Culture

The bulk of the DNA in the cells of higher organisms is confined to the nucleus, while all other organellar DNAs are restricted to defined intracellular compartments in the cytoplasm. The appearance of DNA in the soluble phase of the cytoplasm is therefore interpreted by the innate immune system as signaling the presence of intracellular pathogens - usually bacteria or viruses, although tumor cells and senescent cells can also release nuclear or mitochondrial DNA into the cytosol. Misplaced DNAs - whether nuclear, mitochondrial or extracellular in origin - elicit a strong immune reaction, which is initiated by the enzyme cGAS. Researchers had long assumed that cGAS is itself localized exclusively in the cytosol. However, recent studies have shown that the protein is in fact preferentially found in the cell nucleus. This finding naturally raises the question of what prevents cGAS from binding to nuclear DNA and triggering an autoimmune reaction. Now a team of scientists in LMU's Gene Center, led by Professor Karl-Peter Hopfner, in collaboration with Professor Veit Hornung and his colleagues, has shown that the nature of the interaction of cGAS with the chromosomal DNA in the nucleus explains why the interaction fails to activate the innate immune system. The new findings appear in the leading journal Nature.

Upon binding to cytosolic DNA, cGAS synthesizes a messenger molecule which triggers an intracellular signaling cascade that results in the production of proteins that mediate an inflammatory reaction. This process is essential for the elimination of infectious pathogens. However, it is also implicated in the development of autoimmune diseases - some of which in fact involve the generation of antibodies directed against the cell's own DNA. The fact that the cGAS occurs in the nucleus therefore seems at odds with the protective function of the innate immune system, as activation of the enzyme in the nucleus itself would be expected to lead to autoimmune reactions against the nuclear DNA itself. "Curiously, recent data actually suggest that tight binding of cGAS to the DNA-protein complex found in the nucleus - which is known as chromatin - is crucial for the prevention of DNA-based autoimmunity," says Hopfner.

In the chromatin complex, the DNA is wrapped around disk-like particles made up of proteins called core histones. The resulting 'nucleosomes' are connected by 'linker DNA' that is not directly associated with core histones. By means of cryo-electron microscopy, Hopfner and colleagues were able to show that cGAS binds exclusively to the protein component of chromatin, and does not interact with the DNA itself. "That was a big surprise," says joint lead author Carina de Oliveira Mann. "Moreover, its mode of binding ensures that the DNA recognition site of cGAS is occluded. As a result, the enzyme is rendered inactive in the nucleus, even when the DNA in its vicinity becomes accessible to other proteins in the course of gene activation. Paradoxically, this implies that, by trapping the enzyme in an inactive state, chromatin actually serves as a reservoir for cGAS."

In fact, cGAS is most effectively inhibited in less tightly packaged regions of the chromatin, in which most of the genes reside. "That could explain why cGAS is activated in what are known as micronuclei in the cytosol, in which chromatin is thought to be densely packed," says Hopfner. Micronuclei consist of chromosome fragments surrounded by nuclear envelope. They are the product of errors in chromosome segregation in fast-growing tumor cells or DNA damage caused by ionizing radiation. "Our study represents an important step forward in our understanding of how cGAS interacts with chromatin," says Hopfner, "and will help us to clarify the inflammatory reaction initiated by the enzyme in the context of cancers and autoimmune diseases."

When volcanos erupt, these geologic monsters produce tremendous clouds of ash and dust--plumes that can blacken the sky, shut down air traffic and reach heights of roughly 25 miles above Earth's surface.

A new study led by the University of Colorado Boulder suggests that such volcanic ash may also have a larger influence on the planet's climate than scientists previously suspected.

The new research, published in the journal Nature Communications, examines the eruption of Mount Kelut (or Kelud) on the Indonesian island of Java in 2014. Drawing on real-world observations of this event and advanced computer simulations, the team discovered that volcanic ash seems to be prone to loitering--remaining in the air for months or even longer after a major eruption.

"What we found for this eruption is that the volcanic ash can persist for a long time," said Yunqian Zhu, lead author of the new study and a research scientist at the Laboratory for Atmospheric and Space Physics (LASP) at CU Boulder.

Lingering ash

The discovery began with a chance observation: Members of the research team had been flying an unmanned aircraft near the site of the Mount Kelut eruption--an event that covered large portions of Java in ash and drove people from their homes. In the process, the aircraft spotted something that shouldn't have been there.

"They saw some large particles floating around in the atmosphere a month after the eruption," Zhu said. "It looked like ash."

She explained that scientists have long known that volcanic eruptions can take a toll on the planet's climate. These events blast huge amounts of sulfur-rich particles high into Earth's atmosphere where they can block sunlight from reaching the ground.

Researchers haven't thought, however, that ash could play much of a role in that cooling effect. These chunks of rocky debris, scientists reasoned, are so heavy that most of them likely fall out of volcanic clouds not long after an eruption.

Zhu's team wanted to find out why that wasn't the case with Kelut. Drawing on aircraft and satellite observations of the unfolding disaster, the group discovered that the volcano's plume seemed to be rife with small and lightweight particles of ash--tiny particles that were likely capable of floating in the air for long periods of time, much like dandelion fluff.

"Researchers have assumed that ash is similar to volcanic glass," Zhu said. "But what we've found is that these floating ones have a density that's more like pumice."

Disappearing molecules

Study coauthor Brian Toon added that these pumice-like particles also seem to shift the chemistry of the entire volcanic plume.

Toon, a professor in LASP and the Department of Atmospheric and Oceanic Sciences at CU Boulder, explained that erupting volcanos spew out a large amount of sulfur dioxide. Many researchers previously assumed that those molecules interact with others in the air and convert into sulfuric acid--a series of chemical reactions that, theoretically, could take weeks to complete. Observations of real-life eruptions, however, suggest that it happens a lot faster than that.

"There has been a puzzle of why these reactions occur so fast," Toon said.

He and his colleagues think they've discovered the answer: Those molecules of sulfur dioxide seem to stick to the particles of ash floating in the air. In the process, they may undergo chemical reactions on the surface of the ash itself--potentially pulling around 43% more sulfur dioxide out of the air.

Ash, in other words, may hasten the transformation of volcanic gases in the atmosphere.

Just what the impact of those clouds of ash are on the climate isn't clear. Long-lasting particles in the atmosphere could, potentially, darken and even help to cool the planet after an eruption. Floating ash might also blow all the way from sites like Kelut to the planet's poles. There, it could kickstart chemical reactions that would damage Earth's all-important ozone layer.

But the researchers say that one thing is clear: When a volcano blows, it may be time to pay a lot more attention to all that ash and its true impact on Earth's climate.

"I think we've discovered something important here," Toon said. "It's subtle, but it could make a big difference."

Highest among cleaners and acute medical and BAME staff

Type of PPE worn may be key, say researchers

Findings relevant for any second coronavirus surge and/or seasonal flu this winter

Contrary to expectations, the risk of COVID-19 infection among hospital staff at the height of the coronavirus pandemic was lowest among intensive care clinicians, reveals a study of one major UK medical centre, published in the journal Thorax.

Infection risk was highest among cleaners, acute and general medicine clinicians, and those of Black, Asian and Minority Ethnic (BAME) backgrounds at University Hospitals Birmingham NHS Foundation Trust (UHBFT).

The findings prompt the researchers to suggest that the type of personal protective equipment (PPE) worn may be key to these differences, which are likely to be relevant for any second surge in COVID-19 and/or seasonal flu this winter.

UHBFT is one of the largest hospital trusts in the UK, with over 20,000 employees caring for 2.2 million people every year. As lead study author Professor Alex Richter explains in a linked podcast, at the height of the pandemic, 5 patients with serious COVID-19 infection were being admitted every hour.

At the time, there was no national NHS staff testing capacity, so no way of knowing who was infected, and therefore at risk of passing it on to patients, or who had already had the infection. "You've got to remember that we are all key workers, so travelling on public transport, and out and about," she says.

To find out, she offered to test staff with no COVID-19 symptoms for both current (throat and nose swabs to detect antigen) and previous (blood test to detect antibodies) infection. "I've never recruited to a study so fast in my life. We recruited 545 staff in 20 hours," she comments.

All the staff were at work over the course of 24 hours between 24 and 25 April 2020, around a month after the UK went into lock down. They were asked to report any illnesses consistent with COVID-19 that they had had in the previous 4 months. Information on ethnicity and department of work was also collected.

Nearly 2.5% (13 out of 545) staff with no symptoms tested positive for SARS-CoV-2, the virus responsible for COVID-19 infection. Of these, 38% (5) subsequently developed COVID-19 symptoms.

Around 1 in 4 (26%; 136) of the 516 for whom serum samples were available said they had previously had symptoms consistent with COVID-19 infection.

Staff with previous symptoms were significantly more likely to have antibodies than those who hadn't had symptoms: 37% (of 136 staff) vs 17% (of 281 staff). And they had higher levels of antibodies.

The overall prevalence of antibody positivity (seroprevalence) was 24% (126/ 516): this compares with 6% generally in the Midlands at the time.

When the researchers looked at the figures by staff area, striking differences in antibody positivity emerged.

Cleaners had the highest seroprevalence (34.5%; 10/29), followed by clinicians working in acute medicine (33%; 10/30) or general internal medicine (30%; 30/99). The lowest seroprevalence was found among staff working in intensive care medicine (15%; 9/61), emergency medicine (13%; 2/15), and general surgery (13%; 3/23).

There was also an ethnic divide: workers of BAME backgrounds were nearly twice as likely to have already had the infection as their White colleagues.

"We presumed intensive care workers would be at highest risk.. But workers in ITU are relatively well protected compared with other areas," explains Professor Richter.

"The reasons underlying this are likely to be multifactorial: in accordance with national guidelines, intensive care units were designated high-risk environments and the use of enhanced personal protective equipment (PPE) including filtered face piece (class 3) respirators mandated. In contrast, fluid-resistant surgical masks were recommended in other clinical areas," note the researchers.

This is an observational study, and not all participants provided all the information requested. Nor is it known whether symptomless infection among staff puts hospital patients at risk.

"However, our data would support the assessment of widespread healthcare worker testing, including track and trace, on viral transmission during future waves of a pandemic," conclude the researchers.

"All these factors are important for considering what's going to happen this winter," suggests Professor Richter. "Cases [of coronavirus] are on the rise. Are we going to have another surge? If there is one, how do we protect healthcare workers this winter?" she asks.

"And let's think not just about SARS-CoV-2 and the lessons we can learn for other pandemics, but seasonal infection. Influenza has a massive impact on the NHS every winter," she adds.

The NHS would spend billions of pounds more on drugs if it had to pay US prices following a US/UK trade deal. According to a new study by researchers at Brigham and Women's Hospital in Boston, Harvard Medical School, and the University of Oxford, published by the Journal of the Royal Society of Medicine, NHS England would have spent over £5 billion more on 50 brand-name prescription drugs widely used in primary care if it had paid US prices in 2018. Drugs on the list included a variety of commonly used medicines, including treatments for diabetes, inhalers and anticoagulants.

Prescription drug prices in the US far exceed prices in the UK, where there are price controls in place to limit NHS spending and restrict the profits that drug manufacturers can earn. The analysis shows that if NHS England had paid US prices for the 50 costliest drugs used in primary care in 2018 it would have spent 4.6 times as much, an increase from £1.39 billion to £6.42 billion.

It is currently unclear whether prescription drug prices will be included in any trade deal between the US and UK following Brexit. The UK government has previously stated that the NHS would not be part of a trade deal with the US, but a recent summary of negotiating objectives stated that the US Trade Representative is pursuing 'full market access' for US pharmaceuticals in the UK.

Lead researcher Michael Liu said: "The UK is working towards a range of external trade deals, which is great news. Our paper sounds a note of caution around the NHS medication spend: if drug prices were to be included in a US/UK trade deal, and current cost-containment mechanisms were compromised, this could result in drug prices more similar to those of the US."

"Because the scale of this difference in pricing is so substantial, we have modelled the possible excess costs, applying current US price data to current UK medicines usage data. We hope this provides helpful context for those evaluating different trade options."

As the first wave of the COVID-19 pandemic was receding in mid-May, some 1.3 million working-age adults reported being home sick with symptoms they attributed to the coronavirus. A new analysis finds that, compared to those still working or those absent with other illnesses or disabilities, the adults home sick with COVID-19 had lower incomes, were more likely to be racial/ethnic minorities, and had less education -- national-level evidence of the disparate impact of the COVID-19 pandemic that bolsters other studies based on diagnosed cases and deaths. The study, published September 10 in the Journal of General Internal Medicine, also found that these adults had very high rates of uninsurance and food insecurity that could compound the health harms of the pandemic, findings with relevance to ongoing debates over coronavirus relief legislation in Washington.

The researchers analyzed the Census Bureau's Household Pulse Survey, a new survey that provides information on the health and financial impact of the COVID-19 pandemic in the U.S. Using data from two weeks of the survey conducted in April and May, the researchers identified working-age adults who reported being out "sick with coronavirus symptoms" (previous research has found that some 83.0% of Americans correctly identify the leading coronavirus symptoms). Compared to those at work the previous week, researchers found that these individuals were more likely to be Black (24.2% vs. 11.5%), Asian (11.7% vs. 5.6%), and Hispanic (26.5% vs. 17.2%). The study authors observed similar patterns when comparing the adults home sick with coronavirus to those not working because of a non-coronavirus illness or disability. Those reporting coronavirus symptoms also had lower incomes and less education, and tended to live in larger households and states with high levels of COVID-19 incidence.

The researchers additionally found that those out sick with coronavirus symptoms had disturbingly high levels of social vulnerability: 29.2% of these individuals were uninsured, compared to 8% among the two comparison groups; and 36.2% reported not being able to obtain enough food, compared to 7.5% of those working and 20.8% of those out of work for another illness or disability.

"We know that Black and Hispanic communities have been the hardest hit by the COVID-19 pandemic, as measured in diagnoses and deaths," noted study author Dr. Steffie Woolhandler, distinguished professor at City of University Hunter College and a Lecturer at Harvard Medical School. "But our study suggests that the disparate impact is larger yet, because many people recover at home without ever being diagnosed. Our study also reveals remediable social vulnerabilities -- lack of health insurance and food insecurity -- that could further compound the inequitable health impact of the coronavirus," she added.

The study builds on previous studies from this research group. An earlier study, also published in the Journal of General Internal Medicine using data that predated the pandemic, found that some 18.2 million adults who were at increased risk of severe COVID-19 because of age or chronic disease were either uninsured or underinsured, and that these individuals were disproportionately people of color and lower income. In another study, published in JAMA: Internal Medicine, the researchers identified a historic rise in work absence for illness of any cause, with a disproportionate impact on immigrants, in April.

"The COVID-19 pandemic has been a disaster for working class Americans of all backgrounds, and for Black and Hispanic communities in particular," noted study author Dr. Adam Gaffney, a pulmonary and critical care physician at Harvard Medical School and the Cambridge Health Alliance. "But in so many ways, this disaster has been manmade. The high levels of uninsurance and food insecurity we observed in those reporting coronavirus symptoms is not an act of nature -- it could be solved today by action from Washington. Universal health coverage, and economic aid to American workers, is an urgent necessity."

UCLA researchers and colleagues who analyzed electronic health records found that there was a significant increase in patients with coughs and acute respiratory failure at UCLA Health hospitals and clinics beginning in late December 2019, suggesting that COVID-19 may have been circulating in the area months before the first definitive cases in the U.S. were identified.

This sudden spike in patients with these symptoms, which continued through February 2020, represents an unexpected 50% increase in such cases when compared with the same time period in each of the previous five years.

The findings, the study authors say, demonstrate the importance of analyzing electronic health records to monitor and quickly identify irregular changes in patient populations. The researchers' novel approach, in which they focused not only on hospitalization data but also on data from outpatient settings, may help epidemiologists and health systems detect future epidemics sooner.

The study appears in the peer-reviewed Journal of Medical Internet Research.

"For many diseases, data from the outpatient setting can provide an early warning to emergency departments and hospital intensive care units of what is to come," said Dr. Joann Elmore, the study's lead author and a professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. "The majority of COVID-19 studies evaluate hospitalization data, but we also looked at the larger outpatient clinic setting, where most patients turn first for medical care when illness and symptoms arise."

As scientists and doctors continue to learn more about SARS-CoV-2, the virus that causes COVID-19, health systems and public health agencies are also attempting to predict and monitor cases. Analyzing electronic patient records, the researchers say, could help health authorities more effectively identify and control outbreaks like the current pandemic, which has killed hundreds of thousands worldwide and disrupted billions of lives.

"The pandemic has really highlighted our need for agile health care analytics that enable real-time symptom and disease surveillance using electronic health records data," said Dr. Michael Pfeffer, a study co-author and chief information officer for UCLA Health. "Technology, including artificial intelligence powered by machine learning, has further potential to identify and track irregular changes in health data, including significant excesses of patients with specific disease-type presentations in the weeks or months prior to an outbreak."

The researchers evaluated more than 10 million health system and patient visit records for UCLA Health outpatient, emergency department and hospital facilities, comparing data from the period between Dec. 1, 2019, and Feb. 29, 2020 -- the months prior to increased public awareness of COVID-19 in the U.S. -- with data from the same period over the previous five years.

They found that outpatient clinic visits by UCLA patients seeking care for coughs increased by over 50% and exceeded the average number of visits for the same complaint over the prior five years by more than 1,000. Similarly, they discovered a significant excess in the number of patients seen in emergency departments for reports of coughs and of patients hospitalized with acute respiratory failure during this time period. These excesses remained even after accounting for changes in patient populations and seasonal variation.

The researchers noted that other factors could be responsible for some of this unexpected increase. For instance, their search of outpatient visit records included only the word "cough" as the reason for clinic visits, which may not have been sufficiently specific, and respiratory illnesses could have been due to vaping, though the use of e-cigarettes had been declining since September 2019. In addition, they could not rule out that the excess cases were due to flu.

"We may never truly know if these excess patients represented early and undetected COVID-19 cases in our area," Elmore said. "But the lessons learned from this pandemic, paired with health care analytics that enable real-time surveillance of disease and symptoms, can potentially help us identify and track emerging outbreaks and future epidemics."

Scientists from the Genotype-Tissue Expression (GTEx) project, a National Institutes of Health-funded consortium including researchers from the Broad Institute of MIT and Harvard, have completed a wide-ranging set of studies documenting how small changes in DNA sequence can impact gene expression across more than four dozen tissues in the human body.

These studies, released in a set of 15 papers published in Science and other journals, constitute the most comprehensive catalog to date of genetic variations that affect gene expression. They also highlight the importance of cell type as a factor in understanding how genes are regulated in human tissues, and provide a rich resource for connecting the functional dots between genetic variation and human traits and diseases.

The NIH launched GTEx in 2010 to identify and map quantitative trait loci (QTLs), namely, associations between genetic variants at specific locations in the genome and gene expression within a variety of tissues. Researchers have mapped the vast majority of genetic variants discovered through genome-wide association studies -- which scan the genome to identify variants linked to traits or disease -- to regions of the genome's non-coding DNA (which does not directly instruct the construction of proteins). This suggests that these variants act by influencing genes' expression, rather than by altering the proteins they encode.

To shed light on these relationships, GTEx set out to genotype and measure gene expression in samples of up to 50 tissue types (brain, heart, lung, prostate, uterus, etc.) from as many as 1,000 deceased donors, with a goals of identifying QTLs for as many genes as possible, and determining whether or not their effects are shared among multiple tissues or cell types.

"GTEx attempted to map, across as many individuals as possible, the basis of gene regulation, starting from how a genetic change might affect how a gene is expressed or how a protein is produced," said Kristin Ardlie, who directs the GTEx Laboratory Data Analysis and Coordination Center at Broad, and who served as co-corresponding author on the project's flagship Science paper with Broad computational biologist François Aguet and Tuuli Lappalainen of the New York Genome Center (NYGC).

A resource for the future

The flagship Science paper details the results of the GTEx Consortium's 10 years of work, efforts that have helped reveal much about the immense complexity underlying genetic control of gene expression. It presents the results of the consortium's analysis of 15,201 samples representing 52 tissues, collected from 838 donors -- a dataset nearly twice the size of that behind the most recent prior GTEx papers published in 2017. Each donor underwent whole genome sequencing to identify the genetic variants present, along with RNA sequencing of all tissue samples to establish the pattern of gene expression within the tissue.

The resulting dataset -- available via the GTEx portal -- catalogs QTLs governing the expression of more than 23,000 genes, with multiple QTLs regulating many genes. These included variants that directly affect expression of (eQTLs) or splicing within genes (sQTLs), both for variants close to the genes they control (cis-QTLs) and ones located on chromosomes other than the one harboring their target gene (trans-QTLs).

The data also confirmed that QTLs tend to be either very tissue-specific in their expression effects, or shared quite broadly across all tissues; and revealed some differences in QTL effects between sexes and across populations.

Mechanistically, the findings suggest that QTLs may often affect how a cell's transcription factors bind to the genome at a gene's promoter or enhancer, which in turn affects that gene's expression. And they also provide a baseline for deeper insights into functional roles QTLs play.

"At this larger sample size, and with the diverse tissues and donors we have, we can start to see that there is more than one regulatory effect per gene, and that these differ not just by tissue but by cell type," Ardlie said. "We can start to map at high resolution the variants that actually impact a trait. And we can begin to relate GWAS signals to QTLs and see whether what appear to be random GWAS hits might actually fall within functional elements that affect gene regulation and complex trait and disease phenotypes."

Tuning in

A key focus for this latest set of GTEx studies was to understand how QTLs mapped not just to tissues, but to specific cell types. With hundreds of samples sequenced from many tissues, GTEx researchers found that many genes were influenced by multiple QTLs. This phenomenon, called "allelic heterogeneity," reflects the fact that the GTEx tissue samples represent mixtures of many types of cells.

To gain a more nuanced understanding of QTLs' cellular specificity and learn the extent to which QTLs from different cell types contributed to their tissue-level observations, a GTEx team led by Aguet at Broad and Lappalainen and Sarah Kim-Hellmuth at NYGC used the project's RNA profiling data to computationally identify the cell types present within GTEx's tissue samples. They then checked whether QTLs mapped within those tissues were likely to be specific to the inferred cell types.

These analyses, reported in a companion Science paper, pinpointed thousands of "cell type interaction QTLs," many of which had not been previously characterized. The results indicate that many more cell type specific QTLs are likely to exist but cannot yet be detected without additional samples or improved methods. They also showed that the patterns of QTL sharing and specificity across tissues could be tied back to whether those tissues shared cell types in common.

The findings also revealed that even at the cell type-level, multiple QTLs can influence any given gene, sometimes acting together to boost expression, sometimes in opposition to tamp expression down, depending on an individual's genotype.

"In a sense, QTLs act like a dial on expression, one that can be adjusted up or down," Aguet explained. "One QTL might increase expression, but another might turn it back down a little. It all adds to the complexity of how genetic variation regulates gene expression."

An end, but also a beginning

This collection of studies comprises the consortium's final analysis of the GTEx dataset, though a great deal of work remains to be done and a great deal of knowledge remains to be gleaned from the catalog of QTLs. For instance, Ardlie noted, QTL analysis provides only one lens through which to view the functional implications of genetic variation, one that complements epigenomic, proteomic, and other forms of genomic and transcriptomic analysis.

"GTEx was an ambitious, complex undertaking, and it remains very difficult to access this breadth of tissues from individuals, and in that sense GTEx was unique and has helped pave the way for studies like the Human Cell Atlas," she said. "But we really need large-scale resources like this and others, such as ENCODE, from which we can glean complementary information to get a more complete picture of the molecular mechanisms that drive biology."

Thanks to various crystalline topologies, tunable chemical composition, high (hydro)thermal stability, and controllable surface acidity/basicity, zeolites are widely used in petroleum refining, petrochemical manufacture, fine chemical synthesis, biomedicine , environmental chemistry, etc. However, for many zeolite-catalyzed reactions, the molecular diameters of the reaction species involved are often larger than the pore apertures of the zeolites. This leads to undesired diffusion resistance between the bulk phase and the active centers of the catalyst, thereby significantly reducing the catalyst efficiency.

Alleviating diffusion resistance and improving catalyst efficiency of the zeolite-based catalyst is always one of the most concerned issues in academia and industry. Within the past decades, tools for integrating hierarchical micro-/mesoporous structures into zeolites for better diffusion and catalyst efficiency have been greatly enriched.

However, in the real industrial catalysis processes, even if zeolitic component contains hierarchically porous structure, it is just one of the components of the multi-component industrial catalyst. The zeolite-based industrial catalyst is essentially hierarchical structure composed of microporous zeolitic and macroporous non-zeolitic components. When the hierarchically porous structure is integrated, the catalyst also has a micro-/meso-/macroporous trimodal hierarchical structure. Obviously, the hierarchical pore structure of industrial zeolite-based catalysts exists in two levels: "inside the zeolitic component" and "between the components of the industrial catalyst".

In a new review paper published in the Beijing-based National Science Review, scientists at the China University of Petroleum in Qingdao, China (Peng Peng, Zi-Feng Yan), China National Petroleum Company in Beijing, China (Xiong-Hou Gao), and French National Center for Scientific Research (CNRS) in Caen, France (Svetlana Mintova) analyzed the state-of-the-arts in rational design of hierarchical micro-/mesoporous structures from catalytic reaction engineering point of view.

From the perspective of catalytic reaction engineering, the quantitative indicators for evaluating catalyst efficiency are catalyst effectiveness factor (η) and Thiele modulus (φ). If the catalyst system undergoes strong diffusion resistance (η

Zeolite with a hierarchical porous structure is just one of the components of real industrial catalysts. In order to meet the requirements of mechanical strength, hydrothermal stability, resistance to poisoning and coking in the industrial catalytic processes, industrial catalysts need to add other non-zeolitic components. Although the interaction mechanism between the industrial catalyst components is not fully understood, the non-ideal matching of the porous structures between the zeolitic and the non-zeolite components can cause reducing performance of the hierarchical pore zeolite components. The coordination of pores interconnectivity of hierarchical zeolites and other non-zeolitic components in industrial catalysts is an urgent issue to be addressed prior the industrial applications of hierarchical zeolites.

The ultimate goal for preparing hierarchically porous material is to fully release its potential at industrial scale by controlling the hierarchical pore structure, different components' locations and interconnectivity that play a pivotal role on enhancing of their catalytic efficiency. Developing combined in-situ or operando spectroscopic, microscopic or diffraction techniques is the key to unravel the structure-activity relationship of hierarchical zeolites as a component in industrial catalysts.

A pneumococcal vaccine was effective at protecting children in Laos against the most severe type of pneumonia, a new study has found.

The research led by the Murdoch Children's Research Institute (MCRI) and published in The Lancet Regional Health - Western Pacific, found the PCV13-vaccine reduced hypoxic pneumonia and pneumonia requiring oxygen support by 37 per cent.

MCRI Dr Cattram Nguyen said although pneumococcal vaccines were known to reduce severe cases of childhood pneumonia, no studies from Asia had measured their effectiveness until now.

The study involved 826 children, aged up to five years, admitted to hospital with pneumonia. PCV13 reduced hypoxic pneumonia and pneumonia requiring extra oxygen by 37 per cent.

Dr Nguyen said because pneumonia was a leading cause of childhood deaths in Laos, the PCV13 vaccine had great potential to alleviate this burden of disease on the most vulnerable. Pneumonia that requires oxygen therapy is one of the severest manifestations of pneumonia.

"Universal health care did not exist in Laos until recently, and supplementary oxygen treatment was prohibitively expensive for families," she said.

In October 2013, Laos introduced the PCV13 vaccine into its national childhood vaccination program, supported by Gavi, the Vaccine Alliance. But the Ministry of Health requested evidence of the health benefits of the vaccine to support its ongoing use.

MCRI Professor Fiona Russell said Asian countries have been very slow to introduce PCV13 into their national immunisation programs.

"These results provide a compelling argument to continue childhood PCV13 vaccination in Laos and for its introduction into similar countries with high death rates from pneumonia," she said.

Professor Russell said the study also described a simple, low-cost single hospital-based method to assess vaccine effectiveness that was feasible for other low and middle-income countries to adopt. Measuring the success of this vaccine would usually require thousands of cases collected over many years of surveillance, and often involving many hospitals, she said

"In this study, we enrolled children hospitalised with hypoxic and non-hypoxic pneumonia in a single hospital and compared pneumococcal vaccination rates between the two groups to determine vaccine effectiveness over about four years," she said.

Globally, lower respiratory infections, including pneumonia, are a leading cause of death in children under five years old, causing 800,000 deaths annually, predominantly in low- and middle-income countries.

Streptococcus pneumoniae (the pneumococcus) is estimated to cause over half of all pneumonia-related deaths in children under five years old.

People all over the world associate colors with emotions. In fact, people from different parts of the world often associate the same colors with the same emotions. This was the result of a detailed survey of 4,598 participants from 30 nations over six continents, carried out by an international research team. "No similar study of this scope has ever been carried out," said Dr. Daniel Oberfeld-Twistel, member of the participating team at Johannes Gutenberg University Mainz (JGU). "It allowed us to obtain a comprehensive overview and establish that color-emotion associations are surprisingly similar around the world."

In the current issue of Psychological Science, the scientists report that the participants were asked to fill out an online questionnaire, which involved assigning up to 20 emotions to twelve different color terms. The participants were also asked to specify the intensity with which they associated the color term with the emotion. The researchers then calculated the national averages for the data and compared these with the worldwide average. "This revealed a significant global consensus," summarized Oberfeld-Twistel. "For example, throughout the world the color of red is the only color that is strongly associated with both a positive feeling - love - and a negative feeling - anger." Brown, on the other hand, triggers the fewest emotions globally. However, the scientists also noted some national peculiarities. For example, the color of white is much more closely associated with sadness in China than it is in other countries, and the same applies to purple in Greece. "This may be because in China white clothing is worn at funerals and the color dark purple is used in the Greek Orthodox Church during periods of mourning," explained Oberfeld-Twistel. In addition to such cultural peculiarities, the climate may also play a role. According to the findings from another of the team's studies, yellow tends to be more closely associated with the emotion of joy in countries that see less sunshine, while the association is weaker in areas that have greater exposure to it.

According to Dr. Daniel Oberfeld-Twistel, it is currently difficult to say exactly what the causes for global similarities and differences are. "There is a range of possible influencing factors: language, culture, religion, climate, the history of human development, the human perceptual system." Many fundamental questions about the mechanisms of color-emotion associations have yet to be clarified, he continued. However, by using an in-depth analysis that included the use of a machine learning approach developed by Oberfeld-Twistel, a computer program that improves itself as the database grows, the scientists have already discovered that the differences between individual nations are greater the more they are geographically separated and/or the greater the differences between the languages spoken in them.

World Health Organization-recommended campaigns to circumcise millions of African boys and men to reduce HIV transmission are based more on systemic racism and 'neocolonialism' than sound scientific research, according to a critical appraisal published in Developing World Bioethics.

More than 25 million men and boys have already been circumcised as a result of voluntary medical male circumcision (VMMC) campaigns in eastern and southern Africa, implemented by the United States government and Western non-governmental organisations (NGOs).

The critical appraisal examined the history and politics of these circumcision campaigns in the context of race and colonialism, and found that they had been started in haste and without sufficient contextual research. The paper concluded that the campaigns have been carried out in a manner that implies troubling assumptions about culture, health and sexuality in Africa. Africans were underrepresented in the decision making process, and needed a greater voice in the planning of such an intimate health intervention.

Max Fish, lead author and founder of the VMMC Experience Project, a grassroots effort to elevate African voices about the effects of the campaigns on their lives, said: "There has been a global spotlight on systemic racism--and racist institutions--following the death of George Floyd, an African American man, at the hands of a White police officer in May. However, unethical human experimentation on Africans and African Americans remains a pervasive problem in Western medicine that has received relatively little attention."

"Africa was targeted, and it is still being targeted," said Cleophas Matete, a Kenyan bishop interviewed by the VMMC Experience Project, who is quoted in the study. "It is used as a continent to experiment. Should they introduce anything that is [morally questionable], they want to experiment in Africa. So I believe that the entire process of trying to test it in Africa was wrong from the beginning, and I say no to it."

Dr Arianne Shahvisi, Senior Lecturer in Ethics at Brighton and Sussex Medical School and second author, said: "We believe the decision to implement the circumcision campaign in southern and eastern Africa was not based on robust scientific evidence, but instead assumed that the results from clinical trials would safely 'scale' to the real world without thinking through the cultural implications. We argue that as a surgically corrective measure, the present circumcision campaigns hinge on racist, homogenising assumptions about the sexuality of those who are targeted, as well as a belief that HIV risk behaviours can be appraised independently of poverty and systemic factors."

There has been a long history of unethical medical research conducted on Africans and African Americans, including the infamous "Tuskegee Study of Untreated Syphilis in the Negro Male," in which African American syphilis patients living in rural poverty were observed but not treated, leading to suffering, the spread of infection and widespread death, and subsequent concerns about medical exploitation among these communities.

The decision to implement the circumcision policies in Africa was based on three clinical trials conducted in South Africa, Uganda, and Kenya, which showed that circumcision reduced men's HIV risk by 50-60% over two years. However, critics have alleged that the trials had serious limitations: they could not be placebo-controlled, and participants were explicitly informed of the study's aim to establish a lower HIV incidence following circumcision.

In addition, HIV prevalence at the start of the campaign was higher in circumcised than uncircumcised men in 10 out of 18 countries where such data was available, including five countries that were targeted for mass circumcision.

A fourth trial seeking to establish an HIV risk reduction for women allowed HIV-positive Ugandan men to infect unknowing partners--one of Tuskegee's ethical violations. This trial was stopped early for "futility" after partners of newly circumcised men became infected at a 55% higher rate, although this has received much less attention from the global public health community.

The critical appraisal was conducted by ethicists, legal and medical experts from the UK, US, Cameroon, Zimbabwe and South Africa.

About one third of the payments received by farmers are linked to specific "greening measures" to promote biodiversity. The cultivation of nitrogen-fixing legumes is very popular. However, these measures have been criticized because the benefits for biodiversity are unclear. Now a team from the University of Göttingen, the Julius Kühn Institute and the Thuenen Institute in Braunschweig has investigated whether the cultivation of the faba bean (Vicia faba - also known as the broad bean or fava bean) can support wild bees. It turns out that bumblebees benefit from the cultivation of faba beans, while all other wild bees depend on the presence of semi-natural habitats. The results of the study have been published in the Journal of Applied Ecology.

The researchers recorded wild bees in various German agricultural landscapes for the study. In one half of the landscapes, conventionally farmed faba beans were cultivated; in the other half there were no bean fields. "The nectar of the faba bean is hidden deep in the flowers and is only easily accessible to larger bees with long tongues, such as bumblebees. We therefore wanted to investigate how groups of wild bees, which differ in their external appearance, react to the cultivation of faba beans and whether they can benefit from it," says first author Nicole Beyer from the Functional Agrobiodiversity Group at the University of Göttingen. The study results show that there were more than twice as many bumblebees in the faba bean landscapes than in the landscapes without beans. In contrast, the cultivation of beans did not affect other wild bees. However, these other wild bees benefited from a high proportion of semi-natural habitats.

"Our research clearly showed that certain bee species can be supported by similar measures in farmed areas. But the benefits depend strongly on the characteristics of the crop and pollinator. In order to encourage the widest possible range of species, we propose a combination of measures: the cultivation of various flowering arable crops such as faba beans and the promotion or preservation of semi-natural habitats with a diverse range of flowers and nesting sites for many other wild bees," concludes Professor Catrin Westphal, Head of Functional Agrobiodiversity at the University of Göttingen.

People who binge-drink show more extensive dysfunction across their brains than previously realised, a new study from the University of Sussex has shown.

The research shows that binge-drinkers' brains have to put more effort into trying to feel empathy for other people in pain.

The paper "Differential brain responses for perception of pain during empathic response in binge drinkers compared to non-binge drinkers" is published in the October 2020 edition of the Neuroimage: Clinical journal. The study involved 71 participants (from France and the UK) whose brain activity was observed in fMRI scanners while undertaking a pain perception task. Half of these people were classified as binge-drinkers and half were not. The binge-drinkers were sober while they were being observed.

In the task participants were shown an image of a limb being injured, and asked to imagine either that the body part was theirs, or that of another person, and to state how much pain was associated with the image. The binge-drinking participants struggled more than their non-binge-drinking counterparts when trying to adopt the perspective of another person experiencing the pain: they took more time to respond and the scans revealed that their brains had to work harder - to use more neural resources - to appreciate how intensely another person would feel pain.

The study also revealed a more widespread dysfunction than previously realised; a visual area of the brain, which is involved in recognising body parts, showed unusually high levels of activation in the binge-drinkers. This was not true in the non-binge drinkers who looked at the same images.

When the binge-drinkers were asked to imagine the injured body part in the picture as their own, their pain estimate was not different from that of their non-binge drinking counterparts.

Professor Theodora Duka from the School of Psychology at the University of Sussex said:

"I have been studying the effects of drinking excessive alcohol for many years. In that time I have built up a strong body of evidence about the widespread way in which binge-drinking is associated with brain dysfunction in areas supporting self-control and attention. Our aim with the present study was to examine whether binge drinkers show less empathy and their brains show different responses to non-binge drinkers, when they imagine another person in pain. Reduced empathy in binge drinkers may facilitate drinking as it can blunt the perception of suffering of self or others during a drinking session. We have shown with this study that dysfunction associated with binge drinking is even more extensive than previously known. A region of the brain called the Fusiform Body Area associated with recognition of body parts showed hyperactivity in binge-drinkers in a situation in which feelings of empathy are experienced.

Dr Charlotte Rae from the School of Psychology at the University of Sussex said:

"Our results are quite surprising. Our data show that binge-drinkers need to work harder to feel empathy for other people in pain. They need to use more resources in terms of higher brain activity than non-binge drinkers. What this means in everyday life is that people who binge-drink might struggle to perceive the pain of others as easily as non-binge drinkers do. It's not that binge drinkers feel less empathy - it's just that they have to put more brain resource into being able to do so. However, under certain circumstances when resources become limited, binge drinkers may struggle to engage in an empathic response to others."

Bring drinking is defined as consuming more than 60 g of pure alcohol - (equivalent to about three quarters of one bottle of wine, or 2½ pints of lager) on at least one occasion in the past 30 days. About 30% of all adults (over 15 years of age) who drink alcohol in UK and France meet this criterion.

Epigenetic* changes in the islets of Langerhans of the pancreas can be detected in patients several years before the diagnosis of type 2 diabetes (T2D). These changes are responsible for the altered methylation activity of specific genes which differs from that in healthy individuals. In humans, 105 such changes have been discovered in blood cells. This was shown in a study by researchers from the DZD/DIfE, which has now been published in the journal Diabetes. These findings could help to develop diagnostic markers for type 2 diabetes.

Several causes play a role in the development of type 2 diabetes. These include a genetic predisposition, epigenetic factors as well as a diet high in fat and sugar, overweight and lack of exercise. In order to prevent the development of the metabolic disease, it is important to identify people with an increased risk for the metabolic disease at an early stage. Since the development of diabetes can also lead to functional disorders in the islets of Langerhans in the pancreas, researchers from the German Institute of Human Nutrition (DIfE) and the German Center for Diabetes Research (DZD) have investigated whether there are epigenetic changes in the islets of Langerhans that are related to the development of diabetes. Lund University also participated in the study.

"Our aim was to identify early changes in DNA methylation and the expression pattern in the islets of Langerhans in a diabetes-prone mouse and then to test which of these can also be detected in the blood of humans before diabetes is diagnosed," said Prof. Dr. Annette Schürmann, spokesperson of the DZD and head of the Department of Experimental Diabetology at DIfE, explaining the translational research approach. For this purpose, obese mice were fed a high-calorie diet for five weeks and divided into diabetes-prone and diabetes-resistant animals on the basis of certain criteria (e.g. the liver fat content). The DNA methylations and expression patterns in the islets of Langerhans were determined for both groups. "We were able to identify 497 candidates which differed both in terms of their expression and their DNA methylation," said first author Dr. Meriem Ouni.

The next step was to search for similar epigenetic changes in blood cells of participants in the EPIC-Potsdam study** (270 controls and 270 incident T2D cases on average 3.8 years before diagnosis). The researchers found altered levels of DNA methylation in 105 genes that were associated with the later diagnosis of diabetes. Most of these changes were also found in the islets of Langerhans in type 2 diabetes patients. The researchers assume that most of the alterations in DNA methylation that can be detected in the blood before diagnosis are still present in the islets of Langerhans later in the course of the disease.

"Our broad and translational research approach has identified a number of interesting genes whose expression and altered DNA methylation are associated with the later diagnosis of diabetes," said Schürmann. "In humans, 105 such differences can be detected in blood cells a few years prior to the diabetes diagnosis. This may open up the possibility of using some of these changes as diagnostic markers for type 2 diabetes in the future. "

Next, the researchers want to investigate whether diets or certain drugs can correct unfavorable DNA methylation patterns. They also want to determine whether the identified markers differ in the various diabetes clusters.

Androids, or robots with humanlike features, are often more appealing to people than those that resemble machines -- but only up to a certain point. Many people experience an uneasy feeling in response to robots that are nearly lifelike, and yet somehow not quite "right." The feeling of affinity can plunge into one of repulsion as a robot's human likeness increases, a zone known as "the uncanny valley."

The journal Perception published new insights into the cognitive mechanisms underlying this phenomenon made by psychologists at Emory University.

Since the uncanny valley was first described, a common hypothesis developed to explain it. Known as the mind-perception theory, it proposes that when people see a robot with human-like features, they automatically add a mind to it. A growing sense that a machine appears to have a mind leads to the creepy feeling, according to this theory.

"We found that the opposite is true," says Wang Shensheng, first author of the new study, who did the work as a graduate student at Emory and recently received his PhD in psychology. "It's not the first step of attributing a mind to an android but the next step of 'dehumanizing' it by subtracting the idea of it having a mind that leads to the uncanny valley. Instead of just a one-shot process, it's a dynamic one."

The findings have implications for both the design of robots and for understanding how we perceive one another as humans.

"Robots are increasingly entering the social domain for everything from education to healthcare," Wang says. "How we perceive them and relate to them is important both from the standpoint of engineers and psychologists."

"At the core of this research is the question of what we perceive when we look at a face," adds Philippe Rochat, Emory professor of psychology and senior author of the study. "It's probably one of the most important questions in psychology. The ability to perceive the minds of others is the foundation of human relationships. "

The research may help in unraveling the mechanisms involved in mind-blindness -- the inability to distinguish between humans and machines -- such as in cases of extreme autism or some psychotic disorders, Rochat says.

Co-authors of the study include Yuk Fai Cheong and Daniel Dilks, both associate professors of psychology at Emory.

Anthropomorphizing, or projecting human qualities onto objects, is common. "We often see faces in a cloud for instance," Wang says. "We also sometimes anthropomorphize machines that we're trying to understand, like our cars or a computer."

Naming one's car or imagining that a cloud is an animated being, however, is not normally associated with an uncanny feeling, Wang notes. That led him to hypothesize that something other than just anthropomorphizing may occur when viewing an android.

To tease apart the potential roles of mind-perception and dehumanization in the uncanny valley phenomenon the researchers conducted experiments focused on the temporal dynamics of the process. Participants were shown three types of images -- human faces, mechanical-looking robot faces and android faces that closely resembled humans -- and asked to rate each for perceived animacy or "aliveness." The exposure times of the images were systematically manipulated, within milliseconds, as the participants rated their animacy.

The results showed that perceived animacy decreased significantly as a function of exposure time for android faces but not for mechanical-looking robot or human faces. And in android faces, the perceived animacy drops at between 100 and 500 milliseconds of viewing time. That timing is consistent with previous research showing that people begin to distinguish between human and artificial faces around 400 milliseconds after stimulus onset.

A second set of experiments manipulated both the exposure time and the amount of detail in the images, ranging from a minimal sketch of the features to a fully blurred image. The results showed that removing details from the images of the android faces decreased the perceived animacy along with the perceived uncanniness.

"The whole process is complicated but it happens within the blink of an eye," Wang says. "Our results suggest that at first sight we anthropomorphize an android, but within milliseconds we detect deviations and dehumanize it. And that drop in perceived animacy likely contributes to the uncanny feeling."