Culture

HANOVER, N.H. - April 14, 2021 - Scientists have searched for years to understand how cells measure their size. Cell size is critical. It's what regulates cell division in a growing organism. When the microscopic structures double in size, they divide. One cell turns into two. Two cells turn into four. The process repeats until an organism has enough cells. And then it stops. Or at least it is supposed to.

The complete chain of events that causes cell division to stop at the right time is what has confounded scientists. Beyond being a textbook problem, the question relates to serious medical challenges: Cells that stop dividing too soon can cause defects in growing organisms. Uncontrolled cell growth can lead to cancers or other disorders.

A study from Dartmouth, published in Current Biology, provides a new answer to the question by tackling the problem in reverse: The research focused on large cells that reduce their size through division until enough cells are formed to move to other stages of development.

"The early embryo is an ideal place to study cell size control," said Amanda Amodeo, an assistant professor of biology at Dartmouth and the lead researcher. "The cells we work with are eggs that are visible to the eye. They don't need to grow before dividing, so it allows us to look at connections that are obscured in adult cells."

According to the study, a set amount of the protein histone H3 is loaded into an embryo before fertilization and is used up as the embryo divides into more cells. As histones are consumed to accommodate the growing number of nuclei, they release the enzyme Chk1 to bind with another protein, CDC25, to stop the multiplication of cells.

The research is technical, but the mechanism is relatively straightforward: With histone H3 out of the way in a growing cell, the stop enzyme Chk1 finds and disables the protein that triggers cell cycle progression, CDC25.

"The key to our research result was coming up with the possibility that unusually large amounts of histone H3 may feed into the stop enzyme," said Yuki Shindo a postdoctoral research fellow at Dartmouth and first author of the paper. "Once we noticed that, we were able to test this idea in our living test tube, fruit fly eggs."

The new research builds on earlier studies which found that a biological constant exists between the size of a genome and the size of a cell. Researchers knew that once a balance point was achieved, cells would stop duplicating, but didn't understand how cells could determine the ratio.

To find the answer to the long-running question, the research team studied fruit fly eggs. Because of their large size compared to other cells, the team was able to get a different perspective on the cell cycle.

"We've had all of the pieces for years but couldn't quite get them to fit together," said Amodeo. "Once we recognized that H3 interacts directly with both DNA and Chk1, the work went very fast. Everything worked the first time, which is a good sign that the hypothesis is right."

Since the same molecules that control cell division--histone H3, CDC25 and Chk1--are all identified in cancer and other ailments, the finding can help researchers that are seeking answers to questions related to development and disease.

"We were originally curious about a basic biological question on how cells in a growing egg make a decision to stop at the correct timing," said Shindo. "We are now excited that our findings may also have an important implication for a broader context such as disease."

A new study based on daily COVID-19 data from Brazil details the fast spread of both cases and deaths in the country, with distinct patterns by state, and where inequities regarding the implementation of policies and resources exacerbated the spread in lower-income regions. Despite an extensive network of primary care availability, Brazil - which did not pursue a coordinated national pandemic response strategy - has suffered greatly during the COVID-19 pandemic. "[T]he federal response has been a dangerous combination of inaction and wrongdoing," write Marcia Castro and colleagues. Using daily data from State Health Offices, Castro et al. comprehensively analyzed the spatial and temporal patterns of COVID-19 cases and deaths in Brazil from February to October 2020. Reflecting problems in surveillance, data reporting, and low testing capacity, deaths clustered about a month before cases were reported, the data show. Patterns suggest undetected (and thus unmitigated) introduction and propagation of the virus for some time. After the virus's introduction in São Paulo, both cases and deaths progressively moved north until week 20 (starting May 10), when the epidemic started to recede in Amazonas and Ceará but gained force in Rio de Janeiro and São Paulo. In Rio de Janeiro, political chaos, among other factors, compromised a prompt and effective response, and cases and deaths were high. Overall, a higher percentage of COVID-19 cases and deaths were observed outside capital cities. Further analyses by Castro and colleagues revealed how policies adopted at the national and local levels impacted movement of COVID-19 toward the interior states. The authors highlight several complex issues unique to Brazil that drove the virus's fast spread but also show that some states, such as Ceará, were resilient; others such as Rio de Janeiro that comparatively had more resources failed to contain the propagation of COVID-19. They conclude by noting Brazil's current perilous state, as a new virus variant of concern (P.1) is circulating. "Without immediate containment, coordinated epidemiological and genomic surveillance measures, and an effort to vaccinate the largest number of people in the shortest possible time, the propagation of [the new variant]" will likely resemble the patterns here demonstrated, leading to unimaginable loss of lives," they say.

A new report tracks the evolution of a variant lineage of SARS-CoV-2 associated with rapid transmission in Manaus, Brazil, that evolved in November 2020. The study's authors suggest this variant, "P.1," may be more transmissible and more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Manaus, Brazil, reached unprecedented levels of SARS-CoV-2 transmission in mid-2020. And after a momentary respite, cases surged with fatal consequences. Using molecular clock analysis, Nuno Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which possesses 17 mutations, including three (K417T, E484K and N501Y) in the spike protein. Following a period of accelerated evolution, this variant emerged in November 2020. It is more transmissible and more lethal than its predecessor and more likely to evade immunity, the authors say. Enhanced global genomic surveillance of such variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness, the authors say.

We refer to the microbiome as the community of microorganisms that exist in or on all organisms, including bacteria and fungi. A team from the Institute of Environmental Biotechnology at Graz University of Technology (TU Graz) led by Institute head Gabriele Berg has now investigated the microbiomes of apples and oil pumpkins in two independent studies. The researchers have found that bacteria useful to plants are largely "inherited," i.e., passed on to the next generation, while the community of fungi in the microbiome is highly dependent on the particular soil microbiome and thus on the locality.

Microbiome-guided breeding of oil pumpkins

The breeding of the Styrian oil pumpkin is relatively recent - it started about 150 years ago and is well documented. Through selective breeding of resistant, increasingly tasty and high-yielding pumpkins, the seed microbiome of the oil pumpkin has changed over the generations. Using a well-documented breeding line, the environmental biotechnologists at TU Graz were able to demonstrate for the first time that the microorganisms on the seeds of the pumpkin are inherited and probably crucial for certain plant traits. Peter Kusstatscher, one of the study authors, explains: "We studied bacteria and fungi on oil pumpkin seeds and found that the plant passes on much of its bacteria on the seed - up to 60 percent, in fact - to the next generation, while fungal diversity on the seed depends largely on the local soil microbiome." Kusstatscher continues, "It's mainly microorganisms that are useful for the plants that are inherited. In this respect, the plant behaves in a similar way to humans: babies also get their microbiome from their mothers."

The results published in Frontiers in Plant Science pave the way towards a microbiome-controlled breeding of oil pumpkins. Selective breeding of a beneficial seed microbiome results in plant traits that have a positive impact on yield, health and storability of oil pumpkins.

On the tracks of the universal apple microbiome

Apples are among the most popular and widely consumed fruits in the world. Fruit quality, yield, and storability are important factors for fruit growers, fruit trade, and consumers. In a worldwide study, the apple of the variety "Royal Gala" was examined for the first time with regard to the composition and possible local differences of its microbiome. An international team was able to show that the nature and structure of the fungal and bacterial communities of the apple at the time of harvest vary from region to region, i.e. they are strongly dependent on the geographical location and thus on the prevailing climatic conditions and management practices. In particular, the fungal diversity of the fruit is significantly dependent on the locality and suggests a relationship to the type and frequency of post-harvest diseases. On the other hand, a continental pattern can be drawn especially for the bacterial community which indicates adaptation of the apple microbiome to local environments.

Ahmed Abdelfattah, Marie Curie post-doctoral fellow at the Institute of Environmental Biotechnology at TU Graz and lead author of the study explains: "Despite the variations we observed in the apple microbiome, we were still able to identify a so-called 'core' microbiome i.e. members of the microbiome that are shared globally among the apples. This global 'core' microbiome is represented by several beneficial microbial indicators and makes up a large portion of the fruit's microbial community."

Similar to the study results on oil pumpkin, this study lays another foundation for new approaches to improving fruit quality and health, in this case of apples. Furthermore, the results form the basis for investigations of complex microbial interactions on the surface of apple fruits. The study results were published in Environmental Microbiology.

Both studies highlight the importance of the microbiome for health issues from the crop in the agro-ecosystem to humans who consume the food. At the same time, new avenues for microbiome management are opening up for environmentally friendly pest control.

A recent study has unveiled the reason behind the exceptional catalytic performance of non-noble metal-base mixed catalysts. This is thanks to a new synthetic strategy for the production of cube-shaped catalysts that could further simplify the structure of complex catalysts.

This breakthrough has been led by Professor Kwangjin An and his research team in the School of Energy and Chemical Engineering at UNIST, in collaboration with Professor Taeghwan Hyeon and his research team from Seoul National University. In their study, the researchers found a new principle that active charge transfer, which appears at the interface created between the two types of non-noble metals, could enhance the catalytic performance of complex oxide catalysts. The research team expects that their findings could contribute to the development of catalysts that could convert methane efficiently to fuels and high value-added chemicals.

The interface created between an active metal and oxide support has been known to affect the catalytic performance due to the charge transfer process. However, owing to their complex interface structures and synthetic challenges, oxide-oxide interfaces produced by supported spinel oxide catalysts have been less studied.

In this work, the research team proposed a synthetic strategy for heterostructured spinel oxide (Co3O4, Mn3O4, and Fe3O4) nanocubes (NCs) with a controlled CeO2 layer that enabled investigation of the role of the interface in catalytic oxidation of CO and H2. They developed a selective deposition process to produce CeO2-deposited spinel NCs with 1, 3, and 6 facets of CeO2 (MCe-1F, MCe-3F, and MCe-6F NCs for spinel oxide).

According to the research team, CeO2-deposited Co3O4 NCs exhibited a 12-times higher CO oxidation rate than the pristine Co3O4 NCs. Furthermore, various in situ characterization techniques, revealed that the deposited CeO2 prevents the reduction of Co3O4 by supplying oxygen. They also found that the maximized interface resulting from Co3O4 NCs with three facets covered by CeO2 layers exhibit the highest CO oxidation rate even under O2-deficient conditions, which resulted from the versatile variation in the oxidation state.

"This study provides a comprehensive understanding of the Mars-van Krevelen (MvK) mechanism, occurring on the nanoscale at the Co3O4-CeO2 interfaces," noted the research team. "The same activity trend and hot electron flow are observed for H2 oxidation reactions using catalytic nanodiodes, thereby demonstrating that the origin of the activity enhancement is charge transfer at the interface."

Intestinal worm infections can leave women in sub-Saharan Africa more vulnerable to sexually-transmitted viral infections, a new study reveals.

The rate and severity of sexually-transmitted viral infections (STI) in the region are very high, as are those of worm infections, which when caught in the intestine can change immunity in other parts of the body.

Researchers at the Universities of Birmingham and Cape Town led an international team which discovered that intestinal worm infection can change vaginal immunity and increase the likelihood of Herpes simplex virus type 2 (HSV-2) infection - the main cause of genital herpes.

Publishing their findings today in Cell Host and Microbe, the research team also notes that worm infections significantly increase the death of tissue in the vagina (necrosis), which can result in gangrene.

However, the researchers found that they could prevent this worm-induced changes in HSV2 pathology by targeting a particular type of immune cell called eosinophils - suggesting that this pathology could be prevented or reduced by using existing drugs.

Co-author Dr. William Horsnell, from the Institute of Microbiology & Infection at the University of Birmingham and Institute of Infectious Disease and Molecular Medicine, University of Cape town commented: "Our work identifies for the first time how a worm infection can influence a very important viral STI. This is important for health workers and may help them to explain why STIs are more virulent in areas where worm infections are common.

"We show that worm infections that never colonise the vagina cause a strong change in vaginal immunity. Following a viral vaginal sexually transmitted infection the pathology caused by the virus is hugely increased. Research into STIs has, until now, largely neglected the role of worm infections in influencing the severity of these important diseases."

Rates and severity of sexually transmitted viral infections in sub-Saharan Africa are very high and are one of the world's leading causes of pathological disease. Worm infection rates are also very high in this region, but do not colonise the female reproductive tract.

"Our research shows that eosinophils can have a very important role to play in vaginal immunity - we hope that this discovery will boost efforts to understand how parasitic worm infection indirectly influence control of sexually transmitted infections," added Dr Horsnell.

The research was funded by DFG, Poliomyelitis Research Foundation, Marie Curie and National Research Foundation (South Africa). The research team is currently studying in West Africa (Togo) and South Africa how existing and past worm infections associate with risk of women having an STI.

Non-alcoholic fatty liver, NAFLD, is associated with several health risks. According to a new registry study led by researchers at Karolinska Institutet in Sweden, NAFLD is linked to a 17-fold increased risk of liver cancer. The findings, published in Hepatology, underscore the need for improved follow-up of NAFLD patients with the goal of reducing the risk of cancer.

"In this study with detailed liver histology data, we were able to quantify the increased risk of cancer associated with NAFLD, particularly hepatocellular carcinoma," says first author, Tracey G. Simon, researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and hepatologist at Massachusetts General Hospital and Harvard Medical School. "We also found that all stages of NAFLD were associated with excess cancer risk, even early stages of the disease."

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Europe and the United States, affecting more than 100 million adults. A large proportion of patients progress to nonalcoholic steatohepatitis (NASH) with fibrosis, which in turn can lead to cirrhosis.

There is relatively little research on cancer development with NAFLD, and prior research has some limitations that make it difficult to draw far-reaching conclusions. Hence, there is a need for more information on links between cancer risk and NAFLD, and for improved monitoring strategies for high-risk patients with NAFLD.

In this study, researchers at Karolinska Institutet, in collaboration with researchers at Harvard University and Columbia University, examined the risk of cancer in people with NAFLD. The registry study included 8,892 Swedish patients with biopsy-confirmed NAFLD and 39,907 healthy controls.

Data on cancer were retrieved through the nationwide Swedish Cancer Register. Patients with NAFLD were identified through the ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden) cohort.

Individuals with NAFLD were at a 27 percent increased risk of any cancer. This risk was to a large extent driven by the 17-fold increased risk of hepatocellular carcinoma (HCC). Furthermore, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma, but no other cancers.

"These findings should be used to develop more targeted interventions designed to reduce cancer risk in patients with NAFLD," says corresponding author Jonas F. Ludvigsson, pediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. "They also highlight the need for more personalized strategies to screen for HCC in certain high-risk patients, such as those with NAFLD fibrosis and type 2 diabetes."

An outbreak of vomiting among dogs has been traced back to a type of animal coronavirus by researchers.

Vets across the country began reporting cases of acute onset prolific vomiting in 2019/20.

The Small Animal Veterinary Surveillance Network (SAVSNet) at the University of Liverpool asked vets for help in collecting data, with 1,258 case questionnaires from vets and owners plus 95 clinical samples from 71 animals.

Based on this data, a team from the universities of Liverpool, Lancaster, Manchester and Bristol identified the outbreak as most likely to be a variant of canine enteric coronavirus (CeCoV).

Canine coronavirus only affects dogs and is not the same as Sars Cov2 which causes Covid in humans. Researchers found no evidence of any similar illness in people.

The work is published in Emerging Infectious Diseases.

The team are working on a project funded by the Dogs Trust called SAVSNet-Agile which aims to develop a national surveillance system for canine health.

Dr Barry Rowlingson from Lancaster University said: "We've developed complex statistical models to look for disease outbreaks. Being able to rapidly detect increased incidence, without triggering a false alarm from a natural random variation, is the key problem here. Early detection is crucial to early treatment and enhanced monitoring.

"The SAVSNet Agile project aims to feed information back to local veterinary practices so they can be alert to any new outbreaks."

Vets began to suspect an infectious cause because vomiting was more frequent than is typical for canine gastroenteritis.

SAVSNet researchers found a specific and significant increase in the number of dogs recorded as exhibiting gastroenteric signs between late December 2019 and March 2020.

As well as reusing health records, SAVSNet also collected questionnaire data from vets and owners caring for affected animals, as well as healthy controls. This showed male dogs were more at risk than females.

Charlotte Appleton, SAVSNet Agile PhD Student, said: "Obtaining such important results at an early stage of my PhD is a wonderful achievement and will hopefully provide a pathway of higher visibility into the health of domestic animals."

Researchers from Tokyo Medical and Dental University (TMDU) use genetic engineering in mice to further understand how cell fate is determined in the head

Tokyo, Japan - Mammalian embryonic development is an extremely complex and precise process. Specific molecular events act as cues that tell cells in the embryo where to move and what type to mature into. The expression levels of different genes in these cells can change at certain points of development, helping produce the signals that further the progression. Now, researchers at Tokyo Medical and Dental University (TMDU) have used experiments with mice to show how a particular gene helps direct generation of tissues in the head.

In an article published in Scientific Reports, a group of researchers from TMDU determined that expression of a gene called Distal-less homeobox 5 (Dlx5) assists certain cells in the mouse head mature into cartilage cells, while others become bone cells. This is critical for proper cranial formation.

Neural crest cells (NCCs) have been a recent focus of developmental biology research because they can transition into many cell types including neurons, and those in the head region additionally differentiate into bone and cartilage. NCCs form an initial layer that constructs dermis and the meninges in early stages of development, then another group of NCCs present at the supraorbital region becomes bone forming cells and the cell domain expands apically as the overlying layer to form the calvarium to protect the brain. From these previous observations, the TMDU group became interested in how experimentally increasing Dlx5 expression would affect NCC differentiation.

"We worked with a mouse model to further understand how over-expressed Dlx5 affects cranial development," says lead author of the study Tri Vu Hoang. "We used a method where we could force higher expression levels of Dlx5 in NCCs in a group of mice, then compared their head development with mice not genetically engineered in this way."

The researchers first confirmed that Dlx5 was being expressed in NCCs in the engineered moue as they expected before examining cranial bone and cartilage formation in the two groups of mice. They observed enhanced layers of both bone and cartilage in the mice with higher NCC Dlx5 expression compared with the controls.

"We saw an interesting response with Dlx5 overexpression in the NCCs," describes Sachiko Iseki, senior author. "NCCs intrinsically forming soft tissues of the initial layer transform into bone and cartilage in the vertex of the Dlx5-engineered mice."

The group also examined expression of several bone and cartilage growth-promoting genes in the regions where new cartilage and bone were formed. They observed upregulation of multiple major genes for bone and cartilage formation including β-catenin and Pdgfrα, bone genes were expressed in the region close to the skin and cartilage genes near the brain in the Dlx5-engineered mice that was not seen in the control animals. The observation shows that the initial soft tissue layer transform into the two different layers around the time of bone and cartilage formation.

"Our results shed light on early development of the head layer of NCCs in the mouse vertex; there two cell layers exhibiting differentiating potential for bone and cartilage." says Vu Hoang. "Overexpression of Dlx5 in NCCs is an artificial situation in embryonic development, but it showed us an interesting phenomenon to discuss uncovered developmental mechanisms in the vertex of the head."

This study provides fascinating data that will help move the developmental biology field forward. The researchers have successfully helped reveal the complicated mechanisms involved with cranial development.

Chronic inflammation is increasingly a focus of research. A recent study has now identified differences in indicators of inflammation between novel diabetes subgroups. But what does this mean for the future?

Symptoms that increase with age, such as cardiovascular disease, kidney damage or dementia, are common consequences of type 2 diabetes. In addition to metabolic disorders, chronic inflammatory reactions are important causes. The inflammatory cytokines typical for this can have numerous effects on various organs. One of the consequences of this is that the organs no longer respond adequately to insulin.

A new analysis of the German Diabetes Study (GDS) from the German Diabetes Centre (DDZ) investigated the differences between individual diabetes subgroups in the biomarkers of inflammation. Biomarkers are indicators that occur in the blood or in tissue and other parts of the body and are typical for certain changes in the body such as inflammation. In the current study, 74 biomarkers covering a broad spectrum of inflammatory processes were measured in over 400 test persons. The result: the novel diabetes subgroups show a number of specific differences that could allow a better determination of the risk for diabetes-related complications.

The German Diabetes Study (GDS) previously made it possible to identify five subgroups (clusters) of diabetes with different courses: severe autoimmune diabetes (SAID), severe insulin deficient diabetes (SIDD), severe insulin resistant diabetes (SIRD), moderate obesity-related diabetes (MOD) and moderate age-related diabetes (MARD). The current study shows that these subgroups differ not only in terms of age and metabolic characteristics, but also in terms of biomarkers of inflammation. Given the critical role of inflammatory processes in diabetes-related complications, these differences may also be related to the severity of clinical courses of diabetes. "It is interesting that this study of people with newly diagnosed diabetes reveals early disorders and can thus contribute to the early detection of diabetes consequences," said Professor Michael Roden, scientific director and board member of the DDZ. "As a result, these findings could enable early therapy in individual diabetes subgroups."

The highest biomarker blood levels were observed in the diabetes subgroup SIRD, which is characterized by pronounced insulin resistance. This underlines the importance of overweight/obesity, which is particularly related to inflammation and insulin resistance. On the other hand, the SIDD subgroup, which is mainly characterized by insulin deficiency, had the lowest biomarker levels. "This correlation between high levels of inflammatory markers and pronounced insulin resistance indicates a particular contribution of inflammatory processes in the SIRD subgroup," said Dr. Christian Herder, who heads the Inflammation working group at the DDZ. "It will take a few more years before we can derive a specific recommendation for diabetes therapy from these findings, but the results are extremely relevant for diabetes complications and their understanding. Future studies are needed to investigate to what extent differences in the profiles of inflammation-related biomarkers can explain the differences between the diabetes subgroups in terms of their risk of developing diabetes-related complications."

Researchers have developed a new superbug-destroying coating that could be used on wound dressings and implants to prevent and treat potentially deadly bacterial and fungal infections.

The material is one of the thinnest antimicrobial coatings developed to date and is effective against a broad range of drug-resistant bacteria and fungal cells, while leaving human cells unharmed.

Antibiotic resistance is a major global health threat, causing at least 700,000 deaths a year. Without the development of new antibacterial therapies, the death toll could rise to 10 million people a year by 2050, equating to $US100 trillion in health care costs.

While the health burden of fungal infections is less recognised, globally they kill about 1.5 million people each year and the death toll is growing. An emerging threat to hospitalised COVID-19 patients for example is the common fungus, Aspergillus, which can cause deadly secondary infections.

The new coating from a team led by RMIT University in Melbourne, Australia, is based on an ultra-thin 2D material that until now has mainly been of interest for next-generation electronics.

Studies on black phosphorus (BP) have indicated it has some antibacterial and antifungal properties, but the material has never been methodically examined for potential clinical use.

The new research, published in the American Chemical Society's journal Applied Materials & Interfaces, reveals that BP is effective at killing microbes when spread in nanothin layers on surfaces like titanium and cotton, used to make implants and wound dressings.

Co-lead researcher Dr Aaron Elbourne said finding one material that could prevent both bacterial and fungal infections was a significant advance.

"These pathogens are responsible for massive health burdens and as drug-resistance continues to grow, our ability to treat these infections becomes increasingly difficult," Elbourne, a Postdoctoral Fellow in the School of Science at RMIT, said.

"We need smart new weapons for the war on superbugs, which don't contribute to the problem of antimicrobial resistance.

"Our nanothin coating is a dual bug killer that works by tearing bacteria and fungal cells apart, something microbes will struggle to adapt to. It would take millions of years to naturally evolve new defences to such a lethal physical attack.

"While we need further research to be able to apply this technology in clinical settings, it's an exciting new direction in the search for more effective ways to tackle this serious health challenge."

Co-lead researcher Associate Professor Sumeet Walia, from RMIT's School of Engineering, has previously led groundbreaking studies using BP for artificial intelligence technology and brain-mimicking electronics.

"BP breaks down in the presence of oxygen, which is normally a huge problem for electronics and something we had to overcome with painstaking precision engineering to develop our technologies," Walia said.

"But it turns out materials that degrade easily with oxygen can be ideal for killing microbes - it's exactly what the scientists working on antimicrobial technologies were looking for.

"So our problem was their solution."

How the nanothin bug killer works

As BP breaks down, it oxidises the surface of bacteria and fungal cells. This process, known as cellular oxidisation, ultimately works to rip them apart.

In the new study, first author and PhD researcher Zo Shaw tested the effectiveness of nanothin layers of BP against five common bacteria strains, including E. coli and drug-resistant MRSA, as well as five types of fungus, including Candida auris.

In just two hours, up to 99% of bacterial and fungal cells were destroyed.

Importantly, the BP also began to self-degrade in that time and was entirely disintegrated within 24 hours - an important feature that shows the material would not accumulate in the body.

The laboratory study identified the optimum levels of BP that have a deadly antimicrobial effect while leaving human cells healthy and whole.

The researchers have now begun experimenting with different formulations to test the efficacy on a range of medically-relevant surfaces.

The team is keen to collaborate with potential industry partners to further develop the technology, for which a provisional patent application has been filed.

A new state-by-state analysis shows a statistical association between high adherence to mask wearing and reduced rates of COVID-19 in the U.S. Charlie Fischer and colleagues at the Boston University School of Public Health in Massachusetts present these findings in the open-access journal PLOS ONE on April 14.

During the COVID-19 pandemic, different states have enacted different policies on mask wearing, with some states having no mask requirements and others requiring masks in all public spaces. Understanding the link between mask wearing and COVID-19 rates could help inform policies to mitigate stress on healthcare systems, economic instability, and death.

To help clarify the effects of mask wearing, Fischer and colleagues examined publicly available data on mask-wearing policies, people's self-reported habits on mask wearing in public, and COVID-19 rates for all 50 U.S. states and Washington, D.C. They accounted for a one-month delay between mask wearing and its subsequent potential impact on COVID-19 rates from May through October 2020. For this analysis, they considered rates of more than 200 cases per 100,000 residents to be high.

The analysis showed that, out of 15 states that did not require people to wear masks in public, 14 had high COVID-19 rates. Meanwhile, eight states had self-reported adherence rates of 75 percent of greater, and none of these states had a high COVID-19 rate. States with the lowest adherence rates had the greatest likelihood of high COVID-19 rates in the subsequent month.

The eight states with at least 75-percent adherence to mask wearing had a mean COVID-19 rate of 109.26 per 100,000 residents in the subsequent month, while the mean COVID-19 rate was 239.99 for states with less than 75 percent adherence.

These findings provide new evidence in support of mask-wearing as a major factor that contributes to reduced COVID-19 rates. They suggest that policies and public health efforts to reduce the spread of COVID-19 should include a focus on improved mask adherence throughout the U.S.

- Study finds for the first time, in Africa, that mutations are associated with delayed clearance of the parasite among children with malaria treated with common Artemisinin-based combination therapies (ACTs).

- While drug efficacy remains high so far, authors call for increased monitoring in the region.

New data provide the first clinical evidence that drug-resistant mutations in the malaria parasite Plasmodium falciparum may be gaining a foothold in Africa. The study, conducted in Rwanda, is published in The Lancet Infectious Diseases journal and finds for the first time that the mutations are associated with delayed parasite clearance, as was first shown in South-East Asia when artemisinin-resistance started to emerge.

The study also finds that the mutations are more prevalent than previous studies have reported, indicating likely transmission of the mutations, and raising concern about further geographical spread of resistance.

There are an estimated 229 million cases of malaria worldwide, and there were 409,000 deaths from malaria in 2019 - of which 274,000 (67%) were among children under 5 years. 94% of all malaria cases and deaths occur in Africa [1], and experts have long been concerned about the potential emergence of drug resistance across the continent. While the efficacy of current therapies remains high, the authors call for more intensive surveillance in Rwanda as well as neighbouring countries to help monitor the spread of mutations and inform public health actions.

"Mutations can emerge spontaneously, and previous studies have pointed to isolated cases of resistance. However, our new study shows that resistant isolates are starting to become more common and most importantly, are associated with clinical implications (delayed parasite clearance)," says lead author Dr Aline Uwimana, Rwanda Biomedical Centre, Kigali, Rwanda [2]

Co-author Dr Naomi Lucchi, CDC Resident Advisor for the U.S. President's Malaria Initiative adds: "our study showed that the treatment for malaria in Rwanda is still 94% effective, but new studies and ongoing monitoring are urgently needed." [2]

Artemisinin-based combination therapies (ACTs), introduced in the early 2000s, are currently the most effective and widely used treatments for malaria caused by Plasmodium falciparum. ACTs combine an artemisinin component that clears most of the parasites from the patient's body within three days, and a long-acting partner drug that clears the remaining parasites.

Resistance to the artemisinin component of an ACT is suspected if the presence of the parasite remains after day three of treatment (called delayed parasite clearance). This drug resistance is associated with parasites carrying mutations in the Plasmodium falciparum kelch 13 gene (pfk13). Currently, ten mutations in pfk13 have been confirmed as markers of artemisinin partial resistance (including R561H, P574L and C580Y), and several other mutations (referred to as candidate markers) have been identified as potentially associated with resistance.

Partial artemisinin resistance was first identified in Cambodia in 2008. It is now well-documented in many South East Asian countries, where the C580Y mutation is common. Evidence from the Mekong region has shown that once artemisinin resistance becomes prevalent, resistance to the partner drug often follows, resulting in ACT treatment failure.

In 2006, Rwanda introduced artemether-lumefantrine (an ACT, and the most widely used antimalarial) as the first-line treatment for malaria. The World Health Organization recommends therapeutic efficacy studies at least every two years for monitoring the efficacy of ACTs and the tracking of resistance through molecular markers. When ACT efficacy is confirmed to be below 90%, replacement with an effective antimalarial is recommended.

One such study was performed in Rwanda among children aged 1-14 years in 2013-2015 in Ruhuha and Masaka. The R561H mutation was observed in 7.4% of P. falciparum parasites collected in Masaka, and a low prevalence of the P574L mutation was reported in isolates collected in Masaka and Ruhuha in 2013-2015 and in Huye in 2015. However, the presence of these mutations was not found to be associated with delayed parasite clearance and the therapeutic efficacy of ACT was confirmed at over 97% in both sites.

In 2018, another therapeutic efficacy study was conducted, the results of which are reported in this new article. The pfk13 R561H and P574L mutations were present in 12.8% (28/218) and 0.9% (2/218) of pre-treatment samples, respectively. For the first time, this study shows that the pfk13 R561H mutation was associated with delayed parasite clearance, although the efficacy of artemether-lumefantrine remained high. Genetic analysis of pfk13 R561H mutants indicated their common ancestry and local origin in Rwanda.

The study was conducted across three sites in Rwanda (Masaka, Rukara, and Bugarama). 224 children aged between 6 months and 5 years who had a P. falciparum infection were treated with a three-day course of artemether-lumefantrine and monitored for 28 days, with weekly blood collections. 8/51 (15.7%) participants in Masaka and 12/82 (14.6%) in Rukara had detectable parasites three days post treatment, according to WHO criteria for partial resistance. The therapeutic efficacy was estimated at 94-97%.

Writing in a linked Comment, Professor Philip Rosenthal, University of California, San Francisco, USA (who was not involved in the study), says: "Recent data suggest that we are on the verge of clinically meaningful artemisinin resistance in Africa, as emerged in Southeast Asia over a decade ago. With resistant genotypes emerging and continued heavy drug pressure, we may anticipate continued selection of resistance. Loss of artemisinin activity will in turn threaten ACT partner drugs. Loss of efficacy of key ACTs, in particular artemether-lumefantrine, the most widely used antimalarial, may have dire consequences, as occurred when chloroquine resistance led to enormous increases in malaria deaths in the late twentieth century. Although it is impossible to predict the pace of progression of drug resistance in Africa, close surveillance for genotypic and phenotypic evidence of artemisinin and partner drug resistance, with prompt replacement of failing regimens, may save many lives."

INDIANAPOLIS, IN AND BERKELEY, CA (April 14, 2021) - Researchers from Indiana University School of Medicine and OMGYES have conducted the first-ever, large-scale, nationally representative study focused on women's techniques for increasing their own pleasure from vaginal penetration. The findings, published today in the scientific journal, PLOS ONE, identify and name four distinct methods: Angling, Pairing, Rocking and Shallowing.

The research was led by Dr. Devon J. Hensel, Associate Professor of Research at Indiana University School of Medicine, and Dr. Christiana von Hippel, an OMGYES Research Scientist.

"For the first time, we have detailed scientific data to understand the different ways that women experience more pleasure with vaginal penetration. This information can help us build a vocabulary to describe female pleasure that currently doesn't exist," explains Dr. Hensel.

"When something doesn't even have a name, it's made literally unspeakable," said Dr. von Hippel. "Until now, there haven't been words for the specific ways women improve their pleasure. By giving these prevalent techniques names and showing how they can be effective, we hope women will be empowered to explore what they like and advocate for what they want, in and outside of the bedroom."

To begin, the researchers gathered discoveries and insights from a community of 4,270 women from around the world and analyzed the results to find themes and underlying patterns. These qualitative findings then informed the quantitative, cross-sectional, nationally representative survey fielded online with 3,017 American women, ages 18-93.

The findings, described in depth in the paper and highlighted below, reveal four distinct ways women have discovered to experience more pleasure during vaginal penetration:

Rocking - 76.4% of women make penetration more pleasurable by 'rocking' the base of a penis or sex toy so it rubs against the clitoris constantly during penetration, staying all the way inside the vagina rather than thrusting in and out.

Angling - 87.5% of women experience more pleasure during penetration by 'angling' which involves rotating, raising, or lowering the pelvis/hips during penetration to adjust where inside the vagina the toy or penis rubs, and what it feels like.

Pairing - 69.7% of women find penetration more pleasurable when 'pairing' where a woman herself (solo pairing) or her partner (partner pairing) reaches down to stimulate the clitoris with a finger or sex toy at the same time as the vagina is being penetrated.

Shallowing - 83.8% of women orgasm more often or increase their pleasure through 'shallowing,' penetrative touch just inside the entrance of the vagina with a fingertip, sex toy, penis tip, tongue or lips.

Costing anywhere from 15 to 70 dollars per mushroom depending on the quality, matsutake mushrooms are some of the most valuable edible fungi in the world. Revered for their delicate scent, matsutake mushrooms are cooked in rice or soups as an Autumn celebration delicacy in Japan. However, there is no way to cultivate matsutake mushrooms and naturally occurring habitats are decreasing with fewer forests conducive to their growth with the changing climate.

Corresponding author Professor Akiyoshi Yamada of Shinshu University's Department of Agriculture, Department of Bioscience and Biotechnology, and Institute for Mountain Science with 9 other researchers set out to present concrete evidence that matsutake spores germinate, reach the roots of the host, and coexist to produce offspring that starts a new symbiosis.

When matsutake spores germinate, mycelia in the soil corresponding to their parents induce germination and form a genetically diverse population on the root system of the host. It is therefore hypothesized that the next generation can be created while maintaining a diverse pool.

With this novel experiment, matsutake mushrooms and Japanese red pine were cultured in a vessel, and spores collected from the fruiting bodies of matsutake mushrooms collected outdoors were inoculated to germinate in order to successfully establish a new hypha in the roots of Japanese red pine.

The researchers were successful in germinating the spore of matsutake by proving that artificially controlling the phenomenon of generational change of matsutake mushrooms in the natural world. They hope to establish an artificial cultivation technique for matsutake mushrooms in the forest.

Since this study introduces fresh matsutake spores into the experimental system, it is difficult to carry out this study unless there is a supply of matsutake nearby. In other words, it can be said that this research finding best utilized the location of the Faculty of Agriculture, Shinshu University to germinate the spore of matsutake, the most valuable wild edible mushrooms in the world.