Culture

Sophia Antipolis, France - 28 Aug 2020: Men with untreated high blood pressure have poorer penile blood flow than those with normal blood pressure, according to research presented today at ESC Congress 2020.1 The differences disappeared with blood pressure medication. The results provide reassurance to men concerned about the effects of blood pressure-lowering medications.

Hypertension (high blood pressure) affects more than one billion people worldwide and is the leading cause of premature death.2 A healthy lifestyle is advised, including salt restriction, alcohol moderation, exercise, weight control, and smoking cessation. Most patients also require drug treatment, which is linked to reduced risks of death, stroke, and heart disease - but around half of patients do not take their pills. Sexual dysfunction is one reason why patients stop medication.

Men with hypertension are almost twice as likely to have impaired penile blood flow and erectile dysfunction compared to men with normal blood pressure, increasing their risk of heart disease and death. High blood pressure damages artery walls, causing them to harden and narrow, and reducing blood flow to the penis. Erectile dysfunction is an early warning sign of damaged blood vessels.

However, previous studies have shown that erectile dysfunction is more common in treated, than untreated, men with high blood pressure. And certain antihypertensive drugs - notably diuretics and beta blockers - have been linked with deterioration in sexual function. This study examined the association between blood pressure level and penile blood flow, and whether blood pressure-lowering medication had an effect on the relationship.

The study included 356 men with erectile dysfunction and no history of diabetes or cardiovascular disease who attended a clinic between 2006 and 2019. The cohort was divided into three categories according to blood pressure: normal, high-normal, and hypertension. A total of 164 (46%) patients were being treated with antihypertensive medications.

All patients underwent a penile colour Doppler ultrasound which is the standard method for evaluating penile blood vessels and erectile dysfunction. The method involves injecting a drug into the base of the penis to open the blood vessels then measuring blood flow. Penile blood flow is considered impaired when the velocity is lower than 25 cm/s.

Among men not receiving antihypertensive medication, penile blood flow velocity progressively decreased with rising blood pressure - i.e. blood flow was fastest in those with normal blood pressure, slower in those with high-normal blood pressure, and slowest in those with hypertension (see Figure). In contrast, among men taking antihypertension therapy, there was no difference in penile blood flow velocity between the three blood pressure categories.

"The progressive decrease in penile blood flow velocity across the three blood pressure categories in men not taking antihypertensive medication indicates significant structural changes in the penile blood vessels from longstanding hypertension," said study author Professor Charalambos Vlachopoulos of the National and Kapodistrian University of Athens, Greece. "The blood flow differences across the three blood pressure categories disappeared with treatment, suggesting a medication effect."

An additional analysis compared treated and untreated men within each blood pressure group. In the hypertension category, treated and untreated patients had similar penile blood flow velocities. However, in the high-normal category, treated men had worse penile blood flow than untreated men. Similarly, in the normal blood pressure category, treated men had worse penile blood flow than untreated men.

Professor Vlachopoulos said: "These results imply that hypertensive patients already have significant structural damage in the penile arteries and adding antihypertensive drugs does not further reduce penile blood flow. But in men with normal or high-normal blood pressure, the penile arteries have minimal structural damage and medications could have a negative impact on penile blood flow."

He urged men with concerns about sexual dysfunction to discuss it with their doctor. "For men with as yet untreated hypertension, older medications (beta blockers and diuretics) are not ideal and should be used only if absolutely indicated," he said.

Professor Vlachopoulos noted that changing hypertensive medications in men with erectile dysfunction must be handled with caution. He said: "First, if a co-existing disease dictates using a specific drug category (for example, beta blockers for coronary artery disease and heart failure, diuretics for heart failure), then switching is not advocated. Alternatives might be considered if patients are at risk of stopping lifesaving therapy because of the detrimental impact of erectile dysfunction on their life."

"Second, switching to another drug class does not guarantee either the restoration or improvement of erectile function. This has to be carefully explained to patients in advance to avoid unreasonable expectations," he said.

Professor Vlachopoulos concluded: "Our study shows that high blood pressure can be treated without causing erectile dysfunction. Patients and doctors need to have open discussions to find the best treatment option."

Figure: Penile blood flow velocity across blood pressure categories in treated and untreated men

BP = blood pressure; PSV = peak systolic velocity.

A protein that's common throughout the body plays a key role in regulating glucose levels, says new research conducted in the Cell Signal Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) and Riken Center of Integrative Medical Sciences. Called CNOT3, this protein was found to silence a set of genes that would otherwise cause insulin-producing cells to malfunction, which is related to the development of diabetes.

Diabetes is a common disorder that causes very high blood glucose levels. Left untreated, it can lead to serious health problems like kidney failure, heart disease, and vision loss. This disorder occurs when there isn't enough insulin in the body or when insulin-induced responses are weakened. Insulin normally lets glucose into cells for energy-use and so, without it, glucose builds up in the blood instead. A lack of insulin is often because the pancreatic beta cells, which normally synthesize and secrete insulin, have stopped functioning correctly.

"We know that defects in beta cells can lead to high levels of glucose in the blood and, eventually, diabetes." said Dr. Dina Mostafa, former PhD student in the Unit and first author of the paper published in Communications Biology. "Our results suggest that CNOT3 has a hand in this and plays a key role in maintaining normal beta cell function."

Knocking out CNOT3 found to lead to diabetes in mice:

CNOT3 is a jack-of-all-trades. Many organs throughout the body express it, and it regulates different genes in different tissues. But its activity has a common basis - it helps to keep cells alive, healthy, and functioning correctly. It does this through several different mechanisms, such as producing the right proteins or suppressing certain genes.

Here, researchers studied its function in islet cells from pancreatic tissue in mice. These islets are notoriously difficult to work with, taking up just only one to two percent of the pancreas, but they're where the beta cells are located.

The researchers first looked at whether CNOT3 expression differed in diabetic mice compared with non-diabetic mice. By looking at these islets, they found that there was a significant decrease in the CNOT3 in the diabetic islets as opposed to the non-diabetic ones.

To further investigate the protein's function, the researchers blocked its production in the beta cells of otherwise normal mice. For four weeks, the animals' metabolism functioned normally, but by the eighth week, they had developed an intolerance to glucose, and by 12 weeks they had full-blown diabetes.

Without CNOT3, the researchers found that some genes, which are normally switched off in beta cells, switch on and start to produce proteins. Under normal circumstances, these genes are silenced because once they switch on, they cause all kinds of problems for the beta cells, such as stopping them from secreting insulin in response to glucose.

"We still don't know that much about these kinds of genes, such as what their normal function is and the mechanism that's involved in their silencing," Dr. Mostafa said. "So, it was very rewarding to find that CNOT3 in an important factor in keeping them switched off."

The messenger RNA connection:

Further research into the cellular mechanisms behind this found a surprising link between CNOT3 and the messenger RNA of these normally switched-off genes. A messenger RNA (mRNA) is a single strand molecule that corresponds to the genetic sequence of a gene and is essential for synthesizing proteins.

Under normal circumstances, the mRNA of these genes hardly expresses. But once CNOT3 was removed, the researchers found that the mRNA was much more stable. In fact, protein was produced from the stabilized mRNA, which have unfavorable effects on normal tissue function. This suggests that at least one way that these genes are kept switch off is through the destabilization of their mRNA, driven by CNOT3.

"This study is a step towards understanding the molecular mechanisms that govern normal beta cell function," Dr. Mostafa said. "Ultimately, it could contribute to new ways of preventing and treating diabetes."

Cells that are infected by a virus or carry a carcinogenic mutation, for example, produce proteins foreign to the body. Antigenic peptides resulting from the degradation of these exogenous proteins inside the cell are loaded by the peptide-loading complex onto so-called major histocompatibility complex molecules (MHC for short) and presented on the cell surface. There, they are specifically identified by T-killer cells, which ultimately leads to the elimination of the infected cells. This is how our immune system defends us against pathogens.

Machine operates with atomic precision

The peptide-loading complex ensures that the MHC molecules are correctly loaded with antigens. "The peptide-loading complex is a biological nanomachine that has to work with atomic precision in order to efficiently protect us against pathogens that cause disease," says Professor Lars Schäfer, Head of the Molecular Simulation research group at the Centre for Theoretical Chemistry at RUB.

In previous studies, other teams successfully determined the structure of the peptide-loading complex using cryo-electron microscopy, but only with a resolution of about 0.6 to 1.0 nanometres, i.e. not in atomic detail. Based on these experimental data, Schäfer's research team in collaboration with Professor Gunnar Schröder from Forschungszentrum Jülich has now succeeded in creating an atomic structure of the peptide-loading complex.

Exploring structure and dynamics

"The experimental structure is impressive. But only with our computer-based methods were we able to extract the maximum information content contained in the experimental data," explains Schröder. The atomic model enabled the researchers to perform detailed molecular dynamics computer simulations of the peptide-loading complex and thus to study not only the structure but also the dynamics of the biological nanomachine.

Since the simulated system is extremely large with its 1.6 million atoms, the computing time at the Leibnitz Supercomputing Centre in Munich aided this task considerably. "Using the high-performance computer, we were able to push into the microsecond time scale in our simulations. This revealed the role of sugar groups bound to the protein for the mechanism of peptide loading, which had previously only been incompletely understood," outlines Dr. Olivier Fisette, postdoc researcher at the Molecular Simulation research group.

Direct intervention in immune processes

The atomic model of the peptide-loading complex now facilitates further studies. For example, some viruses try to cheat our immune system by selectively switching off certain elements of the peptide-loading complex. "One feasible objective we'd like to pursue is the targeted intervention in these processes," concludes Schäfer.

The COVID-19 crisis has increasingly highlighted shortcomings in Australia's National Broadband Network, Flinders University experts say.

With access to high-speed broadband (HSB) and the internet via the NBN now central to people's livelihoods, education, healthcare delivery and even social connections, the Flinders University researchers say the "short-term politics of the 2013 federal election" led to decisions which caused an expensive rollout and current problems with the network.

"Our research shows that the way Australia's NBN was implemented has meant that access to HSB is expensive compared to other countries," Flinders University Southgate Institute for Health, Society and Equity researcher Dr Matt Fisher says in a new paper.

"This contributes to more than one million Australian households not having an internet connection at home."

The paper, 'Implementing Policy On Next-generation Broadband Networks and Implications for Equity of Access To High Speed Broadband: a Case Study of Australia's NBN' published in Telecommunications Policy, examines NBN policy and implementation from 2008 to 2018 through Australian Government policy documents and interviews with experts.

"We found that equity considerations competed with political and commercial imperatives during the rollout of the NBN," the Flinders Southgate researchers conclude.

"This resulted in positive and negative consequences for equity of access to HSB, with a change in policy and implementation in 2013 bringing greater risks to equity of access."

Dr Fisher says the NBN rollout also created differences in the quality of HSB services in different areas. "This is likely to mean that people already well-off will gain more health and social benefits from the NBN than those less well-off.

"As work, education, employment, healthcare and other social services increasingly go online, the inequalities built into the NBN could add to health inequalities in Australia."

Portland State University researchers used advanced electron microscopy to create a 3-D reconstruction of a membrane protein at an unprecedented level of resolution, setting the stage for the development of drugs that could target the protein more effectively to treat a variety of diseases.

The Reichow Lab, led by chemistry professor Steve Reichow and made up of undergraduate and graduate students, uses cryo-electron microscopy (cryo-EM) and computer modeling to visualize how individual proteins in cells interact and function at the molecular level.

The Reichow Lab is particularly interested in a class of proteins known as membrane proteins. Membrane proteins are key for cells to communicate with one another and are the target of 50% of pharmaceutical drugs, Reichow said.

The focus of this research was connexin-46/50, two proteins from the eye lens that form pathways for cell-to-cell communication. The group used lipid nanodisc technology to coax the proteins back into their native-like membrane environment, which allowed them to image the protein at a remarkably high resolution of 1.9-Angstrom (an angstrom is one 100 millionth of a centimeter). The group was the first to image a membrane protein below 2.0-Angstrom using cryo-EM, which momentarily set a world record for this technology.

Reichow said a resolution below 2.0-Angstrom is the precision desired for structure-based drug design, which uses the atomic-level detail of a 3D structure to computationally design novel therapeutic agents. The high resolution provided new insight into how this group of membrane proteins interact with their native lipid environment as well as allowed them to see nearly 400 water molecules, which play an important role in protein structure and function.

"Drugs use water to extend their interaction with proteins," Reichow said. "Drug manufacturers are missing a big piece of the puzzle if they don't know where the water molecules are."

Personality traits help to understand why some people are physically active and others are not. A new study from the Gerontology Research Center and the Faculty of Sport and Health Sciences at the University of Jyväskylä, Finland, shows that the role of personality may vary depending on how physical activity is measured.

Personality traits reflect people's characteristic patterns of thinking, feeling and behaving. A study at the University of Jyväskylä focused on two traits: extraversion and neuroticism. Individuals who score high in extraversion are typically social, active and talkative. High scores in neuroticism indicate a tendency to have negative feelings, such as anxiety and self-pity.

The results showed that high extraversion and low neuroticism were linked to higher leisure time physical activity in middle-aged women. Women who scored high in extraversion reported more physical activity, but this was not seen in the physical activity measured by an activity monitor. Women who scored high in neuroticism reported less physical activity and had less physical activity captured by activity monitors.

"Even though both methods assess the frequency, duration and intensity of physical activity, they measure partly different aspects of physical activity," explains postdoctoral researcher Tiia Kekäläinen from the Gerontology Research Center. "Activity monitors are better at capturing all daily stepping activities whereas self-reporting better accounts for all types of physical activities. Therefore, it is natural that results are partly different between different physical activity measures. It is important to use both ways to assess physical activity behavior."

Personality traits may explain individual tendencies to estimate one's own physical activity level

Personality may explain the way individuals assess their own level of physical activity. The results showed that older adults scoring high in neuroticism reported less physical activity than what was measured by accelerometers.

"Neuroticism describes a predisposition to experience negative feelings," Kekäläinen says. "In addition to lower willingness to participate in physical activities, this kind of tendency seems to be related to underreporting physical activity behavior. The information about the role of personality could be used to help identify risk groups for inactivity and in physical activity promotion work."

Two larger research projects conducted at the Gerontology Research Center and Faculty of Sport and Health Sciences provided data for the study: from a total of 314 older men and women aged 70 to 85 years who participated in the PASSWORD study, and from 1,098 middle-aged women aged 47 to 55 years who participated in the ERMA study.

The pathogenic fungus Candida auris, which first surfaced in 2009, is proving challenging to control. It is resistant to many fungicides and not easy to diagnose. Researchers from Radboud university medical center, Canisius-Wilhelmina Hospital (CWZ) and international colleagues have discovered that the human immune system recognizes the fungus well. The study has been able to pin-point the fungus' Achilles heel for new, effective drugs. Meanwhile, the threat posed by this emerging public health pathogen should not be underestimated.

In 2009, an unknown fungus was discovered in the infected ear of a seventy-year-old Japanese woman; this was called Candida auris. Where C. auris suddenly came from was not clear, but soon after that, different strains appeared all over the world. It turned out to be a persistent, difficult to control fungus, which was also usually resistant to fungicides.

Last year, the New York Times published an alarming article about the growing problem. The authors cited the example of a man infected with C. auris who died after 90 days at Mount Sinai Hospital. The fungus, which in the meantime had settled in the mattress, curtains, walls, telephone, basically everywhere in the hospital room, could only be removed with a lot of effort. Only after special cleaning and removal of part of the ceiling and the tile floor did the hospital control the fungus.

Reduced immunity

"We started to investigate C. auris with international colleagues because there was virtually nothing known about this fungus," says Mariolina Bruno of Radboud university medical center's Department of Internal Medicine. The research results have now been published in Nature Microbiology. The study shows that the fungus is especially dangerous for people with compromised immunity. Bruno: "A well-functioning immune system recognizes the fungus clearly and can control it well."

A careful study of the human immune response to the C auris infection demonstrated that specific components of the cell wall of the fungus play an essential role in this recognition. David Williams, East Tennessee State University: "These are unique structures that you do not encounter with other fungi. Those specific chemical structures stimulate the immune system enough to take action and clear the fungus."

Resistant to fungicides

The fact that C. auris is considered a serious and emerging infectious disease is mainly due to its resistance to many disinfectants and fungicides. People with an invasive C. auris fungal infection have thirty to sixty percent chance of dying, precisely because of the immunity of the fungus to many fungicides. Alistair Brown, University of Exeter: "Our research not only shows that these cell wall components are important for the detection by the immune system, but also that they are indispensable to the fungus. Drugs that selectively block the production and operation of these components are currently being investigated for safety and effectiveness. Perhaps one of these is the ideal candidate to tackle the fungus."

Since these cell wall components are indispensable to C. auris, the risk of resistance to such a new drug is small. In order to develop resistance, the fungus must at least remain alive so that it can gradually adapt to the new drug.

Diagnosis and monitoring

Candida auris is related to the much better-known Candida albicans, which can cause vaginal fungal infections. In the study, C. albicans has therefore served as comparison material. Bruno: "On the one hand, we see that C auris evokes a better immunity reaction than C. albicans. On the other hand, C. auris appears less pathogenic, but once in the bloodstream, both fungi are usually life-threatening."

What makes the problem even worse is that C auris is not so easy to identify. This makes it easy to confuse with other fungi, which can lead to a delay in treatment. Jacques Meis, a physician-microbiologist at the CWZ: "You should determine the fungi type on a molecular level, enabling you to immediately see which fungus you are dealing with, but not every laboratory has the facilities for that." Earlier this year, he and Paul Verweij (Radboud university medical center) called for the nation-wide monitoring of serious fungal infections to gain a better understanding of the burden of disease and mortality rates.

Global warming?

The question why C auris suddenly appeared in 2009 has still not been answered. The fungus was not found in stored patient material from previous years, so it seems to be a new or mutated fungus. Perhaps global warming plays a role, suggests American microbiologist Arturo Casadevall in TIME. Most fungi thrive at relatively low temperatures, but due to an increase in the average temperature, it is conceivable that a fungus breaks through its thermal restriction and can suddenly colonize the human body.

"An interesting point of view," says Bruno, "but without further evidence, it is as yet highly speculative. Apart from the actual origin history or 'birth' of C. auris, the article in Nature Microbiology provides information on how the interaction between humans and the fungus C. auris occurs: how the fungus stimulates the immune system, what C. auris' pharmacological Achilles heel is and what the opportunities for immunotherapy are."

The human genome contains over 4.5 million sequences of DNA called "transposable elements", these virus-like entities that "jump" around and help regulate gene expression. They do this by binding transcription factors, which are proteins that regulate the rate of transcription of DNA to RNA, influencing gene expression in a broad range of biological events.

Now, an international team of scientists led by Didier Trono at EPFL has discovered that transposable elements play a significant role in influencing the development of the human brain. The study is published in Science Advances.

The scientists found that transposable elements regulate the brain's development by partnering up with two specialized proteins from the family of proteins known as "Krüppel-associated box-containing zinc finger proteins, or KZFPs. In 2019, another study led by Trono showed that KZFPs tamed the regulatory activity of transposable elements in the first few days of the fetus's life. However, they suspected that these regulatory sequences were subsequently re-ignited to orchestrate the development and function of adult organs.

The researchers identified two KZFPs as specific only to primates, and found that they are expressed in specific regions of the human developing and adult brain. They further observed that these proteins kept controlling the activity of transposable elements - at least in neurons and brain organoids cultured in the lab. As a result, these two KZFPs influenced the differentiation and neurotransmission profile of neurons, as well as guarded these cells against inflammatory responses that were otherwise triggered if their target transposable elements were left to be expressed.

"These results reveal how two proteins that appeared only recently in evolution have contributed to shape the human brain by facilitating the co-option of transposable elements, these virus-like entities that have been remodeling our ancestral genome since the dawn of times," says Didier Trono. "Our findings also suggest possible pathogenic mechanisms for diseases such as amyotrophic lateral sclerosis or other neurodegenerative or neurodevelopmental disorders, providing leads for the prevention or treatment of these problems."

Researchers have revealed a new molecular mechanism by which bacteria adhere to cellulose fibers in the human gut. Thanks to two different binding modes, they can withstand the shear forces in the body. Scientists of the University of Basel and ETH Zurich published their results in the journal "Nature Communications".

Cellulose is a major building block of plant cell walls, consisting of molecules linked together into solid fibers. For humans, cellulose is indigestible, and the majority of gut bacteria lack the enzymes required to break down cellulose.

However, recently genetic material from the cellulose-degrading bacterium R. champanellensis was detected in human gut samples. Bacterial colonization of the intestine is essential for human physiology, and understanding how gut bacteria adhere to cellulose broadens our knowledge of the microbiome and its relationship to human health.

The bacterium under investigation uses an intricate network of scaffold proteins and enzymes on the outer cell wall, referred to as a cellulosome network, to attach to and degrade cellulose fibers. These cellulosome networks are held together by families of interacting proteins.

Of particular interest is the cohesin-dockerin interaction responsible for anchoring the cellulosome network to the cell wall. This interaction needs to withstand shear forces in the body to adhere to fiber. This vital feature motivated the researchers to investigate in more detail how the anchoring complex responds to mechanical forces.

By using a combination of single-molecule atomic force microscopy, single-molecule fluorescence and molecular dynamics simulations, Professor Michael Nash from the University of Basel and ETH Zurich along with collaborators from LMU Munich and Auburn University studied how the complex resists external force.

Two binding modes allow bacteria to stick to surfaces under flow

They were able to show that the complex exhibits a rare behavior called dual binding mode, where the proteins form a complex in two distinct ways. The researchers found that the two binding modes have very different mechanical properties, with one breaking at low forces of around 200 piconewtons and the other exhibiting a much higher stability breaking only at 600 piconewtons of force.

Further analysis showed that the protein complex displays a behavior called a "catch bond," meaning that the protein interaction becomes stronger as force is ramped up. The dynamics of this interaction are believed to allow the bacteria to adhere to cellulose under shear stress and release the complex in response to new substrates or to explore new environments.

"We clearly observe the dual binding modes, but can only speculate on their biological significance. We think the bacteria might control the binding mode preference by modifying the proteins. This would allow switching from a low to high adhesion state depending on the environment," Professor Nash explains.

By shedding light on this natural adhesion mechanism, these findings set the stage for the development of artificial molecular mechanisms that exhibit similar behavior but bind to disease targets. Such materials could have applications in bio-based medical superglues or shear-enhanced binding of therapeutic nanoparticles inside the body. "For now, we are excited to return to the laboratory and see what sticks," says Nash.

Generally speaking, "ridge subduction" involves subduction of spreading oceanic ridges, aseismic ridges or oceanic plateaus and inactive arc ridges, and this common and important geological process has become one of the hot topics in current geological research globally. However, many issues concerning ridge subductions need to be further studied.

A research entitled "Ridge subduction, magmatism and metallogenesis", with Wang Qiang as the first author, Tang Gongjian, Hao Lulu, Wyman Derek, Ma Lin, Dan Wei, Zhang Xiuzheng, Liu Jinheng, Huang Tongyu and Xu Chuanbing as co-authors, is published in Science China Earth Sciences. The researchers aim to provide a systematic review on recent progress in the study of ridge subduction and discuss some developing research frontiers in the fields related to ridge subduction.

Spreading oceanic ridges, aseismic ridges or oceanic plateaus and inactive arc ridges together account for more than 20-30% of the total area of the world's ocean floor (Figure 2). Ridge subduction closely related to "the generation of arc magmatism, material recycling, growth and evolution of continental crust, deformation and modification of overlying plates and metallogenesis", is a significant geological process in modern oceanic plate tectonics.

The perpendicular or highangle subduction of mid-oceanic spreading ridges is commonly characterized by the occurrence of a slab window, and the formation of adakite-high-Mg andesite-Nb-enriched basalt-oceanic island basalt (OIB) or mid-oceanic ridge basalt (MORB)-type rock suite, and is closely associated with Au mineralization.

On the eastern side of the Pacific Ocean, aseismic ridges or oceanic plateaus are being subducted flatly or at low angles beneath South and Central American Continents, which may cause slab rollback or tearing and the formation of an adakite-high-Mg andesite-adakitic andesite-Nb-enriched basalt suite, and is closely associated with Cu-Au mineralization.

However, on the western side of the Pacific Ocean, aseismic ridges and oceanic plateaus are associated with steep subduction (with angles>30°), which generate large scale eruptions of basalts, basaltic andesites and andesite.

The subduction of inactive arc ridges in Southwest Japan generated basalts, high-Mg andesites and adakites, and Au mineralization.

In addition to arc magmatism and metal mineralization, ridge subduction may also trigger subduction erosion in the overlying plate.

"Many issues concerning ridge subductions remain controversial", said the researchers. "Future frontiers of research will include characterizing the spatial and temporal patterns of ridge subduction events, clarifying the associated geodynamic mechanisms, quantifying subduction zone material recycling, establishing the associated deep crustal and mantle events that generate or influence magmatism and Cu-Au mineralization, establishing criteria to recognize pre-Cenozoic ridge subduction, the onset of modern-style plate tectonics and the growth mechanisms for Archean continental crust."

New Orleans, LA - A study of a gateway receptor for SARS-CoV-2 led by Walter J. Lukiw, PhD, Professor of Neuroscience, Neurology and Ophthalmology at LSU Health New Orleans' Neuroscience Center of Excellence and School of Medicine, may help explain the wide variety of symptoms and organs involved with SARS-CoV-2 infection and COVID-19. The results suggest that a multi-organ infection with SARS-CoV-2 may be via the angiotensin-converting enzyme 2 (ACE2) receptor, which is found almost everywhere throughout the body. The findings are published in the journal Cellular and Molecular Neurobiology, available here.

To better understand the mechanism and pathways of SARS-CoV-2 infection and susceptibility to specific cell and tissue types as well as organ systems, the research team analyzed 85 human tissues for the presence of ACE2 receptors. ACE2 is a protein that is found on the surface of many immune and nonimmune cell types. An enzyme, it is part of the system that regulates blood pressure and fluid and electrolyte balance. It may also help regulate cardiovascular, neurovascular and renal function, as well as fertility. ACE2 receptors act like locks on cells, and the SARS-CoV-2 spike proteins act like keys that open the locks letting the virus enter cells to rapidly multiply. As well as controls, tissues tested included lung, digestive, renal-excretory, reproductive, eye tissues, and 21 different regions of the brain.

"Besides strong ACE2 expression in respiratory, digestive, renal-excretory and reproductive cells, high ACE2 expression was also found in the amygdala, cerebral cortex and brainstem," reports Dr. Lukiw. "This may help explain cognitive deficits associated with SARS-CoV-2 infection. Some of the highest ACE2 expression levels were found in the pons and medulla oblongata in the human brainstem, an anatomical region of the brain containing the medullary respiratory centers, and this may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress."

The team further noted that ACE2 receptor activity was also easily detected in the eye, suggesting that the visual system may provide an additional entry point for SARS-CoV-2 invasion and that under certain conditions, eyeglasses or face shields may be as important as face masks in reducing SARS-CoV-2 transmission and infection.

"Several important research gaps remain," Lukiw concludes. "A real danger of SARS-CoV-2 infection is not only its highly transmissible and contagious nature and lethality, but also its simultaneous and multipronged attack on many human cell and tissue types involving vital and critical respiratory, immunological, vascular, renal-excretory and neural systems as well as an unprecedented coordinated disruption of the complex neurophysiology, neurochemistry, neurobiology and neurology of the cells of the brain and central nervous system (CNS) that normally regulate these multiple physiological systems."

The COVID-19 pandemic has deeply affected our daily lives and put individuals, institutions, and societies to the test in several regards. The new policies adopted by governments to contain the pandemic, and the economic and psychological impact it has had on people, have caused significant changes in higher education systems.

The international travel restrictions, growing fear and anxiety, increasing prejudices, and burden of economic slowdowns, among other factors, could become obstacles for international students willing to attend university abroad. However, the present situation is highly dynamic, and predicting the lasting impacts of the COVID-19 crisis on international university education is difficult.

In the latest issue of the East China Normal University (ECNU) Review of Education, four education researchers provide their unique perspectives on how the pandemic will affect international student mobility (ISM) and identity.

In the first article, Dr Jiao Guo from ECNU, China, focuses on how Chinese students and their families are reacting to the pandemic. She recognizes that many Chinese families are understandably stressed not only because of the health risk that COVID-19 poses, but also by the anti-Chinese sentiment that has sadly become more noticeable in many Western countries.

Dr Guo argues, however, that the effect of the current crisis on Chinese student applications to universities abroad will vary. Based on an emotion-moderated sunk cost theory, a concept borrowed from the fields of economics and business decision-making, she speculates that some Chinese families will remain on course towards a university education overseas, perhaps with a destination change or a delay of a year or two. She says, "These are families with children who have nearly finished their K-12 education in international Chinese schools, who feel that they have already invested too much time, money, and effort into their children's education to change plans. On the other hand, working class families with children in public schools should be more inclined to opt for local education in one of China's universities."

In the second article, Dr Hantian Wu from Zhejiang University, China, analyzes the prospects for ISM from a historical perspective. He argues that internationalized higher education systems will have to re-predict their development trends and that studying how previous global crises affected the education sector is a plausible strategy for doing so. He goes over several medieval and premodern crises, including the Black Death and the Spanish flu outbreak of 1918, to prove that higher education systems are remarkably resilient. For instance, Chinese student inflow into western countries increased considerably in the immediate aftermath of the Spanish flu. Modern history also seems to be consistent with this trend, as observed, for example, post the 2001 terrorist attacks on the United States.

Nonetheless, Dr Wu cautions against taking historical events as conclusive evidence: "Discussions about recurring issues in modern history may be convincing, but they also should not be regarded as persuasive evidence for proving that history repeats itself. Still, it seems appropriate to conclude that a single sudden crisis can hardly bring fundamental changes to the overall trend of student mobility."

In the third article, Dr Jie Zheng from ECNU holds forth that the current pandemic might change how students and policy makers view neoliberal globalization. Dr Zheng argues that the optimism surrounding globalization has been a driving factor for the explosive growth of ISM in the past few years. "In the past two decades, we have been proud of our 'global village' and global vision. We have enjoyed a deterritorialization of social life and free mobility worldwide. Indeed, imagination has been transformed by the media and those narratives of possible lives and fantasies might have stimulated people's desire for movement," she states.

The ongoing pandemic challenges this neoliberal logic of "free trade, free market, free mobility." The focus, she concludes, has inevitably shifted to developing online education systems that could, in the future, open doors to possibilities for a more inclusive and environmentally sustainable society.

But such a society will also depend on the global citizen that emerges from the pandemic. In the fourth article, Dr Tao Wang from ECNU argues that the breakdown of neoliberal globalization and the dual stigmatization of the Chinese student, both by Chinese nationalists and by nationalists of several other countries, had made the cosmopolitan identity complex.

Yet, he remains optimistic. He says, "I predict that a new generation of 'glocal' citizens will emerge who can navigate smoothly between their local and global identities, understanding global challenges, respecting cultural diversity, and participating in cross-cultural communication. These citizens will bring about the beginning of a shared positive global future."

The COVID-19 pandemic is certainly changing the education landscape for good. But what the new landscape will look like when the dust settles, remains to be seen. Perhaps these new perspectives will prove useful to individuals and organizations who must take action and, willingly or unwillingly, shape the future.

Linguistic researchers use an extensive body of research on English and other Western languages to make broad assumptions about trends in human language, including an apparent universal preference for suffixes (e.g., less, able, ment) over prefixes (e.g., fore, anti, trans). Since psychological scientists recognize the powerful link between language and cognition, a tendency for suffixes to dominate human language may reflect a universal trait of how we think and process the world around us.

However, new research published in the journal Psychological Science reveals that even though many populations favor suffixes in the same way English speakers do, others do not, including speakers of the African Bantu language Kîîtharaka. This unexpected discovery challenges the idea that Western languages are sufficient when studying language and its connection to psychological science.

"The original hypothesis that humans generally prefer suffixes makes a lot of intuitive sense, at least to us English speakers," said Alexander Martin, a language researcher at the University of Edinburgh and lead author on the paper. "We were surprised, therefore, to see just how starkly the two populations [English speakers and Kîîtharaka speakers] differed in this regard."

For their research, Martin and his colleagues studied specific word characteristics among the two populations--one whose language relies more frequently on suffixes (51 English speakers) and one whose language relies more on prefixes (72 Kîîtharaka speakers). Participants were presented with a sequence of either shapes or syllables followed by two additional sequences. They were then asked to identify the sequence most similar to the original sequence. Based on their results, the researchers were able to identify which parts of sequences the speakers considered most important and therefore less likely to be modified.

English speakers considered the beginnings of words as more important, a language characteristic that reflects English's use of suffixes. Kîîtharaka speakers, however, were inclined to treat endings as more important, opting to select sequences that altered the beginnings of words.

"This finding really challenged a previous claim about human language," said Martin. "It showed that the abundance of suffixes across the world's languages might not simply be a reflection of general human perception."

A preference for prefixes over suffixes by some language speakers has larger implications than diverse human cognition. It might be a sign that language research has not been exhaustive in the past.

"The important take-home here is that if we want to understand how language is shaped by universal features of human cognition or perception, we need to look at a diverse sample of humans," said Martin.

The WEIRD Preference for Suffixes

Prior research has established that English speakers favor the beginnings of words. This is reflected in the structure of English: when modifying a word to change its meaning, English tends to add suffixes. For example, common suffixes in the English language include "-wise," which you might add onto the end of "clock," or "like," or "-al," which often tails behind "accident" or "fiction."

These past language studies, however, have focused predominantly on Western, educated, industrialized, rich, and democratic (WEIRD) populations. Such studies have concluded that suffixes are generally preferred over prefixes. Martin and his colleagues observed that such research excludes populations that do not fall into "WEIRD" categories, and conclusions drawn from them could therefore be unrepresentative of universal human cognition.

The Nexus of Language and Cognition

"How the human brain perceives and processes the world around it impacts language, but not every feature of language is a direct reflection of this," said Martin. "For example, how we use language, like for communication, can also affect language patterns." The study's conclusions further illuminate the relationship between human cognition and language systems and patterns. However, Martin cautioned against assuming that different languages must mean drastically different perceptions of the world.

"When we look at speakers of other languages, especially those who speak languages that haven't been studied extensively, we are able to understand that we've been seeing the world through a biased lens. That's something we think psychologists should care about," he said.

UNIVERSITY PARK, Pa. -- Consumers are expected to spend more than $100 billion at online pharmacies in the next few years, but not all of these businesses are legitimate. Without proper quality control, these illicit online pharmacies are more than just a commercial threat, they can create serious health threats.

In a study, a team of Penn State researchers report that an algorithm they developed may be able to spot illicit online pharmacies that could be providing customers with substandard medications without their knowledge, among other potential problems.

"There are several problems with illicit online pharmacies," said Soundar Kumara, the Allen E. Pearce and Allen M. Pearce Professor of Industrial Engineering. "One is they might put bad content into a pill, and the other problem is they might reduce the content of a medicine, so, for example, instead of taking 200 milligrams of a medication, the customers are only taking 100 milligrams -- and they probably never realize it."

Besides often selling sub-standard and counterfeit drugs, illicit pharmacies may provide potentially dangerous and addictive drugs, such as opioids, without a prescription, according to the researchers, who report their findings in the Journal of Medical Internet Research, a top-tier peer-reviewed open-access journal in health/medical informatics. The paper, "Managing Illicit Online Pharmacies: Web Analytics and Predictive Models Study," can be accessed here.

The researchers designed the computer model to approach the problem of weeding out good online pharmacies from bad in much the same way that people make comparisons, said Kumara, who is also an associate of Penn State's Institute for Computational and Data Sciences.

"The essential question in this study is, how do you know what is good or bad -- you create a baseline of what is good and then you compare that baseline with anything else you encounter, which normally tells you whether something is not good," said Kumara. "This is how we recognize things that might be out of the norm. The same thing applies here. You look at a good online pharmacy and find out what the features are of that site and then you collect the features of other online pharmacies and do a comparison."

Hui Zhao, associate professor of supply chain and information systems and the Charles and Lilian Binder Faculty Fellow in the Smeal College of Business, said that sorting legitimate online pharmacies from illicit ones can be a daunting task.

"It's very challenging to develop these tools for two reasons," said Zhao. "First is just the huge scale of the problem. There are at least 32,000 to 35,000 online pharmacies. Second, the nature of online channels because these online pharmacies are so dynamic. They come and go quickly -- around 20 a day."

According to Sowmyasri Muthupandi, a former research assistant in industrial engineering and currently a data engineer at Facebook, the team looked at several attributes of online pharmacies but identified the relationships between the pharmacies and other sites as a critical attribute in determining whether the business was legitimate, or not.

"One novelty of the algorithm is that we focused mostly on websites that link to these particular pharmacies," said Muthupandi. "And among all the attributes we found that it's these referral websites that paint a clearer picture when it comes to classifying online pharmacies."

She added that if a pharmacy is mainly reached from referral websites that mostly link to or refer illicit pharmacies, then this pharmacy is more likely to be illicit.

Zhao said that the algorithm the team developed could help consumers identify illicit online pharmacies, which are estimated to represent up to 75% of all online drug merchants. As an added danger, most consumers lack the awareness of the prevalence and the danger of these illicit pharmacies and consequently use the site without knowing the potential risks, she said.

The researchers said a warning system could be developed that alerts the consumer before a purchase that the site may be an illicit pharmacy. Search engines, social media, online markets, such as Amazon, and payment or credit card companies could also use the algorithm to filter out illicit online pharmacies, or take the status of the online pharmacies into consideration when ranking search results, deciding advertising allocations, making payments, or disqualifying vendors.

Policy makers, government agencies, patient advocacy groups and drug manufacturers could use such a system to identify, monitor, curb illicit online pharmacies and educate consumers.

Infants from households reporting very low "food security," a measure of access to adequate and healthy meals, tend to weigh more than those from households with relatively high food security, suggests a new study led by a researcher at Johns Hopkins Bloomberg School of Public Health.

The study tracked nearly 700 infants in North Carolina over their first year of life, with regular interviews of the infants' mothers. The researchers found that when mothers reported very low food security per a standard government questionnaire, the infants were more likely to have above-average body mass indices (BMIs), higher fat levels, and other measures indicating greater obesity risk.

The reasons for the association between food insecurity and higher obesity risk are not yet understood but may be related to poor nutrition and overfeeding. The results suggest that household food insecurity may be especially hazardous for infants, given that diet and weight gain in infancy are thought to have a potentially large impact on the future risks of obesity and related health conditions.

The study was published August 28 in Pediatrics.

Study lead author Sara Benjamin-Neelon, PhD, JD, the Helaine and Sidney Lerner Associate Professor in the Bloomberg School's Department of Health, Behavior and Society, began the study in 2013 when she was a faculty member at Duke University's School of Medicine, and completed data collection in 2017 at the Bloomberg School. The 666 infants tracked in the study were from lower-income households in Durham, NC. Most of the infants (68.6 percent) were African American, 14.9 percent were white, and 55.4 percent of the households reported annual incomes below $20,000. Benjamin-Neelon and her colleagues visited the homes of the infants when they were 3, 6, 9, and 12 months old, and interviewed the mothers by phone an additional eight times over the year.

"The findings are especially relevant today when there is such widespread food insecurity in the U.S. due to the COVID-19 crisis," says Benjamin-Neelon, PhD, JD, who also directs the Lerner Center for Public Health Promotion at the Bloomberg School.

For their analysis, the researchers compared the weight and length of infants in the study to a global population of healthy infants from eight counties to determine "at risk of overweight." They found that infants from households categorized as low and very low food security tended to move into this overweight risk category over the 3-month visit to the 12-month visit period (53.2 percent to 66.9 percent), whereas infants from households with high and marginal food security--those with moderate access to adequate, healthy food--tended to move out of this category (46.8 to 33.1 percent) during the period.

Infants in households with low and very low food security also were generally more likely (1.72 and 1.55 times more likely) to be at risk of overweight. Additionally, infants from very low food security households were significantly heavier by comparison with infants from food-secure households, and had more fat accumulation by standard caliper-based measures.

"One possible explanation for this link is that food insecurity is associated with lower quality diets that promote obesity, although infants, especially in the first six months of life, should be consuming limited foods-mainly just human breastmilk or infant formula," Benjamin-Neelon says. "Another possibility may be related to infant feeding practices. Mothers wanting to make sure their infants are fed enough could be overfeeding or feeding in a way that overrides infant fullness cues like propping a bottle or encouraging infants to finish the bottle."

Benjamin-Neelon and colleagues found, to their surprise, that mothers' participation in either of two federal food assistance programs, WIC and SNAP, did not modify the apparent links between food insecurity and being overweight.

"As a former WIC nutritionist, I thought it was important to assess whether such programs modified the association between food insecurity and obesity," Benjamin-Neelon says. "However, just because it didn't make a difference in this study does not mean that women with infants and young children should not participate in these valuable programs."

She and her colleagues believe that larger and longer-term studies are needed to resolve the many questions about food insecurity and obesity, including whether the association in infancy continues into later childhood.