical challenge in the future will be to characterise the antiviral cell status attributed to AID/APOBECs specific to patients and/or patient groups and to correlate the cell-type-specific AID/APOBEC gene expression signature with the organs affected by SARS-CoV-2 infection and the severity of COVID-19," explains Mechtcheriakova.

A particular role in this process is attributed to AID, since it co-determines the strength of an adaptive immune response. "The AID-driven, highly coordinated sequence of events, which all occur in specialised immunological lymphoid structures with germinal centres, results in the production of high-affinity antibodies by plasma cells or memory B cells. These antibodies are directed against the pathogen causing the disease, such as SARS-CoV-2, either in the course of infection or of an immune response to a vaccine," explains Anastasia Meshcheryakova. The role of these complex lymphoid structures and of AID is of great importance for our further understanding of the pathobiology of COVID-19, and consequently for the development of new therapeutic approaches.

Sleep deprivation - from lifestyle choices, pandemic stress, or late-night computer study - can quickly lead to loss of energy and function during the day and even feelings of anger and depression, an Australian sleep institute study has shown.

The study, led by Flinders University, asked 34 health teenagers (20 males) aged between 15 and 17 to spent 10 days and nine nights in a specially designed sleep centre.

They were allocated to one of three sleep 'doses' for five consecutive nights- from five hours, 7.5 hours, or 10 hours in bed per night - with two baseline and two 'recovery' nights of up to 10 hours' time in bed.

Their mood was measured every three hours after waking up to assess responses to feelings such as 'depressed', 'afraid', 'angry', 'confused', 'anxious', 'happy' and 'energetic'.

Using unipolar visual analogue scales measuring the mood states, the study found:

Participants in the five-hour group, but not the 7.5- or 10-hour groups, reported being significantly more depressed, angry, and confused during sleep restriction than at baseline

Happiness and energy decreased significantly following sleep restriction to five hours' sleep opportunity

When the participants had 10 hour sleep opportunities, their happiness significantly increased

No statistically significant effects of sleep restriction were found for fear or anxiety, although small-to-moderate effects of sleep restricted to five or 7.5 hours were found.

"The two nights of recovery sleep was not sufficient to recover from increased negative mood states for the five-hour group, although recovery occurred for positive mood states," says lead author Flinders University research fellow Dr Michelle Short.

"Given the prevalence of insufficient sleep and the rising incidence of mood disorders and dysregulation in adolescents, our findings highlight the importance of sufficient sleep to mitigate these risks."

The article, Sleep duration and mood in adolescents: an experimental study (2021) by SA Booth (CQU), MA Carskadon (US), R Young and MA Short, has been published in Sleep, Volume 44, Issue 5, May 2021, https://doi.org/10.1093/sleep/zsaa253

Adolescence is a critical maturational stage in terms of heightened risk of the onset of mood disorders, with researchers stressing that sufficient sleep crucial to guard against mood deficits in otherwise healthy adolescents.

The results of the experimentally manipulated sleep duration and mood study confirm that adolescents report deterioration in moods in terms of depression, happiness, anger, confusion and energy.

The relationship between experimentally manipulated sleep duration and mood in adolescents used mixed models analyses with adhoc comparisons.

Dysmenorrhea, that is, frequent severe and painful cramps during menstruation from abnormal contractions of the uterus, is the most common of all gynecological disorders. It affects between 16-91% of girls and women of reproductive age, of whom 2%-29% have symptoms severe enough to restrict their daily activity. Now, for the first time, researchers from China Medical University Hospital in Taiwan have shown that long-term exposure to air pollutants such as nitrogen and carbon oxides and fine particulate matter greatly raises the risk of developing dysmenorrhea. Based on long-term data on air quality and public health from national databases, they show that the risk to develop dysmenorrhea over a period of 13 years (2000-2013) was up to 33 times higher among Taiwanese women and girls who lived in areas with the highest levels of air pollutants compared to their peers exposed to lower levels of pollutants. These results were recently published in the open access journal Frontiers in Public Health.

A common debilitating disorder with no known cure

Dysmenorrhea can be due to hormonal imbalances or to underlying gynecological conditions such as endometriosis, pelvic inflammatory disease, ectopic pregnancy, or tumors in the pelvic cavity. Symptoms are often life-long: they include cramps and pain in the lower abdomen, pain in the lower back and legs, nausea and vomiting, diarrhea, fainting, weakness, fatigue, and headaches. In addition to reducing quality of life, dysmenorrhea also has a major socioeconomic impact, as females with dysmenorrhea may be temporarily unable to work, attend school, or engage in leisure activities. Dysmenorrhea has no known cure, but its symptoms may be managed with anti-inflammatory drugs and hormonal contraceptives.

"Research has already shown that women who smoke or drink alcohol during their periods, or who are overweight, or have their first period very young, run a greater risk of dysmenorrhea. Women who have never been pregnant are likewise known to be at greater risk. But here we demonstrate for the first time another important risk factor for developing dysmenorrhea: air quality, in particular long-term exposure to pollution. We don't yet know the underlying mechanism, but emotional stress in women exposed to air pollutants, or higher average levels of the hormone-like prostaglandins in their body, might be part of the answer," says one of the authors, Prof Chung Y. Hsu at the College of Medicine, China Medical University, Taichung, Taiwan.

The authors, led by Prof Chia-Hung Kao, the Director of the department of nuclear medicine and the Center for Positron Emission Tomography (PET) at China Medical University, studied de-identified health measures from a total of 296,078 women and girls (approximately 1.3% of the total population) between 16-55 years old. These data came from Taiwan's Longitudinal Health Insurance Database starting 2000 (LHID 2000), a representative subsample from Taiwan's nation-wide health insurance database.

The study sample exclusively included women and girls without any recorded history of dysmenorrhea before 2000. The authors looked for a long-term association between the risk of dysmenorrhea and air quality, in particular the mean exposure over the years to air pollutants - nitrogen oxide (NOx), nitric oxide (NO), nitrogen dioxide (NO2), carbon monoxide (CO), and particles smaller than 2.5 μm in diameter ('PM2.5') - obtained from the 'Taiwan Air Quality Monitoring Database' (TAQMD) of the Environmental Protection Agency.

Air pollutants are an important new risk factor

They found that from 2000- to 2013, 4.2% of women and girls in the studied sample were diagnosed with dysmenorrhea for the first time. As was expected from previous studies, younger women, women of lower incomes, and living in more urbanized areas tended to have a higher risk of developing dysmenorrhea over the study period. But importantly, the 'hazard ratio' (that is, the age- and year-specific risk) of developing dysmenorrhea increased by 16.7 to 33.1 fold for women and girls from the 25% of areas with the highest yearly exposure to air pollutants, compared to those from the 25% of areas with the lowest exposure. NOx, NO, NO2, CO, and PM2.5 levels each contributed separately to the increased risk, but the greatest individual effect was from long-term exposure to high PM2.5.

"Our results study demonstrate the major impact of the quality of air on human health in general, here specifically on the risk of dysmenorrhea in women and girls. This is a clear illustration of the need to for actions by governmental agencies and citizens to reduce air pollution, in order to improve human health," concludes Prof Hsu.

A study led by University of Barcelona researchers and carried out together with more than 1,650 students and their family members from 18 educational centres in Barcelona shows that citizen science is a valid approach able for doing high quality science, and in this case, able to provide nitrogen dioxide values with an unprecedented resolution and to assess the impact of the pollution in the health of their inhabitants.

The journal Science of the Total Environment has published the results of a study carried out by the research group OpenSystems of the University of Barcelona, the Barcelona Institute for Global Health (ISGlobal), promoted by La Caixa Foundation and the 4Sfera company, that shows the key role of citizen science in the relationship between the assessment of the exposure to air pollution and the collective action for the improvement of air quality.

The publication describes the xAire project, which involved the organization of collective data gathering in Barcelona regarding the concentration of nitrogen dioxide, a pollutant related to the motorized vehicles. This concentration was measured during a 1-month period between February and March 2018 thanks to the families with children aged between 7 and 18, from 18 public primary schools in the different districts of the city.

The results provide unprecedented information on the pollution of the air in the city with a notable precision. The location of the measuring spots was decided autonomously among the students and their families following the same scientific process. "xAire has not only shown the problems surrounding the schools and the neighbourhoods but it has also provided arguments to the families and schools to ask for improvements in their environment according to the data they gathered", notes Professor Josep Perelló, leader of the study and member of the Institute of Complex Systems of the UB (UBICS).

Air pollution in Barcelona, a serious and underestimated problem

The results of the research show a wide and representative distribution of nitrogen dioxide concentration levels of the city regarding population density. The study analysed very high levels, with an annual average of 49 μg/m3, above the thresholds of the European directive and the WHO, which are 40 μg/m3. More than 5% of the samples double the threshold value of 40 μg/m3, thus confirming that air quality is a serious problem in Barcelona. The measured levels also show large differences between districts and within the same district, depending on the street. The average values obtained in Ciutat Vella, Sants / Montjuïc, Les Corts and Horta / Guinardó by xAire are particularly worrying, as they are higher than those of the nearest official stations.

Improvements in a model of the pollution impact on health

The obtained data have also made it possible to obtain a more up-to-date and accurate estimation of the models for estimating the impact of NO2 on health used by the scientific community. Specifically, the study has estimated that 1,084 new cases of childhood asthma are attributable to NO2 each year in Barcelona, an equal figure to 48% of the total annual cases. According to Mark Nieuwenhuijsen, head of Urban Planning, Environment and Health Initiative of ISGlobal, "if we reduce NO2 levels, especially around schools, we could significantly reduce cases of childhood asthma".

A coordinated effort to measure pollution in 725 areas of the city

xAire was born with the aim to expand the detail and representativeness of the city's levels of pollution, provided by the city's seven official stations. The effort with more than 1,600 involved people has resulted in measurements of nitrogen dioxide in 725 locations. The number of obtained samples exceeds previous campaigns conducted by professional scientists, who gathered the concentration of nitrogen dioxide in a maximum of 200 locations simultaneously.

The xAire project returned the data to each school group and these are available publicly on an interactive map. The results were discussed in the schools mainly considering the WHO and EU limit values. The discussions showed a clear understanding of the follow-up data and the scientific research process.

Boys and girls aged between seven and eight were able to perfectly explain the scientific protocol and the meaning of the data in the InfoK of the Super 3 Channel, during the Science Congress, organized by the Barcelona Education Consortium and in front of the city mayor Ada Colau (Escola El Sagrer). The same schools provided the data to City Council officials along with a set of proposals based on scientific evidence, at an event held in Saló de Cent. The proposed measures range from the promotion of public transport in the neighbourhood and pedestrian routes to the need to cover part of the ronda de Dalt (Dolors Monserdà, Sarrià) or to accelerate the reform of Avinguda Meridiana (El Sagrer).

Large-scale citizen science campaigns on air quality should not be seen simply as a public awareness activity and an education program. "In this intense participatory component, citizens can be actors in research and not just recipients of a message. This approach to citizen science adds sophistication and diversity to the scientific research process, as it requires multidisciplinary professional scientists and the participation of non-academic organizations", says Isabelle Bonhoure, researcher at the OpenSystems Group of the UB.

Although hypomorph mammals (or equids) are currently represented by only one genus ('Equus') and just a handful of species of horses, donkeys and zebras, they were more diverse during the Eocene epoch (between 56 and 33.9 million years ago). One of the most widespread groups in Europe, which was an archipelago at that time, were the palaeotheriidae, named after the genus 'Palaeotherium', described in 1804 from fossils originating in the quarries of Montmartre (Paris) by the famous French naturalist George Cuvier.

The international Journal of Vertebrate Paleontology has recently published a paper on a study led by Leire Perales-Gogenola describing two new species of palaeotheriidae mammals that inhabited the subtropical landscape of Zambrana (Álava) 37 million years ago. Together with their collaborators from the UPV/EHU's Vertebrate Palaeontology research group, they described the new species 'Leptolophus cuestai' and 'Leptolophus franzeni', naming them in memory of the palaeontologists Miguel Ángel Cuesta from Palencia, and Jens Lorenz Franzen from Bremen, specialists in mammal fauna of the Eocene epoch in Europe.

Palaeotheriidae (or pseudo-horses) were represented across the European archipelago by more than half a dozen genera, more than half of which were endemic to the Iberian island, and became extinct during the climatic-biological crisis of the Eocene-Oligocene transition, also known as Stehlin's 'Grande Coupure'. Palaeotheriidae were mammals similar in terms of body shape to today's horses, but smaller in size. "Can one imagine animals similar to horses with three toes, the size of a fox terrier, a Great Dane and a donkey living in a subtropical landscape in Alava? Many of these pseudo-horses have been described at the Zambrana site," said one of the team members Dr Ainara Badiola. "Examples of them are the 'Pachynolophus zambranensis' and 'Iberolophus arabensis' species, which were first specified in this palaeontological enclave".

The two new species not only expand the fossil record and the biodiversity of palaeotheriidae fauna, but also display dental features atypical for equids of the Eocene. "Their molars have a very high crown and are covered with a thick layer of cementum. This type of dentition, also present in other endemic Iberian palaeotheriidae, could be indicative of a difference in environmental conditions between the Iberian and Central European areas, with more arid conditions or less dense or closed forests and the presence of more open areas in Iberia," explained Perales-Gogenola.

At the end of the Eocene in Europe, forests of an intertropical type gradually disappeared, giving way to plant communities of a more temperate type with more open areas. Modern horses or equids appeared in Europe later on during the Miocene (23-5.3 Ma). Their dentition, with very high crowns, is adapted for eating vegetation with a high grit content (grasses). The new species 'Leptolophus cuestai' from the Upper Eocene site at Zambrana (Álava) also displays molars with atypically high crowns, similar to those of some of the earliest equids in Europe.

In addition to its palaeobiological interest, the diverse fossil association of mammals from Zambrana, which comprises primates, rodents, marsupials, carnivores, artiodactyla and perissodactyla, provides new information on the climatic and environmental changes that occurred in Europe and in our environment over geological time.

The UPV/EHU's Vertebrate Palaeontology group is currently immersed in the description of more palaeotheriidae material, which could facilitate the description of new genera and species with unusual dental features among the equoid perissodactyla.

Big hydropower plants are an important source of clean and cheap electricity for many countries in Southeast Asia. However, dams harm the environment and have dire consequences on local communities. Building more dams would therefore pose major trade-offs between electricity supply and environmental protection.

A team of scientists based in Singapore showed that these two challenges can be decoupled. Their study, titled "Solar energy and regional coordination as a feasible alternative to large hydropower in Southeast Asia", recently published in Nature Communications, showed that there are more sustainable pathways to a clean energy future (refer to image).

Building on high resolution mathematical models of the Thai, Laotian, and Cambodian power systems, the team of scientists led by Dr Stefano Galelli from the Singapore University of Technology and Design (SUTD) demonstrated that future electricity demands and CO2 emission targets could be met with much less hydropower dams than currently planned.

In particular, the scientists found that only 82% of the planned dams in the Mekong River basin, a major biodiversity hotspot, are actually needed. In fact, it would be possible to halt the construction of all planned dams without major implications on the cost of electricity.

"The explanation behind these results lie in the cost and flexibility of other renewable technologies," said Dr Kais Siala, fromTUMCREATE Ltd. "The decreasing cost of solar energy is an essential factor of sustainable energy plans. Moreover, solar photovoltaic modules have the advantage of being scalable and deployable in any province of the Mekong countries".

"We have tangible opportunities for rethinking our regional energy plans," explained Dr Galelli. "So far, we have often prioritised the construction of big dams over the protection of our ecosystems. New technologies and their dropping costs provide us with concrete options for resolving this long-standing issue".

These findings are beneficial for many other countries striving to meet their energy demands without further imposing costly effects on their natural environments. From Southeast Asia to South America, many free-flowing rivers are being dammed to produce electricity. New developments in the power market could help us change the tide.

TAMPA, Fla. (July 6, 2021) - All it takes is three consecutive nights of sleep loss to cause your mental and physical well-being to greatly deteriorate. A new study published in Annals of Behavioral Medicine looked at the consequences of sleeping fewer than six hours for eight consecutive nights - the minimum duration of sleep that experts say is necessary to support optimal health in average adults.

Lead author Soomi Lee, assistant professor in the School of Aging Studies at the University of South Florida, found the biggest jump in symptoms appeared after just one night of sleep loss. The number of mental and physical problems steadily got worse, peaking on day three. At that point, research shows the human body got relatively used to repeated sleep loss. But that all changed on day six, when participants reported that the severity of physical symptoms was at its worst.

"Many of us think that we can pay our sleep debt on weekends and be more productive on weekdays," Lee said. "However, results from this study show that having just one night of sleep loss can significantly impair your daily functioning."

Data provided by the Midlife in the United States study included nearly 2,000 middle-aged adults who were relatively healthy and well-educated. Among them, 42% had at least one night of sleep loss, sleeping 1 ½ fewer hours than their typical routines. They recorded their mental and physical behaviors in a diary for eight consecutive days, allowing researchers to review how sleep loss causes wear and tear on the body.

Participants reported a pile-up of angry, nervous, lonely, irritable and frustrated feelings as a result of sleep loss. They also experienced more physical symptoms, such as upper respiratory issues, aches, gastrointestinal problems and other health concerns. These negative feelings and symptoms were continuously elevated throughout consecutive sleep loss days and didn't return to baseline levels unless they had a night sleep of more than six hours.

About one-third of U.S. adults sleep less than six hours per night. Lee says once that becomes a habit, it's increasingly difficult for your body to fully recover from lack of sleep, continuing the vicious cycle of worsening daily well-being, which could impact one professionally. A previous study led by Lee found losing just 16 minutes of sleep could impact job performance. Her previous findings also show that minor sleep loss can decrease daily mindfulness, which is a critical recourse for managing stress and maintaining healthy routines.

Lee says the best way to maintain a strong daily performance is to set aside more than six hours to sleep every night.

Announcing a new article publication for BIO Integration journal. In this article the authors Daowei Lin, Zhixiao Han, Yanni Fu, Xiaoqiu Zhu, Jin Li, Hui Xu, Jing Wen, Fei Wang and Mingyan Guo from Sun Yat-sen University, Guangdong, China, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China and University of Virginia, Charlottesville, VA, USA discuss how interscalene brachial plexus block combined with general anesthesia attenuates stress and inflammatory response in arthroscopic shoulder surgery.

In arthroscopic shoulder surgery, general anesthesia (GA) is the common method of anesthesia. Recently, the combined usage of interscalene brachial plexus block with general anesthesia (ISB/GA) was reported to have a lower incidence of adverse side effects than GA alone. However, to date, no study has compared stress and inflammatory responses between these two methods. Since stress and inflammatory responses are critical on intraoperative management and postoperative recovery, the authors of this study integrated the laboratory and clinical methods and compared the stress and inflammatory factors, such as epinephrine, norepinephrine, glucose, lactate, inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), as well as the clinical outcomes to determine whether ISB/GA provides an advantage on stress and inflammatory inhibition.

Data showed that ISB/GA resulted in significantly lower epinephrine, norepinephrine, and glucose levels perioperatively. Six hours after operation, the TNF-α and IL-6 levels were also significantly lower in the ISB/GA group. ISB/GA patients had lower blood pressure, a more stable heart rate, lower visual analog scale score, and less opioid consumption during and after surgery. The results indicate that ISB/GA is a better choice for arthroscopic shoulder surgery, owing to less stress and inflammatory responses during and after operation, which provides better clinical outcomes.

Historically most scientists thought that once a satellite galaxy has passed close by its higher mass parent galaxy its star formation would stop because the larger galaxy would remove the gas from it, leaving it shorn of the material it would need to make new stars. However, for the first time, a team led by the researcher at the Instituto de Astrofísica de Canarias (IAC), Arianna di Cintio, has shown using numerical simulations that this is not always the case. The results of the study were recently published in the journal Monthly Notices of the Royal Astronomical Society (MNRAS).

Using sophisticated simulations of the whole of the Local Group of galaxies, including the Milky Way, the Andromeda galaxy and their respective satellite galaxies, the researchers have shown that the satellites not only can retain their gas but can also experience many new episodes of star formation just after passing close to the pericentre of their parent galaxy (the mínimum distance they reach from its centre).

The satellite galaxies of the Local Group show a wide variety of star formation histories, whose origin has not previously been fully understood. Using hydrodynamic simulations within the project Constrained Local UniversE (CLUES) the authors studied the star formation histories of satellite galaxies similar to those of the Milky Way in a cosmological context.

While in the majority of the cases the gas of the satellite is sucked out by the parent galaxy due to gravitational action and transfers itself to the larger galaxy, interrupting star formation in the satellite, in a process known as accretion; in some 25% of the sample they found that star formation was clearly enhanced by this interactive process.

The results show that the peaks of star formation are correlated with the close pass of the satellite around the parent galaxy, and occasionally by the interaction of two satellites. The researchers identified two key features to the star formation: the satellite must enter the parent galaxy with a large reserve of cold gas, and a minimum distance not too small, so that stars may form due to compression of the gas. On the contrary, galaxies which pass too close to the parent galaxy, or to a parent galaxy with little gas, are stripped of their gas and thereby lose the possibility of forming new stars.

"The passage of satellites also coincide with peaks in the star formation of their parent galaxies, which suggests that this mechanism causes bursts of stars equally in both parent galaxies and satellites, in agreement with recent studies of the history of star formation in our own Galaxy", explains Arianna di Cintio, the lead author on the paper.

"This is very important when we try to understand how star formation is produced in the smaller dwarf galaxies of our Local Group, an unresolved question", she adds.

This finding will shed light on the episodes of star formation which are observed in the dwarf galaxies of the Local Group, such as Carina and Fornax, giving an attractive explanation of their existence. It also requires a revision of the theoretical models used to explain the formation of stars in dwarf galaxies.

By analyzing the genomes of 99 species of vinegar flies and evaluating their chemical odor profiles and sexual behaviors, researchers at the Max Planck Institute for Chemical Ecology show that sex pheromones and the corresponding olfactory channels in the insect brain evolve rapidly and independently. Female flies are able to recognize conspecific males through their specific odor profiles. Interestingly, closely related species show distinct differences in odor profiles, which helps to prevent mating between different species. Males, in turn, chemically mark females during mating so that they become less attractive to other males. The results of this study are a valuable basis for understanding how pheromone production, their perception and processing in the brain, and ultimately the resulting behavior drive the evolution of new species (Nature Communications, July 2021, DOI: 10.1038/s41467-021-24395-z).

A large family with extravagant relatives

As in most animals, mate choice in vinegar flies is primarily based on chemical signals. There are several reasons why the genus Drosophila is ideally suited for studying the evolution and diversity of sex pheromones. The more than 1.500 known species of vinegar flies are found all over the world in a wide variety of different habitats: in deserts, rainforests, caves, swamps, or mountains. Often, rotting fruit and the yeasts responsible for fermentation are the primary food source. Some species also feed on fresh fruit, mushrooms, tree bark, flowers, bacterial slime, or frog spawn. In many species, especially in the model organism Drosophila melanogaster, the processing of olfactory information in the brain has already been well described. The receptors for the sex pheromones are precisely tuned to detect the odor of the conspecific mating partner.

In a new study published now in Nature Communications, researchers led by Mohammed Khallaf and Markus Knaden investigated how sex pheromones evolved in 99 different species of the genus Drosophila. "We identified the sex pheromones and the corresponding olfactory channels in the olfactory system of flies to explore the evolution of pheromone signaling with respect to phylogenetic relationships," said Mohammed Khallaf, first author of the study. 41 of the species under investigation had already been fully sequenced. By sequencing the whole genomes of further 58 species, the scientists presented the most comprehensive phylogenetic analysis of the genus Drosophila to date.

By using the genomic data, it was possible to genetically compare differences in chemical profiles as well as differences in odor detection and processing. The researchers collected the odors of individual flies: Five males, virgin and mated females from each species, resulting in odors of over 1500 flies in total, were analyzed. "While the comparison of male and virgin female flies informed us about sex-specific differences, variations between mated and virgin females informed us about male-specific compounds transferred to females during mating," Markus Knaden, head of the project group Odor-guided Behavior in the Department of Evolutionary Neuroethology, summarized.

The difference lies in the detail

In all 99 fly species studied, 52 different odor compounds were identified. In 81 species, the scientists found pheromones that are only produced by male flies. Of these species, males produce 58 different odor blends, which can consist of up to seven individual odors. While the males attract attention with a sophisticated chemistry, it is ultimately the females who decide whether mating occurs or not. "Interestingly closely related species often show clear differences in their pheromone profile. At the same time, individual pheromones show up again and again along the phylogenetic tree. For example, males of 34 of the 99 species studied produce cis-vaccenyl-acetate (cVA), a well described Drosophila melanogaster pheromone. Most of the male-derived pheromones fulfill the same functions: Firstly, they attract females and secondly, they are transferred to the females during mating to make them smell less attractive to other males. This ensures the males' reproductive success," said Markus Knaden.

The significant differences in the pheromone profile of males of closely related species suggest that the selection pressure to prevent mating between these species that have evolved from a common ancestor is high. On the other hand, the fact that as many as 34 species produce cis-vaccenyl acetate as a sex pheromone shows that there may only be a limited number of genes responsible for pheromone production. As long as there is no pressure to mark a difference from an evolutionary perspective, different species produce the same pheromone.

A key observation is that it is mostly the male fly in the genus Drosophila that is the transmitter of the chemical signal, while the females, as receivers, recognize and interpret the signal. "The diversity and abundance of male-specific compounds compared to female ones is astonishing: Of the 52 different odor compounds, 43 are produced exclusively by males, while only 9 are produced by females. Moreover, 81 Drosophila species communicate via male pheromones, while only 15 species have specifically female pheromones," said Mohammed Khallaf.

From odor to behavior

The study is the first comprehensive analysis of the mating behaviors of a large number of Drosophila species. "While we were performing mating experiments we could already observe that some of the species showed very specific behaviors. Some of them were driven by olfaction and only started their mating dance when the partner had the right smell. Sometimes, however, the right wing pattern or the male's song also triggered the female's mating behavior," Bill Hansson, who heads the Department of Evolutionary Neuroethology where the study was performed, described the observations in the mating arena. Presumably, sex pheromones play a crucial role as the first cue to identify the right partner before mating. Once a female has been attracted and is ready to mate, other mating rituals may also be initiated, including dance, nuptial gift or song. The researchers will further evaluate the recorded mating experiments for future studies and hope that these materials motivate other research groups to take a closer look at the mating strategies of different drosophilids as well.

July 6, 2021 - Traumatic brain injury (TBI) has a major impact on the lives of affected patients and families. But it doesn't necessarily lead to an increased risk of marital instability, as two-thirds of patients with TBI are still married to the same partner 10 years after their injury, reports a study in the July/August issue of the Journal of Head Trauma Rehabilitation (JHTR). The official journal of the Brain Injury Association of America, JHTR is published in the Lippincott portfolio by Wolters Kluwer.

For marriages that do end, divorce most often occurs within the first year after TBI, according to the new research by Flora M. Hammond, MD, of Indiana University School of Medicine, Indianapolis, and colleagues. "Our data dispel myths about risk of divorce after TBI and suggest a message of hope," the researchers write.

Findings may help in assessing risk and targeting timing marital interventions after TBI

Dr. Hammond and colleagues analyzed long-term follow-up data on 1,423 patients with TBI, all of whom were married at the time of their injury. Patients were drawn from the Traumatic Brain Injury Model Systems (TBIMS) database enrolling persons hospitalized with TBI. Average age at the time of injury was 44 years; about three-fourths of patients were men.

Ten years after TBI, 66 percent of patients with TBI remained married to the same person, without separation or divorce. Of marriages that ended, 68 percent did so within five years after TBI, including 39 percent within the first year.

The study also looked at factors associated with a higher or lower risk of divorce or separation. "Marital stability over the 10-year period was higher for those who were older, were female, and had no problematic substance use history," the researchers write. The risk of a breakup didn't seem to be related to race/ethnicity, education, cause of injury, or injury severity.

Marital stability has a major impact on the ability to resume normal life and functioning in persons with TBI. Some reports have suggested high divorce rates after TBI. However, in previous studies, reported rates of marital instability after TBI varied widely: from 22 to 85 percent. Long-term follow-up in a large sample of patients with TBI are major strengths of the new study.

The results question previous studies suggesting a high divorce rate among patients who are married at the time they sustain a TBI. The study also provides insights into risk factors for a marital breakup after TBI. The findings are consistent with the known bidirectional link between TBI and substance use. "While substance use itself may not cause marital instability, a spouse's perception that substance use is problematic may contribute to marital instability," Dr. Hammond and coauthors write.

The high risk of marital loss within the first few years after TBI suggests that early education and support might be helpful. The researchers note some important limitations of their study - including the lack of information on the quality of the marital relationship before TBI.

The findings may help to identify couples who may be at high risk of marital instability after TBI, and to guide patient and family education, relationship counseling, and other marital interventions, Dr. Hammond and colleagues believe. They conclude, "Interventions aimed at substance use prevention and functional improvement may also have relevance to facilitating marital stability."

Chromosomal instability is a feature of solid tumours such as carcinoma. Likewise, cellular senescence is a process that is highly related to cellular ageing and its link to cancer is becoming increasingly clear. Scientists led by ICREA researcher Dr. Marco Milán at IRB Barcelona have revealed the link between chromosomal instability and cellular senescence.

"Chromosomal instability and senescence are two characteristics common to most tumours, and yet it was not known how one related to the other. Our studies indicate that senescence may be one of the intermediate links between chromosomal alterations and cancer," says Dr. Milan, head of the Development and Growth Control laboratory at IRB Barcelona.

"The behaviour we saw in cells with chromosomal instability made us think that they could be senescent cells and indeed that was the case!" says Dr. Jery Joy, first author of the article published in Developmental Cell.

The study has been conducted on the fly Drosophila, an animal model commonly used in biomedicine, and the mechanisms described may help to understand the contribution of chromosomal instability and senescence to cancer, and facilitate the identification of possible therapeutic targets.

Reversing the effects of chromosomal instability

The researchers from the Development and Growth Control lab have shown that, in an epithelial tissue with high levels of chromosomal instability, those cells with an altered balance of chromosome number detach from their neighbouring cells and enter senescence. Senescent cells are characterised by a permanently halted cell cycle and by the secretion of a large number of proteins. This abnormal secretion of proteins alters the surrounding tissue, alerting the immune system and causing inflammation.

If the senescent cells are not eliminated by the body immediately, they promote abnormal growth of the surrounding tissue, leading to malignant tumours. "If we identify the mechanisms by which we can lower the number of senescent cells, then we will be able to reduce the growth of these tumours," says Dr. Milan. "In fact, this study shows that this is possible, at least in Drosophila," says Dr. Joy.

Cells with an unbalanced number of chromosomes accumulate a high number of aberrant mitochondria and, therefore, a high level of oxidative stress, which in turn activates the JNK signalling pathway, triggering entry into senescence. "We have shown that reducing this high anomalous number of mitochondria, or regulating the oxidative stress that they induce, is sufficient to decrease the number of senescent cells and the negative effects of chromosomal instability," reiterates Dr. Joy.

These findings open new avenues of research to find therapeutic targets and reduce senescence levels caused by chromosomal instability in solid tumours.

Extrapolating from the fly to mammals

The vinegar fly, Drosophila melanogaster, is a widely used in biomedicine. It is a valuable animal model in cancer research because of its short life cycle, the availability of a large number of genetic tools, and the presence of the same genes as in humans, but with a lower level of redundancy.

In fact, experiments designed to dissect the causal relationship between cellular behaviour or characteristics in human tumours, such as chromosomal instability and senescence, are more easily analysed in this model organism.

Future laboratory work will continue to dissect the molecular mechanisms responsible for cellular behaviours found in solid tumours of epithelial origin produced by the mere induction of chromosomal instability. "The more we understand the biology of a tissue subjected to chromosomal instability and the molecular mechanisms responsible for the cellular behaviours that emerge and give rise to malignant tumours, the greater our chances of designing effective therapies and reducing the growth and malignancy of human carcinomas," concludes Dr. Milan.

(Boston)--During neuropsychological assessments, participants complete tasks designed to study memory and thinking. Based on their performance, the participants receive a score that researchers use to evaluate how well specific domains of their cognition are functioning.

Consider, though, two participants who achieve the same score on one of these paper-and-pencil neuropsychological tests. One took 60 seconds to complete the task and was writing the entire time; the other spent three minutes, and alternated between writing answers and staring off into space. If researchers analyzed only the overall score of these two participants, would they be missing something important?

"By looking only at the outcome, meaning what score someone gets, we lose a lot of important information about how the person performed the task that may help us to better understand the underlying problem," explains lead author Stacy Andersen, PhD, assistant professor of medicine at Boston University School of Medicine (BUSM).

Researchers with the Long Life Family Study (LLFS) used digital pens and digital voice recorders to capture differences in study participants' performance while completing a cognitive test and found that differences in 'thinking' versus 'writing' time on a symbol coding test might act as clinically relevant, early biomarkers for cognitive/motor decline.

Participants in the LLFS were chosen for having multiple siblings living to very old ages. Longevity has long been associated with an increased health span and thus these families are studied to better understand contributors to healthy aging. The participants were assessed on a number of physical and cognitive measures, including a symbol coding test called the Digit Symbol Substitution Test.

This timed test requires participants to fill in numbered boxes with corresponding symbols from a given key and assesses both cognitive (attention and processing speed) and non-cognitive factors (motor speed and visual scanning). To allow researchers to collect data about how a participant went about completing the task, the participants used a digital pen while completing the test. On the tip of this pen was a small camera that tracked what and when a participant wrote. The LLFS researchers divided the output from this digital pen into 'writing time' (the time the participant spent writing) and 'thinking time' (the time not spent writing) and looked at how these changed over the course of the 90-second test.

The researchers then identified groups of participants that had similar patterns of writing time and thinking time across the course of the test. They found that although most participants had consistent writing and thinking times, there were groups of participants who got faster or slowed down. "This method of clustering allowed us to look at other similarities among the participants in each group in terms of their health and function that may be related to differences in writing and thinking time patterns," said coauthor and lead biostatistician Benjamin Sweigart, a biostatistics doctoral student at Boston University School of Public Health. The researchers found that those who got slower in writing the symbols during the test had poorer physical function on tests of grip strength and walking speed. In contrast, those who changed speed in thinking time had poorer scores on memory and executive function tests suggesting that writing time and thinking time capture different contributors to overall performance on the test.

According to the researchers, these findings show the importance of capturing additional facets of test performance beyond test scores. "Identifying whether poor test performance is related to impaired cognitive function as opposed to impaired motor function is important for choosing the correct treatment for an individual patient" adds Andersen. "The incorporation of digital technologies amplifies our ability to detect subtle differences in test behavior and functional abilities, even on brief tests of cognitive function. Moreover, these metrics have the potential to be very early markers of dysfunction."

Scientists at the University of Leeds have developed an approach that could help in the design of a new generation of synthetic biomaterials made from proteins.

The biomaterials could eventually have applications in joint repair or wound healing as well as other fields of healthcare and food production.  

But one of the fundamental challenges is to control and fine tune the way protein building blocks assemble into complex protein networks that form the basis of biomaterials.  

Scientists at Leeds are investigating how changes to the structure and mechanics of individual protein building blocks - changes at the nanoscale - can alter the structure and mechanics of the biomaterial at a macro level while preserving the biological function of the protein network.  

In a paper published by the scientific journal ACS Nano, the researchers report that they were able to alter the structure of a protein network by removing a specific chemical bond in the protein building blocks. They called these bonds the "protein staples". 

With the protein staples removed, the individual protein molecules unfolded more easily when they connect together and assemble into a network. This resulted in a network with regions of folded protein connected by regions containing the unfolded protein resulting in very different mechanical properties for the biomaterial.  

Professor Lorna Dougan, from the School of Physics and Astronomy at Leeds, who supervised the research, said: "Proteins display amazing functional properties. We want to understand how we can exploit this diverse biological functionality in materials which use proteins as building blocks. 

"But to do that we need to understand how changes at a nano scale, at the level of individual molecules, alters the structure and behaviour of the protein at a macro level."  

Dr Matt Hughes, also from the School of Physics and Astronomy and lead author of the paper, said: "Controlling the protein building block's ability to unfold by removing the "protein staples" resulted in significantly different network architectures with markedly different mechanical behaviour and this demonstrates that unfolding of the protein building block plays a defining role in the architecture of protein networks and the subsequent mechanics." 

The researchers used facilities at the Astbury Centre for Structural Molecular Biology and School of Physics and Astronomy at Leeds and the ISIS Neutron Muon Source facility at the STFC Rutherford Appleton Laboratory in Oxfordshire. Using beams of neutrons, it allowed them to identify critical changes to the protein network's structure when the nano-staples where removed.

In conjunction with the experimental work, Dr Ben Hanson, a Research Associate in the School of Physics and Astronomy at Leeds, modelled the structural changes taking place. He found that it was specifically the act of protein unfolding during network formation, that was crucial in defining the network architecture of the protein hydrogels.   

Professor Dougan added: "The ability to change the nanoscale properties of protein building blocks, from a rigid, folded state to a flexible, unfolded state, provides a powerful route to creating functional biomaterials with controllable architecture and mechanics."   

The death of cells is well regulated. If it occurs too much, it can cause degenerative diseases. Too little, and cells can become tumours. Mitochondria, the power plants of cells, play a role in this programmed cell death. Scientists from the University of Groningen (the Netherlands) and the University of Pittsburgh (U.S.) have obtained new insights in how mitochondria receive the signal to self-destruct. Their results were published in the Journal of Molecular Biology.

How does a cell kill itself? The details of this process are still unclear. Patrick van der Wel, associate professor of Solid-State NMR Spectroscopy at the University of Groningen, is working together with colleagues at the University of Pittsburgh to see how cell death is initiated on a molecular level. 'The membranes of mitochondria play a key role', he explains. Cardiolipin, a special type of membrane lipid, acts as an important signal. 'If it gets reshuffled inside the membrane and oxidized, this can trigger cell death.'

Unfolding

Another factor is the small protein cytochrome c. This plays an important role in energy production by mitochondria, but it can also bind to cardiolipin. 'We believe it may control oxidation of the cardiolipin, which is part of the initiation process for programmed cell death', explains Van der Wel. It was previously thought that the unfolding of cytochrome c on the cell membrane was important, as this allows it to oxidize cardiolipin, a step that triggers cell death. However, in a previous paper, Van der Wel and his U.S. colleagues published evidence that cytochrome c is not unfolded.

'In our new study, we have looked in even more detail at the interaction between cytochrome c and the mitochondrial membrane', says Van der Wel. They used solid-state NMR to detect the position and the status of all 105 amino acids in the protein. The NMR signals of two connected carbon atoms in an amino acid depend on how they interact with other atoms in the molecule. Therefore, the measured spectrum of the carbon atoms can show in which amino acid they are located. Such information can be used to get an idea of the protein's structure, even if it is not well ordered.

Discrepancy

'Furthermore, with this technique, an amino acid is only visible in a fixed part of the protein structure. If it is in an unfolded part, it can move more freely and becomes invisible.' Thus, solid-state NMR spectroscopy can show which parts of the protein are folded or unfolded. 'What we saw is that cytochrome c is not fully unfolded when attached to the cardiolipins in the mitochondrial membrane.'

Proteins fold in a particular order: the first fold induces a second, third, and so on. 'These steps are called foldons. What we saw in our experiments is that when binding to the membrane, different foldons in cytochrome c unfold at different stages. And some parts do not unfold at all.' This finding explains the discrepancy between the results of Van der Wel and his colleagues and those of previous papers: these studies were too coarse-grained to be able to clearly see which parts of cytochrome c were still folded.

Drugs

These results are interesting, as they provide fundamental insight into how programmed cell death is regulated at the molecular level. 'They add to our previous idea that oxidation of cardiolipin by cytochrome c is a very well-controlled, specific process.' Furthermore, knowing which parts of the protein unfold means that it will be possible to develop drugs that stabilize or destabilize them. Such drugs could be used as regulators that could increase or reduce programmed cell death. Van der Wel: 'We would like to use our data to construct a realistic computer model for this protein interaction so that it is possible to design these drugs in silico.'

Simple Science Summary

There is a continuous turnover of cells in our body. New cells are 'born', and old ones die, often through a process called 'programmed cell death'. This type of cell death must be tightly regulated. If it occurs too much, it can cause degenerative diseases, too little, and cells can become tumours. An important step in programmed cell death is the binding of a protein (called cytochrome c) to the membrane of mitochondria, the power plants inside cells. Scientists have now discovered that cytochrome c is partly unfolded during this important step, and they can pinpoint which parts of the protein are folded or unfolded. This could lead to the development of drugs that could regulate programmed cell death by increasing or reducing the unfolding.