Culture

The study by scientists from Duke-NUS Medical School, in close collaboration with the National University of Singapore (NUS) Yong Loo Lin School of Medicine, Singapore General Hospital (SGH) and National Centre for Infectious Diseases (NCID) was published in Nature. The findings suggest infection and exposure to coronaviruses induces long-lasting memory T cells, which could help in the management of the current pandemic and in vaccine development against COVID-19.

The team tested subjects who recovered from COVID-19 and found the presence of SARS-CoV-2-specific T cells in all of them, which suggests that T cells play an important role in this infection. Importantly, the team showed that patients who recovered from SARS 17 years ago after the 2003 outbreak, still possess virus-specific memory T cells and displayed cross-immunity to SARS-CoV-2.

"Our team also tested uninfected healthy individuals and found SARS-CoV-2-specific T cells in more than 50 percent of them. This could be due to cross-reactive immunity obtained from exposure to other coronaviruses, such as those causing the common cold, or presently unknown animal coronaviruses. It is important to understand if this could explain why some individuals are able to better control the infection," said Professor Antonio Bertoletti, from Duke-NUS' Emerging Infectious Diseases (EID) programme, who is the corresponding author of this study.

Associate Professor Tan Yee Joo from the Department of Microbiology and Immunology at NUS Yong Loo Lin School of Medicine and Joint Senior Principal Investigator, Institute of Molecular and Cell Biology, A*STAR added, "We have also initiated follow-up studies on the COVID-19 recovered patients, to determine if their immunity as shown in their T cells persists over an extended period of time. This is very important for vaccine development and to answer the question about reinfection."

"While there have been many studies about SARS-CoV-2, there is still a lot we don't understand about the virus yet. What we do know is that T cells play an important role in the immune response against viral infections and should be assessed for their role in combating SARS-CoV-2, which has affected many people worldwide. Hopefully, our discovery will bring us a step closer to creating an effective vaccine," said Associate Professor Jenny Low, Senior Consultant, Department of Infectious Diseases, SGH, and Duke-NUS' EID programme.

"NCID was heartened by the tremendous support we received from many previous SARS patients for this study. Their contributions, 17 years after they were originally infected, helped us understand mechanisms for lasting immunity to SARS-like viruses, and their implications for developing better vaccines against COVID-19 and related viruses," said Dr Mark Chen I-Cheng, Head of the NCID Research Office.

The team will be conducting a larger study of exposed, uninfected subjects to examine whether T cells can protect against COVID-19 infection or alter the course of infection. They will also be exploring the potential therapeutic use of SARS-CoV-2-specific T cells.

The vast universe can always arise people's infinite imagination and yearning. Black hole, as one of the most attractive heavenly bodies in the universe, are waiting to be explored and studied. However, due to the limitations of technology, human is still unable to go into the depths of universe, let alone reach the vicinity of a black hole.

Fortunately, based on the equivalence between the metric of curved space-time in general relativity and the electromagnetic parameters in electromagnetic materials, the physical scientist has developed the method of transformation optics to simulate the curved space-time of gravitational field. Now, the scientist is able to study and demonstrate the evolution of particles in curved space-time experimentally. However, up to now, these simulations are limited either in classical regime or in flat space whereas quantum simulation related with general relativity is rarely involved. In the quantum field related with the gravitational effect, there are many striking phenomena, such as Hawking radiation.

Recently, Yao Wang and Xianmin Jin from Shanghai Jiao Tong University and Chong Sheng and Hui Liu from the Nanjing University made an exciting progress in observing particle behavior near the event horizon of block hole.

Based on femtosecond laser direct write technology, the waveguide on-site energy and the coupling between waveguides can be well controlled. Inspired by the concept of transformation optics, the team successfully constructed a one-dimensional artificial black hole using a single-layer non-uniform-coupling photonic waveguide lattice. Comparing to linear time evolution in the flat space, the dynamic behavior of single-photon wave packets near the horizon of a black hole accelerates exponentially, and its exponential index depends on the curvature of the black hole.

The team further designed the two-layer photonic waveguide lattice and experimentally observed the acceleration, generation, and evolution of fermion pairs near the event horizon of the black hole: a single-photon packet with positive energy successfully escaped from the black hole, while a single-photon packet with negative energy was captured. The result, which deviates from the intuition that photons are always trapped by black holes, is found well analogue to Hawking radiation which completely origins from quantum effects associated with gravitational effects. Due to vacuum fluctuations, particle-antiparticle pairs are generated near the event horizon of the black hole. Particles with negative energy fall into the black hole, while particles with negative energy escape. This causes the black hole to lose mass, and it would appear that the black hole has just emitted a particle.

Finally, the team think that higher-dimensional curved space-time can be constructed based on the experimental platform. For example, a two-dimensional waveguide array can be used to simulate three-dimensional space-time, and a two-dimensional waveguide array with photon polarization or frequency can be used to simulate four-dimensional space-time. Furthermore, due to the propagation direction plays the role as the time in our experimental platform, dynamics metric can also be emulated based on this experimental platform, such as FRW metric, a model describing cosmic expansion as time evolution, and gravitational wave, which is the ripple of spacetime.

"A lack of intensive care ventilation units owing to rapidly increasing infection rates numbers among the most significant nightmare scenarios of the corona pandemic," says Mathias Wirth, Head of the Ethics Department in the Faculty of Theology at the University of Bern, because: "Shortages of supply can result in triage of patients suffering from severe cases of COVID-19 and thus force a life or death decision." Here, triage means favoring some COVID-19 patients over others depending on urgency and prognosis. Together with experts from Yale University, King's College London, Charité Berlin and Essen University Hospital, medical ethicist Mathias Wirth has prepared a statement on these difficult decisions. The statement was published in the American Journal of Bioethics (AJOB), the most frequently cited scientific journal in the entire field of ethics.

Triage is only ethically justifiable under very specific circumstances

The experts warn against the possibility of prematurely implementing triage; even though triage allows for decisions based on fairness in extreme situations, it leads to significant strain on the affected parties, relatives and medical personnel. In order to avoid it, every effort must be made to transfer seriously ill patients to other hospitals without shortages of supply - across country borders in case of emergency, according to the authors.

In concrete terms, Mathias Wirth's team of researchers recommend increased regional, national and even international collaboration in intensive care for COVID-19 patients in preparation for future waves of infection. "Just because triage is correct under some circumstances does not mean that it is correct under all circumstances," says Wirth. "There is no real and legitimate triage situation as long as treatment spaces are available elsewhere."

Negative decision requires special care

Secondly, a negative triage decision for individual people should not under any circumstances mean that their medical and psychological care is neglected. Quite the opposite: If they are deprived of a ventilator, maximum effort is required for their care and treatment, both for them and for their relatives.

The statement from Wirth et al. presents all stakeholders who advocate for more collaboration in the future situation with strong arguments. Because the judgments associated with triage give too little consideration to moral problems, according to medical ethicists. "The suffering that triage decisions involved for patients, relatives and medical personnel in the epicenters of the first wave attests to this," says Wirth. Thanks to the recommendations, triage planning can be classified more clearly as a last resort, meaning that alternatives must be afforded greater attention.

New research out of the Japan Advanced Institute of Science and Technology (JAIST) utilizes digital image analysis technology to shed light on some of the challenges children face when representing their imaginations through the medium of paint. The research also offers concrete insight into the development of children's psyches, and importantly, offers suggestions for educators to improve children's cognitive, spatial, and artistic abilities.

Painting is a recreational and creative activity enjoyed by children across the world. However, children's paintings also serve as crucial artifacts of their perceptions, as they contain the sum of what children see as "essential." The spatial relationships between objects in paintings represent painters' experiences and technical prowess, and tend to indicate shortcomings of either. These are often perceived by viewers of paintings, but until now, detailed evaluation and analysis of children's art has been subjective, relying on the trained eye of an artist or critic.

JAIST researchers Lan Yu and Yukari Nagai have developed and tested a digital analysis process by which children's paintings can be digitized, categorized, and then thoroughly analyzed. Content, scale, patterns, details, and the relationships between objects in the paintings are objectively quantified and calculated.

Trends identified among the subjects sampled, 182 girls and 234 boys in the Republic of China, indicate that children who have not received instruction display poor abilities to recognize and emulate spatial relationships. The younger the painter, the less likely that he or she will have developed these cognitive abilities. Lack of detail and inability to imitate objects is identified as common to children's painting. Statistical analysis of the boys and girls in this study indicated that they have different attitudes toward painting; girls preferred participating in painting more than boys did. It was also apparent that girls were more able to accurately imitate real objects when representing them in their paintings.

This research has implications in art education, suggesting that art teachers focus on several key elements which are useful to the cognitive development of young painters. Guiding children to paint objects outside could enhance their awareness of their natural environments. Focusing instruction on object size, and the ability to recognize and control it, could remedy this crucial deficit in children's paintings. Specifically training students to imitate objects could show significant results in the overall quality of children's paintings. And finally, instruction in composition and creative methods is correlated to increasing the enjoyment and reducing children's perception of difficulty toward painting as a creative process.

Researchers at Pompeu Fabra University have shown for the first time that blood vessels communicate with neurons in the peripheral nervous system, regulating their proliferation and differentiation. The study is published today in the journal Cell Reports and was conducted using zebrafish as a model. It was led by Berta Alsina, principal investigator of the Morphogenesis and Cell Signaling in Sensory Systems group, and involved Laura Taberner and Aitor Bañón.

The researchers, using real-time videos, have discovered that both the neurons and the cells of blood vessels emit dynamic protrusions to be able to 'talk' to each other. These protrusions are called signalling filopodia or cytonemes and they have a receptor or ligand at the tip that allows them to send signals. It was only very recently discovered and it is a highly precise signalling mechanism, both in space and in time.

"It was known that vessel cells and stem cells in the brain communicate but this is the first time it has been witnessed through cytonemes in the peripheral nervous system", Berta Alsina explains. "By using high resolution spatiotemporal visualization techniques in vivo we have seen them in real time and they might also be in the brain", she adds.

This communication allows maintaining some precursors of neurons in quiescence, i.e., dormant, and they constitute a reservoir of stem cells. So, if later on in adulthood an injury occurs, quiescent cells can be activated and replace damaged neurons.

Laura Taberner, first author of the study, explains that "if all neuronal precursors proliferated and differentiated we would not have this reservoir and there would not be the opportunity for regeneration. In the auditory and vestibular system, which is what we are studying, cases of deafness or vertigo may arise".

The study also concludes that the precursors are initially in a hypoxic environment, i.e., lacking oxygen, which keeps them proliferating. When blood vessels connect to each other during development, oxygen is transported by the blood vessels and the environment becomes normoxic. The researchers have found that oxygen is the second signal of the vessels and in this case, instead of regulating quiescence, oxygen regulates the differentiation of neuronal precursors to neurons.

This study shows that during the development of the peripheral nervous system, the formation of new neurons and the maintenance of stem cells is highly dependent on signals from the blood vessels. Neurons receive signals from all the surrounding cells, which are part of the environment in which they reside and the vessels are part of this niche. "This new knowledge will help understand the connection between hearing loss and cardiovascular diseases, as well as improve protocols for in vitro differentiation of neurons for regenerative therapies", Taberner adds.

A research team led by the German Center for Neurodegenerative Diseases (DZNE) concludes that personal perception can be an important indicator for the early detection of Alzheimer's disease. In a new study involving 449 older adults, published in Neurology®, the medical journal of the American Academy of Neurology, the scientists report that individuals with subjectively felt memory problems also exhibited on average measurable cognitive deficits that were associated with abnormalities in the spinal fluid. Early diagnosis and therapy development could benefit from these findings.

When memory deteriorates according to one's own perception, but mental performance - following objective criteria - is still within the normal range, this is referred to as "subjective cognitive decline" (SCD). "People with SCD have an increased risk of developing dementia in the long term. However, little is known about the mechanisms underlying subjective memory problems," said Prof. Michael Wagner, head of a research group at the DZNE and a senior psychologist at the memory clinic of the University Hospital of Bonn. "The effects are subtle and previous studies have included relatively small groups of people, which makes statistically reliable assessments difficult. Therefore, we have now examined the largest sample of individuals to our knowledge."

A nationwide study

A network of German universities and university hospitals was involved in the investigations, which were coordinated by the DZNE. A total of 449 women and men - their average age was about 70 years - participated in the study. Of this group, 240 individuals were included via memory clinics of the participating university hospitals. These persons had consulted the clinics for diagnostic clarification of persistent subjective cognitive complaints, usually after a doctor's referral. However, in the usual tests they were assessed as cognitively normal. It was thus determined that they had SCD. The other 209 study participants were classified as cognitively healthy based on interviews and the same cognitive testing. They had decided to participate in the study following newspaper advertisements.

"We were able to show that those people who turned to a memory clinic because of SCD had measurable, albeit only mild cognitive deficits," explained Dr. Steffen Wolfsgruber, lead author of the current publication. The findings are based on extensive testing, refined data analysis and the relatively large number of people examined. "This significantly improved measurement sensitivity. Thus, we found that study participants considered to be healthy generally scored better in mental performance than memory clinic patients with SCD. These differences are hardly detectable with standard methods of analysis and in small groups of people. Especially not on an individual level. In any case, you need a large data set."

An extensive test series

The women and men who took part in the study underwent various tests of their mental abilities. In addition to memory performance, the focus was also on attention capacity and the ability to concentrate in various situations. Among other things, language skills and the ability to recognize and correctly name objects were also tested.

In addition, the cerebrospinal fluid of 180 study subjects - 104 of them with SCD - was analyzed. This liquid is present in the brain and the spinal cord. Levels of specific proteins were measured, namely of "amyloid-beta peptides" and "tau proteins". "These biomarker data allow conclusions on potential nerve damage and mechanisms associated with Alzheimer's disease," said Wolfsgruber.

"We found that our study subjects with SCD had mild cognitive deficits on average and that these defictis were associated to proteins that indicate early Alzheimer's disease. Therefore, we assume that both the subjective complaints and the minimal objective cognitive deficits are due to Alzheimer's processes. That's not something that can be taken for granted, because there are many reasons for memory problems," said Michael Wagner, who led the current study. "It is important to stress that these individuals had visited a memory clinic because of their complaints, or had been referred to one. Therefore, these findings cannot be generalised, because many elderly people suffer from temporary subjective memory disorders without having early Alzheimer's disease."

Early treatment

The now published results are based on data from the so-called DELCODE study of DZNE that investigates the early phase of Alzheimer's disease - the time period before marked symptoms manifest. Within the framework of DELCODE, the cognitive development of a total of about 1000 participants is monitored over several years. "It will then become clear who is actually developing dementia and how well the risk of dementia can be estimated in advance by means of SCD. Data on this still being collected and evaluated," said Wagner. "In any case, our current results support the concept that SCD can contribute to detect Alzheimer's disease at an early stage. However, SCD can certainly only provide a part of the larger picture that is necessary for diagnosis. One will also have to consider biomarkers."

The current findings could also help in the development of novel treatments. "Current therapies against Alzheimer's start too late. Then the brain is already severely damaged. A better understanding of SCD could create the basis for an earlier treatment. In order to test therapies that are intended to have an effect in the early stages of Alzheimer's, it is necessary to identify people at increased disease risk. For this, SCD could be an important criterion," said Wagner.

CHICAGO--July 16, 2020--A rapid laboratory test, the eosinophil count, readily obtained from a routine complete blood cell count (CBC) can aid in the early recognition of COVID-19 in patients, as well as provide prognostic information, according to new research in The Journal of the American Osteopathic Association.

Current testing, which relies on diagnosis of COVID-19 by nasopharyngeal swab PCR assay, remains unreliable due to variable turnaround time and a high false-negative rate.

"We found that the absence of eosinophils on presentation can aid in early diagnosis, and in general, a persistent low count correlated with a poor prognosis for the patient," said Muhammad M. Zaman, MD, an infectious disease specialist affiliated with Coney Island Hospital in Brooklyn. "Review of the eosinophil count can be a useful tool in deciding whether to promptly isolate someone and initiate specific therapies while waiting for confirmatory test results."

In the study, eosinopenia correlated with diagnosis of COVID-19, and its persistence correlated with high disease severity and low rates of recovery. Low eosinophil count, or eosinopenia, is defined as having

"The trend of the eosinophil count has been known to correlate with viral infections, but we did not know the correlation was so significant in the case of COVID-19," says Dr. Zaman.

Actionable clinical information

Coney Island Hospital, part of the New York City Health and Hospitals system, serves a diverse population in Brooklyn, New York. The site experienced a sharp incline in COVID-19 cases during March and April 2020, when the study data was collected.

Researchers compared the eosinophil results of routine CBC from the first 50 admitted COVID-19-positive patients with the eosinophil results of 50 patients with confirmed influenza infection at the time of presentation to the emergency department at Coney Island Hospital in Brooklyn.

Of the patients with COVID-19, 60% had zero eosinophils at presentation, compared to 16% of influenza patients. An additional 28% of COVID-19 patients had zero eosinophils within 48 hours of admission, thus a total of 88% had zero eosinophils during hospitalization.

"In COVID-19, a disease that has substantial symptom overlap with influenza, eosinopenia could help to distinguish which patients likely have COVID-19," said Dr. Zaman.

A total of 23 of the 50 patients in the COVID-19 group (46%) passed away. Eighteen out of 21 (86%) deceased patients in the COVID-19 group who initially presented with eosinopenia remained eosinopenic versus 13 out of 26 (50%) survivors who had eosinopenia on presentation.

"As you can see from the data, continued low counts of eosinophils trended with mortality rates," said Dr. Zaman. "Patients whose eosinophil count rose tended to have better disease outcomes."

Existing testing is challenging

The clinical diagnosis of COVID-19 is confirmed by laboratory testing with a reverse-transcription polymerase chain reaction (RT-PCR) assay, which remains a challenge due to limited test availability, variable turnaround time, and low sensitivity of RT-PCR. In many hospitals, test results may take days to return.

"If a patient comes in on the first day of symptom onset, typically day five after exposure, the false-negative rate is as high as 38%," says Dr. Zaman. "This means a high number of potentially infectious patients are being misinformed of their true diagnosis--and a simple blood test could dramatically lower that number and the subsequent spread of disease."

One of Charles Darwin's long-standing questions on how turtles find their way to islands has been answered thanks to a pioneering study by scientists.

A team from Deakin University, University of Pisa and Swansea University equipped 33 green sea turtles with satellite tags and recorded unique tracks of green turtles migrating long distances in the Indian Ocean to small oceanic islands.

The study provides some of the best evidence to date that migrating sea turtles have an ability to redirect in the open ocean, but only at a crude level rather than at fine scales.

Seven turtles travelled only a few tens of kilometres to foraging sites on the Great Chagos Bank, six travelled over 4,000km to mainland Africa, one to Madagascar, while another two turtles ventured north to the Maldives.

Most of the species tracked (17) migrated westward to distant foraging sites in the Western Indian Ocean that were associated with small islands.

It shows that the turtles can travel several hundred kilometres off the direct routes to their goal before reorienting, often in the open ocean.

In 1873, Charles Darwin marvelled at the ability of sea turtles to find isolated islands where they nest. However, the details of how sea turtles, and other groups such as seals and whales, navigate during long migrations remains an open question.

Answering this question using free-living individuals is difficult due to thousands of sea turtles being tracked to mainland coasts where the navigational challenges are easiest.

The study also showed that turtles frequently struggled to find small islands, overshooting, and/or searching for the island in the final stages of migration.

These satellite tracking results support the suggestion, from previous laboratory work, that turtles use a crude true navigation system in the open ocean, possibly using the world's geomagnetic field.

Swansea University's Dr Nicole Esteban, a co-author in the study said:

"We were surprised that green turtles sometimes overshot their ultimate destination by several hundred kilometres and then searched the ocean for their target. Our research shows evidence that turtles have a crude map sense with open ocean reorientation."

After interviewing smallholder farmers throughout South and Southeast Asia, one of the top needs they mentioned is development of shorter duration rice varieties with only 100 days from sowing to harvest. Some farmers want to have more time to prepare for the next season crop, whereas other farmers are concerned about irrigation water running out during the dry season. Another benefit in countries such as the Philippines is reducing the risk of adverse weather (e.g., typhoons) affecting the crop compared to longer duration varieties.

In an article recently published in Crop Science, a diverse group of researchers from the International Rice Research Institute (IRRI) comprising agronomists, physiologists and breeders report on the advanced high-yielding, earlier-maturing lines for tropical Asia. The lines were developed from the IRRI's irrigated rice breeding pipeline.

The research team identified key agronomic traits for high yield in short-duration rice (SDR) that will assist future breeding efforts. The team found that low source-to-sink ratio was the major yield constraint of SDR and suggested that breeding should aim to enhance source capacity during grain filling. Importantly, some new SDR breeding lines yielded 11-38% higher than the most popular short-duration variety. Taken together, these findings indicate enormous potential for developing improved short-duration rice varieties in the future.

A key mystery about the gas comprising most of our atmosphere is closer to being solved following a discovery by University of California, Irvine biologists. Their findings are the first step in understanding the biological mechanism for breaking down nitrogen gas. Besides yielding groundbreaking knowledge, the information holds promise for developing environmentally friendly and cheaper ways to make products such as fertilizer and fuel. The team's research has just been published in the journal Science.

Activation of the nitrogen gas (N2), which composes 78% of the atmosphere, has long stymied scientists. "The strong triple-bond between the nitrogen atoms in N2 makes this compound difficult to break apart, and thus nearly inert." said Molecular Biology and Biochemistry Chancellor's Professor Markus Ribbe. "Researchers have worked for decades to fully understand how nature can activate the nitrogen gas and break it down for biological purposes."

However, the teams of Professors Yilin Hu and Markus Ribbe, from the department of moleculary biology and biochemistry, have discovered how the enzyme nitrogenase can bind to N2 as the initial step towards its activation. X-ray crystallographic analysis showed that the three sulfur sites at the "belt region" of the FeMo cofactor in the active site of the enzyme are labile during catalysis, with the cofactor in one subunit of the enzyme having one, and the other subunit of the enzyme having two, of the three belt sulfur atoms replaced by distinct nitrogen species during the binding and reduction of N2. These findings are entirely unexpected and shed light on the sparsely understood mechanism of N2 reduction, pointing to a key role of belt sulfur displacement in proper nitrogenase function.

"We are optimistic that with further research, we will be able to demonstrate how this entire mechanism works," said Professor Hu.

In addition to revealing important scientific insights, the discovery could ultimately transform manufacturing. Because this natural process is poorly understood, industries turn nitrogen gas into commercial products through other methods that take an environmental toll. For example, the most common procedure for breaking down N2 to produce ammonia fertilizer for agriculture, called the Haber-Bosch process, relies on very high heat and pressure.

Professor Ribbe said: "Once we understand how nature activates nitrogen gas under ambient conditions, it opens the way for developing manufacturing processes that use less energy and are also cheaper." In addition to fertilizer, the discovery could have implications for alternative fuel production. Professors Hu and Ribbe, who have focused much of their research on nitrogenase over the years, have already discovered that the enzyme can convert carbon dioxide and carbon monoxide into hydrocarbons, which are major components in carbon fuels.

World-first research by Monash University in Australia has been able to detect positive COVID-19 cases using blood samples in about 20 minutes, and identify whether someone has contracted the virus.

In a discovery that could advance the worldwide effort to limit the community spread of COVID-19 through robust contact tracing, researchers were able to identify recent COVID-19 cases using 25 microlitres of plasma from blood samples.

The research team, led by BioPRIA and Monash University's Chemical Engineering Department, including researchers from the ARC Centre of Excellence in Convergent BioNano Science and Technology (CBNS), developed a simple agglutination assay - an analysis to determine the presence and amount of a substance in blood - to detect the presence of antibodies raised in response to the SARS-CoV-2 infection.

Positive COVID-19 cases caused an agglutination or a clustering of red blood cells, which was easily identifiable to the naked eye. Researchers were able to retrieve positive or negative readings in about 20 minutes.

While the current swab / PCR tests are used to identify people who are currently positive with COVID-19, the agglutination assay can determine whether someone had been recently infected once the infection is resolved - and could potentially be used to detect antibodies raised in response to vaccination to aid clinical trials.

Using a simple lab setup, this discovery could see medical practitioners across the world testing up to 200 blood samples an hour. At some hospitals with high-grade diagnostic machines, more than 700 blood samples could be tested hourly - about 16,800 each day.

Study findings could help high-risk countries with population screening, case identification, contact tracing, confirming vaccine efficacy during clinical trials, and vaccine distribution.

This world-first research was published today (Friday 18 July 2020) in the prestigious journal ACS Sensors.

A patent for the innovation has been filed and researchers are seeking commercial and government support to upscale production.

Dr Simon Corrie, Professor Gil Garnier and Professor Mark Banaszak Holl (BioPRIA and Chemical Engineering, Monash University), and Associate Professor Timothy Scott (BioPRIA, Chemical Engineering and Materials Science and Engineering, Monash University) led the study, with initial funding provided by the Chemical Engineering Department and the Monash Centre to Impact Anti-microbial Resistance.

Dr Corrie, Senior Lecturer in Chemical Engineering at Monash University and Chief Investigator in the CBNS, said the findings were exciting for governments and health care teams across the world in the race to stop the spread of COVID-19. He said this practice has the potential to become upscaled immediately for serological testing.

"Detection of antibodies in patient plasma or serum involves pipetting a mixture of reagent red blood cells (RRBCs) and antibody-containing serum/plasma onto a gel card containing separation media, incubating the card for 5-15 minutes, and using a centrifuge to separate agglutinated cells from free cells," Dr Corrie said.

"This simple assay, based on commonly used blood typing infrastructure and already manufactured at scale, can be rolled out rapidly across Australia and beyond. This test can be used in any lab that has blood typing infrastructure, which is extremely common across the world."

Researchers collaborated with clinicians at Monash Health to collect blood samples from people recently infected with COVID-19, as well as samples from healthy individuals sourced before the pandemic emerged.

Tests on 10 clinical blood samples involved incubating patient plasma or serum with red blood cells previously coated with short peptides representing pieces of the SARS-CoV-2 virus.

If the patient sample contained antibodies against SARS-CoV-2, these antibodies would bind to peptides and result in aggregation of the red blood cells. Researchers then used gel cards to separate aggregated cells from free cells, in order to see a line of aggregated cells indicating a positive response. In negative samples, no aggregates in the gel cards were observed.

"We found that by producing bioconjugates of anti-D-IgG and peptides from SARS-CoV-2 spike protein, and immobilising these to RRBCs, selective agglutination in gel cards was observed in the plasma collected from patients recently infected with SARS-CoV-2 in comparison to healthy plasma and negative controls," Professor Gil Garnier, Director of BioPRIA, said.

"Importantly, negative control reactions involving either SARS-CoV-2-negative samples, or RRBCs and SARS-CoV-2-positive samples without bioconjugates, all revealed no agglutination behaviour."

Professor Banaszak Holl, Head of Chemical Engineering at Monash University, commended the work of talented PhD students in BioPRIA and Chemical Engineering who paused their projects to help deliver this game changing COVID-19 test.

"This simple, rapid, and easily scalable approach has immediate application in SARS-CoV-2 serological testing, and is a useful platform for assay development beyond the COVID-19 pandemic. We are indebted to the work of our PhD students in bringing this to life," Professor Banaszak Holl said.

"Funding is required in order to perform full clinical evaluation across many samples and sites. With commercial support, we can begin to manufacture and roll out this assay to the communities that need it. This can take as little as six months depending on the support we receive."

COVID-19 has caused a worldwide viral pandemic, contributing to nearly 600,000 deaths and more than 13.9 million cases reported internationally (figures dated 17 July 2020).

To download a copy of the research, please visit https://doi.org/10.1021/acssensors.0c01050 . To watch a video of this research in action, please visit https://www.youtube.com/watch?v=9WBQUC43u9Q&feature=youtu.be.

Dr. Jeffrey L. Cummings, UNLV research professor and a leading expert on Alzheimer’s disease clinical trials, led a five-year review of all Alzheimer’s drugs in the development pipeline. He says today there is more hope than ever that we'll one day solve Alzheimer’s. 
 
The paper, “Alzheimer's disease drug development pipeline: 2020,” was published this week in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions.
 
The first time his team published an analysis of experimental drugs in 2014, they quantified a 99 percent failure rate of all therapies in the pipeline. It was the first analysis of its kind and has proven enormously popular with roughly 67,000 downloads and 260 citations. 
 
Currently, there are 121 unique therapies in 136 clinical trials in the pipeline. We recently met with Cummings from the UNLV School of Integrated Health Sciences to understand what has changed in the world of Alzheimer’s drug development over the last five years.

Tell us about this five-year review. What is its primary purpose?

We want to continue to analyze how the ecosystem and process of drug development is working over time to accelerate getting treatments to patients. I have been involved with clinical trials for the past 20 years and there have been very few studies showing how the process of drug development works. To get a treatment for patients, it’s a complicated process involving many entities along the way including labs, biotech firms, pharmaceutical companies, the federal government, and the marketplace. Scientists, funders and, ultimately, patients want to understand what potential therapies are being developed. 

What are the key takeaways over the past five years of the drug development pipeline? 

We have yet to have a successful drug move across the finish line since our original publication in 2014. It is striking that there has been an increase in the number of repurposed agents compared to five years ago. Several drugs approved to treat other conditions are now being tested to see if they work for Alzheimer’s disease. There are several benefits because the drug’s properties and safety issues are already known. 
 
Another thing we learned is that patient participation is critical and recruitment is too slow, challenging, and expensive. A typical drug trial lasts 18 months and the patient recruitment period may be two years longer than it takes to show efficacy. The company funding the trial has to pay expenses the entire duration, which can mean $30 million to $50 million or more per trial. 

Does this mean there aren’t any new drugs in the pipeline? 

There are new drugs but not as many as we need to advance toward our goal of meaningful therapy for patients. The expense of developing new drugs is exorbitant. It can be $400 million for an entire development program. Currently, there are an estimated 100 million Americans suffering from at least one brain disorder, including Alzheimer’s, costing the health care system nearly $790 billion annually. Investment in new and innovative approaches is needed from public and private funders to help us solve these problems for millions of people. 
 
Thankfully, the Alzheimer’s Association has stepped in to fill part of the gap. Many funding initiatives — specifically their International Research Grants Program and Part the Cloud — were created to fund much needed novel therapies.

How has the recent discovery of new biomarkers impacted the pipeline?

This is an exciting development that offers hope for successful Alzheimer's treatments. In the past two years, several new biomarkers [a measurement, like a blood test, that reveals what's happening in the body] for Alzheimer’s have been developed and some have been approved for use by the FDA, which means we can offer a more precise clinical trial process. We can now use biomarkers to better define our patient populations. It is something new, precise and powerful.   

Recently, you proposed a new scoring method for the pipeline to determine readiness to move from one phase to the next. What inspired you to do so and what are you hoping to achieve? 

We know there is a 99 percent failure rate of drugs in the pipeline. Translational scoring addresses issues in the testing process with rigorous criteria that can consistently be applied to all the therapies in development. The result is a semi-quantitative rating that shows the flaws in a drug development program early on. This is especially critical information for a funding agency to compare treatments to each other and to understand which drug is least risky. 

What is your team at UNLV focusing on?

The recently established Chambers-Grundy Center for Transformative Neuroscience in the department of brain health is focusing on analyzing clinical trial methods to see which strategies, what targets, and what biomarkers are succeeding and how we can use these lessons to get better drugs to our patients faster.  For me, this is enormously exciting.  

How optimistic does this make you about conquering Alzheimer’s?

We’ve never seen more promise in the pipeline than there is today. The very recent discovery of relevant biomarkers allows us to develop drugs with a precision we’ve never had before. We are going to solve this problem.

What can real people do to help advance the science of Alzheimer’s treatments?

We are working with our patients and families to solve the brain disease they have. We can have success only if they participate in the clinical trials. There is a critical alliance between the scientists, a patient, and their family to accelerate drug development. We need our “citizen scientists” because they are contributing in such an important way to a future without Alzheimer’s disease. 

As a researcher yourself, where do you learn about other’s work?

The upcoming Alzheimer’s Association International Conference is the major information sharing opportunity among Alzheimer's disease researchers across the world each year. It’s an enormously important conference where we share and learn about each other’s work. I am presenting at four sessions — virtually this year given the pandemic — and am looking forward to hearing ideas from new researchers to senior ones like myself. Since it is virtual, it is offered at no cost and open to everyone. 

DOI

10.1002/trc2.12050

Molecular biologists and bioengineers at the University of California San Diego have unraveled key mechanisms behind the mysteries of aging. They isolated two distinct paths that cells travel during aging and engineered a new way to genetically program these processes to extend lifespan.

The research is described July 17 in the journal Science.

Our lifespans as humans are determined by the aging of our individual cells. To understand whether different cells age at the same rate and by the same cause, the researchers studied aging in the budding yeast Saccharomyces cerevisiae, a tractable model for investigating mechanisms of aging, including the aging paths of skin and stem cells.

The scientists discovered that cells of the same genetic material and within the same environment can age in strikingly distinct ways, their fates unfolding through different molecular and cellular trajectories. Using microfluidics, computer modeling and other techniques, they found that about half of the cells age through a gradual decline in the stability of the nucleolus, a region of nuclear DNA where key components of protein-producing "factories" are synthesized. In contrast, the other half age due to dysfunction of their mitochondria, the energy production units of cells.

The cells embark upon either the nucleolar or mitochondrial path early in life, and follow this "aging route" throughout their entire lifespan through decline and death. At the heart of the controls the researchers found a master circuit that guides these aging processes.

"To understand how cells make these decisions, we identified the molecular processes underlying each aging route and the connections among them, revealing a molecular circuit that controls cell aging, analogous to electric circuits that control home appliances," said Nan Hao, senior author of the study and an associate professor in the Section of Molecular Biology, Division of Biological Sciences.

Having developed a new model of the aging landscape, Hao and his coauthors found they could manipulate and ultimately optimize the aging process. Computer simulations helped the researchers reprogram the master molecular circuit by modifying its DNA, allowing them to genetically create a novel aging route that features a dramatically extended lifespan.

"Our study raises the possibility of rationally designing gene or chemical-based therapies to reprogram how human cells age, with a goal of effectively delaying human aging and extending human healthspan," said Hao.

The researchers will now test their new model in more complex cells and organisms and eventually in human cells to seek similar aging routes. They also plan to test chemical techniques and evaluate how combinations of therapeutics and drug "cocktails" might guide pathways to longevity.

"Much of the work featured in this paper benefits from a strong interdisciplinary team that was assembled," said Biological Sciences Professor of Molecular Biology Lorraine Pillus, one of the study's coauthors. "One great aspect of the team is that we not only do the modeling but we then do the experimentation to determine whether the model is correct or not. These iterative processes are critical for the work that we are doing."

Two thirds of children and young people have their first sexual activity unexposed to herpes but risk catching it in adulthood, say researchers

Fewer people are being exposed to herpes simplex type 1 - also known as oral herpes - in their childhood and the prevalence amongst the population in Europe is falling by 1% per year, suggests research published in the journal BMJ Global Health.

The prevalence of the virus, which often manifests itself with cold sores, appears to be declining in younger people but it could be increasingly likely to be transmitted sexually.

Herpes simplex type1 (HSV-1) is mainly transmitted by oral-to-oral contact during childhood, causing oral herpes, but it can also cause genital herpes. The other form of the virus (HSV-2) is sexually transmitted and causes genital herpes.

Both forms of the virus are lifelong and the World Health Organization estimates there are 3.7 billion people under age 50 (67%) who have HSV-1 infection globally and 491 million people aged 15-49 (13%) worldwide with HSV-2 infection.

Previous research data focused on North America and Europe has suggested that there is a decrease in acquisition of HSV-1 in childhood, a decline in its population prevalence in youth, and an increase in genital herpes cases that are caused by HSV-1.

A team of researchers from Weill Cornell Medicine-Qatar of Cornell University set out to examine the epidemiology of HSV-1 in Europe.

They systematically reviewed HSV-1 related publications, conducted various meta-analyses, assessed pooled prevalence rates in populations, and estimated pooled proportions of HSV-1 viral detection in clinically diagnosed genital ulcer disease and in genital herpes.

Their analysis gathered information from 142 suitable previous publications.

From these publications, they extracted 179 overall population prevalence measures, four overall proportions of HSV-1 in genital ulcer disease, and 64 overall proportions of HSV-1 in genital herpes.

The results showed that more than two-thirds (67.4%) of the population in Europe tested positive for HSV-1, which is far lower than the historical level of universal infection in childhood in other parts of the world, such as Africa. Around 32.5% of children and 74.4% of adults were infected in Europe.

Prevalence in the population increased steadily with age, being lowest in those aged below 20 years and highest in those aged over 50 years.

Population prevalence in Europe was declining by 1% per year, and the contribution of HSV-1 to genital herpes was rising, also by 1% per year.

As many as two-thirds of European children were reaching their first sexual activity unexposed to this infection and were at risk of acquiring the virus sexually in adulthood, said the researchers.

They speculated that reasons for falling prevalence rates of HSV-1 could include a general decrease in both family size and school crowding, as well as improved hygiene and living conditions.

The results also showed that half of first episode genital herpes cases in Europe were already due to HSV-1, as opposed to HSV-2 infection.

The authors acknowledged that their systematic review had some limitations, primarily the unavailability of data for 25 of 53 European countries, and had comparatively less data for genital ulcer disease and genital herpes than population prevalence.

Nevertheless, these limitations did not appear to have posed a barrier to the interpretation of the results of the study, they said.

They conclude: "HSV-1 epidemiology in Europe is in transition and shifting away from its historical pattern of oral acquisition in childhood.

"HSV-1 transition in Europe is leading to more heterogeneous and variable transmission by age and geography, and an increasing role for HSV-1 in genital herpes and as a sexually transmitted disease.

"The findings highlight the importance of disease surveillance and monitoring of HSV-1 seroprevalence and genital herpes aetiology, and strengthen the case for an HSV-1 vaccine to limit transmission."

Over one in four adults over the age of 65 may have chronic kidney disease (CKD) defined as a reduced kidney function. While serum creatinine remains the most practical biomarker for estimation of kidney function because it is part of metabolic panels, other biomarkers such as cystatin C may be more informative; unlike creatinine, cystatin C is not influenced by muscle mass or function. As people age, muscle mass declines and this may influence the estimation of kidney function based on serum creatinine and it may influence frailty and falls. Dr. Potok and colleagues examined the difference in estimated kidney function based on cystatin C and serum creatinine in 9,029 adults with a mean age of 68 +/- 9 years enrolled in the Systolic Blood Pressure Intervention trial. The difference between kidney function measured with these two markers (cystatin C-based kidney function - creatinine-based kidney function) was associated with lower odds of frailty, falls, and cardiovascular disease events. These findings emphasize the fact that muscle mass and function influence serum creatinine values but do not influence serum cystatin C values. The investigators state that the difference in cystatin C- and creatinine-based kidney function could be used to predict adverse outcomes in older adults.