Culture

Scientists have created an unprecedented 3-dimensional structural model of a key molecular "machine" known as the BAF complex, which modifies DNA architecture and is frequently mutated in cancer and some other diseases. The researchers, led by Cigall Kadoch, PhD, of Dana-Farber Cancer Institute, have reported the first 3-D structural "picture" of BAF complexes purified directly from human cells in their native states - rather than artificially synthesized in the laboratory -providing an opportunity to spatially map thousands of cancer-associated mutations to specific locations within the complex.

"A 3-D structural model, or 'picture,' of how this complex actually looks inside the nucleus of our cells has remained elusive - until now," says Kadoch. The newly obtained model represents "the most complete picture of the human BAF complex achieved to date," said the investigators, reporting in the journal Cell.

These new findings "provide a critical foundation for understanding human disease-associated mutations in components of the BAF complex, which are present in over 20% of human cancers and in several intellectual disability and neurodevelopomental disorders," the authors said. These insights could help scientists understand how mutations in proteins making up the complex lead to disruption of the normal regulation of DNA and hence the expression of genes in cells, potentially causing cancerous growth of cells to form tumors. Mutations in the BAF complex, for example, are the sole cause of rare childhood cancers such as synovial sarcoma and malignant rhabdoid, and contribute to common cancers such as ovarian and lung cancers.

The BAF complex is "molecular machine," a group of proteins that remodel the way DNA is packaged in cells. It is made up of a dozen protein subunits specified by 29 different genes. Previous attempts to obtain a structural 3-D model of the BAF complex were based on protein molecules recombinantly engineered in the laboratory, "which were unable to recreate the entire complex," says Kadoch. She said she and her colleagues have been trying to solve the 3-D structure of BAF since 2014, their primary goal being a structural model that could help them inform the impact of the mutations and ultimately, help classify mutations based on where they are located on the "picture" of BAF. Extracting BAF complexes from human cells was an enormous challenge: "we devised a new way of purifying these complexes - it took years," she says.

BAF is one of several molecular "machines" that regulate the expression of genes in cells by modifying chromatin, a substance composed of DNA and protein. Chromatin packages the long DNA strand containing genes into more condensed units. A single cell contains hundreds of thousands of chromatin-modifying complexes, of which BAF is one type. Mutations in BAF, while they don't alter the DNA code of genes to cause cancer, disrupt DNA topology and accessibility, leading to aberrant gene expression and the growth of malignant tumors.

Using several powerful new analytic tools in combination, the investigators produced a model of the BAF complex's structure both as an isolated complex and in the form BAF takes when it binds to nucleosomes - spool-like units of chromatin around which DNA segments are wound. Binding to nucleosomes is necessary for BAF complexes to remodel chromatin and influence gene expression. One of the newest and most helpful tools the researchers used to obtain the structure of BAF bound to nucleosomes is called cryo-EM, a form of electron microscopy that can create high-resolution models of molecules in their native environment, and which scientists say is revolutionizing the field of structural biology. The developers of cryo-EM won a Nobel Prize in 2017. In this case, the human BAF complexes were too heterogeneous and flexible for the method to alone produce a high-resolution structure, but when paired with two other methods, known as cross-linking mass-spectrometry and homology modeling, the structural connectivity between the subunits became clearer.

Kadoch and her colleagues report that the BAF complex is made up of three modules which form a "C" shape and grip the nucleosome on opposite sides like a carpenter's C-clamp holds pieces of wood together. They discovered that the two regions of the BAF structure that grip the nucleosome are "hot spots" where cancer-causing mutations frequently occur and used experiments to show how mutations disrupt the normal regulation of chromatin by BAF complexes. The group also found other locations within the complex as to where known cancer mutations, contained in a database known as COSMIC (the Catalogue of Somatic Mutations in Cancer), structurally "cluster" and resolved their functions.

"Mapping such mutations on the structure of the BAF complex and understanding their functional impact has remained a major, unmet goal of the field at-large for decades," said Kadoch. "This marks the beginning of an era in which we will be able to functionally "group" mutations that define specific tumor features and inform therapeutic opportunities."

Researchers at the Cyber-Physical Systems Group at the USC Viterbi School of Engineering, in conjunction with the University of Illinois at Urbana-Champaign, have developed a new model of how information deep in the brain could flow from one network to another and how these neuronal network clusters self-optimize over time. Their work, chronicled in the paper "Network Science Characteristics of Brain-Derived Neuronal Cultures Deciphered From Quantitative Phase Imaging Data," is believed to be the first study to observe this self-optimization phenomenon in in vitro neuronal networks, and counters existing models. Their findings can open new research directions for biologically inspired artificial intelligence, detection of brain cancer and diagnosis and may contribute to or inspire new Parkinson's treatment strategies.

The team examined the structure and evolution of neuronal networks in the brains of mice and rats in order to identify the connectivity patterns. Corresponding author and Electrical and Computing Engineering associate professor Paul Bogdan puts this work in context by explaining how the brain functions in decision-making. He references the brain activity that occurs when someone is perceived to be counting cards. He says the brain might not actually memorize all the card options but rather is "conducting a type of model of uncertainty." The brain, he says is getting considerable information from all the connections the neurons.

The dynamic clustering that is happening in this scenario is enabling the brain to gauge various degrees of uncertainty, get rough probabilistic descriptions and understand what sort of conditions are less likely.

"We observed that the brain's networks have an extraordinary capacity to minimize latency, maximize throughput and maximize robustness while doing all of those in a distributed manner (without a central manager or coordinator)." said Bogdan who holds the Jack Munushian Early Career Chair at the Ming Hsieh Department of Electrical Engineering. "This means that neuronal networks negotiate with each other and connect to each other in a way that rapidly enhances network performance yet the rules of connecting are unknown."

To Bogdan's surprise, none of the classical mathematical models employed by neuroscience were able to accurately replicate this dynamic emergent connectivity phenomenon. Using multifractal analysis and a novel imaging technique called quantitative phase imagining (QPI) developed by Gabriel Popescu, a professor of electrical and computer engineering at the University of Illinois at Urbana-Champaign, a co-author on the study, the research team was able to model and analyze this phenomenon with high accuracy.

HEALTH APPLICATIONS

The findings of this research could have a significant impact on the early detection of brain tumors. By having a better topological map of the healthy brain and brain's activities to compare to--it will be easier to early detect structural abnormalities from imaging the dynamic connectivity among neurons in various cognitive tasks without having to do more invasive procedures.

Says co-author Chenzhong Yin, a Ph.D. student in Bogdan's Cyber Physical Systems Group, "Cancer spreads in small groups of cells and cannot be detected by FMRI or other scanning techniques until it's too late."

"But with this method we can train A.I. to detect and even predict diseases early by monitoring and discovering abnormal microscopic interactions between neurons, added Yin.

The researchers are now seeking to perfect their algorithms and imaging tools for use in monitoring these complex neuronal networks live inside a living brain.

This could have additional applications for diseases like Parkinson's, which involves losing the neuronal connections between left and right hemispheres in the brain.

"By placing an imaging device on the brain of a living animal, we can also monitor and observe things like neuronal networks growing and shrinking, how memory and cognition form, if a drug is effective and ultimately how learning happens. We can then begin to design better artificial neural networks that, like the brain, would have the ability to self-optimize."

USE FOR ARTIFICIAL INTELLIGENCE

"Having this level of accuracy can give us a clearer picture of the inner workings of biological brains and how we can potentially replicate those in artificial brains," Bogdan said.

As humans we have the ability to learn new tasks without forgetting old ones. Artificial neural networks, however, suffer from what is known as the problem of catastrophic forgetting. We see this when we try to teach a robot two successive tasks such as climbing stairs and then turning off the light.

The robot may overwrite the configuration that allowed it to climb the stairs as it shifts toward the optimal state for performing the second task, turning off the light. This happens because deep learning systems rely on massive amounts of training data to master the simplest of tasks.

If we could replicate how the biological brain enables continual learning or our cognitive ability for inductive inference, Bogdan believes, we would be able to teach A.I. multiple tasks without an increase in network capacity.

University of Guam researchers continue to expand knowledge of a unique group of plants called cycads. The world's contemporary cycad plants depend on small insects for pollination services. The Guam team's 2017 discovery of the new Cycadophila samara beetle and its pollination of cycads is now contributing to an international effort to more fully understand the intimate relationship between plant and insect.

The culmination of several decades of research on the subject is enabling a consortium of international scientists to describe the taxonomic relationships among the pollinators and their cycad hosts. The most recent compilation is published in the August issue of the journal Insecta Mundi, published by the Center for Systematic Entomology.

The most important step in biodiversity conservation is to first understand what is out there that is in need of protection, and the ongoing work on cycad pollinators highlights how little is known about the biodiversity of island habitats. How can the insular ecosystems of the islands of Guam and the Philippines be conserved if all of the biological connections that sustain the native organisms are not understood?

"The contributions from Guam expand the efforts of a synergistic team from India, Thailand, Vietnam, and the United States," said William Tang, lead author of the article. "The exploratory work of the scientists from the University of Guam has clarified which pollinators provide services to multiple Philippine cycad species."

Mutually dependent organisms equally threatened

The relationships between the insect pollinators and their cycad host plants are what scientists call mutualisms. The adult pollinators must find a male cycad cone in order to participate in regeneration of the next generation. Similarly, the male and female cycad trees must attract the services of the pollinators in order to adequately produce seeds. Neither organism can persist into the future without the other.

In addition to the beetle pollinating the Philippine cycads, the Guam-based work has led to an unexpected discovery that the Guam cycad tree relies on small moths as the pollinators rather than beetles.

"The cycad pollinators in the Philippines are cute little beetles, but the moth pollinator of the Guam cycad looks like something you might want to flatten with a flyswatter," said Benjamin Deloso, University of Guam cycad specialist.

Indeed, Guam's tiny brown moth pollinator largely goes unnoticed while it provides crucial pollination services to ensure the future of the endangered cycad tree.

The Guam team's extensive cycad research has also identified a native beetle stem borer that relies on the native cycad tree for larval food. These two native insect species that depend on the cycad tree in order to regenerate are no less threatened than the plant species.

Lessons learned for conservation

The continuing expansion of knowledge by the University of Guam research is showing how conservation planning should highlight the interplay among all three organisms, not just the cycad species.

The team's progress on cycad pollinators illuminates two phenomena that conservationists are expected to understand as they develop conservation plans.

First, linkages between organisms may break down and stop functioning properly if the population of one of the partners in the mutualism declines. For example, even if the cycad tree population persists in Guam's forests, if the intimate relationship between the tree and the moth pollinators becomes threatened, this may cause a subsequent collapse in the population of both native species.

Second, the concept of co-extinction should inform conservation decisions by honoring the fact when one of the organisms becomes locally extirpated, the second organism will also inadvertently become extirpated.

Global loss of flying insect pollinators

The timing of the new cycad pollinator publication comes at an age when documented global loss of flying insect pollinators is being highlighted as the precursor to an ecological Armageddon. Researchers have found that more than 40% of the world's insect species are at risk of extinction in the near future due to human activity. The value of insect pollination of crops is estimated to be at least $3 billion annually in the United States alone.

"Almost 90% of the world's flowering plants depend on animal pollinators," Deloso said. "Since most of the food crops of the world are flowering plants, the need to conserve the world's pollinators cannot be overstated."

Until a vaccine and/or effective cure for COVID-19 becomes available, battling the current pandemic strongly relies on how well people follow behavioural advice, such as adhering to local restrictions, social distancing rules, and engaging in effective personal hygiene. However, overcoming the relationship between risk perceptions and comparative optimism during the pandemic is a major hurdle for engaging the public in behavioural advice.

In a paper published in the journal Health Expectations, Health Psychologists and Sociologists from King's College London investigated comparative optimism for infection and recovery from COVID-19, and the implications this may have had on following lockdown advice. The study found that during the first lockdown period, most respondents believed that compared to others, they were unlikely to be at risk of COVID-19.

Dr Koula Asimakopoulou, Reader in Health Psychology at King's College London explains: "Comparative optimism is a well-established concept in health risk research, where people believe negative events are more likely to happen to others than themselves. Most people of all genders and ages show comparative optimism for a wide variety of risks, including many health hazards. For example, most people believe that they are less likely than others to be involved in a car accident."

Researchers believe that comparative optimism may have brought out the anecdotally observed, lack of compliance with lockdown guidelines in the UK. Despite public agreement for safety measures, 25% of the inhabitants of some areas admitted breaking lockdown rules. It is thought that people who perceive COVID-19 is less likely to happen to them than others may also believe strict adherence to lockdown restrictions is unnecessary in their case.

Using an online snowball sampling method through social media and anonymous UK surveys, researchers collected data from 645 UK adults during weeks 5-8 of the UK COVID-19 lockdown. The sample was normally distributed in terms of age, and reflected the UK ethnic and disability profile.

"Controllability of COVID-19 risk has been a prominent factor of the UK Government Public Health advice" said Dr Sasha Scambler, Senior Lecturer in Sociology at King's College London. "At the start of the lockdown the Government communication focused on the idea that staying home would have direct positive impacts on curbing COVID-19. The slogans Stay Alert, Control the Virus, Save Lives had at their heart the idea that this pandemic was controllable by individuals taking personal action. However, greater perceived controllability of an event enhances the likelihood of greater comparative optimism."

In contrast, participants showed comparative pessimism about COVID-19 infections for the more distant future. They felt that compared to others, they were quite likely to contract the virus in the next year and develop COVID-19 related symptoms, as staying at home would be less possible, plausible or practical.

"These perceptions will have important consequences for people's psychological well-being, and their likelihood of engaging in risk behaviours or responding to further lockdown measures which may soon be upon us", said Dr Asimakopoulou.

"If people continue to believe COVID-19 'will not happen to me' they may be more relaxed about future lockdown advice. We know that one of the factors that fuel comparative optimism is that people think that if a negative event has not happened to them so far, it is unlikely to happen to them in future.

"The implication for potentially walking into a second lockdown is that where people's experience so far may be that they have not been ill with COVID, they are likely to be even more comparatively optimistic than they were in March. Thinking that COVID has not happened to you so far so it is unlikely to happen to you now, can be even more dangerous than it was earlier in the spring."

Empathy for vulnerable people in risk groups motivates us to use face masks and keep our distance, so that we help to prevent the spread of COVID-19, according to the study, which has just been published in the journal Psychological Science.

"We show that empathy for the most vulnerable is an important factor, and that it can be used actively to combat the pandemic. I believe that policy makers can use our new knowledge in their efforts to get more people to follow the guidelines - and ultimately save lives," says Stefan Pfattheicher, an associate professor at the Department of Psychology and Behavioural Sciences at Aarhus BSS, Aarhus University.

He is heading the study in which researchers have initially tested the relationship between participants' empathy and their attitude to social distancing. They tested this in two questionnaire-based studies in the United States, the United Kingdom, and Germany. For example, on a scale from 1 to 5, participants were asked how concerned they are about those who are most vulnerable to the coronavirus. Subsequently, they were asked about the extent to which they themselves avoid social contact due to the coronavirus. The relationship is clear. The higher the degree of empathy, the greater the focus on reducing social contact.

Equally importantly, the study shows that it is possible to induce empathy among people, and thereby also make more people willing to keep social distance and wear face masks.

Real people induce empathy

In two experiments, the researchers tested the differences in participants' willingness to follow the two recommendations, depending on whether they are just informed about the effect of the two initiatives, or whether they are also presented with a vulnerable person. In the two experiments, the participants were presented with people who, each in their own way, have been affected by and suffer from the coronavirus. There were also control groups who only received information about the effect of keeping social distance and wearing face masks. And the conclusion is clear: The participants who received the story about people suffering from the coronavirus reported a higher degree of empathy. And also a greater willingness to physically distance and use face masks.

"Our results suggest that we need stories of real people suffering. It's not enough just to tell us that we must keep a distance and wear a face mask for the sake of vulnerable citizens in general. If we're confronted with a specific person who is vulnerable to COVID-19, it is clear that empathy is strengthened, and that we are more likely to follow the guidelines," says Stefan Pfattheicher.

"Our clear recommendation is that policy makers incorporate this knowledge using empathy in their communication initiatives," says Michael Bang Petersen, a professor at the Department of Political Science, and co-author of the scientific article.

The species richness of zoo and wild animals is reflected in the diversity of infectious agents they harbour. However, our knowledge is sparse and pathogen detection remains challenging. For streptococci, a bacterial family of importance to human and animal health, wildlife research has taken a step forward: A research team led by Kristin Mühldorfer from the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) and Tobias Eisenberg from the Hessian State Laboratory investigated the causes of severe respiratory disease in peccaries and taxonomically characterised a novel Streptococcus species (Streptococcus catagoni sp. nov.) based on its phenotypic properties and genetic features. The results, published in the International Journal of Systematic and Evolutionary Microbiology, contribute to a better understanding and reliable identification of this novel bacterial species.

The family Streptococcaceae consists of bacteria inhabiting the skin and mucous membranes and includes important pathogens. Despite Streptococcus species with a broad host range infecting humans and vertebrates, the family includes bacterial species that seems to be exclusively adapted to certain hosts or habitats, such as Streptococcus castoreus of beavers, Streptococcus didelphis of certain marsupial species or Streptococcus phocae of marine mammals and fish.

In the present paper the authors analysed a previously unknown Streptococcus species that was responsible over two consecutive years for severe disease in a group of Chacoan peccaries (Catagonus wagneri) kept in a zoo. Animals were mainly affected within the first year of life and showed suppurative infections of the upper and lower respiratory tract. At least five peccaries had died from the infection. The novel bacterial species has been named according to its origin as Streptococcus catagoni sp. nov.

„These are the first confirmed cases in Chacoan peccaries", says Dr Kristin Mühldorfer, scientist from the Leibniz-IZW. The Chacoan peccary is an endangered species that shows a continuing decline in its population size. "Unfortunately, we often do not know the impact of infectious diseases on wildlife populations and associated pathogens", says Mühldorfer. The reasons for these deficits include animal species richness, the lack of knowledge of wildlife health and restricted accessibility of wild animals in their habitats.

Novel infectious agents frequently occur in zoo and wild animals but they are often not identified with established test systems and data bases, thereby increasing time and methodical requirements of laboratories considerably. MALDI-TOF mass spectrometry provides a good solution because newly created reference spectra enable rapid and reliable bacterial identifications. The data base entries of Streptococcus catagoni were generated at the Chemical and Veterinary Analysis Agency Stuttgart and are available for exchange via the MALDI-TOF MS User Platform.

„We are glad to have established this successful collaboration of the participating institutions which we hope will continue", say Kristin Mühldorfer and Tobias Eisenberg. The microbiologists aim to characterise uncommon bacterial agents, their occurrence in specific hosts and importance for certain wildlife species. Modern approaches to wildlife disease will help to detect pathogens and develop diagnostics to overcome current limitations and support conservation efforts.

At present, the formation of galaxies is difficult to understand without the presence of a ubiquitous, but mysterious component, termed dark matter. Astronomers have measure how much dark matter there is around galaxies, and have found that it varies between 10 and 300 times the quantity of visible matter. However, a few years ago, the discovery of a very diffuse object, named Dragonfly 44, changed this view. It was found that this galaxy has 10,000 times more dark matter than the stars. Taken back by this finding, astronomers have made efforts to see whether this object is really anomalous, or whether something went wrong in the analysis of the observations. Now we have the answer.

An international team led by the Kapteyn Institute of the University of Groningen (the Netherlands), with participation by the Instituto de Astrofísica de Canarias (IAC) and the University of La Laguna (ULL), has found that the total number of globular clusters around Dragonfly 44 and, therefore, the dark matter content, is much less than earlier findings had suggested, which shows that this galaxy is neither unique nor anomalous. The result was recently published in Monthly Notices of the Royal Astronomical Society (MNRAS).

The galaxy Dragonfly 44 was discovered in a deep survey of the Coma cluster, a cluster with several thousand galaxies. From the start, the galaxy was considered remarkable by the researchers because the quantity of dark matter they inferred was almost as much as that in the Milky Way, the equivalent of a billion solar masses.

However, instead of containing around a hundred thousand million stars, as has the Milky Way, DF44 has only a hundred million stars, a thousand times fewer. This means that the amount of dark matter was ten thousand times greater than that of its stars. If this had been true, it would have been a unique object, with almost 100 times as much dark matter as that expected from the number of its stars.

Nevertheless, by an exhaustive analysis of the system of globular cluster around Dragonfly 44, the researchers have detected that the total number of globular clusters is only 20, and that the total quantity of dark matter is around 300 times that of the luminous matter, which means that it is not way outside the normal value for this type of galaxies.

"The fact that in our work we found only 20 globular clusters, compared with the 80 previously claimed, reduces drastically the amount of dark matter which the galaxy is believed to contain", explains Ignacio Trujillo, an IAC researcher and a co-author of the article. "Moreover, with the number of globular clusters we found, the amount of dark matter in Dragonfly 44 is in agreement with what is expected for this type of galaxies. The ratio of visible to dark matter is no longer 1 in 10,000 but one in 300", adds Trujillo.

"Dragonfly 44 has been an anomaly all these years that could not be explained with the existing galaxy formation models. Now we know that the previous results were wrong and that DF44 is not extraordinary. It is time to move on", points out Teymoor Saifollahi, researcher at the Kapteyn Institute and the first author of the article.

"Our work shows that this galaxy is not so singular nor unexpected. That way the models of galaxy formation can explain it without the need for modification", says Michael A. Beasley, another IAC researcher, specialist in globular clusters, and a co-author of the article.

The total number of globular clusters is related to the total mass of a galaxy. So, if the number of globular clusters is measured, the quantity of dark matter can be found, especially if the quantity of visible matter is only a small fraction of the total.

"However, we don't have a physical explanation for this relation between the total number of globular clusters and the total mass of the galaxy. This is purely observational knowledge. It could be that it has to do with the quantity of the original gas from which the stars, and the globular clusters themselves, have formed. The more dark matter there is in a galaxy, the more gas it contains", suggests Johan H. Knapen, an IAC researcher and also a co-author of the article.

SPOKANE, Wash. - One in four adults reported a change in alcohol use almost immediately after stay-at-home orders were issued, according to a study of twins led by Washington State University researchers.

The study, published recently in Frontiers in Psychiatry, surveyed more than 900 twin pairs from the Washington State Twin Registry from March 26 to April 5, 2020, just after stay-at-home orders were issued in Washington on March 23. An estimated 14% of survey respondents said they drank more alcohol than the week prior and reported higher levels of stress and anxiety than those who did not drink alcohol and those whose use stayed the same.

"We expected that down the road people might turn to alcohol after the stay-at-home orders were issued, but apparently it happened right off the bat," said Ally Avery, lead author of the study and a scientific operations manager at WSU's Elson S. Floyd College of Medicine. "It shows the need to make sure there is more mental health support since it had an impact on people right away."

Surprisingly, the study showed that the 11% who decreased their drinking also had higher levels of stress and anxiety than the groups with no change--suggesting that any change in alcohol use may be associated with mental health issues.

The study did not examine the reasons behind the link between a decrease in drinking and increase in stress and anxiety, but Avery said one possibility is that these were social drinkers who were missing out on after-work happy hours and other occasions where they drank with friends.

The researchers conducted the study with twins so that they could look at whether changes in alcohol use and mental health were mediated by genetic or shared environmental factors since twins raised in the same family share many formative experiences. Twins also have common genetics with fraternal twins sharing approximately half of their genes while identical twins share all of their genes.

In this study, the researchers found that the association between changes in alcohol use, and stress and anxiety were relatively small and confounded by between-family factors and demographic characteristics.

Still the link between the pandemic, alcohol use, and stress and anxiety is concerning, Avery said. The researchers are continuing to survey this group at longer intervals to see if the increased drinking persists and whether it becomes a bigger problem.

Storage jars form one of the main ceramic types which were produced and abundantly used ever since pottery was invented. The need to collect, store, and distribute agricultural products such as grains, oils and wine in large vessels has littered excavation sites with an abundance of ceramic jar fragments of various designs, sizes and shapes. However, for all of their variety, three Israeli archaeologists Hebrew University of Jerusalem's Ortal Harush, Israel Antiquities Authority's Avshalom Karasik and Weizmann Institute's Uzy Smilansky found an astonishing common denominator among storage jars in Israel over a period of 350 years: the inner-rim diameter of the jar's neck.

The distribution of this diameter is consistent with measurements of the palm of a (male) hand and, according to the authors, this match is not coincidental. It may reflect the use of the original metrics for the biblical measurement of the "tefach," a unit of measurement that was used primarily by ancient Israelites, appears frequently in the Bible, and is the basis for many Jewish laws. Their findings were published in BASOR, the Bulletin of the American Schools of Oriental Research.

"It was natural for the ancient potters to adopt the handbreadth--tefach--standard. It was a unit of length that was widely used in ancient times, and is mentioned both in Assyrian and Egyptian sources and in the Old Testament, for instance: Numbers 25-25, Numbers 37-12," the researchers shared.

The team did 3-D scans of 307 Iron-Age jars found in Khirbet Qeiyafa (Judah Kingdom; early 10th century BC), "hippo" jars from northern Israel (Israelite Kingdom, 9th Century BC--nicknamed for their large size and loop handles which resemble hippopotamuses) and royal Judah Kingdom storage jars (8-7th Century BC). The researchers observed large variations between the jars--even those from the same time period and geographic region. Only one measure remained constant: the averaged inner-rim diameter which always measured, with a standard deviation, between 8.85 and 8.97 centimeters.

The distribution of this diameter is statistically identical to the hand's breadth of modern man. To gain data on the standard measure of a modern man's palm, the team tapped measurements taken by the USA Army when ordering gloves for their soldiers, the mean value being 8.67±0.48 cm, which is consistent with the measurements taken from the ancient jars. Though human heights and weights have changed over time due to improved diet and health, previous research has shown that palm dimensions have not changed much over the last 3,000 years.

As to why the inner rim remained consistent while the overall shape of the jar varied so much, our Israeli group of researchers has several theories. It was a natural choice for ancient potters to use their palms as the standard diameter for jar openings--it was easy to implement when working on the wheel: the potter could simply use her/his palm as a tool. Further, storage jars were multiuse items, which meant their openings had to be large enough to allow for cleaning between uses and this involves fitting your hand into the jar.

However, there is another, ancient aspect which may explain the connection between the uniform neck diameters. It is based on the highly-regarded and observed purity laws in The Old Testament. The Book of Numbers deals with the question: What is the status of jars that were left in the vicinity of a corpse--are they impure or pure?

"This is the law, if a man dies in a tent, anyone entering the tent and anything in the tent shall be unclean for seven days. Any open vessel which has no seal fastened around it becomes unclean." (Numbers 19: 14-15)

It is clear from this passage that the contents of a jar become impure--and therefore unusable-- unless there is a special seal on its top. This ruling had serious economic ramifications. Imagine having to throw out valuable stores of grain and oil after Grandpa Ezekiel died in the family tent. Subsequent Jewish traditions quantified these rules of impurity, stating that the minimal opening size through which impurity may enter is the square of a hand's breadth by hand's breadth.

"Impurity does not enter a shelter, nor does it depart from it if there is an opening less than a handbreadth [tefach] by a handbreadth [tefach]." (14.1)

"According to the Oral Tradition, it was taught that the verse is speaking only about a ceramic container, for it is a container that contracts impurity only through its opening." (21.1) - Maimonides's Code of Jewish Religious Law, Mishneh Torah.

Here Maimonides brings down an ancient tradition vis a vis the laws of impurity, stating that a round opening with a maximum diameter of one hand's breadth, or tefach, would ensure that the jar's content would still be pure even if it were stored near a corpse. From here it would make sense that potters would create storage jars with a tefach, or hand's breadth, opening.

For the purposes of storage and transport, a jar opening should be small. On the other hand, pouring, cleaning and easy manufacturing would dictate a large opening, at least a hand's-width. Perhaps, the final convergence to a one handbreadth opening killed several birds with one stone and kept in mind the spiritual, legal traditions regarding the minimal window through which impurity could defile the contents of a ceramic vessel and thus make them unusable.

Over time, different rabbis attempted to provide conversions of the traditional biblical measurements to our modern measurement. The conversions for the tefach vary, with competing theories brought forth by Avraham Chaim Naeh and the Chazon Ish, both 20th century Orthodox rabbis who lived in pre-State Palestine. According to Rabbi Chaim Naeh, one tefach = 8 cm, whereas according to the Chazon Ish one tefach = 9.6 cm. The uniform opening of the ancient storage jars, which falls between 8.85-8.97 cm, falls squarely in between these two opinions and may shed light on the dimensions of the biblical tefach and, because we no longer hold by purity laws when it comes to the contamination of stored items, elucidate just how tall your sukkah can be, down to the last centimeter.

A research team from Cologne has discovered that a change in the DNA structure - more precisely in the chromatin - plays a decisive role in the recovery phase after DNA damage. The key is a double occupation by two methyl groups on the DNA packaging protein histone H3 (H3K4me2). The discovery was made by scientists under the direction of Prof. Björn Schumacher of the Cluster of Excellence for Aging Research CECAD, the Center for Molecular Medicine Cologne (CMMC), and the Institute for Genome Stability in Aging and Disease at the University of Cologne. The specific change enables genes to be reactivated and proteins to be produced after damage: The cells regain their balance and the organism recovers. The protective role of H3K4me2 was identified in experiments with the nematode Caenorhabditis elegans. The study has now been published in the journal Nature Structural & Molecular Biology.

The genome in every human cell is damaged on a daily basis, for example in the skin by UV radiation from the sun. Damage to the DNA causes diseases such as cancer, influences development, and accelerates aging. Congenital malfunctions in DNA repair can lead to extremely accelerated aging in rare hereditary diseases. Therefore, preservation and reconstruction processes are particularly important to ensure development and to maintain tissue function. DNA, which is rolled up on packaging proteins - the histones - like on cable drums, is regulated by methyl groups. Various proteins are responsible for placing methyl groups on histones or removing them. The number of groups on the packaging proteins affects the activity of genes and thus the protein production of the cell.

In experiments with the nematode, the research team showed that after repairing damaged DNA, two methyl groups were increasingly found on the DNA packages. Furthermore, they found that errors in placing these two methyl groups on the histones (H3K4me2) accelerated the damage-induced aging process, while increased position of this histone alteration prolongs the lifespan after DNA damage. By controlling the proteins that either set or remove these methyl groups, the resistance to DNA damage - and thus the aging process of the animals - could be influenced.

Further analysis of the role of these two methyl groups showed that the enrichment of H3K4 after genome damage with two methyl groups supports the cells in restoring the balance after DNA damage.

'Now that we know the exact changes in chromatin, we can use this to precisely limit the consequences of DNA damage,' said Schumacher. 'I hope that these findings will enable us to develop therapies for hereditary diseases characterized by developmental disorders and premature aging. Due to the fundamental importance of DNA damage in the aging process, such approaches could also counteract normal aging and prevent age-related diseases.'

A new IU study examining effects of low-level developmental lead exposure in mice could explain why some people dependent on alcohol return to using.

The study, published in Neuropharmacology, looked at whether developmental lead exposure can increase the propensity to relapse to alcohol consumption in mice. The researchers also looked at the effects on the expression of synaptic and non-synaptic glutamate transporters -- regulators of brain motivation and reinforcing circuits-- in brain regions associated with drug addiction.

"Our data in mice suggests that early life, low-level lead exposure does not lead to the development of an alcohol use disorder in adults per se," said Stephen Boehm, professor in the Department of Psychology at IUPUI. "However, it does alter brain circuits in such a way that once a dependency is developed, it makes it harder to refrain from turning back to alcohol."

Although there have been efforts to reduce environmental exposure to lead and to prevent lead poisoning, Boehm said exposure still exists and can cause serious harm and significant health problems, even at low levels. Studies of adults with a history of childhood lead exposure have consistently demonstrated cognitive impairments associated with sustained glutamate signaling.

Boehm and his team studied whether developmental lead exposure increased motivation to consume alcohol by testing mice in an alcohol self-administration paradigm.

The study suggests that low-level lead exposure for humans during childhood and adolescence - so low that kids growing up in old industrial cities might be exposed by merely kicking up dirt during normal play - may be sufficient to enhance relapse to alcohol use in adults struggling with alcohol use disorder.

Their study also suggests that reduced expression of proteins responsible for taking up the neurotransmitter glutamate in dorsolateral striatum - a brain region believed to be involved in the development of compulsive drug taking - may be associated with this effect. Glutamate is a key player in the executive control of dorsolateral striatal function. So, dysfunction in glutamate signaling may well have implications for the development of compulsive drinking (characteristic of individuals with alcohol use disorder).

Boehm said future work is needed, but the current project demonstrates the need for additional policies around environmental lead exposure.

"This study not only gives us further insight into addiction and the brain, but it might also lead to a call for changes in policies around lead exposure that could help keep our children safe."

A team of scientists led from Uppsala University have described the earliest known example of dentary bone with two rows of cusps on molars and double-rooted teeth. The new findings offer insight into mammal tooth evolution, particularly the development of double-rooted teeth. The results are published in the scientific journal PNAS.

The first mammals originated in the latest Triassic period, around 205 million years ago. An ancestor to mammals were the therapsids, "mammal-like reptiles" referred to as stem mammals or proto-mammals, which originated about 320-300 million years ago. One unique characteristic of the lineage that included mammals and animals related to mammals (synapsids) was that they developed complex occlusion. Close ancestors to mammals, called mammaliaforms, developed rows of cusps on molar-like teeth adapted for more omnivorous feeding. The origin of this multicusped pattern and double-rooted tooth has thus far remained unclear.

A team of scientists led by Grzegorz Niedzwiedzki from Uppsala University have investigated the jaw anatomy and tooth structure of a recently described new mammaliaform species named Kalaallitkigun jenkinsi. It was discovered on the eastern coast of Greenland and was a very small, shrew-like animal, probably covered with fur. It would have been the size of a large mouse and lived during the Late Triassic, around 215 million years ago.

"I knew it was important from the moment I took this 20 mm specimen off the ground," says Niedzwiedzki, researcher at Uppsala University and the corresponding author of the publication.

Kalaallitkigun jenkinsi exhibits the earliest known dentary with two rows of cusps on molars and double-rooted teeth. The anatomical features place Kalaallitkigun jenkinsi as an intermediate between the mammals and the insectivorous morganucodontans, another type of mammaliaform.

The researchers believe that the structural changes in the teeth are related to changed feeding habits. In this case study, the animals were switching to a more omnivorous/herbivorous diet and the tooth crown was expanding laterally. Broader teeth with "basins" on the top surface are better for grinding food. This development also forced changes in the structure of the base of the tooth.

The biomechanical analysis that was carried out within the study found that multi-rooted teeth are better able to withstand mechanical stresses, including those of upper and lower tooth contact during biting, compared to single-rooted teeth. Human teeth, for instance, have this characteristic. The results suggest that the development of molar-like teeth with complex crowns may have developed together with biomechanically optimised dual roots.

"The early evolution of mammals is a particularly interesting topic in evolutionary studies. This tiny jaw from Greenland shows us how complex mammalian teeth arose and why they appeared," says Niedzwiedzki.

"Our discovery of the oldest mammalian ancestor with double-rooted molars shows how important the role of teeth was in the origin of mammals. I had this idea to look at the biomechanics and the collaboration with the engineers turned out great," says Tomasz Sulej, researcher at the Polish Academy of Sciences, first author of the publication.

"It seems that the fossils of close mammalian ancestors must be looked for in even older rocks," says Sulej.

Scientists from Russia and Switzerland have probed into nanostructures covering the corneas of the eyes of small fruit flies. Investigating them the team learned how to produce the safe biodegradable nanocoating with antimicrobial, anti-reflective, and self-cleaning properties in a cost-effective and eco-friendly way. The protection coating might find applications in diverse areas of economics including medicine, nanoelectronics, automotive industry, and textile industry. The article describing these discoveries appears in Nature.

Scientists from Far Eastern Federal University (FEFU, Russia) teamed up with colleagues from University of Geneva, The University of Lausanne, and Swiss Federal Institute of Technology in Zurich for an interdisciplinary research project during which they were able to artificially reproduce the nanocoating of the corneas of fruit flies (Drosophila flies) naturally designed to protect the eyes of the insects from the smallest dust particles and shut off the reflection of light.

The craft of nanocoating meets demands in various fields of economics. It can wrap up any flat or three-dimensional structure, and, depending on the task, give it anti-reflective, antibacterial, and hydrophobic properties, including self-cleaning. The latter, for example, is a very important feature for expensive reusable overnight ortho-k lenses that correct the eyesight. Similar anti-reflective coatings are already known though created by more complex and costly methods. They are being used on the panels of computers, glasses, paintings in museums can be covered with them in order to exclude reflection and refraction of light.

"We are able to produce the nanocoating in any required quantity given that its design is more cost-effective compared to the modern methods of manufacturing similar structures. The work with natural components requires no special equipment nor significant energy consumption and constraints of chemical etching, lithography, and laser printing," Vladimir Katanaev explains, the head of the research and Head of the Laboratory of Pharmacology of Natural Compounds in the School of Biomedicine of FEFU. "The development has broad applications. For example, it could be the structural dying of textiles that would change the color depending on the angle of view. It is possible to create a disguise coat based on metamaterials, an antibacterial layer for medical implants, and a self-cleaning coating for contact lenses and windshields. We also believe that if we reinforce the nanocoating, it might be utilized as a basis of flexible miniature transistors prototypes designed for modern electronics."

Scientists managed to rebuild the corneal coating of small fruit flies via direct and reverse bioengineering methods. First, they took the protective layer apart into its constituent components, which turned out to be retinin (protein) and corneal wax (lipids) and then reassemble it under room temperature conditions, covering glass and plastic surfaces.

According to Vladimir Katanaev, any other types of materials can be nanocoated too. Combinations with different types of wax and genetic manipulations of the retinin protein allow the design of highly diverse and complex functional nanocoatings.

The scientist explains that the mechanism underlying the formation of the protective nanostructures on the corneas of Drosophila flies is a self-organizing process, described by Alan Turing back in 1952 as a reaction-diffusion mechanism. That is consistent with the mathematical modelling performed during the research. This mechanism is also responsible for the patterns forming, for example, on the fur of a zebra or a leopard. The nanostructures that protect the corneas of Drosophila eyes are the first established example of Turing patterns at the nanoscale.

In the course of the research project, scientists made a detailed characterization of the properties of retinin, as this protein has been little studied so far. It turned out that this initially unstructured protein forms a globular structure when interacting with corneal waxes. Thus, scientists took a look deep into the biophysical nature of the self-organization abiding to the Turing model, highlighting an important molecular process likely at the core of the self-organization - the initiation of the protein structuring.

At next stages, the research team aims at developing a model of three-dimensional nanostructuring (with nano-funnels, nanocolumns, nanorolls within the layer of the coating), also based on the Turing mechanism. This work would lie at the very frontier of modern scientific knowledge and can have promising fundamental and technological consequences.

Professor Vladimir Katanaev started studying the structure of the eye of Drosophila fly about 10 years ago. According to the scientist, the first data were obtained almost impromptu by means of atomic force microscopy. During collaboration with the laboratory of Prof. Igor Serdyuk from the Institute of Protein Research (Russian Academy of Sciences), it was discovered that the surface of the corneas of the flies was not smooth but was covered with beautiful patterns of pseudo-ordered nanoscale outgrowths. As it turned out, nanocoatings of this kind were described back in the late 1960s on the surface of the eyes of moths, larger insects to whom these structures also provide an anti-reflex function, reducing the reflection of incident light to zero and allowing to optimize light perception in the darkness.

(Boston)--Despite working for more than two decades to address underrepresentation of women in cardiology, disparities among cardiovascular professionals continue to exist. Profound inequities also exist for individuals underrepresented in medicine, such as African Americans, Hispanic Americans and Native Americans, who constitute 32 percent of the U.S. population but only eight percent of practicing cardiologists.

"The disparities amplified by the COVID-19 pandemic present disturbing evidence that we are far from cardiovascular healthcare equity in the work place," says Emelia J. Benjamin, MD, ScM, professor of medicine at Boston University School of Medicine (BUSM) and corresponding author of a Comment in the journal Nature Reviews Cardiology. "Individuals, leaders and institutions must prioritize research, policies, and structures to advance diversity, equity, inclusion, and belonging that is essential to advancing workforce excellence and cardiovascular health."

Diversity and equity in the health-care workforce have been shown to benefit patients and increase access to health care for underserved populations. Data also support that diverse organizations perform better and show more innovative thinking and problem-solving. In science, diverse teams by race, ethnicity and gender on average publish in higher impact journals than non-diverse teams; ethnically diverse teams on average had 10 percent more impact for papers and almost 50 percent higher impact for authors.

In the U.S. as well as in England and Australia, women constitute only a quarter of cardiology trainees, 15 percent of cardiologists and 4.8 percent of the interventional cardiologist workforce. According to Benjamin, over the past decade the number of female cardiology trainees has hardly increased and socioeconomic disparities between women and men cardiologists persists.

On average, women cardiologist still earn only approximately 92 percent of their male counterparts, translating to $2.5 million less over a 35-year career. In addition, Benjamin points to evidence of structural sexism persists such as a lack of sufficient childcare, adequate family leave policies, designation of endowed chairs and institutional responses to sexual harassment.

Evidence of structural racism includes an over reliance on board scores and rank of institutions.

Benjamin calls upon academic health sciences to engage in transformative personal and structural anti-racist, anti-sexist and anti-classist work to promote diversity, equity, inclusion and belonging (DEIB). "A DEIB commitment will harness the innovation of all voices in the academic field to collectively address profound, persistent global structural healthcare and workforce inequities."

To achieve equity in the cardiovascular workforce and health-care delivery, Benjamin believes DEIB must be explicitly addressed, funded, prioritized and quantified over time at the personal, local and health-care system level. "Only through establishing equity in the health-care workforce we can achieve global health-care equity."

Artificial intelligence has arrived in our everyday lives--from search engines to self-driving cars. This has to do with the enormous computing power that has become available in recent years. But new results from AI research now show that simpler, smaller neural networks can be used to solve certain tasks even better, more efficiently, and more reliably than ever before.

An international research team from TU Wien (Vienna), IST Austria and MIT (USA) has developed a new artificial intelligence system based on the brains of tiny animals, such as threadworms. This novel AI-system can control a vehicle with just a few artificial neurons. The team says that system has decisive advantages over previous deep learning models: It copes much better with noisy input, and, because of its simplicity, its mode of operation can be explained in detail. It does not have to be regarded as a complex "black box", but it can be understood by humans. This new deep learning model has now been published in the journal Nature Machine Intelligence.

Learning from nature

Similar to living brains, artificial neural networks consist of many individual cells. When a cell is active, it sends a signal to other cells. All signals received by the next cell are combined to decide whether this cell will become active as well. The way in which one cell influences the activity of the next determines the behavior of the system--these parameters are adjusted in an automatic learning process until the neural network can solve a specific task.

"For years, we have been investigating what we can learn from nature to improve deep learning," says Prof. Radu Grosu, head of the research group "Cyber-Physical Systems" at TU Wien. "The nematode C. elegans, for example, lives its life with an amazingly small number of neurons, and still shows interesting behavioral patterns. This is due to the efficient and harmonious way the nematode's nervous system processes information."

"Nature shows us that there is still lots of room for improvement," says Prof. Daniela Rus, director of MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL). "Therefore, our goal was to massively reduce complexity and enhance interpretability of neural network models."

"Inspired by nature, we developed new mathematical models of neurons and synapses," says Prof. Thomas Henzinger, president of IST Austria.

"The processing of the signals within the individual cells follows different mathematical principles than previous deep learning models," says Dr. Ramin Hasani, postdoctoral associate at the Institute of Computer Engineering, TU Wien and MIT CSAIL. "Also, our networks are highly sparse--this means that not every cell is connected to every other cell. This also makes the network simpler."

Autonomous Lane Keeping

To test the new ideas, the team chose a particularly important test task: self-driving cars staying in their lane. The neural network receives camera images of the road as input and is to decide automatically whether to steer to the right or left.

"Today, deep learning models with many millions of parameters are often used for learning complex tasks such as autonomous driving," says Mathias Lechner, TU Wien alumnus and PhD student at IST Austria. "However, our new approach enables us to reduce the size of the networks by two orders of magnitude. Our systems only use 75,000 trainable parameters."

Alexander Amini, PhD student at MIT CSAIL explains that the new system consists of two parts: The camera input is first processed by a so-called convolutional neural network, which only perceives the visual data to extract structural features from incoming pixels. This network decides which parts of the camera image are interesting and important, and then passes signals to the crucial part of the network - a "control system" that then steers the vehicle.

Both subsystems are stacked together and are trained simultaneously. Many hours of traffic videos of human driving in the greater Boston area were collected, and are fed into the network, together with information on how to steer the car in any given situation--until the system has learned to automatically connect images with the appropriate steering direction and can independently handle new situations.

The control part of the system (called neural circuit policy, or NCP), which translates the data from the perception module into a steering command, only consists of 19 neurons. Mathias Lechner explains that NCPs are up to 3 orders of magnitude smaller than what would have been possible with previous state-of-the-art models.

Causality and Interpretability

The new deep learning model was tested on a real autonomous vehicle. "Our model allows us to investigate what the network focuses its attention on while driving. Our networks focus on very specific parts of the camera picture: The curbside and the horizon. This behavior is highly desirable, and it is unique among artificial intelligence systems," says Ramin Hasani. "Moreover, we saw that the role of every single cell at any driving decision can be identified. We can understand the function of individual cells and their behavior. Achieving this degree of interpretability is impossible for larger deep learning models."

Robustness

"To test how robust NCPs are compared to previous deep models, we perturbed the input images and evaluated how well the agents can deal with the noise," says Mathias Lechner. "While this became an insurmountable problem for other deep neural networks, our NCPs demonstrated strong resistance to input artifacts. This attribute is a direct consequence of the novel neural model and the architecture."

"Interpretability and robustness are the two major advantages of our new model," says Ramin Hasani. "But there is more: Using our new methods, we can also reduce training time and the possibility to implement AI in relatively simple systems. Our NCPs enable imitation learning in a wide range of possible applications, from automated work in warehouses to robot locomotion. The new findings open up important new perspectives for the AI community: The principles of computation in biological nervous systems can become a great resource for creating high-performance interpretable AI--as an alternative to the black-box machine learning systems we have used so far."

Code Repository: https://github.com/mlech26l/keras-ncp