Culture

In March, researchers in the Department of Biomedical Engineering-- a shared department in the schools of Dental Medicine, Medicine, and Engineering--began to develop a new, low-cost, CRISPR-based diagnostic platform to detect infectious diseases, including HIV virus, the novel coronavirus (SARS-CoV-2). Today, the method is one step closer to being a cutting-edge diagnostics technology for rapid detection of infectious diseases.

Lead by associate professor Changchun Liu, the "All-In-One-Dual CRISPR-Cas12a" (AIOD-CRISPR) method enables simple, rapid, ultrasensitive, visual detection of SARS-CoV-2, intended for use at home or in small clinics.

In a paper published in Nature Communications, the researchers validated the clinical feasibility of the platform using COVID-19 clinical swab samples. Additionally, the researchers used a low-cost hand warmer as an incubator to detect clinical sample results within 20 minutes.

"The usage of disposable hand warmers to heat the AIOD-CRISPR assay eliminates need for expensive electric equipment, enabling instrument-free point of care molecular diagnostics of COVID-19," says Liu.

The publication was co-authored by postdoctoral researchers Xiong Ding and Kun Yin; PhD student Ziyue Li; professor and Associate Dean for Research Dr. Rajesh Lalla; Dr. Enrique Ballesteros, associate professor and chair, pathology and laboratory medicine; and Dr. Maroun Sfeir, assistant professor in pathology and laboratory medicine.

Nucleic acid amplification testing (PCR/RT-PCR) is currently the most sensitive and specific method for early detection of pathogens, but is not suitable for rapid point-of-care diagnostics because of the need for specialized laboratory equipment and trained technicians. Highly contagious pathogens, however, need real-time monitoring to prevent spreading from person to person.

In the study, Liu and his team evaluated their AIOD-CRISPR method using the RNA extract of 28 clinical COVID-19 swab samples, which included eight COVID-19 positive samples. To ensure the reliability of detection, each sample was tested twice in two independent trials. All eight of the COVID-19 positive samples were identified as positive in 40 minutes, which was also confirmed by visual detection. The results were also consistent with those of the CDC-approved RT-PCR method.

The researchers also used a low-cost hand warmer as an incubator to detect the patient samples to eliminate the need for an electric incubator. The AIOD-CRISPR tubes were directly placed on an air-activated hand warmer, and the results were visible by the naked eye under LED light. Two COVID-19 positive samples incubated in the hand warmer bag were visually detected and identified as positive in 20 minutes.

"Such simple, portable and sensitive detection platform has the potential to provide rapid and early diagnostics of COVID-19 and other infectious diseases at home, in doctor's office, and even at drive-thru testing sites," says Liu.

The melanoma is a malignant tumor of the pigment cells. If diagnosed early, the tumor can be removed completely - and the chances of recovery are good. But in later stages, when the tumor has already spread or formed metastases in other parts of the body, the prospects become worse for those affected.

No effect for a good half of patients

The so-called immune checkpoint inhibitors, which have been approved in the last ten years, are a ray of hope - and the medical profession has achieved spectacular treatment successes with these medicines. However, in a good half of all patients these therapies show no benficial effect.

But now, the work of the research group led by Mirjam Schenk from the Institute of Pathology at the University of Bern shows a promising way of increasing the effectiveness of the treatment and helping many more patients than before.

In collaboration with researchers from the USA, the team led by Schenk has uncovered the role of a signal molecule which the cells of the body's immune system use to coordinate their functions.

The molecule is called Interleukin-32, IL-32 for short. In the complex interplay of immune cells within and in the immediate area around a tumor, it soon revealed a double effect. "It hits two birds with one stone," says Schenk.

Making tumors attackable again

On one hand, IL-32 leads to the maturation and activation of so-called dendritic cells which are responsible for the recognition of foreign structures. In addition, IL-32 also triggers macrophages or scavenger cells to secrete attractants for the T cells. This is how these immune cells find their way to the tumor, where they can eliminate the cancer cells.

Tumors have to escape detection by the immune system for them to be able to grow. This is why they settle in immunosuppressed environments which are hospitable for cancer growth. Clearly, IL-32 is capable of making these protective niches of the tumor accessible to the immune system again.

With trials on mice, the researchers led by Schenk have proven that the efficacy of immune checkpoint inhibitors can be improved by the simultaneous administration of IL-32.

Combination treatment a "promising therapeutic strategy"

In animal models, the additionally administered IL-32 did not cause any side effects. Whether these results can be transferred to humans remains to be seen, says Schenk. However, a further argument certainly speaks for the fact that the combination treatment represents a "promising strategy for treatment", as the researchers led by Schenk write in their recently published specialist article in the &laquoThe Journal of Clinical Investigation insight».

As they have been able to prove with bioinformatic analyses, melanoma patients with more IL-32 activity have an improved life expectancy, from a statistical point of view.

Announcing a new article publication for BIO Integration journal. In this opinion article the authors Fengyi Zeng, Xiaowen Liang and Zhiyi Chen from The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China consider new roles for clinicians in the age of artificial intelligence (AI).

With the rapid developments of digital picture processing, pattern recognition, and intelligent algorithms, artificial intelligence (AI) applications are now widely used in medicine. Applications of artificial intelligence in medicine (AIM) include diagnosis generation, therapy selection, healthcare management and disease stratification. AIM focuses on assisting clinicians in disease detection, quantitative measurements, and differential diagnosis which improves diagnostic accuracy and optimizes treatment selection.

However, there is little research on the consideration of clinicians in the age of AI. Concerns have been raised as to whether doctors will eventually be replaced by AI. From this viewpoint, the authors elaborate on the unlikelihood of AI completely replacing doctors and explore how doctors can adapt their roles to assist successful integration of AI into current medical techniques and procedures.

By André Julião | Agência FAPESP – Researchers at the University of São Paulo (USP) in Brazil have characterized a novel family of anti-bacterial toxins present in bacteria, including Salmonella enterica. This species uses toxic proteins to kill other bacteria in gut microbiota and facilitate colonization of the infected host’s gut.

The study is published in Cell Reports and featured on the cover of the journal.

The novel family’s founding member is the protein Tlde1 (type VI L,D-transpeptidase effector 1), which attacks bacterial cell wall precursors. It is secreted via the type VI secretion system or T6SS. Targeted bacteria continue growing but because their cell walls are weakened they eventually die as cell contents leak owing to osmotic pressure and lysis.

“This family of toxins has a hitherto undescribed mechanism. While other anti-bacterial toxins secreted by the same system destroy the already formed cell walls of target bacteria, this one acts on precursors so that they’re weak or cannot form at all,” said Ethel Bayer-Santos, a researcher in the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) and principal investigator for the project, which is supported by FAPESP.

In a previous study, a research group that included Bayer-Santos described another secretion system (T4SS) in opportunistic bacteria of the species Stenotrophomonas maltophilia. They also described a toxin that inhibits bacterial growth (read more at: agencia.fapesp.br/32157).

“Bacteria selected these toxins during evolution and have been using them for thousands of years, so these discoveries point to therapeutic targets. Bacterial toxins may always have biotechnological potential and become anti-bacterial compounds in the future,” Bayer-Santos said.

Search

In their search for the protein Tlde1, the scientists analyzed the genome of Salmonella in the region neighboring the genes that encode the structural proteins in the secretion system (T6SS). They found a pair of genes with traits that signaled a toxic protein and another that conferred immunity. Anti-bacterial toxins are usually located in bacterial genomes near proteins that contain antidotes to the toxins. These antidotes are required to protect the microorganisms from their own weapons.

To test the function of this gene pair, the researchers first expressed a gene they thought was probably responsible for the toxic protein in a susceptible bacterium, Escherichia coli. It survived when the probable toxic gene was expressed in cytoplasm but died when expression occurred in periplasm, suggesting the toxin targets some structure in this part of the cell wall.

Next, they expressed in E. coli’s periplasm both the toxic protein and the probable immunity protein. This co-expression neutralized the toxic effect and the bacteria survived, confirming that the proteins in question are indeed a toxin and an immune protein respectively.

In evolutionary terms, T6SS is related to the apparatus of bacteriophages, viruses that infect bacteria. It comprises 13 structural proteins that are assembled into a weapon resembling a spear or harpoon with a sharp tip inside a retractable cytoplasmic sheath. The attacking cell ejects the harpoon full of toxic proteins from the sheath into the target cell.

Bioinformatics analysis showed that members of the Tlde1 family are present in several species of bacterium and that the family probably evolved from bacterial enzymes with a key role in cell wall synthesis. The next step in the project is an effort to understand by structural biology how an enzyme that had this role has ended up doing the opposite.

The first authors of the published paper are Stephanie Sibinelli-Sousa and Julia Takuno Hespanhol, who received scientific initiation scholarships (respectively grant no. 18/13819-1 and grant no. 18/25316-4). Sibinelli-Sousa is currently researching for a master’s degree at ICB-USP with FAPESP’s support.

The other authors are Gianlucca Gonçalves Nicastro, Robson Francisco de Souza and Cristiane Rodrigues Guzzo Carvalho, all of whom are affiliated with ICB-USP; Bruno Yasui Matsuyama, affiliated with the same university’s Chemistry Institute (IQ-USP); and Stephane Mesnage and Ankur Patel of Sheffield University in the UK.

The article “A family of T6SS antibacterial effectors related to l,d-transpeptidases targets the peptidoglycan” can be read at: www.cell.com/cell-reports/fulltext/S2211-1247(20)30794-4.

Journal

Cell Reports

DOI

10.1016/j.celrep.2020.107813

A new hollow optical fiber greatly reduces the "noise" interfering with the signals it transmits compared to the single-mode fibers now widely used, researchers at the University of Rochester report.

The anti-resonant hollow-core fiber, created by researchers at the University of Central Florida, produces a thousand times less "noise" - and the lowest levels ever recorded from interference caused by acoustic phonons arising from the glass in the fiber at room temperatures.

To document this, researchers in the lab of William Renninger, assistant professor of optics, developed a highly sensitive measuring technique. Their findings are reported in a paper published in APL Photonics.

"It's a very valuable fiber, and despite a lot of interest in it by researchers and some companies, nobody had really studied the behavior of phonons supported by the structure, and to what extent it actually reduced 'noise,' " says Renninger, an expert in experimental and theoretical nonlinear optics.

The lab's findings conclusively demonstrate that the fiber is a "promising platform for low noise applications, such as for quantum information processing and optical communications," writes lead author Arjun Iyer, a graduate research associate in Renninger's lab.

A unique answer to 'noise'

"Noise" refers to any disturbance that masks or disrupts a signal being sent by light through an optical fiber. One such disturbance is caused by phonons - quantized acoustic or sound waves that occur at atomic and subatomic levels, in this case in the glass of an optical fiber.

Phonons cause a beam of light to "scatter" off the acoustic waves, creating splinter beams of different frequencies, or colors, that can interfere with, and reduce the energy of, the main beam. While some forms of scattering can be useful for specific applications, it interferes with quantum applications and even basic optical communications.

Noise can be reduced by cooling the fibers to extremely low, cryogenic temperatures, but that's "very expensive and complicated," Renninger says. Another approach is to attempt to use complicated error-correcting algorithms to correct for noise.

The anti-resonant hollow-core fiber, however, represents a straightforward solution that works even at room temperatures. Created by co-author Rodrigo Amezcua Correa and other researchers at CREOL, the College of Optics and Photonics at the University of Central Florida, the fiber features a unique arrangement of seven hollow capillaries arranged around a hollow core inside the fiber.

This results in minimal overlap between the fiber's outer layer of glass and the light traveling through the core, eliminating interference from acoustic phonons emanating from the glass.

Tests by Renninger's lab showed that the arrangement is 10 times more effective at reducing noise than other hollow fiber designs. "The little noise that's left is caused by acoustic waves in the air inside the fiber, so if you were to evacuate the air it would be another 100 times more effective," Renninger says. "You would have incredibly low noise".

"If the fate of the world depended on reducing acoustic noise in optical fibers, this is the one you would want to use."

Despite the important advances in research in recent years, the etiopathogenesis of Alzheimer's disease is still not fully clarified. One of the key questions is to decipher why the production of beta amyloid, the protein that produces the toxic effect and triggers the pathology, increases in the brain of people with Alzheimer's.

The research has focused on the different fragments of the Amyloid Precursor Protein (APP) until now, but the results have been inconclusive, "because this protein is processed so quickly that its levels in the cerebrospinal fluid or in the plasma do not reflect what is really happening in the brain," explains Dr. Javier Sáez-Valero, head of the group on "Altered Molecular Mechanisms in Alzheimer's Disease and other Dementias" at the UMH-CSIC Neuroscience Institute in Alicante.

Dr. Sáez-Valero's laboratory has carried out a novel approach that shows great promise: "We have discovered that the glycosylation of the amyloid precursor in the brain of Alzheimer's patients is altered. And, therefore, this protein is probably being processed in a different way. We believe that this different way of processing leads to more beta-amyloid, and to the triggering of the pathology".

Glycosylation consists of adding carbohydrates to a protein. This process determines the destiny of the proteins to which a sugar chain (glycoproteins) has been added, which will be secreted or will form part of the cellular surface, as in the case of the Amyloid Precursor Protein (APP). The alteration of this glycosylation process is related with the origin of various pathologies.

In the specific case of Alzheimer's, the results of the study led by Sáez Valero suggest that the altered glycosylation could determine that the APP is processed by the amyloidogenic (pathological) pathway, giving rise to the production of the beta-amyloid, a small protein with a tendency to cluster forming the amyloid plaques characteristic of Alzheimer's disease.

"The fact that the glycosylation of the amyloid precursor is altered indicates that this amyloid precursor may be located into areas of the cell membrane that are different from the usual, interacting with other proteins and therefore probably being processed in a pathological way," clarifies this expert in Alzheimer's disease.

With this new finding of Dr. Saez-Valero's group, published in Alzheimer's Research & Therapy, "analyzing the glycosylation of beta-amyloid fragments opens the possibility of finding a good biomarker for diagnosis in the short term. And in the longer term to intervene therapeutically".

Previously, amyloid fragments of APP had been studied in the cerebrospinal fluid for these purposes, "but the results did not indicate that it could be a good diagnostic marker. However, in view of our new results, we propose to repeat the studies carried out to date not only by looking at the different types of fragments of the beta-amyloid protein, but also at its glycosylation," highlights Sáez-Valero.

The presence of the beta-amyloid protein in the cerebrospinal fluid does not provide much information at present either, "since in the brain this small protein forms amyloid plaques, thus, the paradox is that in the cerebrospinal fluid there are lower levels than would be expected," explains Sáez-Valero.

The other option is to study the long fragments of the APP, "but they are processed so quickly that they do not really reflect anything pathological. However, looking at the glycosylation we have seen that, although the total levels are not altered, there is an indication that the protein is synthesized differently and therefore can be processed in a different way, giving rise to the toxic cascade that triggers Alzheimer's disease," this expert points out.

This work has been carried out on post-mortem brain samples and on cell cultures. The next step will be to analyze the glycosylation of the app fragments in the cerebrospinal fluid. "Right now we have a new tool that can be used in the short term for biochemical diagnosis of Alzheimer's patients in the laboratory," concludes Dr. Sáez-Valero.

BUFFALO, N.Y. -- Researchers know from many previous studies what prevents cash-strapped shoppers in underserved communities from buying more fresh produce. But little is known about which strategies are most likely to reach the people who need them, or have the most success in improving the diets of people in lower income areas.

A new University at Buffalo study based in Western New York is the first that simultaneously examined the preferences of community members and compared those with the community-based programs and resources available to identify the most viable strategies for addressing disparities in healthy food consumption.

Previous research has shown that only 12% and 7% of adults living at or below the poverty line meet fruit and vegetable recommendations, respectively.

"We continue to find that cost, food preferences, availability, access and limited food assistance eligibility and/or benefits are persistent barriers. Residents of underserved communities feel that increasing the affordability of fruits and vegetables through incentives, nutrition education, and increased access to healthy food options will help them to eat more fruits and vegetables," said Christina Kasprzak, lead author on the study published in the Journal of Hunger & Environmental Nutrition.

"We also found that healthy food incentives, mobile produce markets, and nutrition education are acceptable and preferred food access strategies," added Kasprzak, a PhD candidate in community health and health behavior in UB's School of Public Health and Health Professions.

Researchers conducted 13 focus groups with 98 lower-income participants in urban areas of Western New York. Eight of the focus groups were conducted at local Women, Infant and Children (WIC) offices, while the remaining five were recruited by community organizations that serve lower-income families. The research team also interviewed 17 grocery store owners or managers, farmers, food distributors, and representatives from community organizations that currently or would be willing to address food access issues.

How to match needs

"Our research evaluated the capacity among local stakeholders to address the needs of lower-income communities, and made recommendations of how we can match this capacity to the preferences voiced in the focus groups with lower-income individuals," Kasprzak said.

"By capitalizing on where there are matches between lower-income communities' preferences and stakeholders we can ensure our efforts to expand healthy food access are viable," Kasprzak said. "We don't necessarily need to completely abandon the mismatches between programs and preferences, but we should heed community members' suggestions for these programs and avoid blindly establishing programs that may not be fruitful."

Cost, limited availability and accessibility, taste preferences and limited federal nutrition eligibility and benefits were the most frequently mentioned barriers to fruit and vegetable consumption. Study participants expressed frustration with having to decide between buying fresh produce and less healthy food options because of cost differences.

Another recurring theme among study participants was that they said they often had to travel outside their neighborhood, which required transportation, to find affordable and high-quality produce.

Researchers also reported that twice as many participants felt they lacked access to healthy food as those who said they had access.

What did participants say would help them buy and eat more fresh foods? Increasing the affordability, as well as nutrition education and recipe ideas. Some participants expressed a desire to learn healthier ways to prepare foods unique to their culture.

Include the working poor

Many participants favored increasing federal nutrition program benefits -- such as Supplemental Nutrition Assistance Program (SNAP) -- or expanding the eligibility requirements for these programs to include the working poor.

On the retail side, store owners and managers interviewed said they'd be willing to expand their fresh produce offerings to meet customers' demands, while supporting efforts to improve the health of the community.

For corner stores -- whose prices generally are known to be higher -- owners wanted guidance on what to stock, how to price and promote those items, and where to source fruits and vegetables.

Farmers expressed a willingness to accept SNAP benefits for Community Supported Agriculture (CSA) shares, and to provide produce to urban corner stores.

Kasprzak was pleasantly surprised to learn that there is ample opportunity for local stakeholders to help lower-income communities access and eat more fruits and vegetables.

"By connecting the dots, we can potentially enhance the reach of existing programs that are preferred by these communities," she said.

Ultimately, though, the barriers of cost of fruits and vegetables and limited eligibility and benefits for nutrition assistance programs are not wholly addressed by the food access programs discussed in the research paper, Kasprzak notes.

"For example, an incentive program makes fruits and vegetables more affordable but does not directly drive down the cost of produce. Therefore, more concerted efforts at the state or national level are needed."

"We know that many of the programs that community members would like to see already exist, but budget and expertise to market these programs are often lacking in small organizations," added Lucia Leone, PhD, the senior author on the paper and an assistant professor of community health and health behavior at UB. "Support from local policy makers is crucial for both getting the word out about these programs and ensuring their sustainability."

BIRMINGHAM, Ala. - Stroke patients who also have COVID-19 showed increased systemic inflammation, a more serious stroke severity and a much higher rate of death, compared to stroke patients who did not have COVID-19, according to University of Alabama at Birmingham research led by Chen Lin, M.D., an assistant professor in the UAB Department of Neurology.

The research, published in the journal Brain, Behavior & Immunity - Health, is a retrospective, observational, cross-sectional study of 60 ischemic stroke patients admitted to UAB Hospital between late March and early May 2020. Ischemic stroke occurs when a blood vessel for the brain is blocked by a clot, depriving some brain tissue of oxygen. All patients were tested for COVID-19 at admission.

The UAB researchers mined electronic medical records of confirmed stroke cases for information on age, gender and race; clinical variables; laboratory data, including complete blood counts, blood chemistry and coagulation tests; and outcomes, including death, length of hospital stay and condition at discharge.

The ratio of the number of neutrophils to the number of lymphocytes, or the NLR, as calculated from blood count data, served as an index of the systemic inflammatory response. While other researchers have associated NLR with COVID-19 disease severity, refractory disease and even as an independent factor for mortality, "our study is the first to associate the NLR in patients with COVID-19 and ischemic stroke and stroke severity," Lin said.

Of the 60 hospitalized patients with acute systemic stroke, nine were positive for a COVID-19 infection.

The UAB research had four major findings. First, patients who were positive for COVID-19 presented with a more severe neurological deficit at admission, as measured by the National Institutes of Health Stroke Scale, or NIHSS, score, which averaged 18.4. Second, all patients with an NIHSS score higher than 4 -- including uninfected patients -- had a significantly higher NLR than those with lower scores. The NIHSS is used to predict lesion size and gauge stroke severity.

Third, patients with COVID-19 had an increased inflammatory response, including significantly higher neutrophil counts, lower lymphocyte counts and an increased NLR, compared with uninfected patients. Finally, stroke patients with COVID-19 had a significantly higher mortality
rate -- 44.4 percent, versus 7.6 percent for uninfected stroke patients.

Two other studies this year have reported clinical and laboratory differences in ischemic stroke patients with and without COVID-19, Lin says, but neither addressed racial differences or NLR differences between groups.

"We have reported the first experience within the 'Stroke Belt' of the Southern United States, which has the highest proportion of African American stroke patients," said Lin, who is also the director of the Stroke Recovery Clinic in the UAB Division of Cerebrovascular Disease. In the UAB study, African Americans comprised 55.6 percent of those who had COVID-19 and stroke and 37.7 percent of those with only stroke.

"Interestingly, in our patients with stroke and COVID-19, the neutrophil and lymphocyte levels were only borderline high and low, respectively," Lin said, "yet the NLR was almost twice as high as in patients without COVID-19. This potentially indicates that the systemic inflammatory response triggered by COVID-19 can cascade from multiple components."

An international team of plant scientists have shown the potential to rapidly improve the quality of barley grain through a genetic tool known as CRISPR or gene editing.

Published in The Plant Journal, researchers from the University of Adelaide's Waite Research Institute working with the James Hutton Institute in Scotland and other colleagues in the UK and Melbourne, describe how the levels of beta-glucan in barley grain can be influenced through gene editing.

Joint senior author Associate Professor Matthew Tucker, Deputy Director of the Waite Research Institute, says: "Barley grain is comparatively rich in beta-glucan, a source of fermentable dietary fibre that protects against various human health conditions. However, crops with a low content of this compound are preferred for brewing and distilling.

"The research has given us further insight into key genes responsible for barley grain composition and, by using CRISPR gene editing, plant breeders will have the potential to accelerate plant breeding and deliver new crop varieties that are best suited to their target markets."

This work was carried out by Dr Guillermo Garcia-Gimenez during his PhD at the James Hutton Institute and the University of Adelaide. It is the first published use of the CRISPR technique to influence barley grain quality in Australia and Scotland.

Dr Garcia-Gimenez says: "We used what's called a reverse genetics approach, using CRISPR to generate changes in members of the gene superfamily responsible for making beta-glucan. The results led to specific differences in grain quality, composition and content of beta-glucan.

"We hope this work will contribute to creating awareness about the potential of this technique and we look forward to trialling the new plants in field conditions."

Associate Professor Tucker says: "This study has brought real immediate benefit in terms of understanding how gene editing can help improve the quality of barley crops. And it's part of our overall ongoing efforts to apply the latest genetic techniques to deliver improvements for the food and feed industries."

Professor Matthew Gilliham, Director of the Waite Research institute, says: "Barley is Australia's second most important cereal crop behind wheat, contributing around $3 billion to the economy. Despite recent market fluctuations, this discovery is important and opens the door to significant economic impact for breeders and growers.

"The Waite Research Institute, in partnership with The International Barley Hub, is showing again that research in this area can yield great returns on investment in the basic understanding of barley."

A study conducted by Hiroshima University researchers found that using Ultraviolet C light with a wavelength of 222 nanometers which is safer to use around humans effectively kills SARS-CoV-2 -- the first research in the world to prove its efficacy against the virus that causes COVID-19.

Other studies involving 222 nm UVC, also known as Far-UVC, have so far only looked at its potency in eradicating seasonal coronaviruses that are structurally similar to the SARS-CoV-2 but not on the COVID-19-causing virus itself. A nanometer is equivalent to one billionth of a meter.

An in vitro experiment by HU researchers showed that 99.7% of the SARS-CoV-2 viral culture was killed after a 30-second exposure to 222 nm UVC irradiation at 0.1 mW/cm2. The study is published in the American Journal of Infection Control.

Tests were conducted using Ushio's Care222TM krypton-chloride excimer lamp. A 100 microliter solution containing the virus (ca. 5 × 106 TCID50/mL) was spread onto a 9-centimeter sterile polystyrene plate. The researchers allowed it to dry in a biosafety cabinet at room temperature before placing the Far-UVC lamp 24 centimeters above the surface of the plates.

222 nm vs 254 nm UVC

A wavelength of 222 nm UVC cannot penetrate the outer, non-living layer of the human eye and skin so it won't cause harm to the living cells beneath. This makes it a safer but equally potent alternative to the more damaging 254 nm UVC germicidal lamps increasingly used in disinfecting healthcare facilities.

Since 254 nm UVC harms exposed human tissues, it can only be used to sanitize empty rooms. But 222 nm UVC can be a promising disinfection system for occupied public spaces including hospitals where nosocomial infections are a possibility.

The researchers, however, suggest further evaluation of the safety and effectiveness of 222 nm UVC irradiation in killing SARS-CoV-2 viruses in real-world surfaces as their study only investigated its in vitro efficacy.

Changing skins

Cells are surrounded by a layer of membrane lipids that protect them from changes in their environment such as temperature, much in the same way that our skin changes when we are cold or exposed to the sun. Lead author and NIOZ senior scientist Laura Villanueva explains why they make such interesting biomarkers. 'When a cell dies, these lipids preserve like fossils and hold ancient-old information on Earths' early environmental conditions.' Our tree of life includes small and simple cells (Bacteria and Archaea) and more complex cells (Eukaryotes), including animals and humans. Bacteria and Eukaryotes share a similar lipid membrane. Looking at Archaea, their 'skin' or membrane looks very different and is primarily designed to help these microorganisms to survive in extreme environments. Villanueva: 'This "lipid divide", or difference in membranes between Bacteria and Eukaryotes on the one hand and Archaea on the other, is believed to have happened after the emergence of Bacteria and Archaea from the last universal cellular ancestor (LUCA).'

Missing piece hidden in the deep Black Sea

The leading theory is that Eukaryotes evolved from a symbiosis event between archaeal and bacterial cells in which the archaeal cell was the host. But how does this work when their 'skins' are so different and share no sign of common ancestry? Villanueva: 'To explain the creation of more complex life-forms, the archaeal membrane must have made a switch to a bacterial type membrane. Such a switch likely needed a transition period in which the two membrane types were mixed.' However, mixed lipid membranes had never been found in microbes until the team of Villanueva made an unexpected discovery in de deep waters of the Black Sea.

Villanueva: 'We found a possible missing piece of this puzzle in the Black Sea. Here, an abundant group of bacteria thrive in the deep-sea, absent of oxygen and with high sulfide concentration. We discovered that the genetic material of this group did not only carry pathway genes for bacterial lipids but archaeal ones as well.' The peculiarity was also found in the genetic material of other, closely related Bacteria and supports the idea that this ability to create 'mixed' membranes is more widespread than previously thought. This discovery sheds new light on the evolution of all cellular life forms and may have important consequences for the interpretation of archaeal lipid fossils in the geological record and paleoclimate reconstructions.

Climate changes associated with global warming can affect astronomical observations. That is the result of a study involving scientists from the University of Cologne. The international research team investigated a range of climate parameters at the Very Large Telescope (VLT) at the Paranal in the Atacama Desert in Chile, where the European Southern Observatory (ESO) operates its telescopes. Among other things, the team evaluated the data for temperature, wind speed and wind direction, and the water vapour content in the atmosphere over a period of several decades. This revealed an increase in temperatures above the world average and also increasing image blur due to air turbulence - so-called seeing.

The study 'The impact of climate change on astronomical observations' was published in the current issue of Nature Astronomy and can be viewed online. Its results are not only important for astronomers to adapt their observations to changing environmental conditions, but must also be taken into account when planning new large telescopes - such as the Extremely Large Telescope (ELT), which is currently being built near the Paranal.

The Cologne-based scientists Professor Dr Susanne Crewell and Christoph Böhm from the Institute of Geophysics and Meteorology were involved in the study. In the past, they had already explored various aspects of the past, present and future climate at the telescope's site in the framework of Collaborative Research Centre 1211 'Earth - Evolution at the Dry Limit'. The first author of the article is Faustine Cantalloube from the Max Planck Institute for Astronomy in Heidelberg.

The researchers investigated the extent to which climate change affects astronomy and in particular the quality of observations. The team focused on the Paranal Observatory in northern Chile because it has a whole range of environmental sensors that document local meteorological conditions. These measurements yielded one of the most comprehensive data sets over the last three decades at a largely untouched location.

Based on this data set, astronomers, climate researchers, atmosphere scientists, and meteorologists joined forces to identify important meteorological parameters that play a role in the quality of astronomical observations. The data allowed them to analyse long-term trends over a period of more than thirty years to determine the impact of climate change on future observations. Using four examples, they showed how climate change is already affecting, or might affect the operation of an astronomical observatory in future. The VLT, operated by ESO, was served as an example.

'The data showed a 1.5 ° C increase in near-ground temperature over the last four decades at the Paranal Observatory. This is slightly higher than the worldwide average of 1°C since the pre-industrial age,' said Susanne Crewell. Since the original telescope cooling system was not designed for such warm conditions, the quality of observations is increasingly endangered by more frequent turbulences - a consequence of the rise in temperature. The expected rise of 4° C (the most pessimistic scenario of the ICCP climate simulations) within the next century thus has to be taken into account in the construction of the 39-metre Extremely Large Telescope (ELT) at a nearby site.

In particular, astronomers face the challenge of a reduction in the so-called 'dome seeing', a reduction in resolution due to turbulence within the telescope dome. The researchers furthermore noticed an increase in turbulence in the air layer near the ground, making images blurred since cold and warm air layers with different refractive indices alternate more quickly. However, attributing this to climate change is difficult, since there were also constructional changes. The increase in wind shear in the upper troposphere in connection with the jet stream also leads to a so-called 'wind-driven halo'. This phenomenon appears when atmospheric turbulence conditions vary faster than the telescope's control system can correct them. This limits the contrast capabilities of the instrument and could potentially limit exoplanet studies. An increase in water vapour in the atmosphere moreover could lead to a reduction of the astronomical signal.

Through their unique perspective on the universe, astronomers know that the origin of life on Earth was a complex process made possible only by the coincidence of extremely rare circumstances. There is no second Earth in our neighbourhood. For this reason, the current issue of Nature Astronomy, published on September 10, is dedicated to the topic climate. The special issue aims to raise awareness in astronomy for climate aspects that are important for the work of astronomers.

The spike protein on the surface of the SARS-CoV-2 coronavirus can adopt at least ten distinct structural states, when in contact with the human virus receptor ACE2, according to research from the Francis Crick Institute published in Nature today (Thursday).

This new insight into the mechanism of infection will equip research groups with the understanding needed to inform studies into vaccines and treatments.

The surface of SARS-CoV-2, the virus that causes COVID-19, is covered in proteins called spikes, which enable the virus to infect human cells. The infection begins when a spike protein binds with ACE2 cell surface receptors and, at later stages, catalyses the release of the virus genome into the cell.

However, the exact nature of the ACE2 binding to the SARS-CoV-2 spike remains unknown.

In the first study to examine the binding mechanism between ACE2 and the spike protein in its entirety, researchers in the Crick's Structural Biology of Disease Processes Laboratory, have characterised ten distinct structures that are associated with different stages of receptor binding and infection.

The team incubated a mixture of spike protein and ACE2 before trapping different forms of the protein by rapid freezing in liquid ethane. They examined these samples using cryo-electron microscopy, obtaining tens of thousands of high-resolution images of the different binding stages.

They observed that the spike protein exists as a mixture of closed and open structures., Following ACE2 binding at a single open site, the spike protein becomes more open, leading to a series of favourable conformational changes, priming it for additional binding. Once the spike is bound to ACE2 at all three of its binding sites, its central core becomes exposed, which may help the virus to fuse to the cell membrane, permitting infection.

"By examining the binding event in its entirety, we've been able to characterise spike structures that are unique to SARS-CoV-2," says Donald Benton, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick.

"We can see that as the spike becomes more open, the stability of the protein will reduce, which may increase the ability of the protein to carry out membrane fusion, allowing infection."

The researchers hope that the more we can uncover about how SARS-CoV-2 differs from other coronaviruses, the more targeted we can be with the development of new treatments and vaccines.

Antoni Wrobel, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick, says: "As we unravel the mechanism of the earliest stages of infection, we could expose new targets for treatments or understand which currently available anti-viral treatments are more likely to work."

Steve Gamblin, group leader of the Structural Biology of Disease Processes Laboratory at the Crick says: "There's so much we still don't know about SARS-CoV-2, but its basic biology contains the clues to managing this pandemic.

"By understanding what makes this virus distinctive, researchers could expose weaknesses to exploit."

The team are continuing to examine the structures of spikes of SARS-CoV-2 and related coronaviruses in other species to better understand the mechanisms of viral infection and evolution.

A milk-tooth found in the vicinity of "Riparo del Broion" on the Berici Hills in the Veneto region bears evidence of one of the last Neanderthals in Italy. This small canine tooth belonged to a child between 11 and 12 that had lived in that area around 48,000 years ago. This is the most recent Neanderthal finding in Northern Italy.

The study uncovering this tooth was carried out by a group of researchers from the Universities of Bologna and Ferrara, who have recently published a paper in the Journal of Human Evolution. "This work stems from the synergy between different disciplines and specializations", says Matteo Romandini, lead author of this study and researcher at the University of Bologna. "High-resolution prehistoric field-archaeology allowed us to find the tooth, then we employed virtual approaches to the analyses of its shape, genome, taphonomy and of its radiometric profile. Following this process, we could identify this tooth as belonging to a child that was one of the last Neanderthals in Italy".

The genetic analysis reveals that the owner of the tooth found in Veneto was a relative, on their mother's side, of Neanderthals that had lived in Belgium. This makes this site in Veneto a key-area for comprehending the gradual extinction of Neanderthals in Europe.

"This small tooth is extremely important", according to Stefano Benazzi, professor at the University of Bologna and research coordinator. "This is even more relevant if we consider that, when this child who lived in Veneto lost their tooth, Homo Sapiens communities were already present a thousand kilometres away in Bulgaria".

Researchers analysed the tooth by employing highly innovative virtual methods. "The techniques we employed to analyse the tooth led to the following discovery: this is an upper canine milk-tooth that belonged to a Neanderthal child, aged 11 or 12, that lived between 48,000 and 45,000 years ago", as report Gregorio Oxilia and Eugenio Bortolini, who are co-authors of the study and researchers at the University of Bologna. "According to this dating, this little milk-tooth is the most recent finding of the Neanderthal period in Northern Italy and one of the latest in the entire peninsula".

The findings retrieved from the "Riparo del Broion" are still being analysed. However, preliminary results show that this site had been used for a long period of time as there are signs of hunting activities and butchering of large prays. "The manufacturing of tools, mainly made of flint, shows Neanderthals' great adaptability and their systematic and specialized exploitation of the raw materials available in this area", adds Marco Peresanti, a professor of the University of Ferrara who contributed to the study.

Up to one in four Danes has an unhealthy accumulation of fat in the liver, also known as fatty liver. Fatty liver is rarely the cause of symptoms in itself, but people with fatty liver have an increased risk of developing diabetes. Exactly how the two diseases are linked has, however, so far been unknown.

Now, a new study from the Faculty of Health and Medical Sciences at the University of Copenhagen shows that people with fatty liver have reduced sensitivity to glucagon which increases the glucagon secretion and leads to increased amounts of glucagon in the blood. The same is seen in patients with type 2 diabetes, the vast majority of whom have increased fat in the liver.

'The reduced glucagon sensitivity means that the secretion of glucagon is increased via a so-called feedback system between the liver and the pancreas. An elevated level of glucagon is undesirable as it increases sugar production in the liver and thus creates a high blood sugar level', says Nicolai J. Wewer Albrechtsen, Assistant Professor at the Novo Nordisk Center for Protein Research and Resident at the Department of Clinical Biochemistry, Rigshospitalet.

With the study, the researchers are introducing an entirely new concept within the field of diabetes: glucagon resistance. They believe that the concept is so fundamental to the understanding of diabetes that it should not be limited to laboratories and research environments.

'Glucagon resistance is an entirely new biological concept that we will include in the future teaching of medical students, just as we do today with insulin resistance', says Nicolai J. Wewer Albrechtsen.

Potential New Treatment

The decreased glucagon sensitivity may help to explain the connection between fatty liver and type 2 diabetes. And with new knowledge come new opportunities. If you can detect decreased glucagon sensitivity, you can start treatment earlier. That way, you can stop the glucagon level and thus the blood sugar from running wild.

'Our study points to a new biomarker (the glucagon-alanine index) that may be useful in identifying persons with impaired glucagon sensitivity. If we can detect glucagon resistance from a blood test, we can start treatment early and thus prevent the development of type 2 diabetes', says PhD student at the Novo Nordisk Foundation Center for Protein Research and the Department of Biomedical Sciences, Marie Winther-Sørensen.

The treatment consists primarily of weight loss, which will limit the amount of fat in the liver, but may also include drugs that go in and inhibit the hormone glucagon.

'We know that the pharmaceutical industry has just started using our marker for glucagon sensitivity in studies where new treatments are tested. Our study has the potential to demonstrate glucagon resistance in fatty liver based on a simple blood test, and we must now investigate this in a so-called lottery experiment', says Marie Winther-Sørensen.