Culture

June 4, 2020 - Compared to other groups of healthcare practitioners, nurses may have the poorest perceptions of workplace safety climate and the highest rates of injuries and sick time, suggests a single-hospital study in the May/June issue of the Journal of Healthcare Management, an official publication of the American College of Healthcare Executives (ACHE). The journal is published in the Lippincott portfolio by Wolters Kluwer.

Low ratings of workplace safety may also be associated with increased job stress and decreased job satisfaction for nurses, healthcare aides, and allied healthcare professionals, according to the new research by Gwen E. McGhan, PhD, and colleagues of University of Calgary. They write, "Considering the importance of safety climate perceptions for the well-being of care practitioners, healthcare organizations need to prioritize workplace safety to optimize practitioners' perceptions."

Safety Climate Perceptions Affect Job Stress, Turnover, and Satisfaction

The survey study included three groups of healthcare professionals at one Canadian hospital: nurses, healthcare aides, and allied health professionals (for example, physical and occupational therapists). All groups completed a 10-item individual workplace safety climate scale, rating their agreement/disagreement with job descriptions such as "unsafe," "risky," or "could get hurt."

Perceptions of workplace safety climate were compared among groups, and associations with ratings of job stress, job satisfaction, and turnover intentions were assessed. The analysis included 144 responses (survey response rate 28 percent) from three hospital units where all three groups of professionals worked.

Nurses had the lowest ratings of workplace safety climate, followed closely by healthcare aides. In contrast, allied health professionals had significantly higher safety perceptions. "Nurses reported the poorest safety perceptions, lowest job satisfaction, and highest stress, while allied health professionals reported the highest safety perceptions and job satisfaction and the lowest stress," Dr. McGhan and coauthors write. Turnover intentions (for example, "How often do you consider leaving your job?") were also highest for nurses and lowest for allied health professionals.

Workplace safety climate perceptions were also related to reported injuries and illnesses: 68.3 percent of all injuries occurred in nurses, compared to 23.3 percent for healthcare aides and 8.3 percent for allied health professionals. As individual safety perceptions decreased, the odds of being injured at work more than doubled.

The higher injury rates in nurses and aides might reflect their greater involvement in direct, hands-on patient care, the researchers suggest. Nurses accounted for 53.2 percent of all paid sick time, healthcare aides for 42.2 percent, and allied health professionals for 4.6 percent.

"Healthcare organizations are struggling to cope with a growing global shortage of healthcare practitioners," according to the authors. Along with growing caseloads and other factors, rates of injuries and illness in healthcare professionals - among the highest of any occupational group - may affect the ability to retain qualified practitioners.

The new findings suggest that different groups of healthcare practitioners have differing perceptions of workplace safety climate, and that these perceptions affect job stress, job satisfaction, and injury/illness rates. Dr. McGhan and coauthors conclude: "By focusing on position, role, and perceptions of safety climate, healthcare leaders can provide safety processes and training to improve how employees perceive the safety of their workplace."

Researchers at Wake Forest School of Medicine have discovered that nicotine promotes the spread of lung cancer cells into the brain, where they can form deadly metastatic tumors. The study, which will be published June 4 in the Journal of Experimental Medicine (JEM), suggests that nicotine replacement therapies may not be suitable strategies for lung cancer patients attempting to quit smoking. In addition, the researchers show that the naturally occurring drug parthenolide blocks nicotine-induced brain metastasis in mice, suggesting a potential therapeutic option in humans.

Up to 40% of lung cancer patients develop brain metastasis, and the average survival time for these patients is less than six months. “There is an urgent need to understand the mechanisms that drive brain metastasis so that more effective therapies can be developed,” says Dr. Kounosuke Watabe, a professor of cancer biology at Wake Forest School of Medicine in Winston-Salem, NC.

Cigarette smoking is a major risk factor for lung cancer, but how it affects the development of brain metastasis is unclear. Watabe and colleagues studied 281 patients with advanced lung cancer and found that brain metastasis was much more common in patients who continued to smoke compared with patients who had never smoked or had successfully quit.

Watabe and colleagues found that, in mice, the spread of lung cancer cells to the brain is driven by nicotine, a major component of tobacco smoke that isn’t, in and of itself, carcinogenic. “Many cancer patients find it difficult to quit smoking even after their diagnosis due to nicotine addiction,” Watabe says. “E-cigarette, nicotine patch, and nicotine gum are commonly used as nicotine replacement therapies to help these patients cease smoking. However, our results clearly show that nicotine has profound and long-term effects on brain metastasis progression, suggesting that cancer patients should be cautious in their use of nicotine for smoking cessation.”

The tumors in patients’ brains contained large numbers of M2 microglia, a type of immune cell that secretes several molecules capable of enhancing tumor growth. The researchers found that nicotine stimulates the formation of M2 microglia in mice. Removing microglia from mouse brains prevented nicotine from inducing brain metastasis and enhanced the survival of mice with lung cancer.

Watabe and colleagues then looked for drugs that might reverse the effects of nicotine and identified parthenolide, a compound present at high levels in the medicinal herb Feverfew (Tanacetum parthenium), which has been used for centuries to treat headaches and inflammation. Treating mice with parthenolide prevented nicotine from stimulating the formation of M2 microglia and inhibited the spread of lung cancer cells to the brain, thereby improving the animals’ survival.

“We therefore think that parthenolide could be useful for the prevention and treatment of brain metastasis, particularly for patients with past and current smoking history,” Watabe says.

WASHINGTON -- Neurodegenerative diseases such as Alzheimer's and Parkinson's are often accompanied by amyloid proteins in the brain that have become clumped or misfolded. A newly developed technique that measures the orientation of single molecules is enabling optical microscopy to be used, for the first time, to reveal nanoscale details about the structures of these problematic proteins.

Researchers from Washington University in St. Louis describe their new approach in Optica, The Optical Society's journal for high impact research.

"Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are leading causes of death all over the world," said Tianben Ding, co-first author of the new paper. "We hope our single-molecule orientation imaging approach can provide new insights into amyloid structure and possibly contribute to the future development of effective therapeutics against these diseases."

Biological and chemical processes in the brain are driven by complicated movements and interactions between molecules. Although most amyloid proteins may be non-toxic, the misfolding of even a few could eventually kill many neurons.

"We need imaging technologies that can watch these molecular movements in living systems to understand the fundamental biological mechanisms of disease," explained Matthew D. Lew, leader of the research team. "Amyloid and prion-type diseases like Alzheimer's, Parkinson's and diabetes are our first targets for this technology, but we see it being applied in many other areas too."

Selecting the best microscope

Lew's lab has developed several single-molecule super-resolution microscopy methods that measure the orientation and location of fluorescent molecules attached to single proteins. The orientation information is obtained by measuring not only the location of fluorescence in the sample but also characteristics of that light, such as polarization, which are typically ignored in most other microscopy approaches.

In their Optica article, the researchers described a performance metric they designed to characterize how sensitively various microscopes can measure orientations of fluorescent molecules. Using the new performance indicator, the researchers found that a microscope that splits fluorescence light into two polarization channels (x and y) provides superior and practical orientation measurements.

"The metric we developed calculates the performance of a particular microscope design 1,000 times faster than before," said Tingting Wu, co-first author of the work. "By measuring the orientations of single molecules bound to amyloid aggregates, the selected microscope enabled us to map differences in amyloid structure organization that cannot be detected by standard localization microscopes."

Since there is no artificial link between the fluorescent probes and amyloid surfaces, the probes' binding orientation to the amyloid surfaces conveys information about how the amyloid protein itself is organized. The researchers quantified how the orientations of fluorescent molecules varied each time one attached to an amyloid protein. Differences in these binding behaviors can be attributed to structure differences between amyloid aggregates. Because the method provides single-molecule information, the researchers could observe nanoscale differences between amyloid structures without averaging out details of local features.

Opportunities for long-term studies

"We plan to extend the method to monitor nanoscale changes within and between amyloid structures as they organize over hours to days," said Ding. "Long-term studies of amyloid aggregates may reveal new correlations between how amyloid proteins are organized and how quickly they grow or spontaneously dissolve."

The researchers note that the set-up they used for orientation-localization microscopy consisted of commercially available parts that are accessible to anyone performing single-molecule super-resolution microscopy. Their analysis code is available at https://github.com/Lew-Lab/RoSE-O.

"In optical microscopy and imaging, scientists and engineers have been pushing the boundaries of imaging to be faster, probe deeper and have higher resolution," said Lew. "Our work shows that one can shed light on fundamental processes in biology by, instead, focusing on molecular orientation, which can reveal details about the inner workings of biology that cannot be visualized by traditional microscopy."

Meningococci are bacteria that can cause life-threatening meningitis and sepsis. These pathogens use a small protein with a large impact: The RNA-binding protein ProQ is involved in the activation of more than 250 bacterial genes.

ProQ ensures that meningococci can better repair their DNA if damaged and it makes them resistant to oxidative stress. Both these factors contribute significantly to the bacteria's pathogenic properties.

This was reported by research groups led by the Würzburg scientists Christoph Schoen and Jörg Vogel in the journal Nature Communications.

"We were surprised that a comparatively small protein can have such a great influence on bacterial gene regulation," says Christoph Schoen, professor at the Institute of Hygiene and Microbiology at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

ProQ only consists of about 120 amino acids. By comparison, many other proteins are usually made up of several hundred amino acids.

ProQ interacts with 200 RNAs

The mini-protein belongs to the group of RNA-binding proteins. RNA molecules play an important role as regulators in many biological processes. They often perform their functions in combination with the binding proteins.

ProQ is a key player in this respect: "In meningococci, the protein interacts with almost 200 different RNA molecules," says Jörg Vogel. "It binds to structured regions of the RNA and thus stabilises its binding partners."

The researchers made the discovery using modern high-throughput processes. These methods were developed in Vogel's group at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg. Vogel is director of HIRI and heads the JMU Institute for Molecular Infection Biology.

Looking for new drugs against bacteria

The scientists are interested in the processes in bacteria because they hope to find new targets for antibacterial agents. The pathways regulated by RNA and its binding proteins in particular offer a promising field of activity. "We hope to be able to disrupt the binding proteins in their function with small molecules and hence weaken the pathogens," explains Vogel.

Objective: to identify all RNA binding proteins

For two thirds of all RNAs in meningococci, the associated binding proteins have not yet been identified. This raises questions: Is it possible that the majority of RNAs does not need proteins to carry out their regulatory function in bacterial cells? And which processes are actually regulated by RNA-binding proteins?

"This is what we would like to find out - and meningococci are particularly well suited for this task because of their relatively small genome," says Schoen. "Our goal is to systematically identify the entire family of RNA-binding proteins in meningococci using established high-throughput methods."

Physicists have created the most sensitive strain sensor ever made, capable of detecting a feather's touch.

The sensor, developed by the Materials Physics Group at the University of Sussex, can stretch up to 80 times higher strain than strain gauges currently on the market and show resistance changes 100 times higher than the most sensitive materials in research development.

The research team believe the sensors could bring new levels of sensitivity to wearable tech measuring patients' vital signs and to systems monitoring buildings and bridges' structural integrity.

Marcus O'Mara, from the School of Mathematical and Physical Sciences at the University of Sussex, said: ""The next wave of strain sensing technology uses elastic materials like rubber imbued with conductive materials such as graphene or silver nanoparticles, and has been in development for over a decade now.

"We believe these sensors are a big step forward. When compared to both linear and non-linear strain sensors referenced in the scientific literature, our sensors exhibit the largest absolute change in resistance ever reported."

Alan Dalton, Professor of Experimental Physics at the University of Sussex, said: "This promising technology may prove especially useful in established fields such as healthcare, sports performance monitoring and rapidly growing fields such as soft robotics.

"Our research has developed cheap, scalable health monitoring devices that can be calibrated to measure everything from human joint motion to vitals monitoring. Multiple devices could be used across the body of a patient, connected wirelessly and communicating together to provide a live, mobile health diagnostics at a fraction of the current cost."

The new paper, published in the journal Advanced Functional Materials, details the process for incorporating large quantities of graphene nanosheets into a PDMS matrix in a structured, controllable fashion that results in excellent electromechanical properties.

The authors say the method has the potential to be extended to a wide range of two-dimensional layered materials and polymer matrices. The sensors deliver greatly enhanced conductivity at all measured loading levels with no apparent percolation threshold.

Commercial gauge devices suffer from relatively low sensitivity and strain range, with gauge factors ranging from 2-5 and maximum strains of 5% strain or less, resulting in the resistance increasing by less than 25% and preventing high-strain sensing required for bodily motion monitoring.

The new sensors are able to detect strains less than 0.1%, due to their higher gauge factor of ~20, and up to 80% strain, where the exponential response leads to the resistance changing by a factor of more than one million.

This allows both high-sensitivity low-strain sensing for pulse monitoring and high-strain measurement of chest motion and joint bending as a result of the record resistance change.

Dr Sean Ogilvie, Research Fellow in Materials Physics at the University of Sussex, said: "Commercial strain sensors, typically based on metal foil gauges, favour accuracy and reliability over sensitivity and strain range. Nanocomposites are attractive candidates for next generation strain sensors due to their elasticity, but widespread adoption by industry has been hampered by non-linear effects such as hysteresis and creep due to the liquid like nature of polymers at the nanoscale which makes accurate, repeatable strain readouts an ongoing challenge.

"Our sensors settle into a repeated, predictable pattern which means that we can still extract an accurate read-out of strain despite these effects."

The work was made possible with the support of US-based rubber company Alliance.

Jason Risner, V.P. of Sales & Marketing at Alliance, said: "Alliance has a long history of innovation and it is vital for us to play an active role in leading edge rubber technology that uses a disruptive nanomaterial like graphene. It is critical that we partner with scientific leaders like Professor Alan Dalton at the University of Sussex.

"We are thrilled to see the products that could potentially come out of our partnership. Graphene is an astonishing material that can revolutionize our lives. Our company is proud to be on the cutting edge of something so new."

CHAMPAIGN, Ill. -- Researchers report that the Asian tiger mosquito, Aedes albopictus, has become more abundant across Illinois in the past three decades. Its spread is problematic, as the mosquito can transmit diseases - like chikungunya or dengue fever - to humans.

The Asian tiger mosquito originated in the forests of southeast Asia. It found its way to Texas around 1985 and very quickly spread to Illinois.

"The global trade in used tires facilitates the spread of the mosquito," said Chris Stone, a medical entomologist at the Illinois Natural History Survey and the lead author of the new study. "The eggs get stuck to the walls of the tires and can survive even in dry conditions. Tires are also great at retaining rainwater, which is perfect for the larvae to develop in."

Stone and his colleagues wanted to understand how the mosquitoes were able to spread across Illinois, given how cold the state's winters can be.

"We looked at historical records to see where the mosquito has been observed in the state. We then compared that information to the winter temperatures in different counties," said Rebecca Smith, a professor of pathobiology at the University of Illinois at Urbana-Champaign who led the research with Stone. "Winters are fairly warm in cities like Chicago because of all the roads and concrete. There are a lot of places like sewers and subways where these mosquitoes can live in the winter."

The spread of the Asian tiger mosquito in Illinois also is a result of repeated introductions from neighboring counties.

"We used the historical observations to look at whether the mosquitoes were present in one county during a particular five-year period, and whether they were then present in a neighboring county in the previous five-year period," Smith said.

The researchers also used genetic information to track the spread of the mosquitoes, focusing on mitochondrial DNA, which is abundant in cells. Comparing mitochondrial DNA sequences is an established method for studying the spread of mosquitoes globally.

"We found that there is a surprising diversity of Aedes albopictus in Illinois," Stone said. "Some were from the Texas population, but a few had previously been found only in Japan. This observation supports the idea that we see multiple introductions of these mosquitoes from different places."

The data was compiled from a variety of sources, the researchers said.

"We had some collections of mosquitoes from our partners in public health, and we set out some mosquito traps in counties that had not been looked at previously," Stone said. "Unfortunately, we did not have samples that went back as far as the historical observations."

Asian tiger mosquitoes are good at outcompeting other mosquitoes, the researchers said. This can have both beneficial and harmful effects.

"There have been studies from Florida and Texas where Aedes albopictus has displaced Aedes aegypti, a closely related mosquito known as the yellow fever mosquito that can transmit dengue and yellow fever," Stone said. "The implications of the establishment of the Asian tiger mosquito in Illinois on other mosquito species is a topic that needs further study."

"The ability of the Asian tiger mosquito to establish itself in Illinois could be problematic from a public health perspective," Smith said. "Although it is not as bad as the yellow fever mosquito, it has the potential to introduce diseases."

The researchers hope to expand the historical database of disease-carrying mosquitoes. "The biggest drawback with this study was that there are many places where mosquito surveillance has been limited," Smith said. "We need to increase the surveillance so that we can track the spread of these mosquitoes more comprehensively and study them more intensively."

The researchers report their findings in the Journal of Medical Entomology.

WEST LAFAYETTE, Ind. - A Purdue University data science and machine learning innovator wants to help organizations and users get the most for their money when it comes to cloud-based databases. Her same technology may help self-driving vehicles operate more safely on the road when latency is the primary concern.

Somali Chaterji, a Purdue assistant professor of agricultural and biological engineering who directs the Innovatory for Cells and Neural Machines [ICAN], and her team created a technology called OPTIMUSCLOUD.

The system is designed to help achieve cost and performance efficiency for cloud-hosted databases, rightsizing resources to benefit both the cloud vendors who do not have to aggressively over-provision their cloud-hosted servers for fail-safe operations and to the clients because the data center savings can be passed on them.

"It also may help researchers who are crunching their research data on remote data centers, compounded by the remote working conditions during the pandemic, where throughput is the priority," Chaterji said. "This technology originated from a desire to increase the throughput of data pipelines to crunch microbiome or metagenomics data."

The Purdue technology works with the three major cloud database providers: Amazon's AWS, Google Cloud, and Microsoft Azure. Chaterji said it would work with other more specialized cloud providers such as Digital Ocean and FloydHub, with some engineering effort.

It is benchmarked on Amazon's AWS cloud computing services with the NoSQL technologies Apache Cassandra and Redis.

"Let's help you get the most bang for your buck by optimizing how you use databases, whether on-premise or cloud-hosted," Chaterji said. "It is no longer just about computational heavy lifting, but about efficient computation where you use what you need and pay for what you use."

Chaterji said current cloud technologies using automated decision making often only work for short and repeat tasks and workloads. She said her team created an optimal configuration to handle long-running, dynamic workloads, whether it be workloads from the ubiquitous sensor networks in connected farms or high-performance computing workloads from scientific applications or the current COVID-19 simulations from different parts of the world in a rush to find the cure against the virus.

"Our right-sizing approach is increasingly important with the myriad applications running on the cloud with the diversity of the data and the algorithms required to draw insights from the data and the consequent need to have heterogeneous servers that drastically vary in costs to analyze the data flows," Chaterji said. "The prices for on-demand instances on Amazon EC2 vary by more than a factor of five-thousand, depending on the virtual memory instance type you use."

The Purdue team's technology has been accepted for publication at the 2020 USENIX Annual Technical Conference, taking place as a virtual event in July.

Chaterji said OPTIMUSCLOUD has numerous applications for databases used in self-driving vehicles (where latency is a priority), health care repositories (where throughput is a priority), and Internet of Things (IoT) infrastructures in farms or factories.

OPTIMUSCLOUD is a software that is run with the database server. It uses machine learning and data science principles to develop algorithms that help jointly optimize the virtual machine selection and the database management system options.

"Also, in these strange times when both traditionally compute-intensive laboratories such as ours and wet labs are relying on compute storage, such as to run simulations on the spread of COVID-19, throughput of these cloud-hosted VMs is critical and even a slight improvement in utilization can result in huge gains," Chaterji said. "Consider that currently, even the best data centers run at lower than 50% utilization and so the costs that are passed down to end-users are hugely inflated."

The other members of the team that developed OPTIMUSCLOUD are Saurabh Bagchi, a Purdue professor of electrical and computer engineering and computer science (by courtesy); Ashraf Mahgoub, a Ph.D. student in computer science; and Karthik Shankar, an undergraduate researcher in Chaterji's lab headed to Carnegie Mellon for graduate school in computer science.

"Our system takes a look at the hundreds of options available and determines the best one normalized by the dollar cost," Chaterji said. "When it comes to cloud databases and computations, you don't want to buy the whole car when you only need a tire, especially now when every lab needs a tire to cruise."

PHILADELPHIA -- Young patients with no risk factors for stroke may have an increased risk if they have contracted COVID-19, whether or not they are showing symptoms of the disease. Surgeons at Thomas Jefferson University and collaborators analyzed patients presenting with stroke from March 20th until April 10th at their institutions. The strokes they observed were unlike what they usually see.

"We were seeing patients in their 30s, 40s and 50s with massive strokes, the kind that we typically see in patients in their 70s and 80s," says Pascal Jabbour, MD, Chief of the Division of Neurovascular Surgery and Endovascular Surgery in the Vickie & Jack Farber Institute for Neuroscience - Jefferson Health. He is a senior author of a study published in the journal Neurosurgery June 4th, that examines and characterizes strokes of patients who tested positive for COVID-19, done in collaboration with surgeons from NYU Langone Medical Center in New York.

"Although we have to stress that our observations are preliminary, and based on observations from 14 patients, what we have observed is worrying," says Dr. Jabbour. "Young people, who may not know they have the coronavirus, are developing clots that cause major stroke."

The researchers, including first author Ahmad Sweid, MD, examined 14 patients who had come into their Neurointerventional room for stroke. Eight patients were male, six were female, 50%, did not know they had the coronavirus, while the remainder were already being treated for other symptoms of the disease when they developed stroke.

Some of the paper's major points:

- Patients with signs of stroke were delaying coming to the hospital for fear of getting the coronavirus. There's a small window of time in which strokes are treatable, so delays can be life threatening.

- The mortality rate in these covid-19 stroke patients is 42.8%. The typical mortality from stroke is around 5 to 10%.

- 42% of the stroke coronavirus positive patients studied were under the age of 50. Most strokes, over 75% of all strokes in the US, occur in people over the age of 65.

- The incidence of coronavirus in the stroke population was 31.5%, according to this sample of patients.

- Patients observed had stroke in large vessels, in both hemispheres of the brain, and in both arteries and veins of the brain - all of these observations are unusual in stroke patients.

Why is the coronavirus, which was assumed to be a disease of the lungs, causing blood clots that lead to a higher incidence of stroke? Researchers have shown that the coronavirus enters human cells via a very specific access point - a protein on human cells called ACE2. But the coronavirus latches onto this protein and uses it to as a gateway into the cell, where the virus can replicate. Not all cells have the same amount of ACE2. This protein is very abundant on cells that line blood vessels, the heart, kidney, and of course, the lungs. Dr. Jabbour and colleagues speculate that the virus may be interfering with this receptor's normal function, which controls blood flow in the brain, in addition to using it as an entry point to the cell.

Another possibility is that the inflammation of the blood vessels causing vasculitis with injury to the cells lining the lumen of the vessel, called endothelium and causing micro thrombosis in small vessels.

"Our observations, though preliminary, can serve as a warning for medical personnel on the front lines, and for all of those at home," says Dr. Jabbour. "Stroke is occurring in people who don't know they have COVID-19, as well as those who feel sick from their infections. We need to be vigilant and respond quickly to signs of stroke."

LA JOLLA--(June 4, 2020) Cancer is often the result of DNA mutations or problems with how cells divide, which can lead to cells "forgetting" what type of cell they are or how to function properly. Now, Professor Martin Hetzer and a team of scientists have provided clarity into how new cells remember their identity after cell division. These memory mechanisms, published in Genes & Development on June 4, 2020, could explicate problems that occur when cell identity is not maintained, such as cancer.

"We gained new insights into the memory mechanisms that allow the right genes to turn on at the right time, so that a new cell can become the same type of cell as the parent cell," says Hetzer, the paper's senior author and holder of the Jesse and Caryl Philips Foundation Chair and Salk's Chief Science Officer. "Our findings lay the foundation for understanding this brief and dynamic cell life stage that is critical for cellular identity."

Cell division is one of the most critical periods of tissue development and homeostasis. During this process, called mitosis, cells have to copy all their DNA correctly and then split evenly in two. To reduce distractions, gene activity turns off during mitosis, right before the cells divide, stopping the production of proteins. After the cell divides into two cells, gene expression turns back on, in a coordinated fashion, to restart protein production. This process of starting up the production of specific proteins informs the cell of what it should become. Yet, scientists did not know how exactly this process worked.

"We wanted to understand the molecular mechanisms of cell identity and transcriptional memory," says the paper's first author, Hyeseon Kang, a UC San Diego graduate student in Hetzer's lab. "How does the mother cell pass on identity to the daughter cells through cell division?"

Under normal conditions, cultured cells in the laboratory are at multiple stages of the cell cycle. This makes it difficult to pinpoint the time period right after mitosis when the cells are remembering what type of cell to become. Hetzer's team synchronized retinal cells and bone cancer cells using a chemical inhibitor, which aligned them to the same stage of the cell life cycle. The scientists were then able to examine the short window when genes are active after mitosis. This technique provides a complete picture of the reactivation of the cell's entire genome after mitosis, for the first time.

The team found that many genes are activated immediately after cell division. The genes act in a cascade, like a row of falling dominos, to send critical signals to activate additional genes. This process of activation allows the cell to "wake up" from its cellular amnesia and become its destined identity.

"This research focuses on a fundamental question: How does a cell remember who it is and what it's supposed to be doing?" says Jesse Dixon, an author of the paper and a fellow in the Helmsley-Salk Fellows Program. "We have mapped out when and where a lot of these memory features are established. Next, we can start to manipulate specific features to gain a better mechanistic understanding of cell identity."

A team of scientists from Stanford University is working with researchers at the Molecular Foundry, a nanoscience user facility located at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab), to develop a gene-targeting, antiviral agent against COVID-19.

Last year, Stanley Qi, an assistant professor in the departments of bioengineering, and chemical and systems biology at Stanford University and his team had begun working on a technique called PAC-MAN - or Prophylactic Antiviral CRISPR in human cells - that uses the gene-editing tool CRISPR to fight influenza.

But that all changed in January, when news of the COVID-19 pandemic emerged. Qi and his team were suddenly confronted with a mysterious new virus for which no one had a clear solution. "So we thought, 'Why don't we try using our PAC-MAN technology to fight it?'" said Qi.

Since late March, Qi and his team have been collaborating with a group led by Michael Connolly, a principal scientific engineering associate in the Biological Nanostructures Facility at Berkeley Lab's Molecular Foundry, to develop a system that delivers PAC-MAN into the cells of a patient.

Like all CRISPR systems, PAC-MAN is composed of an enzyme - in this case, the virus-killing enzyme Cas13 - and a strand of guide RNA, which commands Cas13 to destroy specific nucleotide sequences in the coronavirus's genome. By scrambling the virus's genetic code, PAC-MAN could neutralize the coronavirus and stop it from replicating inside cells.

It's all in the delivery

Qi said that the key challenge to translating PAC-MAN from a molecular tool into an anti-COVID-19 therapy is finding an effective way to deliver it into lung cells. When SARS-CoV-2, the coronavirus that causes COVID-19, invades the lungs, the air sacs in an infected person can become inflamed and fill with fluid, hijacking a patient's ability to breathe.

"But my lab doesn't work on delivery methods," he said. So on March 14, they published a preprint of their paper, and even tweeted, in the hopes of catching the eye of a potential collaborator with expertise in cellular delivery techniques.

Soon after, they learned of Connolly's work on synthetic molecules called lipitoids at the Molecular Foundry.

Lipitoids are a type of synthetic peptide mimic known as a "peptoid" first discovered 20 years ago by Connolly's mentor Ron Zuckermann. In the decades since, Connolly and Zuckermann have worked to develop peptoid delivery molecules such as lipitoids. And in collaboration with Molecular Foundry users, they have demonstrated lipitoids' effectiveness in the delivery of DNA and RNA to a wide variety of cell lines.

Today, researchers studying lipitoids for potential therapeutic applications have shown that these materials are nontoxic to the body and can deliver nucleotides by encapsulating them in tiny nanoparticles just one billionth of a meter wide - the size of a virus.

Now Qi hopes to add his CRISPR-based COVID-19 therapy to the Molecular Foundry's growing body of lipitoid delivery systems.

In late April, the Stanford researchers tested a type of lipitoid - Lipitoid 1 - that self-assembles with DNA and RNA into PAC-MAN carriers in a sample of human epithelial lung cells.

According to Qi, the lipitoids performed very well. When packaged with coronavirus-targeting PAC-MAN, the system reduced the amount of synthetic SARS-CoV-2 in solution by more than 90%. "Berkeley Lab's Molecular Foundry has provided us with a molecular treasure that transformed our research," he said.

The team next plans to test the PAC-MAN/lipitoid system in an animal model against a live SARS-CoV-2 virus. They will be joined by collaborators at New York University and Karolinska Institute in Stockholm, Sweden.

If successful, they hope to continue working with Connolly and his team to further develop PAC-MAN/lipitoid therapies for SARS-CoV-2 and other coronaviruses, and to explore scaling up their experiments for preclinical tests.

"An effective lipitoid delivery, coupled with CRISPR targeting, could enable a very powerful strategy for fighting viral disease not only against COVID-19 but possibly against newly viral strains with pandemic potential," said Connolly.

"Everyone has been working around the clock trying to come up with new solutions," added Qi, whose preprint paper was recently peer-reviewed and published in the journal Cell. "It's very rewarding to combine expertise and test new ideas across institutions in these difficult times."

You are alone on a small sailing boat, more than four thousand miles of ocean ahead and you are up against approximately 80 sailors. It will take you three or four weeks to get to the finishing line. But how will you manage to sleep and which sleeping strategy will pay off during the race? For the first time, a group of researchers of the University of Bologna identified and analysed the different sleeping strategies employed by solo skippers.

"Especially during singlehanded transatlantic races, sailing needs a skipper that is ready to intervene rapidly and with soundness of mind in full control of his body and brain. This is the only way to be able to quickly modify the yacht route and attitude", explains Giuseppe Plazzi, study coordinator and Unibo professor. "Moreover, sailors are forced to be vigil for long periods of time as they need to face unstable and adverse weather conditions. Appropriate sleep management even before the race can be a decisive factor in their sailing performance and safety".

A number of sleep management strategies emerge from this study published in Nature and Science of Sleep. Some sailors stock up on sleep before the race, some others prefer short and frequent naps, while some other skippers get used to increasingly shorter sleeping periods. The study also brings to the fore a "natural selection" among sailors, one that favours early birds (who wake up early in the morning and are more active in the first hours of the day) and excludes night owls (who instead are more active during the evening and night). These results could be useful in preparing athletes for endurance competitions.

FROM FRANCE TO THE CARIBBEAN

To study sailors' sleep management, the researchers focused on the participants in the Mini Transat La Boulangère, one of the most crowded solo regattas. On odd-numbered years, more than 80 sailors race across the Atlantic Ocean for 4,050 miles and live aboard 6 meters boats. The race presents two stops. The boats set sail from France west coast, La Rochelle, then after 1,350 miles they stop at the Canary Islands. From there, they cross the Atlantic for 2,700 miles and, thanks to the trade winds, they reach Martinique, an island in the Caribbean.

Researchers analysed a sample of 42 skippers, gathering data and information about the training weeks preceding the regatta. They asked the skippers about the quality of their sleep, their level of somnolence and their chronotype, i.e. the propensity for the individual to sleep at a particular time during a 24-hour period.

SLEEP MANAGEMENT STRATEGIES

The analysis reveals that more than half of the skippers in the sample (55%) choose to prep for the regatta by devising a sleep management strategy. "Expert skippers often make this choice", says professor Plazzi. "Indeed, expert sailors with a track record of miles and miles of offshore sailing are more mindful of the importance of sleep management".

Which strategies do they employ? The most frequent strategy (52%) is sleep extension, that is stoking up on sleep before the race so to have a sort of "sleep storage" available during the competition when sleep time and quality inevitably decrease. 26% of the skippers adopted polyphasic sleep. In polyphasic sleep, a nap schedule has to be followed throughout the day. This strategy allows to be more vigil and to be absent from the rudder for limited periods of time. Finally, 22% of the sample opted for gradual sleep deprivation in order to strike a balance between a short period of restorative sleep and the psycho-physical conditions to get the race done.

SKIPPERS ARE NOT "NIGHT OWLS"

Chronotype is another interesting matter here. It represents propensity for being more active at a particular time of the day, thus influencing sleep and wake periods. In this case, researchers observed a "natural selection" among the skippers of the Mini Transat La Boulangère. 40% of the sample presents the morning-type profile. These skippers can be defined as "early birds": they wake up early, are more active in the morning and go to sleep early. 60% of the skippers in the sample belongs instead to an intermediate chronotype, the so-called "hummingbird": they do not show a preponderant preference towards being active in the morning or at night. No one in the sample displayed the third chronotype (eveningness or "night owls"), according to which a person tends to go to bed late and wake up late in the morning.

"In our sample, the morning-type chronotype is definitely overrepresented: 'early birds' represent 25% of the general population", explains Plazzi. "Even more surprising is the fact that there aren't any 'night owls' in our sample. This means that 'eveningness' represents a disadvantage in endurance competitions".

CHRONOTYPE AND STRATEGIES

Sleeping management strategies and chronotype also intertwine. A striking majority of the skippers adopting sleeping management strategies belongs to the intermediate-type profile, while those who do not follow sleeping schedules belong to the morning type. According to the researchers, this result can hint at a lack of flexibility among the "early birds". Indeed, it would seem more difficult for them to radically change their sleep-wake cycles.

"The results of our study clearly show the importance of choosing a sleeping management strategy during the psycho-physical preparation for extreme competitions such as single-handed transatlantic crossings", concludes Professor Plazzi. "Our next step will be to closely monitor sleep-wake cycles both during the training and during the race. In this way, we will be able to devise increasingly effective and precise sleep management strategies".

Researchers have uncovered a link between the structure of the protein alpha-synuclein and its likelihood to misfold and aggregate.

Alpha-synuclein aggregates are the hallmark of neurodegenerative disorders, such as Parkinson's disease. Their findings, published today in Nature Communications, identify potential new therapeutic targets in the treatment of Parkinson's disease.

The human brain contains a protein called alpha-synuclein (aSyn), which is found mainly at the tips of neurons in structures called pre-synaptic terminals. In Parkinson's disease and some other neurodegenerative disorders, the aSyn protein becomes destabilised, misfolds and aggregates into insoluble fibrils, which are a hallmark of the disease. Currently we do not understand why aSyn misfolds or how to stop it doing so. This means that diseases like Parkinson's, which affects one in 350 adults in the UK, remains incurable.

"We wanted to understand why the normally healthy, monomeric and soluble aSyn suddenly starts to misfold," says Dr Amberley Stephens, first co-author of the research paper, at the University of Cambridge Department of Chemical Engineering and Biotechnology.

"Understanding these initial steps in the misfolding pathway means we can identify new therapeutic targets to treat aSyn misfolding disorders. However, this is made very difficult because aSyn has no true structure but exists as lots of intermediate structures or conformations that are highly dynamic."

To understand how to stop aSyn from aggregating in neurons, the researchers had to investigate what initial conformations monomeric aSyn forms when it is aggregation-prone compared to when it is non-aggregation prone and thus remains monomeric. The researchers purposefully made the aSyn aggregate faster by adding a known aggregation inducing ion, calcium, to investigate these tiny differences in the dynamic structure of the monomer.

The team used a collection of cutting-edge analytical techniques to investigate the various intramolecular interactions at play when aSyn was in either an aggregation-prone or non-aggregation prone state.

"In this study we used hydrogen-deuterium exchange mass spectrometry, a powerful and versatile biophysical technique that can give information on the structure and dynamics of proteins, such as aSyn. In simple terms, we are capturing the differences in the posture of the protein in different environments. Our collaborators at the University of Exeter have been working on instrument development, so that we are able to detect smaller and smaller differences between protein populations - this is particularly important for such a flexible protein like aSyn," says Maria Zacharopoulou, first co-author of the research paper from the University of Cambridge Department of Chemical Engineering and Biotechnology.

They observed that one specific region called the N-terminus of aSyn, which is at the beginning of the protein sequence, becomes more exposed and the protein structurally opens up when the aggregation inducing ion, calcium, is added. Furthermore, the extent of the exposure correlated with the speed the aSyn aggregated at, while more closed structures did not aggregate.

By using hydrogen-deuterium exchange mass spectrometry the researchers could determine that modifications to the protein sequence, or the presence of hereditary mutations that cause early-onset Parkinson's disease, lead to a change in the structures of the dynamic aSyn monomer. This study brings new insight into Parkinson's disease at the very beginning of the process, when the transition from monomer to aggregate occurs.

The findings could lead to new therapeutic targets, as stabilising the closed structure of aSyn protein may prevent it from aggregating. The next steps will involve isolating specific aggregation-prone and non-aggregation prone structures from the pool of dynamic monomer structures to design therapeutics to stabilise or neutralise the aSyn monomer before it starts to misfold.

Researchers at the Universitat Politècnica de València (UPV) have carried out a comprehensive study of the videos about Covid-19 published on YouTube and directly or indirectly related to the Spanish territory. In total, they have analyzed 39,531 videos, posted between January 1st and April 30th of the present year. In addition, they have characterized their impact, studying the number of views, what were the most liked and least liked videos, the comments generated, etc.

One of the main conclusions of the study, published in El profesional de la información journal, is that the video with most views in this period was Resistiré 2020 ("I will survive 2020"), the tribute song to the pandemic produced by Warner Music Spain and played by more than 30 artists in self-quarantine from their homes. From its release date until April 30th, it totaled almost 28.7 million views. The second most liked video was Canciones del coronavirus, by the Spanish influencer El Rubius - with one million likes.

The study also collected international videos about Covid-19 with a high impact. The one that registered the most comments--almost 86,000--was a video posted by CNN, where Bill Gates made a prediction about when the peak of infections would happen.

"The list of the most popular videos includes documentaries about the origin of coronavirus, not necessarily proven by the scientific community, as well as musical events celebrated as part of the pandemic," adds Enrique Orduña-Malea, researcher at the Department of Audiovisual Communication, Documentation and History of Art (DCADHA, in Spanish) at UPV, and one of the authors of the study.

The results also show that the number of videos about Covid-19 posted on YouTube increased from the declaration of the state of emergency in Spain and gradually reduced, with some upturns linked to political decisions.

"There were upticks of posts linked to social situations--cases detected--and political decisions--approval of the state of emergency and consecutive extensions. All kinds of videos have been posted, from news produced by the mass media to videos disseminated by the health services to prevent infections, as well as academic videos with a technical or scientific point of view about the virus. It is must also be noted that there are several videos from individual users with personal and professional experiences during the self-quarantine, streaming information services with official statistics (such as the Coronavirus Life Map), as well as fake news," explains Cristina Font-Julián, co-author of the study and researcher at the DCADHA of the Universitat Politècnica de València.

Where did the most posts appear?

The channels with the most posts about Covid-19 were mainly mass media, both national (in this order: Europa Press, El Mundo, El País, La Vanguardia, Agencia EFE) and regional (IB3 Notícies, Navarra Televisión, Faro TV Ceuta, Málaga 24h TV Noticias and Radio Televisión de Castilla y León). Moreover, the study showed a high presence of Spanish-language foreign media (Noticias Caracol, TeleSUR and RT).

With regard to entities linked to the health industry, the study carried out by UPV researchers proved that the video with the most views was Cómo afecta el #coronavirus a los niños ("How does coronavirus affect children?"), posted by the Asociación Española de Pediatría (Spanish Pediatric Association), with 428,251 views; and the video with most likes was Paciente con coronavirus recibe el alta de UCI en IMED (Coronavirus patient is discharged from the ICU at IMED), from the Hospital IMED Levante (3,051 likes.)

"Despite the difficulties of extracting massive data from YouTube for specific requests, the results show that the channels with the greatest volume of videos about the pandemic and most impact on average are provided by consolidated media on YouTube and with a large previous audience on this platform. They indirectly reflect, therefore, the audience's preferences and patterns prior to the pandemic," explains José Antonio Ontalba-Ruipérez, researcher at the DCADHA of the UPV and coauthor of the study.

Moreover, among the posts collected, the authors of the study say that they have found serious and useful videos, some of them informative about the disease (how to prevent infection, for example) and others with an academic point of view (origin and explanation of the disease.) "On average, these videos have a moderate to high impact, but they are only a small percentage of the total. News and entertainment videos (including music videos) are not only the most abundant but also the most viewed. Therefore, they occupied the top positions both in importance for YouTube and in the rankings of total views and likes. That is, we need to do a bit of digging to find those academic videos. They are not the first thing that appears if we only look at the highest metrics," concludes Enrique Orduña.

Researcher Judith Lind has studied how staff at fertility clinics view the assessments that childless couples and women undergo in order to access assisted reproduction. It emerges in the interviews that the assessment of the potential parents is based on the child's future welfare and on the responsible use of public resources.

In Sweden, childless couples and single women can access publicly funded fertility treatment. But the legislation differs between different couples. In those cases where the couple requires sperm or eggs from a donor, the legislation demands a special assessment of their suitability as parents.

"Fertility treatment is expensive, and public resources are intended to enable treatment for everyone, regardless of income. At the same time, my study shows how clinic staff argue that access to treatment should be limited specifically because public resources are used", says Judith Lind, senior lecturer at the Department of Thematic Studies, Linköping University.

Judith Lind has previously investigated parent suitability in other contexts, such as adoption. She is interested in how parenthood ideals and the notion of the welfare of the child are expressed in assessments of potential parents.

The new study, "Child welfare assessments and the regulation of access to publicly funded fertility treatment", has been published in the journal Reproductive Biomedicine & Society Online.

Assessment focussing on what's best for the child

In bioethics research, there is a discussion about whether it is reasonable to limit access to fertility treatment with reference to the welfare of the future child, or if everyone should have the right to fertility treatment. Judith Lind wanted to study how clinic staff reason about this ethical issue and how they justify and legitimise that people who want fertility treatments are assessed.

Interviews were conducted with 64 employees in nine focus groups at four of the six publicly funded fertility clinic in Sweden.

The results show that what was considered most important was the future well-being of the child and the responsible use of public resources.

In every focus group, the child's welfare was cited as an argument for why a psychosocial assessment was conducted. The employees at the clinics said that it was their duty to prioritise the best interests of the child, and thus to refuse treatment for the couples and women who they considered unsuitable as parents. However, many questioned why the psychosocial assessment is only conducted when donated gametes are used. One doctor argued that the rights of the child should also "apply to children born with people's own gametes".

Use of public resources

In their work with fertility treatments, the clinics are guided by an assessment of the future welfare of the child as well as by the responsible use of public resources. Taxpayers' money, they argue, should not be used for something that in the end does not turn out well. For instance, if one believes that the future parents would not be able to take care of or provide for a child.

That public resources are used for the treatment justifies, according to the employees, that those who are to undergo it have a psychosocial assessment. The purpose of the assessment is to prevent treatment that results in problems for the child and, by extension, for society.

The aim of assisted reproduction is, for the people who work with it, not children, but functioning families. Some of the employees explained that their job is about creating "children with good lives", or "happy children and super-happy families".

"This argument has not received sufficient attention in previous research. With the study I hope to contribute to a discussion of assisted reproduction and the priorities that guide the treatment", says Judith Lind.

Transcription of genetic information is a fundamental process for life. If it does not work correctly, the consequences for the organism range from lethality to defects during development, genetic diseases, insufficient response to infections and stresses or propensity to develop cancer, given its pleiotropic effect. For this reason, it is important to know in depth the process by which this "DNA copy" is obtained and what elements are involved.

Along these lines, experts from the University of Seville and the Andalusian Center for Molecular Biology and Regenerative Medicine (Cabimer), in collaboration with the research group of Professor Patrick Sung from Yale University (USA), have published a new research article in which they show for the first time, the crucial role that the protein UAP56 / DDX39B plays for a correct transcription of the genetic material and the integrity of the genome.

"DNA-RNA hybrids, or R loops, are structures that generate genomic instability, a common feature of tumor cells. In this article we have discovered that the human protein UAP56 / DDX39B has a key role in the elimination of DNA-RNA hybrids that are accidentally generated during transcription, guaranteeing the integrity of the genome, as well as a correct gene expression", explains Andrés Aguilera, professor at the University of Seville and director of Cabimer.

UAP56 / DDX39B is a protein found in the nucleus of mammalian cells. It is conserved in all eukaryotes and plays an essential role in the transcription and processing of RNAs. Organisms cannot live without this protein, its inactivation produces defects in the expression of genes and in the stability of genomes, which is why it is important to know its functions.

On the other hand, unscheduled R loops are DNA-RNA hybrids that are accidentally generated between the nascent RNA and its template DNA during transcription. They form spontaneously, thanks to the pairing capacity of the nucleic acid chains, and for this reason cells have developed machineries to prevent and eliminate R loops, thus avoiding their negative consequences.

This work is part of the PhD thesis of Dr. Carmen Pérez Calero, defended in February 2020 at the University of Seville, and is part of the ERC Advanced research project of the European Research Council obtained in 2015, funded of 2.35 million euros.