Culture

To simulate in a laboratory what happens in particle accelerators has been an ambitious goal in the study of the fundamental forces of nature pursued by high-energy physicists for many years. Now, thanks to research conducted by the groups of statistical physics of SISSA - Scuola Internazionale Superiore di Studi Avanzati and the "Abdus Salam" International Centre for Theoretical Physics (ICTP), that goal is closer to reach.

"We have dealt with a gauge theory, more precisely the Schwinger model, which mathematically describes the interaction between microscopic charged particles, like electrons and positrons, and an electric field in a spatial dimension,"
said Federica Surace, PhD student at SISSA and lead author of the research, recently published on Physical Review X. "We have shown that this theory can be simulated in an experiment with ultracold atoms better than what calculators have done to date. This experiment was conducted in Prof. Lukin's laboratory at Harvard University."

Investigating the fundamental forces of nature

The study, to which PhD students Paolo P. Mazza, Giuliano Giudici, Alessio Lerose, and their supervisors Andrea Gambassi of SISSA and Marcello Dalmonte of ICTP also contributed, shows that the experiment carried out overseas can be interpreted as a "quantum simulator" of a gauge theory, an important connection because it confirms the potential of the latter to investigate the mysteries associated with the fundamental forces of nature.

"The theories which describe the fundamental interactions, known as gauge theories, are behind our current understanding of the physics of the universe, and to understand their dynamics is one of the most important unanswered questions in theoretical physics," adds Alessio Lerose, co-author of the publication. "To infer from this the behaviour of matter in extreme conditions, as in high energy collisions between heavy atomic nuclei, inside the stars and the primordial universe post Big-Bang, is a very complex challenge which has severely tested the theoretical and computational methods available to physicists."

The gauge theories allow, for example, to understand what happens in experiments like those conducted at CERN in Geneva. "These phenomena are very complex" Federica Surace adds. "Due to their quantum nature, it is very difficult to make reliable predictions, even with the most modern and powerful computers."

Quantum Simulators

One of the methods devised to carry out this type of investigation is precisely that of quantum simulators, made up of components, typically atoms cooled at temperatures close to absolute zero which are controlled by laser and magnetic fields, whose behaviour is governed by mathematical equations similar to those of the systems which scientists want to study, but which are much easier to create.

"These tools," continues Surace, "allow to investigate the gauge theories using experimental equipment as large as a room instead of an accelerator which is tens of kilometres long. The research in this field is just beginning and this goal is still a long way off and yet the first results are encouraging".

This is demonstrated by the work of the physicists of SISSA and of ICTP, and it has already provided important proof of the potential of quantum simulators already available in the laboratory to study the theories behind our understanding of the Universe.

"We have demonstrated that the model implemented by the quantum simulator created in Harvard is none other than one of the simplest gauge theories but which, in any case, foresees highly non-trivial phenomena, such as vacuum decay and the confinement of elementary particles," explains Alessio Lerose, underlining the importance of this result to create a simulator that can be used for all quantum systems. "At present, there is no "universal simulator", namely a quantum device which can be programmed to simulate any other quantum system, but creating one is a key objectives of the research in this area of physics. Quantum simulators now exist that possess an excellent level of control that allows for simulation of less complex systems. In reality, we now know that with some further effort it is also possible to simulate more complex quantum theories, such as the Schwinger model which has been the protagonist of our study".

Spring has sprung earlier than ever before this year, accompanied by temperatures more typical of early summertime. Many plants were already in full bloom by mid-?April, about three to four weeks earlier than normal. These types of seasonal anomalies are becoming increasingly frequent due to climate change, and the resulting uncertainty threatens to disrupt the timing of mutualistic relationships between plants and their insect pollinators.

A research team led by ETH Professors Consuelo De Moraes and Mark Mescher has now discovered that one peculiar bumblebee behaviour may help to overcome such challenges by facilitating coordination between the bees and the plants they pollinate. The group has found that bumblebee workers use their mouth parts to pinch into the leaves of plants that haven't flowered yet, and that the resulting damage stimulates the production of new flowers that bloom earlier than those on plants that haven't been given this "nudge".

Their study has just been published in the journal Science. "Previous work has shown that various kinds of stress can induce plants to flower, but the role of bee-?inflicted damage in accelerating flower production was unexpected," Mescher says.

Surprising behaviour from bumblebees

The researchers first noticed the behaviour during other experiments being undertaken by one of the authors, Foteini Pashalidou: pollinators were biting the leaves of test plants in the greenhouse. "On further investigation, we found that others had also observed such behaviours, but no one had explored what the bees were doing to the plants or reported an effect on flower production," Mescher explains.

Following up on their observations, the ETH researchers devised several new laboratory experiments, and also conducted outdoor studies using commercially available bumblebee colonies - typically sold for the pollination of agricultural crops - and a variety of plant species.

Based on their lab studies, the researchers were able to show that the bumblebees' propensity to damage leaves has a strong correlation with the amount of pollen they can obtain: Bees damage leaves much more frequently when there is little or no pollen available to them. They also found that damage inflicted on plant leaves had dramatic effects on flowering time in two different plant species. Tomato plants subjected to bumblebee biting flowered up to 30 days earlier than those that hadn't been targeted, while mustard plants flowered about 14 days earlier when damaged by the bees.

"The bee damage had a dramatic influence on the flowering of the plants - one that has never been described before," De Moraes says. She also suggests that the developmental stage of the plant when it is bitten by bumblebees may influence the degree to which flowering is accelerated, a factor the investigators plan to explore in future work.

The researchers tried to manually replicate the damage patterns caused by bees to see if they could reproduce the effect on flowering time. But, while this manipulation did lead to somewhat earlier flowering in both plant species, the effect was not nearly as strong as that caused by the bees themselves. This leads De Moraes to suggest that some chemical or other cue may also be involved. "Either that or our manual imitation of the damage wasn't accurate enough," she says. Her team is currently trying to identify the precise cues responsible for inducing flowering and characterising the molecular mechanisms involved in the plant response to bee damage.

Phenomenon also observed in the field

The ETH research team was also able to observe the bees' damaging behaviour under more natural conditions, with doctoral student Harriet Lambert leading follow-?up studies on the rooftops of two ETH buildings in central Zurich. In these experiments, the researchers again observed that hungry bumblebees with insufficient pollen supplies frequently damaged the leaves of non-?blooming plants. But the damaging behaviour was consistently reduced when the researchers made more flowers available to the bees.

Furthermore, it was not only captive-?bred bumblebees from the researchers' experimental colonies that damaged plant leaves. The investigators also observed wild bees from at least two additional bumblebee species biting the leaves of plants in their experimental plots. Other pollinating insects, such as honeybees, did not exhibit such behaviour, however: they seemed to ignore the non-?flowering plants entirely, despite being frequent visitors to nearby patches of flowering plants.

Delicate balance starting to tip

"Bumblebees may have found an effective method of mitigating local shortages of pollen," De Moraes says. "Our open fields are abuzz with other pollinators, too, which may also benefit from the bumblebees' efforts." But it remains to be seen whether this mechanism is sufficient to overcome the challenges of changing climate. Insects and flowering plants have evolved together, sharing a long history that strikes a delicate balance between efflorescence and pollinator development.

However, global warming and other anthropogenic environmental changes have the potential to disrupt the timing of these and other ecologically important interactions among species. Such rapid environmental change could result in insects and plants becoming increasingly out of sync in their development, for example. "And that's something from which both sides stand to lose," Mescher says.

Osaka, Japan - Cells are like tiny self-contained machines that are constantly fine-tuned in response to both internal and external signals. Some of these signals are induced by extracellular ligands, specialized proteins that bind to specific receptors on the cell surface, stimulating signaling pathways and altering gene expression.

One such ligand, called pigment epithelium-derived factor, or PEDF for short, is involved in multiple biological functions. Depending on which of its many cellular receptors it binds to, and even the timing of the binding, PEDF can either promote cell survival or trigger cell death. But until recently, researchers had no idea how PEDF itself was regulated.

In a study published in scientific journal PNAS, a research team led by Osaka University finally explain how cells make sure PEDF is in the right place at the right time.

"Previous studies had shown that collagen binding is very important for the function of PEDF," explains lead author of the study Kazuki Kawahara. "Therefore, we investigated the influence of collagen binding on the function of PEDF by examining the crystal structure of PEDF in complex with collagen."

Collagen is one of the most abundant proteins in the web-like structure called the extra-cellular matrix that surrounds human cells. This tangle of proteins and carbohydrates not only helps hold cells together, but also allows them to communicate with one another. As cells mature, the collagen matrix undergoes remodeling, characterized by tighter binding between collagen fibrils.

"The crystal structure revealed that PEDF binds to a cryptic site on the surface of type I collagen, where it is sequestered away from the cellular receptors," says Kawahara.

However, the researchers also found that a lysine residue in the binding site is involved in the crosslinking of collagen chains during collagen remodeling.

"We showed that PEDF binds to newly synthesized collagen but is gradually displaced as crosslinking increases," says senior author Yuji Kobayashi. "In this way, collagen controls the spatiotemporal accessibility of PEDF, regulating its interaction with target cell surface receptors."

PEDF has known anti-tumor and anti-angiogenic activities. Interestingly, the researchers found that PEDF selectively destroys developing vessels by binding to the newly synthesized collagen that is abundant on endothelial cells, which may then allow interaction with cellular receptors. This activity likely helps maintain homeostasis during tissue remodeling.

The researchers hope that this new information on the spatiotemporal control of PEDF will help in the development of novel therapies for cancer and vascular disease, as well as in the design of therapeutic biomaterials that target angiogenesis.

Antibodies for potential use as medicines can be made rapidly in chicken cells grown in laboratories. Researchers refer to their technique as the human ADLib system, short for autonomously diversifying libraries. The technique automatically builds vast numbers, or libraries, of diverse antibodies using chicken immune system cells' natural method for shuffling their genes.

Often shaped like the letter Y, antibodies are produced by the immune system to fight infections and prevent re-infection. Small portions of that Y shape are highly variable. Antibodies use their unique shape to form a perfect molecular hug with specific antigens, molecules on the surface of the cause of an infection. To effectively eliminate an infection, antibodies must recognize, attach and stay attached to an antigen.

"Our ADLib system can generate human antibodies against various antigens faster than existing methods," said Hidetaka Seo, a project researcher at the University of Tokyo and first author of the recently published scientific paper.

In standard techniques, individual antibodies are first identified and then produced through a slow, multistep process involving bacteria, animal cells, or sometimes isolating antibodies from the blood of vaccinated or infected animals, and then modifying those animal antibodies for safe human use.

The first ADLib system was developed in 2005 by some members of the current research team, who at the time were working at the RIKEN research institute outside of Tokyo. The original ADLib system produced chicken antibodies using chicken immune system cells. In the years since, other researchers have generated human antibodies in whole live chickens.

"We had the idea for the human ADLib system at that time, but the technology was very difficult to develop," said Professor Kunihiro Ohta, a co-author of the recent research paper, who led the original ADLib research group at RIKEN and is currently dean of the Graduate School of Arts and Sciences at the University of Tokyo.

"This is the first case of human gene recombination sequences capable of providing practical antibody libraries being developed using avian cells grown in a laboratory," said Seo.

To develop the human ADLib system, researchers first inserted human genes to replace the chicken immune cells' antibody genes and the surrounding units of DNA known as pseudogenes. The cells then grow in a dish and multiply for several weeks, generating antibody genes of various new combinations. This random antibody-generator quality of the ADLib system leads to many useless antibodies, but it may generate more efficient antibodies than the "built-for-purpose" antibodies that a human or animal immune system naturally produces during an infection.

Separately, researchers coat tiny magnetic beads with antigens of interest. Finally, the chicken cells are burst open and the contents are washed over the magnetic beads. Any antibodies that stick to the antigen-coated magnetic beads are added to the antibody library. After isolating antibodies on the magnetic beads, the entire process of identifying them and checking their specificity can be completed within about 10 days. Researchers state this is much faster than conventional antibody generation methods, which can take a few months.

Many variations of antibodies might be able to bind an antigen, but staying attached is essential for proper immune function. The human ADLib system includes a second phase to strengthen antibodies' ability to attach and stay attached to their antigens, a process called binding affinity maturation.

Although binding affinity maturation is laborious in conventional methods, the human ADLib system provides a simple and effective method. Chicken cells with the desired antibodies are grown in the lab for another short period to further moderately diversify the antibody genes. Antibodies with stronger binding affinities to the antigen can be isolated from this second library.

Researchers have successfully achieved about a hundredfold improvement of the binding affinity.

Researchers have so far tested the human ADLib technique to find antibodies similar to those currently used to treat certain types of cancer.

"In the future, antibodies for therapeutics to overcome currently unmet medical needs could be generated by using the human ADLib system," said Yukoh Nakazaki, a co-author of the recent research paper and head of the research labs at Chiome Bioscience Inc. Chiome is improving this technology in partnership with the University of Tokyo.

The ADLib system is not limited to generating antibodies.

"If we replace the relevant chicken genes and pseudogenes with any other gene of interest, we could generate libraries of other proteins for agricultural, veterinary, or medical uses," said Seo.

There is an extremely high probability that individuals with 22q11.2 micro deletion syndrome - a rare genetic disorder - will develop schizophrenia together with one of its most common symptoms, auditory hallucinations. Scientists at the University of Geneva (UNIGE) and the Synapsy National Centre of Competence in Research (NCCR) have been studying this category of patients. They have succeeded in linking the onset of this hallucinatory phenomenon with the abnormal development of certain substructures of a region deep in the brain called the thalamus. These thalamic nuclei have been identified using a combination of functional and structural magnetic resonance imaging. They are involved in processing memory and hearing among other things. The authors suggest that there might be an explanation for these auditory hallucinations that is almost "mechanical": the immaturity of the axon connections that bind the thalamic nuclei to the cortex areas responsible for hearing. The results, published in the journal Biological Psychiatry: CNNI, pave the way for a new understanding of the pathophysiology and treatment of schizophrenia.

Several studies in recent years have demonstrated a link between schizophrenia and abnormalities in the development of the thalamus, a deep brain region that processes a number of cognitive functions, including working memory and hearing. More specifically, the volume of the thalamus is smaller on average in schizophrenic patients. Accordingly, it has been possible to link the onset of auditory hallucinations with an overly-intense neuronal connectivity between the thalamus and auditory cortex. An auditory hallucination is defined as the perception of sound in the absence of an external sound source. It is one of the most characteristic symptoms of schizophrenia, a psychotic disorder that affects approximately 1% of the population.

"We used a cohort of patients that is unique in the world in an attempt to analyse the mechanism behind this hallucinatory phenomenon in more detail," begins Stephan Eliez, a professor in the Department of Psychiatry in UNIGE's Faculty of Medicine. "For the last 19 years, a program backed by the University of Geneva has helped us enlist and monitor individuals suffering from a rare neurogenetic syndrome: 22q11.2 micro deletion syndrome, which is caused by the absence of a small piece of DNA in chromosome 22. These patients are often prone to auditory hallucinations among other things. More importantly, 30 to 35% of them develop schizophrenia during their lifetime. This is the category with the highest risk of falling victim to the psychotic disorder."

Monitoring from childhood to adulthood

This cohort, made up of over 200 patients living in Switzerland, France, Belgium, Luxembourg and England, represents a unique opportunity to follow individuals from childhood to adulthood and submitting them to a regular battery of tests (medical imaging, genetic analyses, etc. ). It offers the chance to understand the neuro-developmental processes involved in the onset of schizophrenia and possibly to determine potential treatments that could delay, slow down or even halt the progression of psychotic symptoms.

The study focused on 230 people aged 8 to 35 years: 120 from the cohort and 110 healthy individuals who served as controls. Participants underwent a brain scan every three years using functional and structural magnetic resonance imaging. They were not given any task to complete: the machine simply recorded the brain activity generated by floating thoughts activating the major neural networks by turns. The scientists focused in particular on the various sub-structures of the thalamus that each has its own functions.

Unparalleled precision

"We discovered that the thalamic nuclei involved in auditory and visual sensory processing and working memory are smaller in people with deletion syndrome than in others," explains Valentina Mancini, a researcher in UNIGE's Department of Psychiatry and the article's first author. "And among people with deletion syndrome, the volume of the medial geniculate nucleus (the MGN, one of the sub-parts of the thalamus involved in the auditory pathways) and that of the other nuclei used in memory are smaller in the group with auditory hallucinations relative to the group that doesn't experience any. The size of the MGN differs between the two groups from childhood with a divergent developmental trajectory".

The scientists made a further observation: in the patients suffering from auditory hallucinations, they noticed a hyper-connectivity between the thalamic nuclei and cortical areas devoted to the primary processing of hearing and Wernicke's area, which is highly significant for understanding language. This type of thalamo-cortical hyper-connection is normal during childhood, when the neural networks are being formed. The fact that it persists during adolescence and then into adulthood is the sign that the connections have never reached maturity.

"This characteristic could provide an almost mechanical explanation for the hallucinatory phenomenon in these patients," notes Stephan Eliez. "Our results also open up new perspectives for the more general understanding of the pathophysiology of schizophrenia. Identifying the markers that foreshadow the development of the disease in such detail gives us many new targets for action using specific neuroprotective drugs, for example, to prevent symptoms as much as possible."

GP's notes currently unavailable to medical researchers could provide clues to help manage major health crises - like COVID-19.

And according to a 'citizens' jury' study at Brighton and Sussex Medical School (BSMS), the main thing stopping the use of such information - concerns over patient privacy - could be overcome.

Lead author, Dr Elizabeth Ford, Senior Lecturer in Primary Care Research at BSMS
said: "In these times of a new and unknown disease like COVID-19, we really need all the health data we can get, in order to develop effective treatment quickly. For example, we've seen that the number of 'excess' deaths over the last few months doesn't tally with the number of actual deaths attributed to Coronavirus. Maybe information recorded by doctors during patient consultations could give us vital clues to understand these missing diagnoses?

"Patient notes, letters and reports held within medical records contain a range of valuable information that is currently unavailable to researchers. Understandably, there are concerns about private details being made available for research but if we can find a way past that, research could benefit public health hugely. That's why we ran this study, and found that although they were cautious about privacy, members of the public were largely supportive of the information being made available to university researchers."

Currently the structured parts of patients' medical notes are used in an anonymised way for health research, helping to develop major improvements in health care. Until now, however, the patient notes, where a doctor might write a summary regarding a patient's visit, and letters and reports following scans or visits to hospital, have not been available for health research - largely due to concerns about protecting privacy. Advances in computer science and text analytics mean that researchers are now able to extract specific clinical information from large quantities of patient documents and analyse many patient records at once.

During a three-day citizens' jury, 18 members of the public heard a range of expert presentations and arguments for and against sharing free text (from patient letters and notes from general practice and mental health care), and then questioned presenters and deliberated together.

Dr Ford said: "Jurors were largely supportive of using patient notes and letters for medical research, but felt people had the right to know what their medical data might be used for, so they could choose to opt out. They also wanted to see a clear commitment to improving technology to protect patient privacy.

"While this was obviously a small study on a complex subject, the results show a public interest in making free text data available to health researchers. Next steps would involve a larger study to gauge wider public interest in how we might be able to make such health information available while protecting patient privacy."

Few species develop as slowly as humans, both in terms of developing adult skills and in terms of brain development. Human infants are born so underdeveloped that they cannot survive without adult care and feeding for some years after birth. Children still need to learn fundamental skills such as walking, eating, talking, using tools and much more. The timing of when these developmental milestones emerge is used by doctors to determine if your child and your child's brain are developing normally. However, we know little about the timing of when motor and social developmental milestones emerge in other long-lived, closely-related species, such as chimpanzees; nor what this means for their brain development. For example, when do chimpanzees start to walk, feed themselves, groom others and use tools? Fully charting development milestones in wild chimpanzees and other species can help us understand the evolutionary basis of such extended developmental periods.

Researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig have now systematically mapped a wide array of behavioural skills and determined at which point during development these skills emerge in wild chimpanzees. For this study, the researchers observed 19 chimpanzee infants (eight females and 11 males) from the Taï National Park, Côte d'Ivoire, from the first month after they were born until five years of age. The results showed that gross motor skills begin to emerge at around four months, communication traits at 12 months, social interaction skills at 14 months and fine motor skills at 15 months. "Not only the time frame, but also the order of emergence of the different skills is very similar to what we see in humans, reflecting a shared evolutionary history", says first author Aisha Bründl. "Our findings are in line with the delayed benefits hypothesis, which states that extended development is necessary for acquiring adult skills."

"Such developmental milestones may shed light on the maturation of the brain", says senior author Catherine Crockford, a co-leader of the Evolution of Brain Connectivity (EBC) project of the Max Planck Society. "Our findings suggest that some parts of the chimpanzee brain may develop slowly like in humans". This remains to be investigated as part of this new EBC-project, a collaboration between the Max Planck institutes for Evolutionary Anthropology and for Human Cognitive and Brain Sciences, in the context of which researchers collect, scan and analyse post mortem brains of great apes and relate these findings to ape behaviour.

In addition, the researchers found that more complex skills, like tool use and social interactions, emerge later, with larger differences between individual chimpanzees in when they emerge than less complex skills. "This variation may be caused by underlying differences in the social environment a chimpanzee is growing up in, but also other factors such as nutrition, and remains to be investigated further", explains co-author Patrick Tkaczynski.

"Such a developmental study requires long-term data, since chimpanzees have a similarly slow life history as humans", Roman Wittig, another senior author on the study and director of the Taï Chimpanzee Project points out. "We are lucky to have 40 years of observations on the same wild chimpanzees." Overall, this study is the most extensive description of developmental milestones in chimpanzees to date and brings us a step closer to shedding light on shared developmental pathways of great ape species.

At any given moment, a variety of dynamic processes occur inside a cell, with many developing over time. Because current research methods for gene profiling or protein analysis destroy the cell, study is confined to just that one moment in time, and researchers are unable to return to the cell to examine how things change beyond that snapshot.

A team led by Northwestern Engineering faculty has developed a minimally invasive method to sample cells that can be repeated multiple times, one of the first to do so. The process, called localized electroporation, has implications in studying processes that evolve, such as cells' response to treatments for cancer and other diseases.

Horacio Espinosa, James N. and Nancy J. Farley Professor in Manufacturing and Entrepreneurship in the McCormick School of Engineering, led the team that created the live cell analysis device (LCAD), which can non-destructively sample the contents from small number of cells many times.

When LCAD is coupled with SAMDI, a highly sensitive and label-free method for quantification of enzymatic activity using mass spectrometry, the intracellular contents sampled by LCAD are then analyzed for the presence of enzymes. SAMDI (Self-Assembled Monolayer Desorption Ionization) was developed in the lab of Milan Mrksich, Northwestern University vice president for research and Henry Wade Rogers Professor of Biomedical Engineering, Chemistry, and Cell and Molecular Biology.

"By exploiting advances in microfluidics and nanotechnology, localized electroporation can be employed to temporarily open small pores in the cell membrane enabling the transport of molecules into the cells or extraction of intracellular contents. Since the method is minimally invasive to the cells, it can be repeated multiple times without their disruption," Espinosa said.

"Certain enzymes may be linked to disease pathways, such as certain types of cancers, and they may be the target of therapeutics. Using this platform, it is now possible to study how enzymatic activity varies between healthy cells and cells from a tumor biopsy," Mrksich said.

The LCAD-SAMDI platform offers an opportunity for biologists and physicians to investigate how specific treatments may alter these enzymatic activities and the associated diseases over time.

"The platform is one of the world's first technologies allowing this type of research, a biopsy but performed on cells at the nanoscale," Espinosa said.

Said John A. Kessler, Ken and Ruthe Davee Professor of Stem Cell Biology at Northwestern's Feinberg School of Medicine and study coauthor, "Without disrupting the cell, it provides a window to processes inside cells and enables research that can determine the quantity of an active enzyme, how enzymatic activity in cells changes over time, and what changes in the activity occur in response to a treatment."

This method opens up the possibility to investigate time-dependent processes, like cell differentiation, disease progression, or drug response, at regular intervals.

"We envision that this technique can be used in scenarios such as screening drugs or designing and optimizing treatment courses that can arrest disease progression in cells," Espinosa said.

Most established methods require killing the cells being analyzed. Currently, complex computational methods are used for retrieving temporal information from single snapshots, but assumptions about the dynamics and limitations on the time scales and scenarios remain.

The LCAD also can be used to deliver proteins into cells. The combination of delivery and sampling could potentially be used in studies involving delivery of molecules, like DNA and proteins, and investigating its effect on the activity of another via sampling.

"We have used the same concept of localized electroporation to do CRISPR gene editing and we are now using machine learning to automate the process," Espinosa said.

Overall, this method can provide complementary information regarding cellular dynamics, which may not be possible using traditional assays. In the future, as the technology improves and sensitivity increases, it may be possible to sample temporal information for several different types of proteins simultaneously from the same cell populations.

DALLAS, May 26, 2020 -- Higher spirituality among stroke survivors was strongly linked to better quality of life for them and their caregivers who may also feel depressed, according to new research published today in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal. May is American Stroke Month.

For many stroke survivors, a caregiver, often a family member or close friend, may help with daily tasks, making the survivor and the caregiver prone to depression. Depression can impact quality of life for both.

Roughly 200 stroke survivors in Italy, with low-to-medium disabilities and no other major health issues, and their caregivers completed questionnaires measuring spirituality, depression and quality of life between 2016 and 2018. Women and men were nearly equally represented among the stroke survivors, and their average age was 71 years. Among the caregivers, women comprised nearly two-thirds, and their average age was 52.

Spirituality is defined by the World Health Organization (WHO) as an individual's perception of life within the context of the culture and value systems of the society and in relation to the individual's goals, expectations, standards and concerns. "Research shows that spirituality may help some patients cope with illness, yet few studies have looked at its effects on quality of life among stroke survivors and their long-term care partners, who are at increased risk for depression," said lead study author Gianluca Pucciarelli, Ph.D., FAHA, research fellow at the University of Rome in Italy.

Quality of life was measured with a 26-item WHO questionnaire on physical, psychological, social and environmental aspects.

In this analysis, those who scored one-standard deviation above average were considered to have "higher spirituality."

Researchers noted at baseline:

A strong relationship between the degree of spirituality and quality of life even if caregivers were depressed.

Stroke survivors who scored above average on the spirituality questionnaire reported higher psychological quality of life even when their caregivers reported symptoms of depression.

Similarly, the caregivers with above-average spirituality scores reported better physical and psychological quality of life.

In contrast, stroke survivors who scored below average on the spirituality questionnaire had lower quality of life, overall, as did their caregivers with depression symptoms.

"In summary, when care partners feel depressed, something that is common for stroke caregivers, the survivor's spirituality made the difference in whether this was associated with better or worse quality of life. This demonstrates the important protective role of spirituality in illness, and why we must study it more," Pucciarelli said.

He noted that the findings call for greater awareness on the importance of spirituality among health professionals.

"Our study emphasizes the importance of viewing stroke survivors holistically, as a patient with symptoms and disabilities, and as an individual with emotional needs and part of an interdependent unit with their care partner," Pucciarelli said.

The predominant religion in Italy is Roman Catholicism, which could have affected the results. Also, the study included only stroke survivors with low-to-medium disabilities and no other major health issues, so the study's findings may not apply to survivors with more severe disabilities or other underlying illnesses.

A child's unique brain activity reveals how good their memories are, according to research recently published in JNeurosci.

When you scramble to remember a phone number as you enter it into your phone, you rely on your working memory to keep the number at the front of your mind. Briefly holding and manipulating information relies on the activity of the frontoparietal network, a group of brain regions coined the "cognition core." Working memory performance changes throughout development, but can an individual's memory facility be determined based on brain activity?

Rosenberg et al. analyzed fMRI data from the Adolescent Brain Cognitive Development (ABCD) data set, a repository of scans and behavioral tests from over 11,000 children aged nine and ten. Children with better working memory performed better on a range of cognitive, language, and problem-solving tasks. Activity in the frontoparietal network during a memory task reflected the individual working memory capabilities of the children, with an activity pattern unique to working memory. The ABCD data set will reexamine the children for ten years, allowing future studies to explore how the neural signature of working memory evolves across development.

A team led by scientists from the Institut Jacques Monod (CNRS/Université de Paris)* have shown that French prehistory was punctuated by two waves of migration: the first during the Neolithic period, about 6,300 years ago, the second during the Bronze Age, about 4,200 years ago. This study, published in PNAS on May 25, which looked at the genomes of 243 ancient individuals over 7,000 years, demonstrates how admixture between native hunter-gatherers and the first Anatolian Neolithic migrants, who brought with them a lifestyle based on agriculture, persists to this day in the genomes of French people. Admixture of the Neolithic populations with those from the Pontic steppes**, who arrived 4,200 years ago in what is now France, also left a lasting imprint, with the Y chromosome of the majority of French men still bearing the signature of men from the steppes.

When University of Ottawa biologists Kim Mitchell and Vance Trudeau began studying the effects of gene mutations in zebrafish, they uncovered new functions that regulate how males and females interact while mating. We sat down with senior author Professor Trudeau, Research Chair in Neuroendocrinology at the Faculty of Science, to learn more.

Please tell us about this research project.

Kim and I were working with international collaborators from the Institute of Hydrobiology at the Chinese Academy of Sciences in Wuhan. Using gene editing technology set up by our Chinese colleagues, we mutated two related genes and studied the effects on sexual function in zebrafish. They are freshwater fish belonging to the carp and minnow family that are now a widely used model organism in biomedical research.

What did you discover?

We changed the secretogranin-2 genes through specific mutation and found that it affected the ability of females and males to breed. It severely reduced their sexual behaviour.

The fish look normal, but when both sexes are put together, they almost ignore each other!

Normally, within a few minutes after a male and female are introduced for the first time, the male chases the female in a courtship ritual, and shortly therefore they spawn - that is to say, the female releases her eggs to the water, and the male instantly fertilizes them. But we found that only 1 in 10 of the couples with mutated genes could spawn.

The couples carrying the introduced mutations produce eggs and sperm, but they are simply terrible at mating with each other.

This is the first evidence that mutation of these genes leads to disruption of sexual behaviour in any animal.

What role does secretogranin-2 play?

Secretogranin-2 is a large protein that is important for the normal functioning of brain cells and other cells that secrete hormones to control body functions such as growth and reproduction. However, this protein can get chopped up by special enzymes and we found that one small fragment called the secretoneurin peptide is important for stimulating sexual function.

In the genetically altered fish, we can partially restore sexual function by a single injection of the secretoneurin peptide into the body. We believe the peptide acts on cells in the brain and pituitary gland to increase hormone release thereby enhancing the ability of the female to ovulate and lay her eggs.

Why is this important?

We have uncovered new genes that can regulate reproduction, and the secretoneurin peptide is therefore itself a new hormone. The secretoneurin produced in fish is remarkably similar to that found in other animals, including humans. We can now use our genetically modified fish to look for other factors that could enhance sexual function, be it for increased spawning in cultured fish species, or to help with the search for new human infertility treatments.

This is just the beginning of the possibilities. The large secretogranin-2 genes may produce many other hormone-like peptides with unknown functions. It will be exciting to explore this in future research projects.

Patients with heart failure who experience low health literacy are at an increased risk of hospitalization and mortality. This finding has significant clinical and public health implications and suggests that assessing and intervening upon an individual's understanding of their own health could improve heart failure outcomes, according to research published in JACC: Heart Failure.

Heart failure is a chronic condition that requires patients to engage complex self-management skills to monitor weight and blood pressure, control glycaemia, stick to drug and diet guidelines, and occasionally lose weight and exercise. Therefore, greater attention has recently been given to health literacy, which is defined by the authors of this study as "the degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions."

Previous studies have suggested that low health literacy among patients with heart failure could be associated with higher risk of mortality, hospitalizations and emergency department visits, but results have been inconsistent. Researchers in this study sought to determine the effect of health literacy on mortality, while adjusting for important potential confounders, on hospitalizations and emergency department visits among heart failure patients, the first meta-analysis of its kind.

Researchers, with the assistance of a medical librarian, conducted a systematic review across EMBASE, MEDLINE, PsycInfo and EBSCO CINAHL databases from inception to Jan. 1, 2019. Both observational and interventional studies evaluated the impact of health literacy among patients 18 years or older with heart failure on mortality, hospitalizations and emergency department visits for all causes. Interventional studies evaluated interventions among patients with heart failure who had low health literacy. Among the observational studies, 9,171 heart failure patients were included, of which 2,207 (24%) had inadequate or marginal health literacy.

In the studies reviewed, health literacy was assessed using objective or subjective measures--objective health literacy measurement tools evaluate how much the patient comprehends medical information and subjective measurement tools evaluate how much the patients think they understand.

The researchers found that low health literacy was associated with higher unadjusted risk for mortality (RR: 1.67, 95%CI: 1.18, 2.36), hospitalizations and emergency department visits. In adjusted analyses, low health literacy remained statistically associated with mortality and hospitalizations, but no correlation was found for emergency department visits. Among the four interventional studies, two effectively improved outcomes for heart failure patients with low health literacy.

"Our findings showed that an inadequate level of health literacy is associated with increased risks in mortality and hospitalization among patients with Heart Failure," said Lila J. Finney Rutten, PhD, an author of the study and professor of health services research in the Department of Health Sciences at Mayo Clinic in Rochester, Minnesota. "Identifying health literacy as a factor that affects health outcomes and measuring its effect on patients with Heart Failure is essential to allocate more resources for, and research on, interventions to improve health literacy."

Study limitations include the exclusion of publication bias evaluation due to the small number of studies for each outcome, health literacy studies were evaluated with different tools, which could limit comparability, and uncertainty if a health literacy assessment was done in an outpatient or inpatient setting, which may have influenced measurement.

Researchers have found a way to design an antibody that can identify the toxic particles that destroy healthy brain cells - a potential advance in the fight against Alzheimer's disease.

Their method is able to recognise these toxic particles, known as amyloid-beta oligomers, which are the hallmark of the disease, leading to hope that new diagnostic methods can be developed for Alzheimer's disease and other forms of dementia.

The team, from the University of Cambridge, University College London and Lund University, designed an antibody which is highly accurate at detecting toxic oligomers and quantifying their numbers. Their results are reported in the Proceedings of the National Academy of Sciences (PNAS).

"There is an urgent unmet need for quantitative methods to recognise oligomers - which play a major role in Alzheimer's disease, but are too elusive for standard antibody discovery strategies," said Professor Michele Vendruscolo from Cambridge's Centre for Misfolding Diseases, who led the research. "Through our innovative design strategy, we have now discovered antibodies to recognise these toxic particles."

Dementia is one of the leading causes of death in the UK and costs more than £26 billion each year, a figure which is expected to more than double in the next 25 years. Estimates put the current cost to the global economy at nearly £1 trillion per year.

Alzheimer's disease, the most prevalent form of dementia, leads to the death of nerve cells and tissue loss throughout the brain, resulting in memory failure, personality changes and problems carrying out daily activities.

Abnormal clumps of proteins called oligomers have been identified by scientists as the most likely cause of dementia. Although proteins are normally responsible for important cell processes, according to the amyloid hypothesis, when people have Alzheimer's disease these proteins -including specifically amyloid-beta proteins - become rogue and kill healthy nerve cells.

Proteins need to be closely regulated to function properly. When this quality control process fails, the proteins misfold, starting a chain reaction that leads to the death of brain cells. Misfolded proteins form abnormal clusters called plaques which build up between brain cells, stopping them from signalling properly. Dying brain cells also contain tangles, twisted strands of proteins that destroy a vital cell transport system, meaning nutrients and other essential supplies can no longer move through the cells.

There have been over 400 clinical trials for Alzheimer's disease, but no drug that can modify the course of the disease has been approved. In the UK, dementia is the only condition in the top 10 causes of death without a treatment to prevent, stop, or slow its progression.

"While the amyloid hypothesis is a prevalent view, it has not been fully validated in part because amyloid-beta oligomers are so difficult to detect, so there are differing opinions on what causes Alzheimer's disease," said Vendruscolo. "The discovery of an antibody to accurately target oligomers is, therefore, an important step to monitor the progression of the disease, identify its cause, and eventually keep it under control."

The lack of methods to detect oligomers has been a major obstacle in the progress of Alzheimer's research. This has hampered the development of effective diagnostic and therapeutic interventions and led to uncertainty about the amyloid hypothesis.

"Oligomers are difficult to detect, isolate, and study," said Dr Francesco Aprile, the study's first author. "Our method allows the generation of antibody molecules able to target oligomers despite their heterogeneity, and we hope it could be a significant step towards new diagnostic approaches."

The method is based on an approach for antibody discovery developed over the last ten years at the Centre for Misfolding Diseases. Based on the computational assembly of antibody-antigen assemblies, the method enables the design of antibodies for antigens that are highly challenging, such as those that live only for a very short time.

By using a rational design strategy that enables to target specific regions, or epitopes, of the oligomers, and a wide range of in vitro and in vivo experiments, the researchers have designed an antibody with at least three orders of magnitude greater affinity for the oligomers over other forms of amyloid-beta. This difference is the key feature that enables the antibody to specifically quantify oligomers in both in vitro and in vivo samples.

The team hopes that this tool will enable the discovery of better drug candidates and the design of better clinical trials for people affected by the debilitating disease. They also co-founded Wren Therapeutics, a spin-out biotechnology company based at the Chemistry of Health Incubator, in the recently opened Chemistry of Health building, whose mission it is to take the ideas developed at the University of Cambridge and translate them into finding new drugs to treat Alzheimer's disease and other protein misfolding disorders.

The antibody has been patented by Cambridge Enterprise, the University's commercialisation arm.

Space is getting crowded. Aging satellites and space debris crowd low-Earth orbit, and launching new satellites adds to the collision risk. The most effective way to solve the space junk problem, according to a new study, is not to capture debris or deorbit old satellites: it's an international agreement to charge operators "orbital-use fees" for every satellite put into orbit.

Orbital use fees would also increase the long-run value of the space industry, said economist Matthew Burgess, a CIRES Fellow and co-author of the new paper. By reducing future satellite and debris collision risk, an annual fee rising to about $235,000 per satellite would quadruple the value of the satellite industry by 2040, he and his colleagues concluded in a paper published today in the Proceedings of the National Academy of Sciences.

"Space is a common resource, but companies aren't accounting for the cost their satellites impose on other operators when they decide whether or not to launch," said Burgess, who is also an assistant professor in Environmental Studies and an affiliated faculty member in Economics at the University of Colorado Boulder. "We need a policy that lets satellite operators directly factor in the costs their launches impose on other operators."

Currently, an estimated 20,000 objects--including satellites and space debris--are crowding low-Earth orbit. It's the latest Tragedy of the Commons, the researchers said: Each operator launches more and more satellites until their private collision risk equals the value of the orbiting satellite.

So far, proposed solutions have been primarily technological or managerial, said Akhil Rao, assistant professor of economics at Middlebury College and the paper's lead author. Technological fixes include removing space debris from orbit with nets, harpoons, or lasers. Deorbiting a satellite at the end of its life is a managerial fix.

Ultimately, engineering or managerial solutions like these won't solve the debris problem because they don't change the incentives for operators. For example, removing space debris might motivate operators to launch more satellites--further crowding low-Earth orbit, increasing collision risk, and raising costs. "This is an incentive problem more than an engineering problem. What's key is getting the incentives right," Rao said.

A better approach to the space debris problem, Rao and his colleagues found, is to implement an orbital-use fee--a tax on orbiting satellites. "That's not the same as a launch fee," Rao said, "Launch fees by themselves can't induce operators to deorbit their satellites when necessary, and it's not the launch but the orbiting satellite that causes the damage."

Orbital-use fees could be straight-up fees or tradeable permits, and they could also be orbit-specific, since satellites in different orbits produce varying collision risks. Most important, the fee for each satellite would be calculated to reflect the cost to the industry of putting another satellite into orbit, including projected current and future costs of additional collision risk and space debris production--costs operators don't currently factor into their launches. "In our model, what matters is that satellite operators are paying the cost of the collision risk imposed on other operators," said Daniel Kaffine, professor of economics and RASEI Fellow at the University of Colorado Boulder and co-author on the paper.

And those fees would increase over time, to account for the rising value of cleaner orbits. In the researchers' model, the optimal fee would rise at a rate of 14 percent per year, reaching roughly $235,000 per satellite-year by 2040.

For an orbital-use fee approach to work, the researchers found, all countries launching satellites would need to participate--that's about a dozen that launch satellites on their own launch vehicles and more than 30 that own satellites. In addition, each country would need to charge the same fee per unit of collision risk for each satellite that goes into orbit, although each country could collect revenue separately. Countries use similar approaches already in carbon taxes and fisheries management.

In this study, Rao and his colleagues compared orbital-use fees to business as usual (that is, open access to space) and to technological fixes such as removing space debris. They found that orbital use fees forced operators to directly weigh the expected lifetime value of their satellites against the cost to industry of putting another satellite into orbit and creating additional risk. In other scenarios, operators still had incentive to race into space, hoping to extract some value before it got too crowded.

With orbital-use fees, the long-run value of the satellite industry would increase from around $600 billion under the business-as-usual scenario to around $3 trillion, researchers found. The increase in value comes from reducing collisions and collision-related costs, such as launching replacement satellites.

Orbital-use fees could also help satellite operators get ahead of the space junk problem. "In other sectors, addressing the Tragedy of the Commons has often been a game of catch-up with substantial social costs. But the relatively young space industry can avoid these costs before they escalate," Burgess said.