Culture

The genetic variability of immunity lies particularly in the genes of the HLA (Human Leukocyte Antigen) system. These genes produce HLA molecules that are positioned on the surface of cells. When a virus infects an organism, the invader's proteins are first cut into small fragments called peptides. The HLA molecules then bind on to these fragments and expose them to the surface of the cells, thereby triggering a cascade of immunity reactions designed to eliminate the virus.

Alicia Sanchez-Mazas, a professor at the Anthropology Unit in UNIGE's Faculty of Sciences, explains: "From the 450 or so most common HLA molecules in hundreds of populations worldwide, we tried to identify the ones that are most strongly bound to the peptides of the new coronavirus." Over 7,000 peptides can be derived from all of the viral proteins of the coronavirus.

The Geneva-based researcher and her international team used bioinformatic tools to perform the analysis. These can predict the binding affinities between the HLA molecules and the viral peptides on the basis of their physical and chemical properties. The scientists then turned to statistical models to compare the frequencies of these HLA variants in different human populations.

Classification of HLA molecules

The study classified the approximately 450 HLA molecules according to their relative capacity to bind the coronavirus peptides. It provides an essential reference inventory for identifying the genetic resistance or susceptibility of individuals to the virus. The study has also shown that the frequencies of these HLA variants differ significantly from one population to the next.

José Manuel Nunes, a researcher at the Anthropology Unit - and co-author of the article - further explains: "We were surprised to find that Indigenous populations in America had both the highest frequencies of HLA variants that bind the most strongly to the peptides and the lowest frequencies of those that bind the least strongly." However, as José Manuel Nunes continues, we should not draw too hasty a conclusion from these results: "HLA molecules contribute to the immune response but they are far from being the only element that can be used to predict effective or ineffective resistance to a virus. This is also verified on the ground since America's Indigenous populations are apparently no less affected than others by COVID-19."

"Generalist" molecules

In the same study, the authors also analysed the HLA-peptide bindings for all of the proteins of the six other viruses with pandemic potential (two other coronaviruses, three influenza viruses and the HIV-1 virus of AIDS). This showed that many HLA variants are capable of binding strongly to the peptides of all seven viruses studied. Others do the same for all respiratory-type viruses (coronavirus and influenza). This means that there are numerous "generalist" HLA molecules that are effective against a number of different viruses.

"The differences between populations observed in this study are actually differences in the frequencies of the generalist HLA variants that do not bind specifically to the coronavirus but also to other pathogens", points out professor Sanchez-Mazas. "This is what makes us think that the current differences between populations are the result of past adaptations to different pathogenic pressures, which is extremely informative for understanding the genetic evolution of our species."

A logical follow-up to the study will be to determine precisely which coronavirus peptides are most strongly bound to the HLA molecules. It is these peptides that will have the highest chances of triggering an effective immune reaction. Identifying them will be vital for developing a vaccine.

Known as the French paradox, a low incidence of coronary heart disease despite substantial intake of saturated fats is thought to be due to a diet rich in polyphenols. Polyphenols are abundant in plant based foods such as fruits and vegetables. Procyanidins are polyphenols with antioxidant, anti-obesity and anti-inflammatory properties. In this study, PCB2DG, (procyanidin B2 3,3"-di-O-gallate) was examined to see how it inhibits the cytokine production in T cells. Specifically, to understand the mechanism underlying the regulation of tumor necrosis factor (TNF)- α.

The Tanaka Food Immunology Laboratory at Shinshu University has long studied the polyphenol PCB2 and its immunoregulatory function. PCB2DG is a dimer of epicatechin, and is structurally different from other polyphenols which makes it an interesting subject of study. Polyphenols have properties that decrease inflammation and have anti-oxidation properties. Autoimmune diseases such as colitis and rheumatoid arthritis are said to be alleviated by decreasing TNF-α production and signaling because TNF-α is a protein that causes inflammation in the body.

Immune functions and energy metabolism are closely related. Abnormality found in the energy metabolism of immune cells are known to be related to the onset of immune diseases. This is why research continues into the cell metabolism targeted immune suppressant drugs. Polyphenols have been known to have immunosuppressant activities but their cell metabolism was not known. This study succeeded in showing for the first time that PCB2DG, a type of polyphenol supresses cytokine production by inhibiting glycolysis and the mTOR/HIF-1 pathway. Glycolysis is the process of breaking glucose down for the body to use as fuel.

The T helper (Th) cells, also referred to as CD4+ T cells, play a central role in modulating immune responses, and are differentiated into subsets; Th1, Th2, Th17, and regulatory T cells (Treg). The Th1 cells produce TNF-α and interferon (IFN)-γ. Activated Th1 cells cause a metabolic shift toward glycolysis, which is largely regulated by the mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1 (HIF-1) signaling.

Procyanidin B2 (PCB2) gallate; specifically, PCB2 3,3''-di-O-gallate (PCB2DG), inhibits cytokine production in T cells. However, the molecular interactions and partners of PCB2DG underlying this suppression of cytokine production are unclear. The present study aimed to elucidate mechanisms underlying regulation of TNF-α production by PCB2DG. To elucidate the mechanism by which PCB2DG suppresses cytokine production, two points are set as problems: (1) whether PCB2DG acts directly on T cells or (2) whether cytokine production is suppressed by inhibiting glycolysis of T cells. The group hypothesized that the specific inhibitory effect of PCB2DG on cytokine production was due to inhibition of T cell glycolysis and mTOR/HIF-1 pathway. As they proceeded with the verification of this hypothesis, they were able to confirm the decreased expression of mTOR/HIF-1 pathway-related protein by Western blotting analysis.

Dr. Tanaka's group found that production of TNF-α and glycolytic activity in activated CD4+ T cells were suppressed by PCB2DG treatment. The inhibition of TNF-α production was found to be mediated by mTOR and HIF-1 pathway, as PCB2DG suppressed the expression of HIF-1α, p-mTOR, and p-p70S6K (a downstream of the mTOR complex, mTORC1). Moreover, suppression of TNF-α production was mediated by regulation of the glycolytic enzyme lactate dehydrogenase (LDH) at the post-transcriptional level.

These results suggest that PCB2DG regulates TNF-α production by inhibiting glycolytic activity via the mTOR/HIF-1 pathway. This study is the first to report the mechanism by which PCB2DG, a dimeric polyphenol including a gallate group, controls cytokine production. Based on their findings, molecular studies of cellular molecules which interact with PCB2DG are needed to elucidate further mechanisms. Moreover, studies on the effects of PCB2DG in terms of amelioration of TNF-α-mediated pathology using a mouse model would be informative. In the future, PCB2DG may become available as a therapeutic for the treatment and prevention of TNF-α-mediated autoimmune diseases.

Interestingly, a compound with two gallate groups added to PCB2 (PCB2DG) was found to suppress immune cell activation. In addition, the group found that PCB2DG suppresses the production of cytokines involved in the inflammatory response. However, since the mechanism of PCB2DG suppression was unknown, the group decided to tackle this issue.

In order to evaluate the effect of PCB2DG on cytokine production, protein level and gene level of cytokine were analyzed. As a result, although suppression at the protein level was confirmed by the addition of PCB2DG, suppression at the gene level was not confirmed. Usually, cytokines are known to show the same changes at the protein level and at the gene level, so the group thought that there were some deficiencies in the experiment, and repeated experiments were conducted. However, no matter how many times the experiment was carried out, the protein decreased and the gene remained unchanged. Therefore, by changing the approach, the group hypothesized that PCB2DG regulates post-transcriptional protein expression rather than regulating the cytokine gene, and proceeded with verification. The research group eventually were able to prove that this hypothesis was correct, though it was very difficult to get there.

The lab hopes to be able to prevent illness with food in the future. Many foods that are consumed in everyday life regulate immune function. The researchers would like to scientifically demonstrate their usefulness and prove their effectiveness in preventing diseases. In the future, Dr Tanaka would like to identify the target molecule of PCB2DG. She hopes to collaborate with researchers who are analyzing proteins that bind to polyphenols in order to elucidate the matter further.

There is a broad range of mechanisms associated with chemoresistance, many of which to date are only poorly understood. The so-called cellular stress response - a set of genetic programmes that enable the cells to survive under stressful conditions - plays a key role in the development of numerous diseases and in chemoresistance. A better understanding of the cellular stress response pathways is therefore urgently required to develop new therapeutic concepts to overcome chemoresistance. "In this context, we employed comprehensive analytical approaches to gain deep and molecular insight into the Unfolded Protein Response, a cellular stress reaction induced by unfolded proteins", says Robert Ahrends, group leader at the Department of Analytical Chemistry of the Faculty of Chemistry.

Unfolded proteins cause stress and disease

The Unfolded Protein Response (UPR) contributes to cancer development and progression and plays an important role in diseases such as diabetes and neurodegenerative disorders. For their study of the UPR's molecular biological characteristics, the researchers applied state-to-art analytical tools in the context of a multiomics approach, combining large datasets from genetics, proteomics and metabolomics. This allowed them to define the Unfolded Protein Response regulon, a comprehensive list of genes that are activated to promote cell survival under stress.

"Besides the previously known factors, we identified to our surprise numerous genes that have not previously been implicated in stress response pathways", explain the researchers, "and many of them have key functions in cancer development and cellular metabolism."

Changes in 1C metabolism

Changes in cellular metabolism are characteristic of many cancer types and promote a rapid tumour growth, as Nobel Prize winner Otto Warburg demonstrated already in the 1930s in his ground-breaking work. In their study, the researchers discovered stress-mediated genetic regulation of enzymes involved in one-carbon (1C) metabolism which relies on the vitamin folate as a cofactor. Concomitant to the metabolic re-wiring, the stressed cells became fully resistant against chemotherapeutic agents, which target this specific metabolic pathway. This includes Methotrexate, a drug commonly employed in the treatment of cancer and rheumatic diseases. Detailed biochemical and genetic investigations revealed that resistance is driven by a previously unrecognized mechanism. According to the study authors, its precise molecular characterisation might lead to novel therapeutic concepts aimed at overcoming chemoresistance in cancer therapy.

Stay-at-home orders and "lockdowns" related to the COVID-19 pandemic have had a major impact on the daily lives of people around the world and that includes the way that people sleep, two studies report June 10 in the journal Current Biology. Both studies show that relaxed school and work schedules and more time spent at home has led people to sleep more on average with less "social jetlag" as indicated by a reduced shift in sleep timing and duration on work days versus free days. But, at the same time, one of the studies also finds that the pandemic has taken a toll when it comes to self-reported sleep quality.

"Usually, we would expect a decrease in social jetlag to be associated with reports of improved sleep quality," says sleep researcher and cognitive neuroscientist Christine Blume (@christine_blume) from the University of Basel's Centre for Chronobiology, Switzerland. "However, in our sample, overall sleep quality decreased. We think that the self-perceived burden, which substantially increased during this unprecedented COVID-19 lockdown, may have outweighed the otherwise beneficial effects of a reduced social jetlag."

In their study, Blume and colleagues including Marlene Schmidt and Christian Cajochen explored the effects of the strictest phase of the COVID-19 lockdown on the relationship between social and biological rhythms as well as sleep during a six-week period from mid-March until end of April 2020 in Austria, Germany, and Switzerland. Their data showed that the lockdown reduced the mismatch between social and biological sleep-wake timing as people began working from home more and sleeping more regular hours from day to day. People also slept about 15 minutes longer each night. However, the self-reported data indicated a perception that sleep quality had declined.

In the other study, Kenneth Wright at the University of Colorado, Boulder's Sleep and Chronobiology Laboratory and colleagues asked similar questions by comparing sleep prior to and during Stay-at-Home orders in 139 university students as they shifted from taking their classes in-person to taking them remotely. As the team reports, nightly sleep duration increased by about 30 minutes during weekdays and 24 minutes on weekends. The timing of sleep also became more regular from day to day, and there was less social jetlag.

Students stayed up about 50 minutes later while staying home during weekdays and about 25 minutes later on weekends. Students that tended to sleep less before the effects of COVID-19 took hold showed the greatest increase in the amount of sleep after they stopped going to in-person classes. After the Stay-at-Home orders went into effect, 92 percent of students got the recommended 7 hours or more of sleep per night, up from 84 percent before.

"Insufficient sleep duration, irregular and late sleep timing, and social jetlag are common in modern society and such poor sleep health behaviors contribute to and worsen major health and safety problems, including heart disease and stroke, weight gain and obesity, diabetes, mood disorders such as depression and anxiety, substance abuse, and impaired immune health, as well as morning sleepiness, cognitive impairment, reduced work productivity, poor school performance and risk of accident/drowsy driving crashes," Wright said. "Our findings provide further evidence that poor sleep behaviors are modifiable in university students. A better understanding of which factors during Stay-at-Home orders contributed to changed sleep health behaviors may help to develop sleep health intervention strategies."

"Not surprisingly, this unprecedented situation of the pandemic and the lockdown increased self-perceived burden and had adverse effects on sleep quality," Blume said. "On a positive note, though, the relaxation of social schedules also led to an improved alignment between external or social factors determining our sleep-wake timing and our body's internal biological signals. This was also associated with overall, more sleep."

From a sleep health perspective, the increase in sleep duration and regularity are welcome changes, say the researchers. For those having trouble with sleep quality, Blume suggests engaging in physical activity under the open sky.

A large international study coordinated by University Hospital Regensburg and Charité - Universitätsmedizin Berlin has demonstrated the safety of new cell therapy approaches for use in kidney transplant recipients. Transplant recipients were shown to require lower levels of immunosuppression in order to prevent organ rejection. This reduces the risk of side effects such as viral infections. Results from this study have been published in The Lancet.*
 

Transplant recipients usually receive immunosuppressants to prevent organ rejection. However, these drugs cannot provide an absolute guarantee that rejection will not occur at a later stage. Furthermore, immunosuppression is often associated with severe side effects such as intolerances, infections, or other problems. Cell therapy offers an alternative treatment approach. This involves the use of specific immune cells, which are isolated and expanded in vitro. Known as 'regulatory cell products', these cells are then infused into the transplant recipient in order to restore their immune system.            
 

Charité was one of a number of institutions involved in the international ONE Study consortium, which was led by Prof. Dr. Edward K. Geissler of University Hospital Regensburg. The Berlin-based members of the consortium were primarily responsible for testing the safety and efficacy of cell therapy in kidney transplant recipients as well as effects on their immune system. Research centers based in several different countries worked to a standardized protocol to develop a range of regulatory cell products, which were then tested in clinical trials. These therapies, which were administered to transplant recipients either before or after their surgery, comprised regulatory T cell and macrophage products, as well as products made of dendritic cells, which produce anti-inflammatory messengers. Results were then combined and compared with a reference patient group who had received standard-of-care immunosuppression. Patients were then followed up for a further 60 weeks.
 

"The new cell therapy was able to reduce the need for immunosuppression in approximately 40 percent of patients, thereby minimizing the risk of side effects," says the study's first author, Prof. Dr. Birgit Sawitzki of the Institute for Medical Immunology on Campus Virchow-Klinikum. The regulatory cells were shown to be just as safe as the drugs used in standard treatment and did not result in higher rejection rates. "Particularly remarkable was the fact that none of the patients given regulatory cells developed herpes infections, which often lead to dangerous complications in transplant recipients," notes Prof. Sawitzki. 
 

Prof. Sawitzki's team was primarily responsible for the development and implementation of standardized immune monitoring, i.e. the monitoring of immune cell populations in the blood. "Before transplantation, patients showed altered immune cell composition, and regulatory cells were better than standard therapy at restoring normal composition," explains Prof. Sawitzki. She adds: "This means there are new, safe treatment options which can help to reduce the dose of conventional immunosuppressants and the risk of viral infections." There are plans for further, larger studies to confirm the efficacy of regulatory cell therapy. 

Stenotrophomonas maltophilia are increasingly recognized as significant opportunistic pathogens in healthcare settings worldwide, the global spread of multidrug-resistant strains of this species being the most serious concern. Epidemiological studies are important to identify particular lineages or strains exhibiting clinically relevant phenotypes and to make knowledge-driven healthcare decisions.

In this context, researchers from the Bacterial Pathogenesis and Antimicrobials group of the Institut de Biotecnologia i de Biomedicina (IBB) and the Department of Genetics and Microbiology at UAB, in collaboration with the Research Center Borstel - Leibniz Lung Center (Germany) and ISGlobal at Hospital Clínic (Barcelona), have discovered the link between the bacterial communication system (quorum sensing) in Stenotrophomonas maltophilia, and virulence and antibiotic resistance phenotypes. Bacterial QS systems are based on small signalling molecules (the so-called autoinducers) which, depending on population density (hence the term quorum sensing), allow them to coordinate gene expression and cope with changes in their environment.

In this work, the correlation between quorum sensing, virulence and resistance was done in a panel of genetically diverse clinical Stenotrophomonas maltophilia isolates from different European countries. In particular, a clonal group of strains were identified that show an increased ability to form biofilms and exhibit higher resistance to the last-resort antibiotic colistin. In addition, new virulence factors exclusive to this lineage have been identified through a comparative genomics study.

The results, published in Frontiers in Microbiology, demonstrate the pivotal role of the quorum sensing system in the pathogenicity and persistence in Stenotrophomonas maltophilia and alert on the potential risk of resistant and virulent clones circulating in European hospitals.

In connection with this study, the UAB group has also participated in an ambitious project aimed to describe the population structure and spread of Stenotrophomonas maltophilia at a global scale, led by the Research Center Borstel. The results of this project have been published in Nature Communications. The analysis of a worldwide collection of 1.305 isolates detected human-associated lineages with higher proportions of key virulence and resistance genes.

London, 10 June 2020 - Over the past few months at least half of the world's population has been affected by some form of lockdown due to COVID-19, and many of us are experiencing the impact of social isolation. Loneliness affects both mental and physical health, but counterintuitively it can also result in a decreased desire for social interaction. To understand the mechanics of this paradox, UCL researchers based at the Wolfson Institute and the Sainsbury Wellcome Centre investigated social behaviour in zebrafish. Their results are published in eLife.

Most zebrafish demonstrate pro-social behaviour, but approximately 10% are 'loner' fish who are averse to social cues and demonstrate different brain activity than their pro-social siblings. However, even typically social zebrafish avoid social interaction after a period of isolation. PhD students Hande Tunbak and Mireya Vazquez-Prada, Postdoctoral Research Fellow Thomas Ryan, Dr Adam Kampff and Sir Henry Dale Wellcome Fellow Elena Dreosti set out to test whether the brain activity of isolated zebrafish mimics that of loner fish or whether other forces were at play.

To investigate the effects of isolation, the researchers isolated typically social zebrafish from other fish for a period of two days and then compared their brain activity to zebrafish who demonstrated aversion to social interaction without having been isolated. The isolated fish demonstrated sensitivity to stimuli and had increased activity in brain regions related to stress and anxiety. These effects of isolation were quickly overcome when the fish received a drug that reduces anxiety.

The differences between loner fish and their siblings were found mostly in the hypothalamus, the region of the brain responsible for social rewards. The loner fish hypothalamus did not demonstrate the same pattern of activation during social exposure as its typical counterparts, indicating that loner fish do not experience rewards in the same way as typical fish during social interactions.

By contrast, 'lonely' fish--those that demonstrated typical social behaviour and were isolated--demonstrated hypersensitivity to stimuli and activation of brain regions associated with stress and anxiety. Lonely fish experienced actively negative outcomes from social interaction whereas loner fish simply did not experience reward.

"A detailed view of the zebrafish brain can provide important clues for all of us currently experiencing the effects of social isolation," says Dr Elena Dreosti. Our understanding of the neural mechanisms of social behaviour are limited, but we do know that zebrafish and humans share a fundamental drive for social interaction that is controlled by similar brain structures. Although human behaviour is much more complex, understanding how this basic social drive arises--and how it is affected by isolation--is a necessary step towards understanding the impact of the social environment on human brains and behaviour. The zebrafish, which is completely transparent throughout early development, offers neuroscientists a detailed view of its brain circuitry.

We won't all be loners after lockdown, but we will be anxious upon returning to our normal social lives. As we emerge from lockdown, we should be aware of this new sensitivity and anxiety, but recognise that overcoming it is necessary for returning to a normal, healthy, social existence.

There are currently no licensed vaccines available for COVID-19. While several antiviral drugs have been tested, none has proved to be completely effective against the disease. In a study just published in the journal MDPI Vaccines, researchers from Bar-Ilan University have identified a set of potential immunodominant epitopes from the SARS-CoV-2 proteome. These epitopes are capable of generating both antibody- and cell-mediated immune responses. The findings of this work may thus contribute to developing a peptide vaccine against SARS-CoV-2 infections which can stop the COVID-19 outbreak and future pandemics caused by coronaviruses.

Led by Dr. Milana Frenkel-Morgenstern, Head of the Cancer Genomics and BioComputing of Complex Diseases Lab at Bar-Ilan University's Azrieli Faculty of Medicine, the researchers took an immunoinformatics-based computational approach to mine the protein content of SARS-CoV-2 and subsequently identified immunodominant epitopes of the virus. Immune responses that are based on specific immunodominant epitopes involve the generation of both antibody- and cell-mediated immunity against pathogens presenting such epitopes. Such immunity can facilitate fast and effective elimination of the pathogen.

The team of researchers that also includes Sumit Mukherjee, Dmitry Tworowski, Rajesh Detroja and Sunanda Biswas Mukherjee, identified 15 potential immunogenic regions from three proteins of SARS-CoV-2, and mapped 25 immunodominant epitopes on other SARS-CoV-2 proteins. To confirm that these epitopes could serve to provide immunity to a global population, the percentage of individuals that express a major histocompatibility complex (MHC) capable of recognizing any of these epitopes was determined. Accordingly, seven epitopes were deemed to be present in more than 87% of the worldwide virus-affected population. Further structural molecular docking analyses estimated the binding interaction of these potential epitopes with human MHC. Complete lists of MHC proteins that recognize each epitope have been generated and are presented in both the submitted manuscript and a provisional US patent application (US 63/034.416).

The seven epitopes were tested using multiple tools to verify their non-allergenic and non-toxic natures, as well as to demonstrate that they carry a low risk of triggering any autoimmune responses. Together, such results indicate that these seven epitopes represent potentially effective vaccine candidates. Indeed, the development of vaccines using these immunodominant epitopes could activate both humoral and cellular immune responses in humans comprising a major fraction of the world's population.

Scientists have detected RNA from the new coronavirus, SARS-CoV-2, in the feces of people with COVID-19. So it stands to reason that the viral RNA could end up in city sewage, where it could be used to monitor prevalence of the disease. Now, researchers reporting in ACS' Environmental Science & Technology Letters have detected rising SARS-CoV-2 RNA levels in sewage from several cities in the Netherlands at early stages of the pandemic.

Although infectious SARS-CoV-2 has been detected in stool samples, the virus spreads primarily through respiratory droplets when an infected person coughs, sneezes, laughs, speaks or breathes, according to recent studies. However, if the new coronavirus is present at high levels in sewage at treatment plants, it could pose risks to workers at the facilities. Gertjan Medema and colleagues wanted to see if they could detect SARS-CoV-2 in the domestic wastewater of cities in the early stages of the COVID-19 pandemic in the Netherlands. They also wanted to determine if levels of the virus's RNA correlated with the COVID-19 prevalence in each city. If so, sewage surveillance could be a helpful tool to monitor the circulation of SARS-CoV-2 in communities, especially since clinical testing likely underestimates the actual number of people infected with the virus.

As the new coronavirus took hold in other parts of the world, the researchers collected sewage samples from wastewater treatment plants that serve six cities in the Netherlands to see if the virus could be detected in this way. Samples were taken 3 weeks before the first reported COVID-19 case in the Netherlands, and then at 1, 2.5 and 4 weeks after the first case. The team measured SARS-CoV-2 levels in the sewage using a technique called quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Then, the researchers correlated viral RNA levels with the number of COVID-19 cases reported in each city on the day of sampling. SARS-CoV-2 was undetectable in sewage from all cities 3 weeks before the first reported case, but as the outbreak progressed, the concentration of SARS-CoV-2 RNA in sewage increased with the number of reported COVID-19 cases in each city. Although more research is needed, this study and similar ones in different locations suggest that sewage surveillance of SARS-CoV-2 RNA could serve as a sensitive early warning system for increased virus circulation in the population, the researchers say.

With summer on the way, and some beaches reopening after COVID-19 shutdowns, people will be taking to the ocean to cool off on a hot day. But those unlucky enough to encounter the giant jellyfish Nemopilema nomurai (also known as Nomura's jellyfish) might wish they had stayed on shore. Now, researchers reporting in ACS' Journal of Proteome Research have identified the key toxins that make the creature's venom deadly to some swimmers.

Found in coastal waters of China, Korea and Japan, Nomura's jellyfish can grow up to 6.6 feet in diameter and weigh up to 440 pounds. This behemoth stings hundreds of thousands of people per year, causing severe pain, redness, swelling, and in some cases, even shock or death. The jellyfish's venom is a complex brew of numerous toxins, some of which resemble poisons found in other organisms, such as snakes, spiders, bees and bacteria. Rongfeng Li, Pengcheng Li and colleagues wanted to determine which of the many toxins in the jellyfish's venom actually cause death. The answer could help scientists develop drugs to counteract jellyfish stings.

The researchers captured N. nomurai jellyfish off the coast of Dalian, China, and collected their tentacles, which contain the venom. They extracted venom proteins and separated them into different fractions using chromatography. By injecting each protein fraction into mice, the team identified one that killed the animals. Autopsies revealed damage to the mice's heart, lungs, liver and kidneys. The researchers used mass spectrometry to identify 13 toxin-like proteins in this lethal fraction. Some of the jellyfish proteins were similar to harmful enzymes and proteins found in poisonous snakes, spiders and bees. Instead of any one toxin being lethal, it's likely that multiple poisons work in concert to cause death, the researchers say.

Washington, DC - Up to 76 percent of all outpatient antibiotic prescriptions in the United States may be inappropriate, with peak prescribing associated with the flu season. Evidence suggests that influenza vaccines may reduce overall and inappropriate antibiotic use by reducing the burden of influenza-like illness commonly mistreated with antibiotics, as well as preventing secondary bacterial infections. While flu vaccines have been proven to reduce severe illness, evidence is lacking on the link between flu vaccination and antibiotic prescribing at the population level in the US.

To examine this association, researchers analyzed state-level data from IQVIA and the US Centers for Disease Control and Prevention's FluVaxView on antibiotic prescribing rates and influenza vaccine coverage between January and March of each year from 2010 to 2017.

"Getting the flu vaccine doesn't guarantee you will not get sick, but it is effective at reducing both the likelihood and the severity of disease at the individual level, which for individuals would translate into fewer trips to the doctor and less chance of being prescribed antibiotics. Since people who don't get sick don't transmit the disease to others, we believed that the more people who got a vaccine in an area, the less illness there would be and the fewer antibiotic prescriptions there would be," said Eili Klein, lead study author and CDDEP Senior Fellow.

Utilizing fixed-effects regression analysis adjusted for socioeconomic differences, access to health care, childcare centers, climate, vaccine effectiveness, and state-level differences, the study found that a ten percent increase in influenza vaccination coverage was associated with a 6.5 percent reduction in antibiotic use, or 14.2 fewer antibiotic prescriptions per 1,000 individuals. Increased vaccination rates were tied to significant reductions in antibiotic prescribing rates among pediatric (6 percent), elderly (5.2 percent), and adult populations (4.2 percent). Specifically, the researchers found that across all ages, flu vaccine coverage was significantly and negatively associated with prescribing rates for macrolides, tetracyclines, narrow-spectrum penicillins, and aminoglycosides- all of which are antibiotic classes commonly prescribed for upper respiratory tract infections or severe infections, which flu vaccines prevent.

"The flu is more common in children and the elderly, and thus this is fairly suggestive that the vaccine is limiting the severity of disease in these populations leading to lower rates of antibiotic prescribing," said Klein.

Overall, results indicate that flu vaccination is associated with reduced antibiotic use in the United States, which suggests that expanding flu vaccine coverage could reduce inappropriate antibiotic prescribing. The study titled, "The Impact of Influenza Vaccination on Antibiotic Use in the United States, 2010-2017" was published on June 6, 2020 in Open Forum Infectious Diseases.

Power plants that burn coal and other fossil fuels emit not only planet-warming carbon dioxide, but also pollutants linked to breathing problems and premature death. Policies proposed to mitigate climate change, however, often fail to fully account for the health benefit of switching to cleaner technologies. In a new study published in ACS' Environmental Science & Technology, researchers show that emphasizing health concerns in such policies can alter the optimal locations of these upgrades. 

Location matters little for carbon dioxide emissions -- no matter where the gas is emitted, it eventually mixes into the atmosphere and contributes to global climate change. However, location makes a big difference for air pollutants such as sulfur dioxide and nitrogen oxides, since those emissions tend to concentrate near their source and can impact the health of people living nearby. Studies have been exploring the connection between reducing climate-warming emissions and healthier air, and how that plays out at a local level. But Brian Sergi, Inês Azevedo and colleagues wanted to take an even more granular, county-by-county approach to assess how a combined climate-and-health-driven strategy for the U.S. electricity system might play out compared to one prioritizing only climate. 

In the study, the researchers started out with a goal of reducing carbon dioxide emissions by 30%. Using computer models, they examined the effects of two approaches: one in which reducing carbon dioxide is the only goal, and another in which reducing both carbon dioxide and local air pollution are prioritized equally. These two scenarios produced markedly different results for some states. When undertaken with only climate implications (carbon dioxide levels) in mind, the transition to cleaner power required retiring many coal-powered plants in the West and Southwest. However, when health (pollution levels) was also considered, it was better to retire more coal-powered plants in the Midwest and Mid-Atlantic regions. The combined approach could help states better determine how to prioritize upgrades for power plants within their borders, the researchers say. 

An autism diagnosis can present a number of challenges for families from learning about the neurodevelopment disorder and accessing support services and resources to financial struggles. A new report from the A.J. Drexel Autism Institute at Drexel University highlighted the financial challenges facing households of children with autism spectrum disorder (ASD) in the United States. According to the report, households of children with ASD experience higher levels of poverty, material hardship and medical expenses than households of children with other special health care needs.

The report also found that over half of children with autism live in low-income households (household income below 200% of the federal poverty level, or FPL, with an income of $48,500 four a family of four) and 30% live in very low-income households (household income below 100% of the FPL, $24,250 for a family of four).

Families living in poverty have fewer resources to spare and are especially vulnerable in the face of burdens like care-related expenses, reduced earnings from taking time off work to cope with caregiving, and disconnection from services and supports.

"I have talked with countless families of children with autism over the past 20 years who are struggling with the dual challenge of parenting a child with special needs AND covering the basic needs of the entire family," said Paul Shattuck, PhD, director of the Autism Institute's Life Course Outcomes Program and co-author of the report. "Our hope for this Indicators Report is that it will raise awareness and spark discussion about the ways in which families are struggling and need our collective societal support."

Safety net programs can help to offset financial challenges through the provision of monetary support and increased access to social services and programs. However, the current understanding of safety net program use among households of children with ASD is limited. And few population-level studies have described the characteristics of children with ASD from low-income households.

"We need exploratory and descriptive research that can chart the types of safety net programs low-income households of children with ASD report using, and how they compare to households of children without ASD," said Kristy Anderson, associate researcher in the Autism Institute and lead author. "Such analyses could help to unveil specific conditions and characteristics that are unique to the subpopulation of children with ASD living in poverty."

The report found households of children with ASD experienced material hardships (not being able to consume goods and services that are deemed minimally necessary) much more often than parents of children with other special health care needs and children with no special health care needs. Nearly half reported difficulty paying for basics like food or housing. Almost one-third had to reduce work to care for their child with autism. About one in five families had problems paying for their child's health care and roughly 15% had difficulty affording food for the family.

Young children with ASD (ages 3-5 years) and those from minority groups faced an increased risk of material hardship. This was especially common for the subset of households living below 200% the federal poverty level, despite high levels of participation in safety net programs. More than two-thirds of low-income households of children with ASD reported that someone in their family received cash assistance; help from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and Supplemental Nutrition Assistance Program (SNAP); and/or free and reduced-price meals during the previous year.

Children with ASD who participated in at least one safety net program fared worse on three indicators of material hardship (difficulty paying bills, parents reduced/stopped work and inability to afford food) and had higher out-of-pocket expenditures than children who were disconnected from the safety net. Families of children who had public health insurance reported lower out-of-pocket expenditures and were less likely to report problems paying for their child's medical care than children with private health insurance.

"Findings from this report indicate that younger children with ASD from minority backgrounds might be particularly vulnerable to the effects of poverty and hardship," said Anderson. "Given what we know about the effects of poverty on the developing brain, and the importance of intervening early to improve outcomes for children with autism, there is a vital need for new resources and programs with targeted support for these families."

The recently published "2020 National Autism Indicators Report: Children on the Autism Spectrum and Family Financial Hardship" uses data from the 2016-2017 National Survey of Children's Health (NSCH) to examine family financial hardship among families of children with ASD (ages 3-17 years) and their participation in four safety net programs: 1) cash assistance for poor families with children; 2) the Special Supplemental Nutrition Program for Women, Infants, and Children; 3) the Supplemental Nutrition Assistance Program (also known as "food stamps"); 4) free and reduced-price meals in schools. The NSCH is a survey of child and family health, health care and wellbeing conducted yearly by the U.S. Census Bureau.

This report builds on the 2018 National Autism Indicators Report that found many low-income families of teenagers on the autism spectrum rely on federal safety net programs to help with things like health insurance and paying for food.

Volume 11, Issue 23 of @Oncotarget reported that the authors have previously established that mi R-151a functions as an onco-mi R in non-small cell lung cancer cells by inducing partial EMT and enhancing tumor growth.

Here, the authors identify anti-mi R-151a as a molecule that promotes endothelial cell contacts and barrier properties, suggesting that mi R-151a regulates cell-cell junctions.

They find that induced mi R-151a expression enhances endothelial cell motility and angiogenesis and these functions depend on mi R-151a-induced Slug levels.

Moreover, The authors show that mi R-151a overexpression enhances tumor-associated angiogenesis in 3D vascularized tumor spheroid assays.

Their results suggest that mi R-151a plays multi-faceted roles in the lung, by regulating multiple functions in distinct cell types.

Dr. Irene Munk Pedersen from The University of California as well as The Scintillon Institute said, "Angiogenesis, or the growth of new networks of blood vessels from existing vessels, is an important natural process used for growth, healing, and reproduction."

"The authors find that anti-mi R-375 and anti-mi R-151a strengthen cell-cell contact and endothelial cell barrier in primary lung endothelial cells, relative to control samples"

Proper regulation of angiogenesis is essential not only for developing an adult's healthy organs to support growth and metabolism but also for disease progression since abnormal vessel growth and/or function are hallmarks of cancer, ischemic and chronic inflammatory diseases.

Slug and Snail may regulate a distinct but overlapping set of genes and therefore Snail may compensate for Slug in the Slug-knock-out context.

There is a need to characterize the repertoire of master mi R regulators in normal and diseased microenvironments to further understand how to restore the delicate balance of cell homeostasis when it has been lost.

The authors find that anti-mi R-375 and anti-mi R-151a strengthen cell-cell contact and endothelial cell barrier in primary lung endothelial cells, relative to control samples.

The Munk Pedersen Research Team concluded in their Oncotarget Priority Research Paper, "Our results show that increased miR-151 expression, significantly promotes endothelial cell motility and angiogenesis in 2D and 3D models and that miR-151a-induced Slug expression is required for these endothelial cell properties. Our findings provide a new avenue to the understanding of the processes in the lung niche environment, and may facilitate the development of potential therapeutics against lung cancer."

PHILADELPHIA -- Prostate cancer is a leading cause of death from cancer in the US and especially in the Philadelphia region. Consistently, Philadelphia has outpaced the state of PA and the nation in diagnoses and death from prostate cancer. A key area impacting prostate cancer risk and treatment is germline genetic testing, which involves testing for hereditary cancer genes. Genes such as BRCA2, BRCA1 and many other genes have been reported to raise the risk for prostate cancer and are increasingly informing treatment and management approaches. However, genetic testing of men for prostate cancer is still not common practice due to inconsistent guidelines and challenges to implementation of genetic counseling.

To address these challenges, experts at Sidney Kimmel Cancer Center - Jefferson Health and the Department of Urology at Thomas Jefferson University hosted the international Philadelphia Prostate Cancer Consensus Conference 2019 entitled Implementation of Germline Testing for Prostate Cancer. The Consensus Conference, co-chaired by Drs. Veda Giri, Karen Knudsen, and Leonard Gomella, had representation from many major Philadelphia healthcare institutions, such as University of Pennsylvania and Fox Chase Cancer Center, as well as centers around the United States, Europe, and Australia. Importantly, the conference addressed key gaps or areas in need of clarity regarding genetic testing for prostate cancer including: which men should undergo genetic testing for prostate cancer, which genes should be tested, how genetic results impact precision medicine and precision management across the stage spectrum, and the impact of genetic testing for cancer risk and screening for men and their families.

Key recommendations which were published in Journal of Clinical Oncology on June 9th include a strong endorsement to perform genetic testing of all men with metastatic prostate cancer to inform precision medicine or clinical trial eligibility, as well as men with a family history suggesting hereditary prostate cancer as well as other cancers such as breast, ovarian, pancreatic, and colon cancers, to inform active surveillance or screening discussions. Recommended priority genes for testing include BRCA2, BRCA1, and DNA mismatch repair genes in metastatic prostate cancer.

The Consensus recommendations come on the heels of two very important FDA approvals for drugs that target metastatic prostate cancer in men who carry BRCA mutations or mutations in other DNA repair genes. Two medications, rucaparib and olaparib, were granted FDA approval recently for treatment among men with specific genetic mutations due to clinical benefit, thus expanding precision medicine for prostate cancer. Therefore, the Conference results have significant impact for treatment decision-making for men with metastatic prostate cancer.

The Conference also addressed how genetic testing may impact management of early-stage prostate cancer. BRCA2 testing was recommended to inform active surveillance discussions and may help men and their doctors make decisions for management of early-stage disease. The Conference also focused on prostate cancer screening strategies such as age to begin screening and which genes to factor into screening discussions between men and their doctors to make an informed and shared decision. For example, BRCA2 and HOXB13 were recommended for testing to inform prostate cancer early detection discussions. The panel also recommended that BRCA2 carriers should begin early PSA screening, such as at age 40 or 10 years prior to the youngest prostate cancer diagnosis in a family. Since genetic testing may uncover hereditary cancer risk, the Conference also addressed genetic testing for male and female relatives of men who test positive for genetic mutations, factoring in family cancer history and other factors.

This was the first conference to propose a model for how to implement genetic testing in medical practices. The Conference included experts in oncology, urology, genetic counseling, primary care, Veterans Affairs, and patient stakeholders. Their guidance was used to develop genetic-evaluation processes that include seeing men in-person, using telehealth, or using videos to provide genetic information to make an informed decision for genetic testing. In this era of COVID-19, remote health services such as telehealth, are increasingly needed to keep ahead of cancer development and to provide high-level cancer care.

Genetic testing is very conducive the telehealth genetic counseling, with at-home sample collection for genetic testing, and discussion of results through telehealth.

Finally, the Consensus Conference addressed approaches to increase knowledge of genetics among doctors and the public along with priorities for research. Many currently available resources were highlighted, with additional patient and public resources under development.

Overall, genetic testing for prostate cancer is now increasingly informing treatment, management, and screening for this potentially lethal disease at high rates in our region. The 2019 Philadelphia Consensus Conference was a major effort to provide guidance to doctors, men, and their families regarding how best to consider and undergo genetic testing to impact prostate cancer care. Importantly, the results can also provide information on other cancer risks impacting males and females in families such as breast cancer, prostate cancer, pancreatic cancer, ovarian cancer, and colon cancer.

This Father's Day, men may consider approaching their doctors and families regarding genetic testing for prostate cancer to be proactive in treatment and screening which may be life-saving from this potentially fatal disease.