Earth

Molecular iodine, a major emission from the ocean, can quickly convert to iodic oxoacids even under weak daylight conditions. These oxoacids lead rapidly to aerosol particles that significantly affect climate and human health.

Iodine-containing vapors that are emitted from oceans are a major source of aerosol particles. "Despite their importance to the climate, the formation of marine particles has been poorly understood," says Siddharth Iyer, Postdoctoral Researcher in Aerosol Physics Laboratory at Tampere University.

In this research, the formation of aerosol particles form from iodine-containing vapours under marine boundary layer conditions were studied. The experiments were carried out in the ultra-clean CLOUD chamber in CERN, where the nucleation and growth rates as well as the composition of freshly formed particles from iodic oxoacids (iodic acid and iodous acid) were measured.

These vapours derive from photolysis and oxidation of molecular iodine, for which the ocean surface is a major source. The conversion to iodine oxoacids were found to be extremely fast, even under weak daylight conditions. Although iodic acid was identified as the key vapour, a related species - iodous acid - was also found to play an important stabilizing role in the initial steps of neutral (uncharged) particle formation.

"Sulfuric acid is known to be key player in new particle formation, but our results indicate that iodine oxoacid particle formation can compete with sulfuric acid in pristine regions of the atmosphere. This significantly advances our understanding of aerosol formation," Iyer sums up.

The lung is a complex organ whose main function is to exchange gases. It is the largest organ in the human body and plays a key role in the oxygenation of all the organs. Due to its structure, cellular composition and dynamic microenvironment, is difficult to mimic in vitro.

A specialized laboratory of the ARTORG Center for Biomedical Engineering Research, University of Bern, headed by Olivier Guenat has developed a new generation of in-vitro models called organs-on-chip for over 10 years, focusing on modeling the lung and its diseases. After a first successful lung-on-chip system exhibiting essential features of the lung, the Organs-on-Chip (OOC) Technologies laboratory has now developed a purely biological next-generation lung-on-chip in collaboration with the Helmholtz Centre for Infection Research in Germany and the Thoracic Surgery and Pneumology Departments at Inselspital.

A fully biodegradable life-sized air-blood-barrier

Pauline Zamprogno, who developed the new model for her PhD thesis at the OOC, summarizes its characteristics: "The new lung-on-chip reproduces an array of alveoli with in vivo like dimensions. It is based on a thin, stretchable membrane, made with molecules naturally found in the lung: collagen and elastin. The membrane is stable, can be cultured on both sides for weeks, is biodegradable and its elastic properties allow mimicking respiratory motions by mechanically stretching the cells."

By contrast to the first generation, which was also built by the team around Olivier Guenat, the developed system reproduces key aspects of the lung extracellular matrix (ECM): Its composition (cells support made of ECM proteins), its structure (array of alveoli with dimension similar to those found in vivo + fiber structure) and its properties (biodegradability, a key aspect to investigating barrier remodeling during lung diseases such as IPF or COPD). Additionally, the fabrication process is simple and less cumbersome than that of a polydimethylsiloxane stretchable porous membrane from the first-generation lung-on-chip.

Broad potential clinical applications

Cells to be cultured on the new chip for research are currently obtained from cancer patients undergoing lung resections at the Inselspital Department of Thoracic Surgery. Department Head Ralph Schmid sees a double advantage in the system: "The second generation lung-on-chip can be seeded with either healthy or diseased lung alveolar cells. This provides clinicians with both a better understanding of the lung's physiology and a predictive tool for drug screening and potentially also for precision medicine, identifying the specific therapy with the best potential of helping a particular patient."

"The applications for such membranes are broad, from basic science investigations into lung functionalities and pathologies, to identifying new pathways, and to a more efficient discovery of potential new therapies", says Thomas Geiser, Head of the Department of Pneumology at the Inselspital and Director of Teaching and Research of the Insel Gruppe.

Powerful alternative to animal models in research

As an additional plus, the new lung-on-chip can reduce the need for pneumological research based on animal models. "Many promising drug candidates successfully tested in preclinical models on rodents have failed when tested in humans due to differences between the species and in the expression of a lung disease," explains Olivier Guenat. "This is why, in the long term, we aim to reduce animal testing and provide more patient-relevant systems for drug screening with the possibility of tailoring models to specific patients (by seeding organs-on-chip with their own cells)."

The new biological lung-on-chip will be further developed by Pauline Zamprogno and her colleagues from the OOC Technologies group to mimic a lung with idiopathic pulmonary fibrosis (IPF), a chronic disease of the lung leading to progressive scarring of the lung tissue within the framework of a research project funded by the Swiss 3R Competence Center (3RCC). "My new project consists in the development of an IPF-on- chip model based on the biological membrane. So far, we have develop a healthy air-blood barrier. Now it's time to use it to investigate a real biological question," says Zamprogno.

Research group Organs-On-Chip Technologies of the ARTORG Center

This specialized group of the ARTORG Center for Biomedical Engineering Research develops organs-on-chip, focusing on the lung and its diseases, in collaboration with the Departments of Pulmonary Medicine and Thoracic Surgery of the Inselspital. The group combines engineering, in particular microfluidics and microfabrication, cell biology and tissue engineering methods, material sciences and medicine.

Their first development of a breathing lung-on-chip is further developed in collaboration with the start-up AlevoliX, with the aim to revolutionize preclinical research. Recently the group has developed an entirely biological second-generation lung-on-chip focusing on recreating the air-blood barrier of the lung. A second research direction aims at developing a functional lung microvasculature. Here, lung endothelial cells are seeded in a micro-engineered environment, where they self-assemble to build a network of perfusable and contractile microvessels of only a few tens of micrometers in diameter.

Next to pharmaceutical applications, organs-on-chip are seen as having the potential to be used in precision medicine to test the patient's own cells in order to tailor the best therapy. Furthermore, such systems have the significant potential to reduce animal testing in medical and life-science research. The OOC group operates the Organs-on-Chip Facility, providing scientists from the University of Bern, the University Hospital of Bern and beyond an infrastructure and equipment to produce microfluidic devices and test organs-on-chips.

A Rochester Institute of Technology researcher has validated a tool measuring adherence to a popular child feeding approach used by pediatricians, nutritionists, social workers and child psychologists to assess parents' feeding practices and prevent feeding problems.

The best-practice approach, known as the Satter Division of Responsibility in Feeding, has now been rigorously tested and peer reviewed, resulting in the quantifiable tool sDOR.2-6y. The questionnaire will become a standard parent survey for professionals and researchers working in the early childhood development field, predicts lead researcher Barbara Lohse, director of RIT's Wegmans School of Health and Nutrition.

"We've shown that the Satter survey can be used to measure that a child from 2 to 6 years old is at nutrition risk," Lohse said. "It's important to identify that early and prevent it from continuing because the last thing we want to have is a child at nutrition risk. They're not going to grow or develop correctly."

Pediatricians and other professionals working with young children require accurate tools to assess risk factors associated with a child's physical and emotional eating environment. The right questionnaire completed by a child's parent or guardian about childhood feeding and eating can lead to timely interventions.

Although many surveys about childhood feeding exist, until now, none have adequately measured the Satter division of responsibility in feeding, Lohse noted. "The theoretically grounded, research-supported approach is used in medical, public health, and in early childhood health-education venues."

Developed by Ellyn Satter, the method is associated with good parenting and positive eating behaviors and family dynamics. The Ellyn Satter Institute offers models for improving feeding dynamics and eating competence and is a resource for healthcare professionals, educators, and the public.

Satter's common-sense approach to childhood feeding and eating lacked the supporting evidence to explain why and how it worked. Lohse and Satter set out to rigorously test and validate the division of responsibility in feeding. They winnowed the survey down from 38 to 12 questions based on interviews with parents, video recorded parent-child interactions around feeding time, and compared it to other validated surveys to create the Satter Division of Responsibility in Feeding tool, the sDOR.2-6y.

"The key thing that is really important is that this 12-item survey was able to identify children at nutrition risk," Lohse said. "The Satter survey clearly correlated with other validated instruments on parent feeding that are much longer and much more in depth."

The survey also provides a view into areas of parent functioning such as sleep, stress, and parenting style, Lohse said. Her research shows that parents who follow the Satter Division of Responsibility tend to be more eating competent and exhibit other related factors. "They tend to have better sleep and less uncontrolled, emotional eating," Lohse said. "That was important to find out that the parents who practice this approach tend to have better habits themselves."

Astronomers may have found our galaxy's first example of an unusual kind of stellar explosion. This discovery, made with NASA's Chandra X-ray Observatory, adds to the understanding of how some stars shatter and seed the universe with elements critical for life on Earth.

This intriguing object, located near the center of the Milky Way, is a supernova remnant called Sagittarius A East, or Sgr A East for short. Based on Chandra data, astronomers previously classified the object as the remains of a massive star that exploded as a supernova, one of many kinds of exploded stars that scientists have catalogued.

Using longer Chandra observations, a team of astronomers has now instead concluded that the object is left over from a different type of supernova. It is the explosion of a white dwarf, a shrunken stellar ember from a fuel-depleted star like our Sun. When a white dwarf pulls too much material from a companion star or merges with another white dwarf, the white dwarf is destroyed, accompanied by a stunning flash of light.

Astronomers use these "Type Ia supernovae" because most of them mete out almost the same amount of light every time no matter where they are located. This allows scientists to use them to accurately measure distances across space and study the expansion of the universe.

Data from Chandra have revealed that Sgr A East, however, did not come from an ordinary Type Ia. Instead, it appears that it belongs to a special group of supernovae that produce different relative amounts of elements than traditional Type Ias do, and less powerful explosions. This subset is referred to as "Type Iax," a potentially important member of the supernova family.

"While we've found Type Iax supernovae in other galaxies, we haven't identified evidence for one in the Milky Way until now," said Ping Zhou of Nanjing University in China, who led the new study while at the University of Amsterdam. "This discovery is important for getting a handle of the myriad ways white dwarfs explode."

The explosions of white dwarfs is one of the most important sources in the universe of elements like iron, nickel, and chromium. The only place that scientists know these elements can be created is inside the nuclear furnace of stars or when they explode.

"This result shows us the diversity of types and causes of white dwarf explosions, and the different ways that they make these essential elements," said co-author Shing-Chi Leung of Caltech in Pasadena, California. "If we're right about the identity of this supernova's remains, it would be the nearest known example to Earth."

Astronomers are still debating the cause of Type Iax supernova explosions, but the leading theory is that they involve thermonuclear reactions that travel much more slowly through the star than in Type Ia supernovae. This relatively slow walk of the blast leads to weaker explosions and, hence, different amounts of elements produced in the explosion. It is also possible that part of the white dwarf is left behind.

Sgr A East is located very close to Sagittarius A*, the supermassive black hole in the center of our Milky Way galaxy, and likely intersects with the disk of material surrounding the black hole. The team was able to use Chandra observations targeting the supermassive black hole and the region around it for a total of about 35 days to study Sgr A East and find the unusual pattern of elements in the X-ray data. The Chandra results agree with computer models predicting a white dwarf that has undergone slow-moving nuclear reactions, making it a strong candidate for a Type Iax supernova remnant.

"This supernova remnant is in the background of many Chandra images of our galaxy's supermassive black hole taken over the last 20 years," said Zhiyuan Li, also of Nanjing University. "We finally may have worked out what this object is and how it came to be."

In other galaxies, scientists observe that Type Iax supernovae occur at a rate that is about one third that of Type Ia supernovae. In the Milky Way, there have been three confirmed Type Ia supernova remnants and two candidates that are younger than 2,000 years, corresponding to an age when remnants are still relatively bright before fading later. If Sgr A East is younger than 2,000 years and resulted from a Type Iax supernova, this study suggests that our galaxy is in alignment with respect to the relative numbers of Type Iax supernovae seen in other galaxies.

Along with the suggestion that Sgr A East is the remnant from the collapse of a massive star, previous studies have also pointed out that a normal Type Ia supernova had not been ruled out. The latest study conducted with this deep Chandra data argue against both the massive star and the normal Type Ia interpretations.

DALLAS - Feb. 8, 2021 - A new nanoparticle-based drug can boost the body's innate immune system and make it more effective at fighting off tumors, researchers at UT Southwestern have shown. Their study, published in Nature Biomedical Engineering, is the first to successfully target the immune molecule STING with nanoparticles about one millionth the size of a soccer ball that can switch on/off immune activity in response to their physiological environment.

"Activating STING by these nanoparticles is like exerting perpetual pressure on the accelerator to ramp up the natural innate immune response to a tumor," says study leader Jinming Gao, Ph.D., a professor in UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and a professor of otolaryngology - head and neck surgery, pharmacology, and cell biology.

For more than a decade, researchers and pharmaceutical companies have been racing to develop drugs that target STING, which stands for "stimulator of interferon genes." The STING protein, discovered in 2008, helps mediate the body's innate immune system - the collection of immune molecules that act as first responders when a foreign agent circulates in the body, including cancer DNA. Research has suggested that activating STING can make the innate immune system more powerful at fighting tumors or infections. However, results from earlier clinical trials involving first-generation compounds targeting STING for activation failed to demonstrate an impressive clinical effect.

"A major limitation of conventional small molecule drugs is that after injection into tumors, they are washed out from the tumor site by blood perfusion, which can reduce antitumor efficacy while causing systemic toxicities," explains Gao.

Gao and his colleagues at UTSW discovered another approach that is different from the earlier or first-generation STING agonist approaches that utilize synthetic cyclic dinucleotide to activate STING in the body. Gao and his team aimed to design a polymer - a manmade macromolecule that can self-assemble into nanoparticles - to effectively deliver cyclic GMP-AMP (cGAMP), a natural small molecule activator of STING, to the protein target. But one polymer they synthesized, PC7A, produced an unexpected and novel effect: It activated STING even without cGAMP. The group reported the initial results in 2017, not knowing at the time exactly how PC7A worked; the polymer didn't resemble any other drugs that activated STING.

In the new paper, Gao's team showed that PC7A binds to a different site on the STING molecule from known drugs. Moreover, its effect on the STING protein is different. While existing drugs activate the protein over the course of about six hours, PC7A forms polyvalent condensates with STING for over 48 hours, causing a more sustained effect on STING. This longer innate immune activation, they showed, leads to a more effective T cell response against multiple solid tumors. Mice survived longer and had slower tumor growth when they received a combination of PC7A and cGAMP, the researchers found.

The polymer also has other advantages. When circulating in the bloodstream, the polymers are present as small round nanoparticles that do not bind to STING. It's only when those nanoparticles enter immune cells that they separate, attach to STING, and activate the immune response. That means that PC7A might be less likely to cause side effects throughout the body than other STING-targeting drugs, says Gao, although clinical trials will be needed to prove that.

Because PC7A binds to a different site of the STING molecule, the compound might work in patients for whom typical STING-targeting drugs do not. Up to 20 percent of people have inherited a slightly different gene for STING; the variant makes the STING protein resistant to several cyclic dinucleotide drugs. Gao and his team demonstrated that PC7A can still activate cells that express these STING variants.

"There's been a lot of excitement about therapies that target STING and the potential role these compounds could play in expanding the benefits of immunotherapies for cancer patients," says Gao. "We believe that our new nanotechnology approach offers a way to activate STING without some of the limitations we've seen with earlier STING agonist drugs in development."

AURORA, Colo. (February 8, 2021) - Researchers from the Barbara Davis Center for Childhood Diabetes at the University of Colorado Anschutz Medical Campus have found that immune responses to insulin could help identify individuals most at risk for developing Type 1 diabetes.

The study, out recently in the Proceedings of the National Academy of Sciences, measured immune responses from individuals genetically predisposed to developing Type 1 diabetes (T1D) to naturally occurring insulin and hybrid insulin peptides. Since not all genetically predisposed individuals develop T1D, researchers sought to examine T-cell immune responses from the peripheral blood that could occur before the onset of clinical diabetes.

"We want to know why people develop T1D, and this research has helped provide a lot more information and data as to what it looks like when genetically at-risk individuals are headed towards clinical diagnosis," says Aaron Michels, MD, the study's lead researcher, Associate Professor of Medicine at CU Anschutz and researcher at the Barbara Davis Center. "Ideally, you want to treat a disease when it's active, so this is a need in our field to understand when people have an immune response directed against insulin producing cells."

Researchers collected blood samples from genetically at-risk adolescents every 6 months for two years. Inflammatory T-cell responses to hybrid insulin peptides correlated with worsening blood glucose measurements and progression to T1D development. The results indicate an important advancement in identifying the risk of T1D early as well as the potential for intervention.

"There are now therapies used in research studies that have delayed the onset of clinical type 1 diabetes," says Michels. "Patients with these specific immune responses, may benefit from immune intervention to delay T1D onset and possibly prevent it for years."

Furthermore, Michels says these results can lead to research beyond T1D. "Our work focused on diabetes, but this has implications for other autoimmune diseases. Understanding how the immune system responds can be crucial in trying to prevent diseases before clinical symptoms are present."

A type of cell derived from human stem cells that has been widely used for brain research and drug development may have been leading researchers astray for years, according to a study from scientists at Weill Cornell Medicine and Columbia University Irving Medical Center.

The cell, known as an induced Brain Microvascular Endothelial Cell (iBMEC), was first described by other researchers in 2012, and has been used to model the special lining of capillaries in the brain that is called the "blood-brain barrier." Many brain diseases, including brain cancers as well as degenerative and genetic disorders, could be much more treatable if researchers could get drugs across this barrier. For that and other reasons, iBMEC-based models of the barrier have been embraced as an important standard tool in brain research.

However, in a study published Feb. 4 in the Proceedings of the National Academy of Sciences, the Weill Cornell Medicine scientists, in collaboration with scientists at Columbia University Irving Medical Center and Memorial Sloan Kettering Cancer Center, analyzed the gene expression patterns of iBMECs and found that, in fact, they are not endothelial cells--specialized cells that line blood vessels--and thus are unlikely to be useful in making accurate models of the blood-brain barrier.

"Models of key tissues and structures using stem cell technology are potentially very useful in developing better disease treatments, but as this experience indicates, we need to rigorously evaluate these models before embracing them," said co-senior author Dr. Raphaël Lis, assistant professor of reproductive medicine in medicine and a member of the Ansary Stem Cell Institute in the Division of Regenerative Medicine at Weill Cornell Medicine. Dr. Lis is also an assistant professor of reproductive medicine in the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine at Weill Cornell Medicine.

Since 2007, researchers have known that they can use combinations of transcription factor proteins, which control gene activity, to reprogram ordinary adult cells, such as skin cells sampled from a patient, into cells resembling the stem cells of the embryonic stage of life. Researchers can then use similar reprogramming techniques to coax these cells, called induced pluripotent stem cells, to mature into different cell types--cells that can be studied in the lab for clues to normal health and disease.

The announcement in 2012 that researchers had made iBMECs, using such techniques, was exciting because the cells seemed to be one of the first highly tissue-specific cell types created with stem cell methods. The cells also seemed especially useful for research, for they were thought to be essentially the same as the vessel-lining endothelial cells that form the blood-brain barrier--which normally prevents most molecules in the blood from crossing into brain tissue. Research using iBMECs to model the blood-brain barrier, to better understand neurological diseases and develop new treatments, has been well funded and has expanded to involve many laboratories around the world.

In trying to work with iBMECs, the collaborating teams noted major unexplained discrepancies between these cells and bona fide endothelial cells, for example in their patterns of gene activity. That prompted them to investigate further, using advanced methods including the latest single-cell sequencing techniques, to rigorously compare the gene activity in iBMECs and in authentic human brain endothelial cells.

They found that iBMECs in fact have a largely non-endothelial pattern of gene activity, with little or no activity among key endothelial transcription factors or other accepted gene signatures. The cells, they found, also lack standard cell-surface proteins found in endothelial cells. Their analysis suggested that iBMECs were mistakenly classified as endothelial cells and rather represent different cell type called epithelial cells. Epithelial cells participate in the formation of a physical barrier shielding the body from pathogens and environmental insults, while supporting the transport of fluids, nutrients and waste. Present in numerous organs like intestines, lungs or skin, the epithelial barrier, unlike endothelial cells, is not equipped to transport blood.

The researchers noted that the initial studies of iBMECs almost a decade ago put more emphasis on the mechanical, barrier-like properties of these cells and less on their actual cellular identity as revealed through gene activity patterns.

Generation of various human tissues from pluripotent stem cells is one the most widely used techniques in laboratories world-wide. This study indicates that such techniques should be studied carefully to avoid misidentification of cells that could result in inaccurate outcomes.

"Previously there were fewer methods for studying gene expression profiles, and there was less understanding of the patterns that make up the identities of distinct cell types," said co-senior author Dr. David Redmond, assistant professor of computational biology research in medicine and a member of the Ansary Stem Cell Institute in the Division of Regenerative Medicine at Weill Cornell Medicine.

The team found that by forcing the activity of three known endothelial cell transcription factors, they could reprogram iBMECs to be much more like endothelial cells.

"We don't yet have a good 'blood-brain barrier in a lab dish' model, but I think we are now a step closer to that goal, and have also corrected an important misconception in the field," said first author Tyler Lu, a research specialist in the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine at Weill Cornell Medicine.

CLEVELAND - A Cleveland Clinic-led team of researchers has developed a personalized genomic medicine platform that will help advance accelerate genomic medicine research and genome-informed drug discovery, according to new study results published recently in Genome Biology.

Known as My Personal Mutanome (MPM), the platform features an interactive database that provides insight into the role of disease-associated mutations in cancer and prioritizes mutations that may be responsive to drug therapies.

"Although advances in sequencing technology have bestowed a wealth of cancer genomic data, the capabilities to bridge the translational gap between large-scale genomic studies and clinical decision making were lacking," said Feixiong Cheng, PhD, assistant staff in Cleveland Clinic's Genomic Medicine Institute, and the study's lead author. "MPM is a powerful tool that will aid in the identification of novel functional mutations/genes, drug targets and biomarkers for cancer, thus accelerating the progress towards cancer precision medicine."

Using clinical data, the researchers integrated nearly 500,000 mutations from over 10,800 tumor exomes (the protein-coding part of the genome) across 33 cancer types to develop the comprehensive cancer mutation database. They then systematically mapped the mutations to over 94,500 protein-protein interactions (PPIs) and over 311,000 functional protein sites (where proteins physically bind with one another) and incorporated patient survival and drug response data.

The platform analyzes the relationships between genetic mutations, proteins, PPIs, protein functional sites and drugs to help users easily search for clinically actionable mutations. The MPM database features three interactive visualization tools that provide two- and three- dimensional views of disease-associated mutations and their associated survival and drug responses.

The results from another study published in Nature Genetics, a collaboration between Cleveland Clinic and several other institutions, motivated the team to develop the platform.

Previous studies have linked disease pathogenesis and progression to mutations/variations that disrupt the human interactome, the complex network of proteins and PPIs that influence cellular function. Mutations can disrupt the network by changing the normal function of a protein (nodetic effect) or by altering PPIs (edgetic effect).

Notably, in the Nature Genetics study, led by Brigham & Women's Hospital and Harvard Medical School, the researchers found that disease-associated mutations were highly enriched where PPIs occurred. They also demonstrated PPI-altering mutations to be significantly correlated with drug sensitivity or resistance as well as poor survival rate in cancer patients.

Collectively, MPM enables better understanding of mutations at the human interactome network level, which may lead to new insights in cancer genomics and treatments and ultimately help realize the goal of personalized care for cancer. The team will update MPM annually to provide researchers and physicians the most complete data available.

"Our Nature Genetics study also demonstrates the effects of mutations/variations in other diseases," added Dr. Cheng. "As a next step, we are developing new artificial intelligence algorithms to translate these genomic medicine findings into human genome-informed drug target identification and precision medicine drug discovery for other complex diseases, including heart disease and Alzheimer's disease."

A new study in Frontiers in Marine Science provides a first-of-its-kind evaluation of which regions of southern European seas are in the most need of fishing restrictions. These areas have persistently shown high numbers of undersized fish and crustaceans, which are typically discarded because they are below the allowable size limit for collection. These findings may offer a strategy for prioritizing conservation efforts and ensuring more sustainable fishery management in the future.

"Natural fish populations need time to reproduce and recover from fishing impacts -- this is the only way to achieve a balance between natural resources and human exploitation," says lead author Dr Giacomo Milisenda, of the Stazione Zoologica Anton Dohrn di Napoli in Italy. "Our findings provide evidence supporting active spatial-based management, such as the designation of Fisheries Restricted Areas (FRAs) in order to minimize the capture of immature or undersized specimens and improve the sustainability of demersal -- that is, sea floor -- fisheries."

According to a draft report from the European parliament in early January, Europe is far from reaching its marine sustainability and biodiversity goals. Despite the aims of the recently reformed EU Common Fishery Policy and commitments made by the European Commission, overfishing, habitat destruction and excessive discarding of unwanted catches are still ongoing problems.

The latest report from the Food and Agriculture Organization (FAO) of the United Nations found that 75% of Mediterranean and Black Sea fish stocks are overfished. Furthermore, past research has shown that, globally, more than 40% of catches are thrown back. The FAO has also found that roughly 50% of the discarded fish from the Mediterranean Sea is the result of demersal trawling -- a method of dragging nets across the sea floor.

To identify the regions that regularly have high proportions of unwanted catches, Milisenda and his collaborators combined bottom trawling surveys with the itineraries of commercial fishing operations from the last 15 years. They focused on four of the most important fishing waters in the area: the continental Portuguese coast, Catalan Sea, South of Sicily and Liguria and northern Tyrrhenian Seas.

Their findings showed that there were patches that were repeatedly trawled, and that these locations frequently coincided with hot spots of undersized animals. These methods may also make it possible to predict and avoid zones that are likely to have too many of these smaller animals.

In response to January's European parliament draft report, a coalition of NGOs has issued an urgent call for additional resources to safeguard European waters. The General Fisheries Commission for the Mediterranean has already been promoting fishing restrictions that prioritize which regions to protect and Milisenda's findings may help better plan current and future fishing operations.

The authors hope that their research will be used by governments and fishing operations to help address these ongoing environmental emergencies.

"Spatial management can only be successful if it is combined with the active collaboration of stakeholders (fishermen) and an effective regulation plan," says Milisenda.

At the time of writing, coronavirus disease 2019 (COVID-19) is seriously threatening human lives and health throughout the world. Before effective vaccines and specific drugs are developed, non-pharmacological interventions and numerical model predictions are essential. To this end, a group led by Professor Jianping Huang from Lanzhou University, China, developed the Global Prediction System of the COVID-19 Pandemic (GPCP).

Jianping Huang is a Professor in the College of Atmospheric Sciences and a Director of the Collaborative Innovation Center for Western Ecological Safety, Lanzhou University, China. He has for a long time been dedicated to studying long-term climate prediction, dust-cloud interaction, and semi-arid climate change by combining field observations and theoretical research. Lockdown in early 2020 seriously affected his research. Therefore, stuck at home, he held online discussions with his team members on how their experience of developing climate system models might be able to contribute to fighting the pandemic. He didn't expect much response, but was surprised and touched when many of his colleagues responded enthusiastically.

Therefore, he and his team combined the results of 30 years of work in statistical dynamic numerical weather prediction methods, and developed the GPCP based on the traditional Susceptible-Infected-Recovered (SIR) infectious disease model. The improved methods and results were published in Atmospheric and Ocean Science Letters.

In order to combine epidemiological data and models, the Levenberg-Marquardt (LM) parameter optimization algorithm was proposed to identify epidemiological models, thereby constructing a Statistical-SIR model. The LM algorithm introduces a damping coefficient when calculating the Hessian matrix by the traditional least-squares method, thereby combining the advantage of the Gauss-Newton method and gradient descent method and improving the stability of parameters.

"From the simulation results of four selected countries with relatively high numbers of confirmed cases, the Statistical-Susceptible-Infected-Recovered model using the LM algorithm was found to be more consistent with the actual curve of the epidemic, being better able to reflect its trend of development," explains Prof. Huang.

In addition, the ensemble empirical mode decomposition (EEMD) model and the autoregressive moving average (ARMA) model were also used in combination to improve the prediction results of the GPCP. The EEMD method has been widely used in the fields of engineering, meteorology, ecology, etc. It can decompose the signal according to its own scale, and is suitable for non-stationary and nonlinear signal processing. The ARMA method can better predict time series.

"We found that the EEMD-ARMA method can be directly used to predict the number of daily new cases in countries with a smaller number of confirmed cases whose development trend cannot be predicted by the infectious disease model. Based on the results, this method is more effective for improving prediction results and making direct predictions," concludes Prof. Huang.

The GPCP model developed by Jianping Huang's team can carry out targeted predictions for different countries and regions, and has achieved good prediction results. The team will continue to improve the model in the future to provide more accurate forecasts for different countries and regions.

PROVIDENCE, R.I. [Brown University] -- A new technique developed by Brown University researchers reveals the forces involved at the cellular level during biological tissue formation and growth processes. The technique could be useful in better understanding how these processes work, and in studying how they may respond to environmental toxins or drug therapies.

As described in the journal Biomaterials, the technique makes use of cell-sized spheres made from a highly compliant polymer material, which can be placed in laboratory cultures of tissue-forming cells. As the tissue-formation process unfolds, microscope imaging of the spheres, which are stained with fluorescent dye, reveals the extent to which they are deformed by the pressure of surrounding cells. A computational algorithm then uses that deformation to calculate the forces at work in that cellular microenvironment.

"We know that mechanical forces are important stimuli in tissue formation and development, but actually measuring those forces is pretty difficult," said Eric Darling, an associate professor of medical science, engineering and orthopedics at Brown. "These spheres that we've developed give us an extremely sensitive technique for measuring those forces over time in the same sample. And we can do this with multiple samples at a time on a 96-well plate, so it's a high-throughput method as well."

The research was a collaboration between Darling's lab and the lab of Haneesh Kesari, an assistant professor of engineering at Brown and an expert in solid mechanics. Darling and graduate student Robert Gutierrez developed the spheres and performed cell culture experiments with them, while Kesari and graduate student Wenqiang Fang developed the computational algorithm to calculate the forces.

The spheres are made from a polymer called polyacrylamide. The spheres have no apparent effect on the behavior of the newly forming tissues, Darling said, and the polyacrylamide material has mechanical properties that are highly consistent and tunable, which made it possible to make spheres soft enough to deform measurably when exposed to cellular forces.

"The key to this is having a highly controlled material, with a very precise shape as well as finely tuned and uniform mechanical stiffness," Kesari said. "If we know the properties of the spheres, then we can take pictures of how their shapes change and back out the forces necessary to make those changes."

As a proof of concept, the researchers performed a series of experiments to measure forces involved in mesenchymal condensation -- a process in which stem cells cluster together and eventually differentiate into tissue-specific cell types. The process is central to the formation of teeth, bones, cartilage and other tissue.

In one experiment, the team included the force-sensing spheres in cultures of cells were coming together to form multicellular balls. Microscope images of the cultures were taken every hour for 14 hours, enabling the team to track changes in the forces involved in each culture over time. The experiments showed that the forces involved in mesenchymal condensation were highly variable for the first 5 or so hours of the process, before settling down into a much steadier force profile. This was the first time such force dynamics had ever been measured, the researchers say.

To help verify that the spheres were truly sensitive to cellular forces, the team repeated the experiment using cultures treated with a cytoskeletal inhibitor, a drug that weakens the tiny contractile motors inside a cell. As expected, the spheres detected markedly weaker forces in the cultures treated with the drug.

In another set of experiments, the researchers added the sensor spheres to preformed cellular masses to observe how the spheres were taken up into the mass. Some of the spheres had been treated with a collagen coating, which enables cells to bind with the sensors, while others were uncoated.

"We were able to see differences in the force profiles between the coated and uncoated spheres," Darling said. "Overall there was a large compressive force, but with the coated cells we could see the cells interacting with the spheres directly, pulling on them and exerting a tensile force as well."

Darling says he's hopeful the technique could reveal fundamental details about how tissue-forming processes work. In the future, it may also be used screen drugs aimed at modulating these processes, or to test the effects of environmental toxins. It could also be useful in tissue engineering.

"If we want to grow cartilage, it might be helpful to know that the types of forces that these cells are exerting on each other because we might be able to apply an external force that matches or complements that force profile," Darling said. "So in addition to fundamental discovery, I think there is some translational potential for this down the road."

A study from the Center for Phage Technology, part of Texas A&M's College of Agriculture and Life Sciences and Texas A&M AgriLife Research, shows how the "hidden" genes in bacteriophages -- types of viruses that infect and destroy bacteria -- may be key to the development of a new class of antibiotics for human health.

The study has been published in Nature Communications and Current Science Daily, as well as featured in a recent Nature Research Microbiology Community blog post.

The need for new antibiotics
Antibiotic-resistant bacteria pose an increasing threat to human health, creating an urgent need for the development of novel antibiotics.

"There has been an increased interest in bacteriophages and their potential as antibacterial agents to fight pathogenic bacteria," said Center for Phage Technology director Ryland Young, Ph.D., who supervised the study research. "This is in large part due to the ability of the 'lysis genes' of the phage to cause a cellular breakdown in the bacterial host."

Gloved lab worker
The need for new and more effective antibiotics has increased interest in bacteriophages as possible agents to fight pathogenic bacteria.
Most phages can cause their host cell to rupture, a process called lysis. They also release new "progeny" phage virions that are genetically and structurally identical to the parent virus.

"Small phages, such as the ones this study focuses on, make a single protein which causes host lysis," Young said. "Basically, the virus produces a 'protein antibiotic' that causes lysis in the same way antibiotics like penicillin do - by disrupting the multistage process of cell wall biosynthesis. When the infected cell tries to divide, it blows up because it can't create the new cell wall between the daughter cells."

He said these small lysis proteins can be the model for a completely new class of antibiotics.

Purpose and key findings of the study
The study focuses on characterizing the lysis genes of leviviruses, bacteriophages containing small single-stranded RNA genomes with only three to four genes. Tens of thousands of leviviruses have been discovered. Among the known levivirus genes is Sgl, which stands for 'single gene lysis.' Sgl encodes a protein that induces the cellular breakdown of bacteria.

Many leviviruses contain Sgl genes, but these have remained "hidden" from researchers as they are small, extremely varied and can be embedded within other genes.

"We wanted to discover these 'hidden' lysis genes in single-stranded RNA phages, as well as understand how their structure and evolution could benefit development of new, more effective antibiotics," said Karthik Chamakura, Ph.D., a postdoctoral research associate at the center and the study's first author. "We also wanted to investigate how certain molecular targets within bacteria could be identified and exploited for antibiotic development."

Dr. Karthik Chamakura in lab at Center for Phage Technology finding new sources of antibiotics
Karthik Chamakura, Ph.D., postdoctoral research associate with the Center for Phage Technology at Texas A&M University, was the study's first author. (Texas A&M AgriLife photo)

In this study, researchers were able to identify 35 unique Sgls that produced a lytic or destructive effect on E. coli bacteria, Chamakura said. The team also determined that each of these Sgls could potentially represent a distinct mechanism for the lysis of host cells.

Chamakura also noted previous research had shown that known single-stranded RNA phages have high mutation rates.

"High mutation rates allow these phages to infect new species of bacteria," he explained. "In order to escape the new hosts, the phages have to either change the existing Sgl gene or evolve a new Sgl. In spite of a very short total length of genomic RNA, these phages can encode two or more Sgls or proto-Sgls for the lytic activity to destroy multiple bacterial hosts."

Another far-reaching aspect of the study was the observation that a large proportion of the Sgls found in the investigation had originated and evolved within the gene for the phage replication protein, or Rep.

"There were a disproportionate number -- 22 of the 35 of Sgls or Sgl candidates -- found embedded within the Rep gene," Chamakura said. "Overlaying the location of Sgl genes on the respective Rep sequences revealed that most of the Sgl genes evolved in less conserved regions of Rep. This could mean more highly divergent regions of the levivirus genome, such as the Rep gene, may serve as 'hotspots' for Sgl evolution."

He said the study's examination of genomes also revealed that closely related phages showed significant evidence of the de novo gene evolution.

"This indicated some of these Sgls did not evolve from existing genes but were essentially made from scratch in sections of the genome that do not code for any functional molecules," Chamakura said. "Therefore, a single-stranded RNA phage might have two or more lysis genes at different stages of gene evolution."

Study research overview and potential

In all, Chamakura said the research suggests Sgls are extremely diverse and remain vastly untapped as a source for peptides that could be used in protein antibiotics to attack the cellular function of bacteria.

Microscopic images of E. coli cells undergoing lysis

"Through the analysis of a relatively minuscule sample of the total leviviral universe, we have uncovered a diversity of small peptides that carry out a critical function in the life cycle of RNA viruses," he said. "We have also shown leviviruses readily evolve Sgl genes and sometimes have more than one per genome. And because these genes share little to no similarity with each other or to previously known Sgl genes, they represent a rich source for potential protein antibiotics."

He said the study should also be useful in helping uncover small genes and their biological functions in RNA viruses of more complex organisms -- such as plants and animals -- as well as provide a good model for studying how new genes evolve.

"Further research could include exploiting these peptides for identifying targets for antibiotic development," he said.

Primeval forests are of great importance for biodiversity and global carbon and water cycling. The three-dimensional structure of forests plays an important role here because it influences processes of gas and energy exchange with the atmosphere, whilst also providing habitats for numerous species. An international research team led by the University of Göttingen has investigated the variety of different complex structures that can be found in the world's forests, as well as the factors that explain this diversity. The results have been published in Nature Communications.

The researchers investigated the structure of primeval forests on several continents in different climate zones. To achieve this, they spent two years travelling to remote primeval forest areas around the world to record the structure of the forests with the help of 3D laser scanners. A laser scanner captures the environment with the help of a laser beam and thus builds a 3D representation of the forest. This allows important metrics to be calculated to describe the structure. They found that the global variability of forest structures can be explained to a large extent by the amount of precipitation and thus by the availability of water in the different ecosystems. Based on these findings and with the help of climate data, they were able to create maps of the world's forests showing the global variability of structural complexity.

The world maps describe the structures that forests can develop free from human influence. Only 30 percent of the world's forests are still primeval forests. "A long-term goal of our research is to better understand how human influence and climate change affect the forest, its structure and the processes linked to it. The structure of primeval forests is an important reference point for this," says first author Dr Martin Ehbrecht from the University of Göttingen. A particular focus here is the question of how changes in precipitation patterns due to climate change affect the structure of forests. "The importance of water for the formation of complex forest structures can be explained by various interacting mechanisms," says Ehbrecht. "The availability of water is an important driver of the diversity of tree species. The more tree species a forest holds, the more pronounced is the coexistence of different crown shapes and sizes of trees. This means that the space available for the crowns of trees can often be utilised more efficiently in species-rich forests, which makes the forest structure more complex."

Tropical rainforests have a more complex structure than the deciduous and coniferous forests found in temperate zones, which are in turn generally more complex in structure than boreal coniferous forests such as those in Scandinavia, or subtropical forest savannahs in Africa. "Nevertheless, forests with high structural complexity can also be found in temperate zones, such as in areas with a high rainfall like the Pacific Northwest of the USA or in coastal forests of Chile," says Professor Ammer, senior author of the study and head of Silviculture and Forest Ecology of Temperate Zones at Göttingen University.

The results of this study are an important starting point for further work. "With the help of satellite-based recording of 3-D forest structure, in the future it will be possible to precisely record the actual complexity of forests," says Ehbrecht. "This will make it possible to better understand the effects of forest management and climate change on the world's forests. Our world maps can serve as an important reference for this."

Fresno, CA - A recent human study published in the Journal of the American Academy of Dermatology found that consuming grapes protected against ultraviolet (UV) skin damage.1 Study subjects showed increased resistance to sunburn and a reduction in markers of UV damage at the cellular level. 2 Natural components found in grapes known as polyphenols are thought to be responsible for these beneficial effects.

The study, conducted at the University of Alabama, Birmingham and led by principal investigator Craig Elmets, M.D., investigated the impact of consuming whole grape powder - equivalent to 2.25 cups of grapes per day - for 14 days against photodamage from UV light. Subjects' skin response to UV light was measured before and after consuming grapes for two weeks by determining the threshold dose of UV radiation that induced visible reddening after 24 hours - the Minimal Erythema Dose (MED). Grape consumption was protective; more UV exposure was required to cause sunburn following grape consumption, with MED increasing on average by 74.8%.3 Analysis of skin biopsies showed that the grape diet was associated with decreased DNA damage, fewer deaths of skin cells, and a reduction in inflammatory markers that if left unchecked, together can impair skin function and can potentially lead to skin cancer. 4

It is estimated that 1 in 5 Americans will develop skin cancer by the age of 70. 5 Most skin cancer cases are associated with exposure to UV radiation from the sun: about 90% of nonmelanoma skin cancers and 86% of melanomas, respectively. Additionally, an estimated 90% of skin aging is caused by the sun.

"We saw a significant photoprotective effect with grape consumption and we were able to identify molecular pathways by which that benefit occurs - through repair of DNA damage and downregulation of proinflammatory pathways," said Dr. Elmets. "Grapes may act as an edible sunscreen, offering an additional layer of protection in addition to topical sunscreen products."

Enterocytes, which line the epithelium of the small intestine, are the sites of absorption and metabolism of most orally consumed medications. For this reason, studies on the absorption of novel oral drugs rely on in vitro or animal models to accurately recreate the environment of the small intestine. Currently, scientists widely use the human colon cancer cell line Caco-2 as a model of the intestinal epithelium. However, this has its drawbacks: Caco-2 cells have been derived from the colon; therefore, they more closely resemble the colon than the small intestine. For example, these cells do not express cytochrome P450 3A4 (CYP3A4), a protein critical for drug metabolism that is abundantly expressed in the small intestine. Moreover, Caco-2 cells tend to show high cell-line to cell-line variations.

To tackle these problems, scientists from the Tokyo Institute of Technology, The University of Tokyo, Kanto Chemical Co. Inc., Shionogi & Co., Ltd. and Shionogi TechnoAdvance Research Co., Ltd., developed novel enterocyte-like cells from human-induced pluripotent stem cells (hiPSCs), which can differentiate into any type of cell when provided with right growth factors.

By modifying a procedure that they previously used on human embryonic stem cells, the scientists initially grew cells that resemble the early stages of small intestine cells, called intestinal progenitor cells. Then, they cultured these progenitor cells on a collagen vitrigel membrane (CVM). Further, they treated the progenitor cells with a maturation medium containing 6-bromoindirubin-3'-oxime, dimethyl sulfoxide, dexamethasone, and activated vitamin D3. Their efforts resulted in the development of enterocyte-like cells that closely resembled actual enterocytes, expressing efflux transporter proteins regulating drug absorption as well as CYP3A4, which Caco-2 cells lack. Dr. Nobuaki Shiraki, Associate Professor at Tokyo Institute of Technology, and one of the corresponding authors of this study, adds, "We established an efficient culture procedure for generating enterocyte-like cells from hiPSCs by culturing the hiPSC-derived endoderm or intestine progenitor cells on CVM."

The scientists claim that these first-of-their-kind enterocyte-like cells can be used as an in vitro model of the small intestine for evaluating the intestinal absorption of drugs in humans. Elaborating on the advantages of using these cells for future studies, Dr. Shoen Kume, Professor at Tokyo Institute of Technology, and co-corresponding author of this study, comments, "The hiPSC-derived enterocyte-like cells established in this study could be used for the quantitative prediction of the intestinal absorption of drugs in humans under special occasions such as alteration of the functions of transporters/metabolic enzymes by drug-drug interactions as well as normal conditions."

Indeed, let us hope that the hiPSC-derived enterocyte-like cells would aid breakthrough research in future pharmacokinetic studies!