Culture

HERSHEY, Pa. -- Over the past year, studies have revealed that certain pre-existing conditions, such as cancer, diabetes and high blood pressure, can increase a person's risk of dying from COVID-19. New research shows that individuals living with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) -- an estimated 38 million worldwide, according to the World Health Organization -- have an increased risk of SARS-CoV-2 infection and fatal outcomes from COVID-19.

In a new study, published in Scientific Reports, Penn State College of Medicine researchers found that people living with HIV had a 24% higher risk of SARS-CoV-2 infection and a 78% higher risk of death from COVID-19 than people without HIV. They assessed data from 22 previous studies that included nearly 21 million participants in North America, Africa, Europe and Asia to determine to what extent people living with HIV/AIDS are susceptible to SARS-CoV-2 infection and death from COVID-19.

The majority of the participants (66%) were male and the median age was 56. The most common comorbidities among the HIV-positive population were hypertension, diabetes, chronic obstructive pulmonary disease and chronic kidney disease. The majority of patients living with HIV/AIDS (96%) were on antiretroviral therapy (ART), which helps suppress the amount of HIV detected in the body.

"Previous studies were inconclusive on whether or not HIV is a risk factor for susceptibility to SARS-CoV-2 infection and poor outcomes in populations with COVID-19," said Dr. Paddy Ssentongo, lead researcher and assistant professor at the Penn State Center for Neural Engineering. "This is because a vast majority of people living with HIV/AIDS are on ART, some of which have been used experimentally to treat COVID-19."

According to the researchers, certain pre-existing conditions are common among people living with HIV/AIDS, which may contribute to the severity of their COVID-19 cases. The beneficial effects of antiviral drugs, such astenofovir and protease-inhibitors, in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in people with living with HIV/AIDS remain inconclusive.

"As the pandemic has evolved, we've obtained sufficient information to characterize the epidemiology of HIV/SARS-CoV-2 coinfection, which could not be done at the beginning of the pandemic due to scarcity of data," said Vernon Chinchilli, fellow researcher and chair of the Department of Public Health Sciences. "Our findings support the current Centers for Disease Control and Prevention guidance to prioritize persons living with HIV to receive a COVID-19 vaccine."

Surgical cesarean births can expose new mothers to a range of health complications, including infection, blood clots and hemorrhage. As part of Healthy People 2020 and other maternal health objectives, the state of California exerted pressure to reduce cesarean deliveries, and statewide organizations established quality initiatives in partnership with those goals. In this study, researchers from Stanford University and the University of Chicago examined unit culture and provider mix differences on hospital and delivery units to identify characteristics of units that successfully reduced their cesarean delivery rates. The mixed-methods study surveyed and interviewed labor and delivery teams from 37 California hospitals that were participating sites in the California Maternal Quality Care Collaborative's Supporting Vaginal Birth initiative. Respondents at successful hospitals included more family physicians and midwives, and physicians who had been in practice for less time. The study identified a number of unit culture factors that also predicted success. The authors conclude, "Family medicine, a discipline that strongly identifies itself as valuing patient-centered care and shared decision-making, may be in a unique position to contribute positively to this aspect of culture change on labor and delivery units."

Most patients with depression are treated in primary care, however, relatively few clinical trials for treating depression have focused on primary care. Researchers at the Vrije University Amsterdam examined the effects of the two major approaches to treating depression: psychotherapy and pharmacotherapy, as well as combined treatment and care-as-usual. The study integrated the results of 58 randomized controlled trials with a total of 9,301 patients. Results concluded that both psychotherapy and pharmacotherapy were significantly more effective than care-as-usual or waitlist control. However, they found no significant difference between psychotherapy and pharmacotherapy as stand-alone treatments. Combined treatment, particularly in studies that included cognitive behavioral therapy, was better than either pharmacotherapy or psychotherapy alone. Treatment in primary care should be organized to accommodate any of these treatments in response to patients' preferences and values, the authors write.

DURHAM, N.C. -- You enter a room and quickly scan the crowd to gain a sense of who's there - how many men versus women. How reliable is your estimate?

Not very, according to new research from Duke University.

In an experimental study, researchers found that participants consistently erred in estimating the proportion of men and women in a group. And participants erred in a particular way: They overestimated whichever group was in the minority.

"Our attention is drawn to outliers," said Mel W. Khaw, a postdoctoral research associate at Duke and the study's lead author. "We tend to overestimate people who stand out in a crowd."

For the study, which appears online in the journal Cognition, researchers recruited 48 observers ages 18-28. Participants were presented with a grid of 12 faces and were given just one second to glance at the grid. Study participants were then asked to estimate the number of men and women in the grid.

Participants accurately assessed homogenous groups - groups containing all men or all women. But if a group contained fewer women, say, participants overestimated the number of women present.

The researchers also tracked participants' eye movements. They found that participants looked more often at whichever group was in the minority - men or women.

All of this occurred very quickly -- during a glance of just one second, said co-author and Duke psychologist Scott Huettel.

"We should recognize that our visual system is set up to orient ourselves towards some types of information more than others," Huettel said. "People form an initial impression very quickly,
and that impression biases where we look next."

Interestingly, the same tendency to focus on the outlier also extended to scanning other kinds of images.

In a second experiment, study participants were shown a grid of nature photos showing a variety of indoor and outdoor scenes. Participants consistently overestimated whatever type of scene appeared less often.

For instance, if a grid of 12 photos contained two outdoor scenes - say, a waterfall and a mountain range -- participants reported, on average, that the grid contained three such scenes.

In other words, the same behavior occurred whether people were looking at faces or scenes. That's important, Huettel said.

"That fact that this occurs with indoor and outdoor scenes suggests that this doesn't represent a social bias," Huettel said. "It really has to do with a fundamental feature of human perception."

And that built-in flaw in human perception suggests our quick judgments should be viewed with caution.

"Snap judgments are powerful," Huettel said. "But they're not perfect."

Co-author Rachel Kranton, an economist, noted that as the research was coming together, she received an invitation to an economics conference including a photo from a past event.

The photo showed a meeting room full of mostly men, a situation Kranton frequently encounters at economics conferences. Kranton said she found herself scanning the photo for the presence of women -- and smiling in recognition.

"When human beings walk into a social situation, we immediately try to suss out the setting," Kranton said. "We scan to see who's there and how we fit in - that's a common human experience. It's one I've experienced many times."

Individuals with diabetes are at greater risk of developing oral health issues, like gum disease, yet care for these linked health issues are usually disconnected, split between primary care and dental care. A research team from the University of Amsterdam developed an intervention that provided primary care-based oral health information and dental referrals for patients with diabetes. In a cluster randomized controlled trial, 764 patients from 24 primary care practices received either the oral health support or standard primary care. Participants were asked to rate their oral health quality of life, as well as their general health and any oral health complaints, at the start and end of the study. Analysis showed that individuals who received the primary care-based oral health support intervention had a significant increase in their self-reported oral health quality of life when compared with the control group. The authors conclude that, "patients with type 2 diabetes who attend primary diabetes care can benefit from extra attention to oral health." They add, "It also further reflects the concept of oral health and general health being connected."

Though different fabrication approaches exist, two-step deposition is one of the main experimental techniques now used to make efficient, stable PSCs, especially on the industrial scale. The process involves first depositing lead iodide (PbI2) and then adding halide salts of monovalent cations such as methylammonium iodide (MAI) and formamidinium iodide (FAI) to convert it to perovskite.

While this two-step deposition is better than other options, it is difficult to maintain reproducible high performance and long-term stability when scaling up, mostly because of a lack of control over the fabrication process. Gaining an understanding of the mechanism behind halide perovskite crystallization at the atomic level is therefore essential.

In the paper A combined molecular dynamics and experimental study of two-step process enabling low-temperature formation of phase-pure α-FAPbI3 the authors chose to study, to this end, the two-step fabrication of methylammonium lead iodide (MAPbI3) and formamidinium lead iodide (FAPbI3).

While the former is a well-studied system, the latter was chosen because of attractive features including a ?1.45-eV bandgap, high-charge carrier mobility, and superior thermal stability that appear in its α-FAPbI3 polymorph. The problem with this perovskite however is that the α phase is metastable and the thermodynamic phase transition requires high temperatures of around 150 degrees Celsius. The combined experimental and theoretical study, published in the 23 April issue of Science Advances, uncovered the microscopic details of the crystallization process, leading the way to the discovery of a low-temperature pathway to the fabrication of the material.

While previous experimental research on MAPbI3 revealed that the two-step process occurs via intercalation of the MA+ cations in PbI2 layers followed by a transformation to the perovskite structure via intermediate phases, the experiments couldn't resolve the nature of these intermediate phases or clarify the underlying atomistic mechanism. Using a molecular dynamics (MD) investigation based on an enhanced sampling technique called metadynamics (WTMetaD), the team found that that transformation takes place through a sequence of intermediates. The theoretical results were in line with experiments, encouraging the researchers to investigate whether a similar process was also behind the transformation of α-FAPbI3. Starting from simulations, they discovered that a two-step process is indeed possible at lower temperatures in this material. A series of in situ x-ray and thin-film experiments then confirmed this result and enabled the low-temperature formation of phase-pure α -FAPbI3 thin films.

Simon Fraser University researchers have designed a remarkably fast engine that taps into a new kind of fuel -- information.

The development of this engine, which converts the random jiggling of a microscopic particle into stored energy, is outlined in research published this week in the Proceedings of the National Academy of Sciences (PNAS) and could lead to significant advances in the speed and cost of computers and bio-nanotechnologies.

SFU physics professor and senior author John Bechhoefer says researchers' understanding of how to rapidly and efficiently convert information into "work" may inform the design and creation of real-world information engines.??

"We wanted to find out how fast an information engine can go and how much energy it can extract, so we made one," says Bechhoefer, whose experimental group collaborated with theorists led by SFU physics professor David Sivak.

Engines of this type were first proposed over 150 years ago but actually making them has only recently become possible.

"By systematically studying this engine, and choosing the right system characteristics, we have pushed its capabilities over ten times farther than other similar implementations, thus making it the current best-in-class," says Sivak.

The information engine designed by SFU researchers consists of a microscopic particle immersed in water and attached to a spring which, itself, is fixed to a movable stage. Researchers then observe the particle bouncing up and down due to thermal motion.

"When we see an upward bounce, we move the stage up in response," explains lead author and PhD student Tushar Saha. "When we see a downward bounce, we wait. This ends up lifting the entire system using only information about the particle's position."

Repeating this procedure, they raise the particle "a great height, and thus store a significant amount of gravitational energy," without having to directly pull on the particle.

Saha further explains that, "in the lab, we implement this engine with an instrument known as an optical trap, which uses a laser to create a force on the particle that mimics that of the spring and stage."??

Joseph Lucero, a Master of Science student adds, "in our theoretical analysis, we find an interesting trade-off between the particle mass and the average time for the particle to bounce up. While heavier particles can store more gravitational energy, they generally also take longer to move up."

"Guided by this insight, we picked the particle mass and other engine properties to maximize how fast the engine extracts energy, outperforming previous designs and achieving power comparable to molecular machinery in living cells, and speeds comparable to fast-swimming bacteria," says postdoctoral fellow Jannik Ehrich.

TORONTO, ON - Geoscientists at the University of Toronto (U of T) and Istanbul Technical University have discovered a new process in plate tectonics which shows that tremendous damage occurs to areas of Earth's crust long before it should be geologically altered by known plate-boundary processes, highlighting the need to amend current understandings of the planet's tectonic cycle.

Plate tectonics, an accepted theory for over 60 years that explains the geologic processes occurring below the surface of Earth, holds that its outer shell is fragmented into continent-sized blocks of solid rock, called "plates," that slide over Earth's mantle, the rocky inner layer above the planet's core. As the plates drift around and collide with each other over million-years-long periods, they produce everything from volcanoes and earthquakes to mountain ranges and deep ocean trenches, at the boundaries where the plates collide.

Now, using supercomputer modelling, the researchers show that the plates on which Earth's oceans sit are being torn apart by massive tectonic forces even as they drift about the globe. The findings are reported in a study published this week in Nature Geoscience.

The thinking up to now focused only on the geological deformation of these drifting plates at their boundaries after they had reached a subduction zone, such as the Marianas Trench in the Pacific Ocean where the massive Pacific plate dives beneath the smaller Philippine plate and is recycled into Earth's mantle.

The new research shows much earlier damage to the drifting plate further away from the boundaries of two colliding plates, focused around zones of microcontinents - continental crustal fragments that have broken off from main continental masses to form distinct islands often several hundred kilometers from their place of origin.

"Our work discovers that a completely different part of the plate is being pulled apart because of the subduction process, and at a remarkably early phase of the tectonic cycle," said Erkan Gün, a PhD candidate in the Department of Earth Sciences in the Faculty of Arts & Science at U of T and lead author of the study.

The researchers term the mechanism a "subduction pulley" where the weight of the subducting portion that dives beneath another tectonic plate, pulls on the drifting ocean plate and tears apart the weak microcontinent sections in an early phase of potentially significant damage.

"The damage occurs long before the microcontinent fragment reaches its fate to be consumed in a subduction zone at the boundaries of the colliding plates," said Russell Pysklywec, professor and chair of the Department of Earth Sciences at U of T, and a coauthor of the study. He says another way to look at it is to think of the drifting ocean plate as an airport baggage conveyor, and the microcontinents are like pieces of luggage travelling on the conveyor.

"The conveyor system itself is actually tearing apart the luggage as it travels around the carousel, before the luggage even reaches its owner."

The researchers arrived at the results following a mysterious observation of major extension of rocks in alpine regions in Italy and Turkey. These observations suggested that the tectonic plates that brought the rocks to their current location were already highly damaged prior to the collisional and mountain-building events that normally cause deformation.

"We devised and conducted computational Earth models to investigate a process to account for the observations," said Gün. "It turned out that the temperature and pressure rock histories that we measured with the virtual Earth models match closely with the enigmatic rock evolution observed in Italy and Turkey."

According to the researchers, the findings refine some of the fundamental aspects of plate tectonics and call for a revised understanding of this fundamental theory in geoscience.

"Normally we assume - and teach - that the ocean plate conveyor is too strong to be damaged as it drifts around the globe, but we prove otherwise," said Pysklywec.

New York, NY--May 11, 2021--Widely used to monitor and map biological signals, to support and enhance physiological functions, and to treat diseases, implantable medical devices are transforming healthcare and improving the quality of life for millions of people. Researchers are increasingly interested in designing wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. These devices could be used to monitor physiological conditions, such as temperature, blood pressure, glucose, and respiration for both diagnostic and therapeutic procedures.

To date, conventional implanted electronics have been highly volume-inefficient--they generally require multiple chips, packaging, wires, and external transducers, and batteries are often needed for energy storage. A constant trend in electronics has been tighter integration of electronic components, often moving more and more functions onto the integrated circuit itself.

Researchers at Columbia Engineering report that they have built what they say is the world's smallest single-chip system, consuming a total volume of less than 0.1 mm3. The system is as small as a dust mite and visible only under a microscope. In order to achieve this, the team used ultrasound to both power and communicate with the device wirelessly. The study was published online May 7 in Science Advances.

"We wanted to see how far we could push the limits on how small a functioning chip we could make," said the study's leader Ken Shepard, Lau Family professor of electrical engineering and professor of biomedical engineering. "This is a new idea of 'chip as system'--this is a chip that alone, with nothing else, is a complete functioning electronic system. This should be revolutionary for developing wireless, miniaturized implantable medical devices that can sense different things, be used in clinical applications, and eventually approved for human use."

The team also included Elisa Konofagou, Robert and Margaret Hariri Professor of Biomedical engineering and professor of radiology, as well as Stephen A. Lee, PhD student in the Konofagou lab who assisted in the animal studies.

The design was done by doctoral student Chen Shi, who is the first author of the study. Shi's design is unique in its volumetric efficiency, the amount of function that is contained in a given amount of volume. Traditional RF communications links are not possible for a device this small because the wavelength of the electromagnetic wave is too large relative to the size of the device. Because the wavelengths for ultrasound are much smaller at a given frequency because the speed of sound is so much less than the speed of light, the team used ultrasound to both power and communicate with the device wirelessly. They fabricated the "antenna" for communicating and powering with ultrasound directly on top of the chip.

The chip, which is the entire implantable/injectable mote with no additional packaging, was fabricated at the Taiwan Semiconductor Manufacturing Company with additional process modifications performed in the Columbia Nano Initiative cleanroom and the City University of New York Advanced Science Research Center (ASRC) Nanofabrication Facility.

Shepard commented, "This is a nice example of 'more than Moore' technology--we introduced new materials onto standard complementary metal-oxide-semiconductor to provide new function. In this case, we added piezoelectric materials directly onto the integrated circuit to transducer acoustic energy to electrical energy."

Konofagou added, "Ultrasound is continuing to grow in clinical importance as new tools and techniques become available. This work continues this trend."

The team's goal is to develop chips that can be injected into the body with a hypodermic needle and then communicate back out of the body using ultrasound, providing information about something they measure locally. The current devices measure body temperature, but there are many more possibilities the team is working on.

2003 was a big year for virologists. The first giant virus was discovered in this year, which shook the virology scene, revising what was thought to be an established understanding of this elusive group and expanding the virus world from simple, small agents to forms that are as complex as some bacteria. Because of their link to disease and the difficulties in defining them--they are biological entities but do not fit comfortably in the existing tree of life--viruses incite the curiosity of many people.

Scientists have long been interested in how viruses evolved, especially when it comes to giant viruses that can produce new viruses with very little help from the host--in contrast to most small viruses, which utilize the host's machinery to replicate.

Even though giant viruses are not what most people would think of when it comes to viruses, they are actually very common in oceans and other water bodies. They infect single-celled aquatic organisms and have major effects on the latter's population. In fact, Dr. Kiran Kondabagil, molecular virologist at the Indian Institute of Technology (IIT) Bombay, suggests, "Because these single-celled organisms greatly influence the carbon turnover in the ocean, the viruses have an important role in our world's ecology. So, it is just as important to study them and their evolution, as it is to study the disease-causing viruses."

In a recent study, the findings of which have been published in Molecular Biology and Evolution, Dr. Kondabagil and co-researcher Dr. Supriya Patil performed a series of analyses on major genes and proteins involved in the DNA replication machinery of Mimivirus, the first group of giant viruses to be identified. They aimed to determine which of two major suggestions regarding Mimivirus evolution--the reduction and the virus-first hypotheses--were more supported by their results. The reduction hypothesis suggests that the giant viruses emerged from unicellular organisms and shed genes over time; the virus-first hypothesis suggests that they were around before single-celled organisms and gained genes, instead.

Dr. Kondabagil and Dr. Patil created phylogenetic trees with replication proteins and found that those from Mimivirus were more closely related to eukaryotes than to bacteria or small viruses. Additionally, they used a technique called multidimensional scaling to determine how similar the Mimiviral proteins are. A greater similarity would indicate that the proteins co-evolved, which means that they are linked together in a larger protein complex with coordinated function. And indeed, their findings showed greater similarity. Finally, the researchers showed that genes related to DNA replication are similar to and fall under purifying selection, which is natural selection that removes harmful gene variants, constraining the genes and preventing their sequences from varying. Such a phenomenon typically occurs when the genes are involved in essential functions (like DNA replication) in an organism.

Taken together, these results imply that Mimiviral DNA replication machinery is ancient and evolved over a long period of time. This narrows us down to the reduction hypothesis, which suggests that the DNA replication machinery already existed in a unicellular ancestor, and the giant viruses were formed after getting rid of other structures in the ancestor, leaving only replication-related parts of the genome.

"Our findings are very exciting because they inform how life on earth has evolved," Dr. Kondabagil says. "Because these giant viruses probably predate the diversification of the unicellular ancestor into bacteria, archaea, and eukaryotes, they should have had major influence on the subsequent evolutionary trajectory of eukaryotes, which are their hosts."

In terms of applications beyond this contribution to basic scientific knowledge, Dr. Kondabagil feels that their work could lay the groundwork for translational research into technology like genetic engineering and nanotechnology. He says, "An increased understanding of the mechanisms by which viruses copy themselves and self-assemble means we could potentially modify these viruses to replicate genes we want or create nanobots based on how the viruses function. The possibilities are far-reaching!"

An international team of researchers at Great Ormond Street Hospital (GOSH), and University of California, Los Angeles (UCLA) have developed a gene therapy that successfully treated 48 out of 50 children with a form of severe combined immunodeficiency that leaves them without an immune system.

Severe combined immunodeficiency due to adenosine deaminase deficiency, also known as ADA-SCID, is a rare, life-threatening disease that prevents children from living a normal life. It is caused by mutations in the gene that creates the enzyme adenosine deaminase, which is essential to a functioning immune system.

Children with ADA-SCID have no immune system and, if left untreated, the condition can be fatal within the first two years of life. Day-to-day activities like going to school or playing with friends can lead to a dangerous infection. Recently, new-born screening for SCID has been implemented in some countries to help diagnose the condition early in life.

In a new study published in the New England Journal of Medicine, co-lead authors Professor Donald Kohn (UCLA) and Dr Claire Booth (GOSH) reported the two- to three-year outcomes of 50 children who were treated in clinical trials with an experimental stem cell gene therapy for ADA-SCID between 2012 and 2017.

The standard treatment for ADA-SCID involves once or twice weekly injections of the ADA enzyme until a matched bone marrow donor - usually a close family member - can be found. If a matched bone marrow donor is not available, patients require lifelong ADA injections along with preventative medicines. These treatments are expensive and therefore out of reach for patients in many countries.

If approved, gene therapy would be a welcome new treatment option for ADA-SCID as it is a one-time procedure that has the potential to provide life-long results.

Two to three years after the treatment, all of the 50 children treated with the new gene therapy at Great Ormond Street Hospital, UCLA Mattel Children's Hospital and the National Institutes of Health (NIH) are alive and well. Of these, 48 are no longer showing symptoms of ADA-SCID, although they will have lifelong monitoring. In the two cases in which treatment wasn't successful, both children were able to return to current standard treatments, with one eventually receiving a bone marrow transplant. No serious side effects have so far been reported, with generally mild or moderate complications experienced from the necessary preparation for the gene therapy.

One of the patients treated was four-year-old Sarah from South Yorkshire. She was less than ten days old when her mum Maria became concerned about her daughter's weight loss and sore, bleeding nappy rash that wouldn't heal. Tests revealed Sarah had ADA-SCID:

"I remember the exact time I saw the paper that had the blood test results on and the diagnosis. I saw it was SCID and I was incredibly upset... I wasn't allowed to kiss my daughter or sleep next to her. Everything had to be highly sterilised to keep her safe. It was horrible to not be able to do normal things with my own daughter."

Sarah was referred to GOSH for gene therapy and several years after her treatment is doing very well:

"Before, her nappy rash was always bleeding and sore, she was being sick and losing weight. Six months after she was given the gene therapy her skin was clean and healthy and the other symptoms got a lot better. She's doing so well now and can do everything a normal child her age would do."

Sarah's treatment has had a huge impact on the whole family, but it also inspired Maria to go back to studying and train to become a nurse.

"I now know how it feels to have your child as a patient and to be so sick, and I want to use my experience to help others in a similar position."

In earlier trials of gamma-retroviral gene therapy for other similar diseases, serious side effects including leukaemia have been seen in some patients. Now, lentiviral gene therapy technology has advanced significantly and offers the potential to improve the safety and efficacy profile of this treatment option for patients.

The gene therapy approach described in the paper involves first removing some of the patient's blood-forming stem cells, which create all types of blood and immune cells. Next, a viral vector is used to deliver a new copy of the ADA gene into the DNA of the patient's cells.

These corrected stem cells are then returned to the patient where, once engrafted, they go on to produce a seemingly continual supply of healthy immune cells capable of fighting infection.

Dr Claire Booth, co-lead author, Mahboubian Associate Professor in Gene Therapy and GOSH consultant in Paediatric Immunology and Gene Therapy: "If approved in the future, this treatment could be standard for ADA-SCID, and potentially many other genetic conditions, removing the need to find a matched-donor for bone marrow transplant and the toxic side effects often associated with that treatment. We need and want guidelines to change so we can start offering this potential cure to children and provide it as a first-choice treatment - this research could set those wheels in motion."

Prof Adrian Thrasher, Professor of Paediatric Immunology at GOSH and Wellcome Principal Research Fellow, said "We started gene therapy at GOSH around 20 years ago and now have refined the process to offer a potential cure for children born with this debilitating condition. Over 200 patients with various genetic conditions across the world have now been treated with this type of gene therapy - this is another very significant breakthrough."

Ten of the children in the study were treated at UCLA using a frozen preparation of corrected stem cells. These children experienced similar outcomes to the children treated with cells that were not frozen. This approach using frozen preparation may allow children to have their stem cells collected locally, have them transported and processed at a manufacturing facility elsewhere, and then shipped back to a local specialised hospital, possibly removing the need to travel long distances to specialist centres.

A trial of the cryopreserved treatment is now underway at the Zayed Centre for Research into Rare Diseases in Children in partnership with Great Ormond Street Hospital, London, UK. The investigational lentiviral vector treatment is licensed to Orchard Therapeutics. Professors Thrasher and Kohn serve on Orchard Therapeutics' scientific advisory board.

Positive results from this trial could support gene therapy to become a possible first-line treatment for this devastating disease.

Saw-toothed grain beetles live in a symbiotic association with bacteria. Their bacterial partners provide important building blocks for the formation of the insect's exoskeleton, which protects the beetles from their enemies as well as from desiccation. In a new study, a team of scientists from the Johannes Gutenberg University in Mainz, the Max Planck Institute for Chemical Ecology in Jena, and the National Institute of Advanced Industrial Science and Technology in Japan demonstrates that glyphosate inhibits the symbiotic bacteria of the grain beetle. Beetles exposed to the weedkiller no longer receive the building blocks they need from the bacteria. The study shows that glyphosate has the potential to harm insects indirectly by targeting their bacterial partners and thus to contribute to their decline (Communications Biology, doi: 10.1038/s42003-021-02057-6, May 2021).

Insects need microbial partners to survive

Organisms exist not in isolation but in an intricate network of ecological interactions. These interactions must be kept in mind when judging the impact of human activities. Insects in particular benefit in diverse ways from microbial symbionts, mostly via supplemented nutrients and chemical defenses. However, the benefits derived from such symbiotic associations may also make the insect more vulnerable. Insect hosts often become so reliant on their microbial partners that they can hardly survive alone. Without symbiosis, insects' development may be delayed or prevented, their susceptibility to natural enemies may be increased, their reproductive potential and competitiveness with conspecifics may be impaired, or they may die.

Glyphosate prevents symbiotic bacteria from providing the building blocks for the insect exoskeleton

Glyphosate is currently one of the most widely used pesticides in agriculture, despite increasing controversy about its potentially harmful side-effects. It is supposed to selectively suppress the growth of plants by inhibiting the biosynthesis of aromatic amino acids via the so-called shikimate pathway, a metabolic pathway occurring in plants and many microorganisms. Animals, on the other hand, do not encode the shikimate pathway, and thus are thought to be unharmed by glyphosate. However, many animals engage in mutualistic interactions with symbiotic microbes that rely on the shikimate pathway to produce amino acids required by these animals. "An impact of glyphosate on animals via their essential bacterial partners that use or even specialize in the shikimate metabolic pathway seems obvious, once the interaction of both partners is understood," explains Tobias Engl, one of the lead authors of the study. Glyphosate has already been shown to negatively affect microorganisms in the gut of honeybees, making the bees more susceptible to various stress factors. Furthermore, mutualistic bacteria across several herbivorous insect taxa provide a core benefit: the aromatic amino acid tyrosine needed for the biosynthesis of the insect exoskeleton (cuticle). This dependence on the symbiosis, in turn, may render insect herbivores particularly vulnerable to glyphosate in agriculture: The herbicide inhibits the shikimate pathway in their symbiotic bacteria and, as a result, important amino acids needed for cuticle formation are missing.

Is dependence on their symbiotic partners the Achilles heel of insects?

In the current study, the scientists show that glyphosate negatively influences the mutualistic bacteria harbored by the saw-toothed grain beetle Oryzaephilus surinamensis, an economically important pest of stored grain products. Exposure to the herbicide completely abolished the mutualistic benefit that symbiotic bacteria provide for the formation of the cuticle, an insect's primary protection against stresses, such as drought or predator attack.

The researchers sequenced the genome of the symbiont associated with O. surinamensis. The tiny symbiont genome (300 kbp) contains the genetic instruction for a metabolism specialized on the synthesis of aromatic amino acids via the shikimate pathway. Interestingly, the genome strongly resembles that of the bacterial partners of the palm weevil, which are also involved in cuticle formation, although these symbionts belong to a different group of bacteria.

"Finding a functionally equivalent symbiotic relationship that arose independently in two different bacteria phyla and distantly related beetle families highlights the importance of cuticle-supporting symbioses in beetles," says Julian Kiefer, the study's first author. The scientists tested the functional benefits for the host experimentally by supplementing the beetles' diet with aromatic amino acids, thus compensating for the elimination of their symbionts. Conversely, glyphosate exposure inhibited the establishment of the symbiotic bacteria throughout the beetle's development and abolished completely the mutualistic benefit for cuticle synthesis.

"When we observed the detrimental impact of glyphosate exposure on this symbiotic association, we wondered whether glyphosate poses a general threat to insects that depend on their microbial partners," explains Engl. By using phylogenetic analyses, the authors demonstrate that many obligate mutualistic bacteria associated with various different insect hosts indeed encode a glyphosate-sensitive enzyme in the shikimate pathway, suggesting that the susceptibility of its microbial symbionts to glyphosate represents an Achilles heel for an insect.

We are currently experiencing insect decline on a massive scale. Insect abundance is decreasing, as is insect diversity, not to mention the impact of the disappearance of bees, beetles and other insects at higher levels in the food chain. The new findings highlight the fact that the use of the herbicide glyphosate in agriculture endangers vital symbiotic relationships between insects and microorganisms and thus poses a serious threat to our ecosystems.

Inks containing metal nanoparticles are among the most commonly-used conductive materials for printed electronics. Ink-jetting layers of MNP materials allows for unpreceded design flexibility, rapid processing and 3D printing of functional electronic devices such as sensors, solar panels, LED displays, transistors and smart textiles.

Inkjet 3D printing of metals typically form a solid printed object via a two-step process: solvent evaporation upon printing (pinning) and subsequent low-temperature consolidation of nanoparticles (sintering). The low temperature is important as in many applications the nanoparticles are co-printed with other functional/structural organic materials that are sensitive to higher temperatures.

However, layers produced by inkjet printing of metal nanoparticles have different electrical conductivity between horizontal and vertical directions. This effect is known as functional anisotropy and is a long-standing problem for the 3D printing of functional electronic devices, preventing its use for advanced applications.

It was previously thought that reduced vertical conductivity through a printed device is mainly caused by shape and physical continuity problems at the interfaces of the constituent nanoparticles (at the very small micro and nanoscale). However, Nottingham researchers used silver nanoparticles to show, for the first time, that it is caused by organic chemical residues in the inks.

These residues, which are added to the inks to help stabilise the nanomaterials, lead to the formation of low-conducting, very thin nanoscale layers which interfere with the electrical conductivity of the printed sample in the vertical direction.

With a clearer understanding of the distribution of residual organic additives within printed layers, the researchers hope to go on to define new techniques and develop new ink formulations to overcome functional anisotropy of inkjet-based 3D printed electronics.

Lead author, CfAM Research Fellow Dr Gustavo Trindade, said, "The conductivity of inkjet-printed metal nanoparticles is known to be dependent on processing temperature and have been previously attributed to changes in the shape and porosity of clustered nanoparticles, with the role of organic residues being only speculated."

"This new insight enables the development of routes to overcome functional anisotropy in inkjet-based nanoparticles, and will therefore improve uptake of this potentially transformational technology, making it competitive with conventional manufacturing. Our approach is transferable to other nanomaterial-based inks including those containing graphene and functionalised nanocrystals, and will enable the development and exploitation of both 2D and 3D printed electronics like flexible and wearable sensors, solar panels, LED displays, transistors and smart textiles."

The study was carried out by the Centre for Additive Manufacturing (CfAM), under the £5.85m EPSRC-funded Programme Grant, Enabling Next Generation Additive Manufacturing. Their findings are published in a new paper 'Residual polymer stabiliser causes anisotropic electrical conductivity during inkjet printing of metal nanoparticles' in the Nature journal Communications Materials.

The researchers used the unique chemical sensitivity of a state-of-the-art 3D orbiSIMS instrument owned by the University of Nottingham. The Nottingham orbiSIMS - the only one at a UK university - allows label-free 3D chemical imaging of materials with very high resolution, revealing insights that have informed this study.

Researchers at the University of Bristol have discovered how microbes responsible for human African sleeping sickness produce sex cells.

In these single-celled parasites, known as trypanosomes, each reproductive cell splits off in turn from the parental germline cell, which is responsible for passing on genes. Conventional germline cells divide twice to produce all four sex cells - or gametes - simultaneously. In humans four sperms are produced from a single germline cell. So, these strange parasite cells are doing their own thing rather than sticking to the biology rulebook.

Trypanosome cell biology has already revealed several curious features. They have two unique intracellular structures - the kinetoplast, a network of circular DNA and the glycosome, a membrane-enclosed organelle that contains the glycolytic enzymes. They don't follow the central dogma that DNA is faithfully transcribed into RNA, but will go back and edit some of the RNA transcripts after they've been made.

Professor Wendy Gibson of the University of Bristol's School of Biological Sciences led the study. She said "We've got used to trypanosomes doing things their own way, but of course what we think of as normal cell biology is based on very few so-called model organisms like yeast and mice. There's a whole world of weird and wonderful single-celled organisms - protozoa - out there that we don't know much about! Trypanosomes have got more attention because they're such important pathogens - both of humans and their livestock."

Biologists think that sexual reproduction evolved very early on, after the first complex cells appeared a couple of billion years ago. The sex cells are produced by a special form of cell division called meiosis that reduces the number of chromosomes by half, so that gametes have only one complete set of chromosomes instead of two. The chromosome sets from two gametes combine during sexual reproduction, producing new combinations of genes in the offspring. In the case of disease-causing microbes like the trypanosome, sex can potentially lead to a lot of harmful genes being combined in one strain. Thus, research on sexual reproduction helps scientists understand how new strains of disease-causing microbes arise and how characteristics such as drug resistance get spread between different strains.

Every high-school physics student learns that sound and light travel at very different speeds. If the brain did not account for this difference, it would be much harder for us to tell where sounds came from, and how they are related to what we see.

Instead, the brain allows us to make better sense of our world by playing tricks, so that a visual and a sound created at the same time are perceived as synchronous, even though they reach the brain and are processed by neural circuits at different speeds.

One of the brain's tricks is temporal recalibration: altering our sense of time to synchronize our joint perception of sound and vision. A new study finds that recalibration depends on brain signals constantly adapting to our environment to sample, order and associate competing sensory inputs together.

Scientists at The Neuro (Montreal Neurological Institute-Hospital) of McGill university recruited volunteers to view short flashes of light paired with sounds with a variety of delays and asked them to report whether they thought both happened at the same time. The participants performed this task inside a magnetoencephalography (MEG) machine, which recorded and imaged their brain waves with millisecond precision. The audio-visual pairs of stimuli changed each time, with sounds and visual objects presented closer or farther apart in time, and with random orders of presentation.

The researchers found that the volunteers' perception of simultaneity between the audio and visual stimuli in a pair was strongly affected by the perceived simultaneity of the stimulus pair before it. For example, if presented with a sound followed by a visual milliseconds apart and perceived as asynchronous, one is much more likely to report the next audio-visual stimulus pair as synchronous, even when it's not. This form of active temporal recalibration is one of the tools used by the brain to avoid a distorted or disconnected perception of reality, and help establish causal relations between the images and sounds we perceive, despite different physical velocities and neural processing speeds.

The MEG signals revealed that this brain feat was enabled by a unique interaction between fast and slow brain waves in auditory and visual brain regions. Slower brain rhythms pace the temporal fluctuations of excitability in brain circuits. The higher the excitability, the easier an external input is registered and processed by receiving neural networks.

Based on this, the researchers propose a new model for understanding recalibration, whereby faster oscillations riding on top of slower fluctuations create discrete and ordered time slots to register the order of sensory inputs. For example, when an audio signal reaches the first available time slot in the auditory cortex and so does a visual input, the pair is perceived as simultaneous. For this to happen, the brain needs to position the visual time slots a bit later than the auditory ones to account for the slower physiological transduction of visual signals. The researchers found that this relative delay between neural auditory and visual time slots is a dynamic process that constantly adapts to each participant's recent exposure to audiovisual perception.

Their data confirmed the new dynamic integration model by showing how these subtle tens-of-millisecond delays of fast brain oscillations can be measured in every individual and explain their respective judgments of perceived simultaneity.

In autism and speech disorders, the processing of the senses, especially hearing, is altered. In schizophrenia as well, patients can be affected by perceived distortions of sensory inputs. The neurophysiological mechanisms of temporal recalibration described in this study may be altered in these disorders, and their discovery may reveal new research goals to improve these deficits.

"Overall, this study emphasizes that our brains constantly absorb and adapt to the bombardment of sensory information from diverse sources," says Sylvain Baillet, a researcher at The Neuro and the study's senior author. "To make sense of our complex environments, including social interactions, brain circuits actively make adjustments of subtle physiological mechanisms to better anticipate and predict the nature and timing of external stimulations. That helps us build a resilient and adaptive mental map of their representation."