Culture

Kidney development is a balancing act between the self-renewal of stem and progenitor cells to maintain and expand their numbers, and the differentiation of these cells into more specialized cell types. In a new study in the journal eLife from Andy McMahon's laboratory in the Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC, former graduate student Alex Quiyu Guo and a team of scientists demonstrate the importance of a molecule called β-catenin in striking this balance.

β-catenin is a key driver at the end of a complex signaling cascade known as the Wnt pathway. Wnt signaling plays critical roles in the embryonic development of multiple organs including the kidneys. By partnering with other Wnt pathway molecules, β-catenin controls the activity of hundreds to thousands of genes within the cell.

The new study builds on the McMahon Lab's previous discovery that Wnt/β-catenin can initiate progenitor cells to execute a lengthy and highly orchestrated program of forming structures in the kidney called nephrons. A healthy human kidney contains a million nephrons that balance body fluids and remove soluble waste products. Too few nephrons results in kidney disease.

Previous studies from the UT Southwestern Medical Center laboratory of Thomas Carroll, a former postdoctoral trainee in the McMahon Lab, suggested that Wnt/β-catenin signaling plays opposing roles in ensuring the proper number of nephrons: promoting progenitor maintenance and self-renewal, and stimulating progenitor cell differentiation.

"It sounded like Wnt/β-catenin is doing two things--both maintenance and differentiation--that seem to be opposite operations," said Guo. "Therefore, the hypothesis was that different levels of Wnt/β-catenin can dictate different fates of the nephron progenitors: when it's low, it works on maintenance; when it's high, it directs differentiation."

In 2015, it became more possible to test this hypothesis when Leif Oxburgh, a scientist at the Rogosin Institute in New York and a co-author of the eLife study, developed a system for growing large numbers of nephron progenitor cells, or NPCs, in a Petri dish.

Relying on this game-changing new system, Guo and his collaborators grew NPCs, added different levels of a chemical that activates β-catenin, and saw their hypothesis play out in the Petri dishes.

They observed that high levels of β-catenin triggered a "switch" in part of the Wnt pathway that relies on another family of transcription factors known as TCF/LEF. There are two types of TCF/LEF transcription factors: one type inhibits genes related to differentiation, and the other activates these genes. In response to high levels of β-catenin, the "activating" members of TCF/LEF switched places with the "inhibiting" members, effectively taking charge. This "switch" triggered NPCs to differentiate into more specialized types of kidney cells.

When they looked at low levels of β-catenin, they saw NPCs self-renewing and maintaining their populations, as expected. However, they were surprised to learn that β-catenin was not engaged with any of the known genes related to self-renewal and maintenance.

"β-catenin does something," said Guo. "That is for sure. But how it does it is kind of mysterious right now."

After publishing these results in eLife, Guo earned his PhD from USC, and began his postdoctoral training at UCLA. Helena Bugacov, a current PhD student in the McMahon Lab and a co-author of the eLife study, is now taking the lead in continuing the project--which has implications far beyond the kidney field, due to the broad role of Wnt throughout the body.

"Understanding how Wnt regulates these two very distinct cell outcomes of self-renewal and differentiation, which is very important for kidney development, is also important for understanding the development of other organs and adult stem cells, as Wnt signaling plays important roles in almost all developmental systems," said Bugacov. "There is also a lot of attention from cancer researchers, as this process can go awry in cancer. Many therapeutics are trying to target this process."

She added, "The more we know about things, the better we can inform work on developing human kidney organoid cultures, which can be more readily used to understand problems in human health, regeneration and development."

FINDINGS

A UCLA research team has shown that using a truncated form of the CD4 molecule as part of a gene therapy to combat HIV yielded superior and longer-lasting results in mouse models than previous similar therapies using the CD4 molecule.

This new approach to CAR T gene therapy -- a type of immunotherapy that involves genetically engineering the body's own blood-forming stem cells to create HIV-fighting T cells -- has the potential to not only destroy HIV-infected cells but to create "memory cells" that could provide lifelong protection from infection with the virus that causes AIDS.

BACKGROUND

CAR therapies have emerged as a powerful immunotherapy for various forms of cancer and show promise for treating HIV-1, the more prevalent of the two main forms of the virus. However, current applications of these therapies may not impart long-lasting immunity. Researchers have been seeking a T cell-based therapy that can respond to malignant or infected cells that may reappear months or years after treatment.

In a previous study, the UCLA researchers described the creation of blood-forming stem cells that carry genes for chimeric antigen receptors, or CARs. Once these genetically engineered stem cells are transplanted into the body, they form specialized infection-fighting white blood cells known as CAR T cells that specifically seek out and kill cells infected with HIV.

METHOD

Because HIV binds to CD4 molecules in order to infect cells in the body, the researchers previously created a CAR molecule containing part of the CD4 molecule to hijack that interaction. When HIV would bind to the CD4 section of the CAR molecule on T cells, other regions of the CAR molecule would signal the cell to become activated and kill the virus. That molecule, however, contained two parts, or "domains," that still had the potential to allow HIV infection.

For the new study, the researchers removed those domains while adding another one that makes the cells resistant to infection and allows for a more efficient and longer-lasting cell response against HIV than before.

While the previous approach allowed for the continuous production of new HIV-fighting T cells that persisted for more than two years, these cells were essentially inactivated until they encountered HIV in the body. The improved CAR therapy engineers the body's immune response to HIV rather than waiting for the virus -- or parts of the virus -- to induce a response, in much the same way vaccines prime one's immune system to respond against a virus. The new approach also leads to the production of a significant number of "memory" T cells, that are capable of more potently and quickly responding to reactivated HIV.

IMPACT

The findings provide critical insights into the types of CAR molecules and approaches that are suitable for CAR therapies using blood-forming stem cells and that allow for optimal function and persistence of CAR T cells after development. The findings could influence the field of immunotherapy focused on engineering T cells with CAR molecules that are able to persist and form immunologic memory, and that can recognize and kill virus-infected or cancerous cells.

A new study indicates holes the solution to operational speed/coherence trade-off, potential scaling up of qubits to a mini-quantum computer.

Quantum computers are predicted to be much more powerful and functional than today's 'classical' computers.

One way to make a quantum bit is to use the 'spin' of an electron, which can point either up or down. To make quantum computers as fast and power-efficient as possible we would like to operate them using only electric fields, which are applied using ordinary electrodes.

Although spin does not ordinarily 'talk' to electric fields, in some materials spins can interact with electric fields indirectly, and these are some of the hottest materials currently studied in quantum computing.

The interaction that enables spins to talk to electric fields is called the spin-orbit interaction, and is traced all the way back to Einstein's theory of relativity.

The fear of quantum-computing researchers has been that when this interaction is strong, any gain in operation speed would be offset by a loss in coherence (essentially, how long we can preserve quantum information).

"If electrons start to talk to the electric fields we apply in the lab, this means they are also exposed to unwanted, fluctuating electric fields that exist in any material (generically called `noise') and those electrons' fragile quantum information would be destroyed," says A/Prof Dimi Culcer (UNSW/FLEET), who led the theoretical roadmap study.

"But our study has shown this fear is not justified."

"Our theoretical studies show that a solution is reached by using holes, which can be thought of as the absence of an electron, behaving like positively-charged electrons."

In this way, a quantum bit can be made robust against charge fluctuations stemming from the solid background.

Moreover, the 'sweet spot' at which the qubit is least sensitive to such noise is also the point at which it can be operated the fastest.

"Our study predicts such a point exists in every quantum bit made of holes and provides a set of guidelines for experimentalists to reach these points in their labs," says Dimi.

Reaching these points will facilitate experimental efforts to preserve quantum information for as long as possible. This will also provide strategies for 'scaling up' quantum bits - ie, building an 'array' of bits that would work as a mini-quantum computer.

"This theoretical prediction is of key importance for scaling up quantum processors and first experiments have already been carried out," says Prof Sven Rogge of the Centre for Quantum Computing and Communication Technology (CQC2T)."

"Our recent experiments on hole qubits using acceptors in silicon already demonstrated longer coherence times than we expected," says A/Prof Joe Salfi of the University of British Columbia. "It is encouraging to see that these observations rest on a firm theoretical footing. The prospects for hole qubits are bright indeed."

LA JOLLA, CA--What's the difference between a giggle and a belly laugh? Or a yelp and an all-out scream? In many species, including humans, the volume and duration of a verbal sound conveys as much information as the noise itself.

A group of scientists, led by Scripps Research, has discovered a node in the brains of male mice that modulates the sounds they make in social situations. This discovery, published in Nature, could help identify similar locations in the human brain, and potentially lead to a better understanding of social disorders such as autism or depression.

"Identifying this node gives us signatures of what to look for when human behavior goes awry," says Lisa Stowers, PhD, a neuroscientist and professor at Scripps Research who led the study. "It's giving us clues to how information is organized in the brain, and how different features of information can be separated out in different brain regions."

As part of their courtship behavior, male mice produce "songs." These complicated whistles, which are too high for the human ear to detect, are louder and longer when the female mouse is nearby or when her scent is stronger. The researchers identified a specific type of neuron in a part of the hypothalamus called the lateral preoptic area that controls the emotional regulation of these sounds.

"The hypothalamus and the rest of the limbic system control body functions such as hunger, thirst and temperature regulation, as well as the basic features of emotional behavior like sex and fear," Stowers says. "It is fitting that the emotional aspect of these social noises are generated in this region of the brain."

By directly stimulating the right nodes from these neurons, the scientists could trigger the whole array of noises that go into a mouse song. Varying the level of stimulation allowed them to control how enthusiastic those sounds were.

When the researchers blocked these nodes, male mice encountering a female would attempt to court her in silence. (Female mice responded by kicking the males and running away.) If the researchers bypassed these nodes and activated the next node downstream, the male mice only made long, loud noises.

"They're basically just shouting," Stowers says. "By finding these neurons, it's telling us that this part of the brain is doing this emotional scaling and persistence. If you take that away, then you lose all of that affect, all of that emotional range, and the ability to have effective social communication."

Most research on noise production in the brain has focused on language development, Stowers says. But the sounds that even an infant can make--a giggle, a cry, a scream--don't have to be learned and are just as vital for communication. Identifying how the brain decides on these responses is the first step to understanding where things can go wrong in social behavioral disorders such as autism and depression.

"We are starting to get a detailed look at where in the brain different types of computations are being made," Stowers says. "Now that we know that this simple behavior is regulated in the hypothalamus, we can study whether others behaviors are also using similar circuits and if so, perhaps find a common mechanism--and drug target--for when emotions are not generated appropriately."

First study in bereaved relatives' experience during Covid-19 pandemic lockdown published today

The study makes important recommendations for health and social care professionals providing end-of-life-care

Bereaved families highlighted their need for practical and emotional support when a family member was at end of life

The study found families have increased communication needs when a family member was at end of life, encompassing holistic as well as clinical connections

Phone calls between patients and their relatives should be prioritised during the pandemic to allow loved ones to say goodbye, a new study providing recommendations to healthcare professionals has suggested.

The study, by researchers at the Universities of Sheffield, Oxford and Liverpool is the first of its kind to give a voice to those bereaved during the pandemic. Published today in Palliative Medicine, it explores the impact of restricted visiting to hospitals and care homes due to Covid-19 on relatives' experience of their loved-one's final days, making important recommendations for health and social care professionals to boost the level of care provided.

Bereaved relatives described the ongoing pain of being absent at the end of a loved-one's life, with many not having seen their relatives for weeks or months due to the pandemic.

Relatives reported relying on connecting virtually with their family members in their final weeks of life, and it seemed these interactions could only happen when they were facilitated by health and social care professionals. There was also a need for more contact highlighted, including holistic as well as clinical communication with healthcare professionals about their loved one's wellbeing and psychological support.

The study makes important recommendations for health and social care professionals providing end-of-life care during a pandemic, finding opportunities must be prioritised for essential connections between families at end-of-life care:

Prioritise connectedness between patients and relatives using video and telephone calls.

Provide relatives with regular telephone updates about personal aspects of care (such as what they had eaten and if they had been able to communicate).

Offer advice and guidance about how to prepare children for the death of a loved one.

Facilitate opportunities for relatives to 'say goodbye' in person before death wherever possible.

The research team says that adopting these recommendations is important as previous research shows when the needs of relatives are addressed at the time a family member is dying, they cope and adjust better in bereavement with improved psychological outcomes and satisfaction with end-of-life care.

During the pandemic, relatives report that they are aware of the multiple demands on health and social care professionals and felt they are 'doing their best given the situation' but identify practical changes that could have made a difference to their experience of bereavement and loss.

Joint Senior Author, Dr Catriona Mayland from the Department of Oncology and Metabolism at the University of Sheffield, said: "Health and social care professionals had very little time to prepare or train for the impact of the pandemic. They faced an increased workload with competing demands and heightened complexity.

"This includes facilitating connectedness between patients and their relatives during the pandemic and they are perceived to be instrumental in this. The study shows the clear need for the opportunity to say goodbye in a meaningful way for families and proactive measures such as protecting time to facilitate connections between patients and relatives will be a valuable way to help families be able to navigate end-of-life care for their loved one and the impact of their grief."

Lead author, Dr Jeff Hanna from the Department of Psychiatry at the University of Oxford, said: "This timely research reports important recommendations for health and social care professionals as they provide end-of-life care during the pandemic. They have a pivotal role in facilitating vital interactions between relatives and their loved ones. The vast number of deaths in the UK means this work provides salient lessons for supporting families at end-of-life."

Dr Stephen Mason, Research and Development Lead for the Palliative Care Unit at the University of Liverpool said: "Our analysis of the experiences of bereaved relatives and health and social care professionals continues, with the hope of providing further insights in how we can maintain and potentially improve care within the limitations of necessary pandemic public health restrictions.

The public could lose trust in science if scientific and medical researchers choose to bypass the traditional high standards of peer-reviewed medical journals in the rush to get research data released, particularly during crises such as the COVID-19 pandemic.

That's the warning from three leading medical communications organizations, that have published a joint statement in the peer-reviewed journal Current Medical Research and Opinion - asserting that the integrity of published scientific and medical research must be protected.

Out today, the joint statement from the American Medical Writers Association (AMWA), the European Medical Writers Association (EMWA), and the International Society for Medical Publication Professionals (ISMPP), argues that although peer-review is still the most common process for vetting scientific publications, there is a worrying trend for manuscripts to be released without pre-publication review.

Especially during the COVID-19 health crisis, medical researchers have felt significant pressure to publish COVID-19 findings as quickly as possible, but the statement emphasizes that having a pre-publication review is still essential. The danger is that once the threshold of publication oversight is lowered, it becomes a precedent that cannot be easily reversed, potentially eroding standards and causing the public to lose trust in medical science. "Medical communicators, including writers, editors, and those involved in quality control, play a critical role in ensuring that clinical and scientific data are published and disseminated in an accurate and clear manner. In the current rush-to-publish environment, all stakeholders in the scientific and clinical research communities and press must ensure that the public have correct and actionable information from which to make health and medical decisions," explained Gail Flores, PhD, President of AMWA.

In particular, the statement highlights the impact of preprints - preliminary scientific reports that are made publicly available online for anyone to read and discuss before they have been peer reviewed. While preprints enable rapid release and discussion of data, many are never revised or corrected, and only about a third-to-a half are ever fully published. This can also occur with articles submitted for post-publication peer review, in which an article is published in its original form, before expert peer reviewers are invited to critique it.

The statement recognizes the benefit of rapid publication but alerts that they have to be vetted against the potential harms associated with an accelerated process. "Particularly in these times, it is more important than ever to retain public trust in science, while balancing the need to report timely and relevant medical research," stated Beatrix Doerr, PhD, President of EMWA. In seeking a resolution, the three organizations present recommendations and a Reviewers' Checklist to provide a minimum standard of pre-publication vetting to enhance preprint publication processes.

Their key recommendations include:

Performing more extensive and consistent checks ?  for example, by preprint server hosts  ? - on articles that have not been peer-reviewed prior to publication.

Referencing preprints and articles uploaded for post-publication peer-review only as in-text reference (with a preprint link, DOI, or both), rather than as a bibliographic reference, and clearly labelled as a preprint, or as undergoing post-publication peer review.

Watermarking articles plus including a disclosure within the body of the article highlighting that the findings have not been formally peer-reviewed.

Educating medical journalists and the public about the differences between preprints, post-publication peer review, and traditional peer review.

Crucially, the organizations have also identified ways in which the peer-review process - renowned for being "laborious and time-consuming" - could be expedited. They call upon each stakeholder - authors, journal editors, and publishers - to play a part in this. Their key suggestions include:

Rapid response team of reviewers

Standardized formatting requirements to shorten the time to re-submission

Portable peer-review

Fast-track options

Incentives for reviewers

"For those engaged in preprints, post-publication peer-review, as well as traditional peer-review publications, our joint statement presents key practical recommendations to safeguard the quality of the publications while supporting their more rapid dissemination. We strongly encourage authors, journal editors, publishers, and other stakeholders to review and apply these practical suggestions, ensuring a high-quality standard for published research, irrespective of the format," emphasized Robert J. Matheis, PhD, MA, President and CEO of ISMPP.

Researchers from the University of Science and Technology of China (USTC) of the Chinese Academy of Science (CAS), teamed up with scientists from Aix Marseille University, discovered that hematopoietic progenitors possessed the differentiation potential to type 1 innate lymphoid cells (ILC1s) in adult liver, and dissected the regulation mechanisms of such cell differentiation, revealing the pathways that lead to the development of tissue-resident lymphocytes. This study was published in Science.

Hematopoiesis occurs at different sites following the development of human body. After birth, the bone marrow (BM) has long been known to be the main hematopoietic organ where immune cells develop.

However, a previous study proposed that liver natural killer (NK) cells, retained in the adult liver without circulating through blood out of liver, which distinguished them from conventional NK (cNK) cells. The liver-resident NK cells, also known as liver ILC1s, were then viewed as one of three innate lymphoid cell subsets,.

Expanding studies were subsequently carried out to demonstrate the functional features and differentiation mechanisms of these cells by USTC scientists. Nevertheless, the origin and development of ILC1s remain unclear.

In this study, researchers investigated whether liver-resident ILC1s could develop from local hematopoietic progenitors during adulthood, as BM hematopoiesis was not the major source of them.

By comparing the fetal liver, the adult liver, BM and peripheral blood hematopoietic progenitors, researchers found that adult mouse liver contained Lin?Sca-1+Mac-1+ (LSM) cells, like hematopoietic stem cells (HSCs) in the fetal liver, at significantly higher frequencies. Experiments transferring purified LSM cells from adult liver into sublethally irradiated mice suggested the development potential to multiple hematopoietic lineages, and preferential differentiation into ILC1s in recipient liver through action on local progenitors, of LSM cells.

Moreover, this study revealed the role of interferon-γ (IFN-γ) playing in regulating ILC1s development. The IFN-γ produced by mature liver ILC1s promoted their own development by giving rise to liver LSM cells, while the absence of IFN-γ signaling had a negative effect on expansion of ILC1s rather than cNK cells.

These findings provide evidence for local development of adult liver ILC1s differentiated from fetal liver-derived hematopoietic progenitors, which is positively regulated by self-produced IFN-γ. This study unveils the pathways leading to extramedullary development of innate lymphoid cells, offering explanations of a distinctive regional immune feature within the liver.

The higher the number of plant and bird species in a region, the healthier the people who live there. This was found by a new study published in Landscape and Urban Planning and led by the German Centre for Integrative Biodiversity Research (iDiv), the Senckenberg Biodiversity and Climate Research Centre (SBiK-F) and the Christian Albrechts University (CAU) in Kiel. The researchers found that, in particular, mental health and higher species diversity are positively related, whereas a similar relationship between plant or bird species and physical health could not be proven.

The study led by researchers from iDiv, SBiK-F and CAU provides an analysis of the relationship between biodiversity and human health in Germany. The scientists used data on mental and physical health provided by the German Socio-Economic Panel (SOEP), including almost 15,000 households and about 30,000 persons. As indicators for species diversity, they used estimates on species richness of plants and birds as well as on bird abundance.

People are healthier in regions with more plant and bird species

The results of the study show better mental health of the people living in regions with higher plant and bird diversity. "A person living in a region with many different plant and bird species is, in average, feeling mentally better than a person living in a region with lower species diversity," said first author Joel Methorst, former doctoral researcher at iDiv, SBiK-F and Goethe University Frankfurt and now researcher at Helmut Schmidt University Hamburg. Furthermore, a positive relation of parks and green spaces in the neighbourhood and mental health was observed - the closer the park, the better.

Contrary to the researchers' expectation, there seems to be no relationship between bird abundance and mental health. „This could be due to the fact that many abundant bird species such as pigeons, seagulls and crows are oftentimes not very popular," explained Joel Methorst.

Indirect effects of biodiversity on human health

The researchers were not able to show a significant relationship between species diversity and physical health. Instead, the relationship could be more indirect: People who enjoy outdoor physical activity to experience plants and birds in their natural environment can improve their health with this activity.

However, positive effects are not only generated by the direct experience of biodiversity, for example a walk in the park or a visit to a garden. Environments with higher plant and bird species richness can also have indirect positive effects on human health as greater species diversity oftentimes correlates with better environmental conditions.

Nature conservation as a means to improve health

The researchers were not able to establish causal links between the number of species and mental or physical health. For this, data for different time periods would be required. To date, sufficient time series data on biodiversity in Germany is not available.

Nonetheless, valuable conclusions can be drawn from this study. "Our results show that nature conservation can, indeed, be understood as a means to promote human health," said senior author Prof Katrin Rehdanz from CAU. "This is particularly relevant for urban planning and management of green spaces. Here, investing in biodiversity can promote the health of the urban population."

Research led by Michigan Medicine's Scleroderma Program and published in Arthritis & Rheumatology found that tocilizumab, a FDA-approved anti-inflammatory drug used to combat rheumatoid arthritis, can prevent lung disease in patients with systemic sclerosis if detected early enough in the disease course.

Systemic sclerosis is an autoimmune disease and the most serious form of scleroderma, the tightening and thickening of the skin. It can affect internal organs and lung disease is its leading cause of death, according to study author Dinesh Khanna, M.B.B.S., M.Sc., director of Michigan Medicine's Scleroderma Program.

"Some people have minimal lung disease; some people have life-threatening disease. The amount of lung scarring plays a major factor in those health outcomes," says Khanna. "When used in patients early in their disease course, those that usually have had the disease five years or less, our study found that tocilizumab preserved lung function over the course of 48 weeks."

When left undiagnosed and untreated, patients with systemic sclerosis can suffer a rapid decline in lung function. And unfortunately, this lung disease is irreversible.

Khanna's research, referred to as the focuSSced trial, was a phase 3, randomized placebo-controlled trial seeking to understand the impact of tocilizumab on lung function preservation in patients with mild, moderate and severe amounts of lung scarring.

"We also wanted to learn more about who would benefit the most from tocilizumab intervention," says study author David Roofeh, M.D., a new member of Michigan Medicine's Scleroderma Program. "Surprisingly, it didn't matter how much lung scarring the patient had or what percentage of the lung was involved in this population. They all reacted the same."

The research team found that of the 210 trial participants, tocilizumab treatment over the course of 48 weeks, compared to the placebo, stabilized forced vital capacity, which is the total amount of air exhaled during forced breathing.

According to Roofeh, this test, the FVC test, is the most important measurement of lung function.

Khanna and Roofeh's work suggests there's a window of opportunity for a select group of patients with systemic sclerosis where the anti-inflammatory drug can halt or prevent irreversible lung damage.

And the FDA agrees, just recently approving tocilizumab for slowing the rate of decline in lung function in adult patients with systemic sclerosis-associated interstitial lung disease. However, more research is needed to better understand this complex illness.

"This cohort of patients was carefully selected to represent those with highly inflammatory disease characteristics. More research is needed in clarifying if other patient demographics may respond to this type of therapy, perhaps earlier in the disease process," says Khanna. "Careful delineation of which patient and disease factors predict response may help improve disease outcomes for more than the select population studied here."

When asked what Khanna and Roofeh hope other health care providers take away from their work, the call was clear: screen, diagnose and treat patients early.

"Historically, a provider would wait to treat someone until they showed signs of illness," says Khanna. "I hope this data suggests a possible paradigm shift in terms of treatment for these patients, providing an option of early detection and secondary-prevention, identifying the disease in the subclinical state, rather than later trying to reduce the impact of clinically significant disease."

A team of neurobiologists at the Institut de Neurosciences de la Timone (CNRS/Aix-Marseille Université) has just shown that within a population of rats it can predict which will become cocaine addicts. One of the criteria for addiction in rats is the compulsive search for a drug despite its negative consequences. Scientists observed abnormal activity in a specific region of the brain, the subthalamic nucleus, only in future addicted individuals, and did so before they were exposed to 'punishment' associated with the seeking for the drug. These results, which have just been published online by PNAS, also indicate that it is possible to reduce this compulsive cocaine-seeking behaviour in rats by stimulating the subthalamic nucleus, confirming its interest as a target in the treatment of addiction.

"SARS-CoV-2 and SARS-CoV are highly similar genetically, generate a homologous repertoire of viral proteins, and use the same receptor to infect human cells. However, despite these similarities, there are also important differences between the two viruses", says Ronald Dijkman from the Institute for Infectious Diseases (IFIK) at the University of Bern. For example, SARS-CoV infection is characterized by severe disease and inflammation in the lower respiratory tract and infected individuals are only contagious after the onset of symptoms, making it easier to identify and interrupt infection chains.

In contrast, SARS-CoV-2 preferentially replicates in the upper airways (nasal cavity, pharynx, trachea) and can be efficiently transmitted from one individual to another before the appearance of disease symptoms. Moreover, the outcome of SARS-CoV-2 infection varies widely from person to person, and can manifest as asymptomatic, mild, or severe disease. Older people as well as individuals with certain underlying medical conditions (heart conditions, diabetes, cancer) are at greater risk of developing severe illness, which is often associated with infection of lower respiratory tissues, high levels of inflammation, and lung failure.

Temperature is key

To better understand why infections with SARS-CoV and SARS-CoV-2 result in such different clinical outcomes, researchers from the University of Bern used specialized human airway cell cultures to investigate the impact of respiratory tract temperatures on SARS-CoV and SARS-CoV-2 replication. The cells originate from human samples and mimic the complexity of the cells found in the respiratory tract. They grow in special containers, are nourished from the bottom side and are exposed to air on the top side, just like the cells in the human trachea. The cultures also make mucus and have cilia that beat very quickly. "Because the organization of these cells greatly resembles the cells found in human tissues, they are a relevant system that can be used in a laboratory to study respiratory viruses", Dijkman explains.

The researchers have now used this existing model for the first time to study the effects of respiratory temperatures on SARS-CoV and SARS-CoV-2 replication. They found that temperature plays an important role as SARS-CoV-2 preferred to replicate at temperatures typically found in the upper airways (33°C). Colder incubation temperatures allowed the virus to replicate faster and to a higher extent than when infections were carried out at 37°C to mimic the lower lung environment. Unlike SARS-CoV-2, replication of SARS-CoV was not impacted by different incubation temperatures. The experiments were conducted both in the high security laboratory of the IVI in Mittelhäusern and in the biosafety laboratory of the Institute for Infectious Diseases (IFIK) at the University of Bern in the building of sitem-insel, the Swiss Institute for Translational Medicine and Entrepreneurship.

Temperature also influences the response from the epithelium

The team also analyzed which genes are turned on and off after infection with SARS-CoV and SARS-CoV-2 to understand how cells from the human respiratory tract respond to infection and which innate immune programs are activated. The innate immune system is our body's "first line of defense" against invading pathogens and is crucial not only to contain the invader, but also to teach other branches of the immune system how to react appropriately.

When mimicking the conditions found in the upper airways (33°C), the team found that infection with SARS-CoV-2 did not stimulate the innate immune response within these cells as strongly as it did when they mimicked conditions found in the lower respiratory tract (37°C). "Since the strength of the innate immune response can directly influence the degree of viral replication, this may help explain why SARS-CoV-2 replicated more efficiently at lower temperatures", says Dijkman. Although mounting a strong innate immune response against the virus is generally beneficial, it is important to note that in some cases the innate immune response can become overactivated. This in turn can be detrimental to the infected individual, as high levels of inflammation can also induce tissue damage and accelerate disease progression - a phenomenon that is often seen in patients suffering from severe COVID19.

"The detailed analysis of SARS-CoV-2 replication and the temperature-induced changes in the host innate immune defense mechanisms helps explain why SARS-CoV-2 replicates so well in the upper respiratory tract, and is perhaps why SARS-CoV-2 exhibits higher human-to-human transmissibility than SARS-CoV", Dijkman explains.

Important knowledge to fight coronavirus infections

The use of this authentic cell culture model in a controlled laboratory setting proved to accurately reflect the different behavior of two similar viruses in the context of a pandemic. "This unique system provides insight into the molecular battle that occurs between virus and host during an infection and underscores the importance of subtle changes in the virus-host microenvironment that may impact virus replication and propagation", says Dijkman. Understanding which key players are involved in this process, and whether they favor the host or virus, opens new opportunities for the establishment of highly targeted intervention strategies and the development of novel pharmaceutical compounds that will help combat coronavirus infections.

Companies could be hiring that bad boss on purpose. According to new research in the Journal of Business Ethics, the "dark" personality traits - questionable ethical standards, narcissistic tendencies - that make a boss bad also make that person much more likely to go along with manipulating earnings and may be the reason they got the job in the first place.

Co-authors Nick Seybert (University of Maryland's Robert H. Smith School of Business), Ling Harris (University of Nebraska-Lincoln), Scott Jackson (University of South Carolina) and Joel Owens (Portland State University) studied the process of hiring executive management accounting candidates and its relation to the company's earnings management practices - that is, a company's tendency to inflate its income. Through several studies, they found that when a company needed to report earnings aggressively, experienced executives and recruiters tended to recommend hiring candidates with dark personality traits over candidates who sought input from others and believed in strong ethical foundations.

"Dark personality traits are often framed as an accidental byproduct of selecting managers who fit the stereotype of a strong leader," says Seybert, an accounting professor. "However, our research found that this is often no accident."

The research for "Recruiting Dark Personalities for Earnings Management" involved three experiments in which different actions were measured. In one experiment, for example, the participants were specifically asked to rate the candidates based on dimensions such as the candidate's ability to manage people and relationships. The only dimension in which candidates with dark personalities were rated higher than their counterparts was in manipulation of ethical boundaries.

"A lot of people assume that these managers must have great self-presentation, promotion, people skills, or confidence" Seybert says. "But our research shows otherwise."

The basic idea behind this research is that these dark personalities can fulfill a specific nefarious purpose, says Seybert. When companies feel as though they need to inflate their earnings, people with dark personalities are more likely to get placed into positions of power to do exactly that. This results in candidates with potentially better management, organizational, and people skills being passed over for management jobs.

Seybert and his colleagues' research is unique in that they recruited experienced executives and executive recruiters to evaluate the candidates in order to simulate the real business hiring environment.

"Very, very few prior studies involved people who have experience recruiting for prior jobs," says Seybert. "Our research involved a lot of time-consuming and creative searching to find the right participants."

Overall, Seybert says he hopes that this research will help candidates better evaluate companies during their job search. "The best takeaway for employees is to avoid companies that might have use for managers with dark personalities, and not to expect support from higher-ups when this is the case. The company might have picked a bad boss on purpose."

ATLANTA -- Assisted living communities can improve the quality of life for residents with dementia by approaching them as individuals and attempting to include all residents in activities, according to a study led by a Georgia State University gerontology researcher.

The typical "activity programming" at many assisted living residences can leave people with dementia on the sidelines, according to the study, "Meaningful Engagement Among Assisted Living Residents With Dementia: Successful Approaches," published in the Journal of Applied Gerontology.

The study found that the keys to improving quality of life for residents with dementia are getting to know them as individuals, meeting people "where they are," being in the moment with people and viewing all interactions with residents as opportunities to connect.

The study, based on interviews and observational visits conducted in 2019, offers initial findings as part of a five-year project being funded by the National Institute on Aging at the National Institutes of Health.

"COVID-19 highlights the importance of meaningful engagement for everyone, especially for persons living with dementia," said Candace Kemp, a professor at Georgia State University's Gerontology Institute and principle investigator of the study. "Doing things that are enjoyable and being engaged to the extent possible and desirable are significant for quality of life and quality of care."

Researchers conducted interviews and observations involving 33 assisted living residents with varying types of dementia and levels of functional ability. They represent a diversity of gender, age, race and ethnicity and socioeconomic backgrounds.

The researchers found that actively "listening and observing verbal and non-verbal cues were keys to connecting and meeting residents on their own terms." The researchers urged caregivers to try to include all residents in activities and not to assume that people with dementia can't benefit from activities simply because they may not be able to respond in the same way as other residents.

The research has implications in the COVID-19 era, which has limited visits by family and friends at many assisted living facilities and restricted group activities and gathering for meals. A greater focus on meaningful engagement with residents "holds promise for offsetting the negative effects of social distancing for residents and for reducing care partner strain," the researchers wrote.

ANN ARBOR--By April last year, up to 28 free-standing alternate care sites ranging in size from 50 to 3,000 beds were underway or finished in the U.S.--the Michigan Medicine Field Hospital among them.

This 500-bed alternate care site was planned and construction underway from March through May to meet the estimated surge in COVID-19 patients, expected to overrun hospitals nationwide and in Michigan. Sue Anne Bell, assistant professor of nursing and a disaster expert, was one of the field hospital's five-member leadership team.

Bell and her colleagues from Michigan Medicine recently published a study in Prehospital and Disaster Medicine about lessons learned from that experience.

The Michigan Medicine Field Hospital was planned to be a step-down care facility where the least ill COVID-19 patients could be safely treated prior to discharge. The idea was to increase bed capacity for more acutely ill patients in the remaining Michigan Medicine hospitals. The majority of field hospitals constructed for COVID patients in the U.S. weren't called into service, including the Michigan Medicine facility.

Planning for the Michigan Medicine Field Hospital was organized into six units: personnel and labor; security; clinical operations; logistics and supply; planning and training; and communications.

"The command structure worked really well," Bell said. "There was a clear reporting structure that made communication among teams straightforward, which was really important given both the urgency of the situation and later the uncertainty."

Another strength was the team's commitment.

"This was all hands on deck to get the field hospital in place as quickly as possible in order to meet the needs of the community," Bell said.

The team visited indoor athletic facilities and dormitories near the hospital, ultimately selecting the new 73,000-square-foot indoor track and performance facility, a 12-minute drive from the main hospital. A draft layout was completed in two days of a 519-bed facility, including a 20-bed higher acuity area for patients requiring a transfer back to Michigan Medicine. The goal was to provide the highest level of comprehensive care possible in a temporary setting, and many of the comforts of traditional hospital stays (visitors, television) weren't possible due to COVID transmission risks.

"They were not really well suited to being a full substitute for acute hospital care of COVID patients, because it was difficult to discern early in the progression of the disease which patients might need ICU care or were at risk of decompensating quickly, and which ones were relatively stable and could be cared for safely in a field hospital setting," said study co-author Keith Dickey, chief strategy officer for Michigan Medicine.

Allocating staffing and personal protective equipment in the convalescent vs. acute care settings was challenging. Because of the nature of COVID, many of the patients would be older adults with preexisting conditions. Decision-making revolved around how to meet the physical therapy and physical medicine and rehabilitation needs of these patients, and PPE needed for those staff.

Sourcing supplies was also challenging, as shortages existed around the country and worldwide, which resulted in massive regional and national competition for supplies.

"Just as we were trying to order cots or IV poles in a large volume, so were other places around the country," Bell said. "Creating a plan for sourcing those resources in the event of a future field hospital is a consideration."

Another challenge was communication at state and federal levels.

"There was so much going on across the country, that trying to get clear information was a challenge, as modeling was shifting and hotspots were emerging," Bell said.

One major advantage of an academic medical center-run facility was physician staffing capacity. Academic physicians are not generally 100% clinical, and Michigan Medicine physicians and resident trainees could provide extra clinical capacity. Tapping into staff with prior military and disaster experience was also critical.

While the experience was specific to COVID-19, much of what was learned is generalizable to other instances requiring a field hospital.

"But what we have now is a clear plan for how we will implement a field hospital in the future," Bell said. "And with that we can change and improve that plan using our baseline knowledge from this experience."

But the study also shows for the first time that performance may be improved by using super recognisers - people who are very skilled at recognising faces. It also reveals that masks do make recognising someone's emotions more difficult.

There are many questions surrounding face masks and the impact that masks will have on face identification. Can we recognise the faces of people who we know well if they are wearing a mask? And, relevant to policing and security scenarios or a supermarket ID check, can an unfamiliar face be recognized across images if it is masked? And how do masks impact our ability to recognize a person's emotions?

Dr Noyes is Senior Lecturer in Cognitive Psychology and conducted the study, published by the Royal Society, in collaboration with researchers at the University of Greenwich, University of Reading, and University of Lincoln. A leading expert in the field, Dr Noyes was intrigued what the enforced wearing of masks due to COVID-19 would have on facial recognition.

The study consisted of three experiments which tested recognition of familiar faces, recognition of an unfamiliar face (comparing images, aka face matching), and emotion recognition. The researchers compared face recognition and emotion recognition for faces with no concealment, faces in masks, and faces in sunglasses - something far more commonplace than masks and often a matter of choice rather than necessity.

In the first experiment, participants were presented with pairs of famous faces, and were asked to decide if the images were of the same person or two different people.

"People are typically very good at identifying the faces of people they know well," says Dr Noyes. "However, we found that face masks reduced accuracy on this task. There was no difference in accuracy for faces in masks compared to faces in sunglasses. Accuracy on the familiar face recognition task remained high - around 90% - even for faces in masks.

"Face comparisons are much more difficult if the faces are unknown to the identifier, but it is this task which mimics what can happen in many security scenarios. In the unfamiliar face comparison task, both masks and sunglasses reduced identification accuracy. Masks impaired performance the most, but only a little more than sunglasses." This difference in recognition was at only around 3%.

A group of people who were known to be 'super recognisers' also took part in the task. Super recognisers have an exceptional natural ability for recognising a face, an ability that only 2% of the population have.

Super recognisers outperformed typical observers for unconcealed faces, faces in masks, and faces in sunglasses, showing that they still outperform typical observers even when looking at concealed faces. This study is the first to test the performance of super recognisers for faces in masks.

What about the recognition of a person's emotional expressions? Participants in the study viewed face images and were asked to decide which emotion had been displayed (see Fig 2).

"The effect of masks on emotion categorization was more complex than the results for the recognition task," Dr Noyes explains. "The emotions 'happiness', 'disgust' and 'surprise' were particularly difficult to recognise when the faces were in masks, but the recognition of the emotions 'anger' and 'fear' were impaired by both masks and sunglasses."

Dr Noyes continues, "The results of the study show that the lower half of the face is important for face identification and emotion recognition. It's not all in the eyes!"