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Plasmonic field enhancement is the cornerstone of a wide range of applications ranging from surface enhance spectroscopy, sensing, and nonlinear optics to light harvesting. The most intense plasmonic fields usually appear within narrow gaps('hotspot') between adjacent metallic nanostructures, especially when the separation goes down to subnanometer scale. However, experimentally probing the plasmonic fields in such a tiny volume still challenges the nanofabrication and detection techniques.

Measuring surface-enhanced Raman scattering (SERS) signal from a probe inside the nanogap region is a promising avenue to do that, but it still faces several intractable issues: (i) how to create a width-controllable subnanometer gap with well-defined geometry, (ii) how to insert the nanoprobe into such narrow gap, and more importantly, (iii) how to control the alignment of the probe with respect to the strongest plasmonic field component. What's more, the excitation laser should match with the plasmonic resonances in both wavelength and polarization, to get the maximum plasmonic enhancement. These requirements are difficult to satisfy simultaneously in traditional SERS using molecules as probe.

To overcome all these limitations, a research group led by Shunping Zhang and Hongxing Xu at Wuhan University, China, has developed a quantitative SERS technique to probe the maximum plasmonic fields before effects such as electron tunneling become dominant. The researchers turned to molybdenum disulfide (MoS2)- a graphene-like, two-dimensional atomic layer to tune the distance between a gold nanoparticle and a smooth gold film. For the first time, the plasmonic near-field components in vertical and horizontal directions within atom-thick plasmonic nanocavities were quantitatively measured by using tiny flakes of two-dimensional atomic crystals as probes.

In their configuration, the researchers can ensure that the probe filled in the gap has a well-defined lattice orientation such that the lattice vibrations are precisely aligned with the plasmonic field components. These lattice probes are free of optical bleaching or molecule hopping (in/out of the hotspot) as in traditional SERS experiments. They achieved the quantitative extraction of plasmonic fields in the nanogap by measuring the SERS intensity from the out-of-plane and in-plane phonon modes of the MoS2.

The robustness of the 2D atomic crystal as SERS probes promote SERS to be a quantitative analytic tool instead of a qualitative one in most previous applications. Also, these unique designs could provide an important guide for further understanding quantum mechanical effects as well as plasmon-enhanced photon-phonon interactions and promoting relevant new applications, such as quantum plasmonics and nanogap optomechanics.

New Rochelle, NY, September 4, 2018--A new study has demonstrated the tissue regenerative potential of a chemoattractant delivery system that can draw mesenchymal stem cells (MSCs) to the site of intervertebral disc (IVD) degeneration. The study, carried out in a cow model of IVD degeneration, not only showed the recruitment of regenerative cells, but also reported increased collagen production, as described in an article published in , peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the article free on the Tissue Engineering website until October 4, 2018.

Raquel Madeira Gonçalves, PhD, Universidade do Porto, Portugal and a team of researchers from Universidade do Porto and the AO Research Institute Davos, Switzerland, described the hyaluronan based-chemoattractant delivery system they developed in the article entitled "Stromal Cell Derived Factor-1-Mediated Migration of Mesenchymal Stem Cells Enhances Collagen Type II Expression in Intervertebral Disc." In the presence of the system, which contained stromal cell derived factor-1 (SDF-1), migration of MSCs to the degenerative site was enhanced. In addition, the researchers measured higher levels of collagen type II and of pro-catabolic factors produced by the MSCs that would contribute to enhanced remodeling of the extracellular matrix.

"This study exemplifies the impact of drug delivery on enhancing a specific cellular activity and thus reverting a tissue degenerative process," says Tissue Engineering Co-Editor-in-Chief Antonios G. Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX.

A new study by an international team of researchers, led by scientists from the University of Bristol, has revealed the origins and evolution of animal body plans.

Animals evolved from unicellular ancestors, diversifying into thirty or forty distinct anatomical designs. When and how these designs emerged has been the focus of debate, both on the speed of evolutionary change, and the mechanisms by which fundamental evolutionary change occurs.

Did animal body plans emerge over eons of gradual evolutionary change, as Darwin suggested, or did these designs emerge in an explosive diversification episode during the Cambrian Period, about half a billion years ago?

The research team tackled this question by exhaustively compiling the presence and absence of thousands of features from all living animal groups.

Professor Philip Donoghue, from the University of Bristol's School of Earth Sciences, said: "This allowed us to create a 'shape space' for animal body plans, quantifying their similarities and differences.

"Our results show that fundamental evolutionary change was not limited to an early burst of evolutionary experimentation. Animal designs have continued to evolve to the present day - not gradually as Darwin predicted - but in fits and starts, episodically through their evolutionary history."

Co-author Bradley Deline, from the University of West Georgia (USA), added: "Our results are important in that they highlight the patterns and pathways in which animal body plans evolved.

"Moreover, major expansions in animal form following the Cambrian aligns with other major ecological transitions, such as the exploration of land.

"Many of the animals we are familiar with today are objectively bizarre compared with the Cambrian weird wonders. Frankly, butterflies and birds are stranger than anything swimming in the ancient sea."

Co-authors James Clark from Bristol's School of Earth Sciences and Dr Mark Puttick from the University of Bath's Department of Biology, worked on trying to fit fossil species into the study.

Dr Puttick said: "One of the problems we had is that our study is mostly based on living species and we needed to include fossils. We solved the problem through a combination of analyzing the fossils and using computer models of evolution."

James Clark added: "The fossils plot intermediate of their living relatives in shape space. This means that the distinctiveness of living groups is a consequence of the extinction of their evolutionary intermediates. Therefore, animals appear different because of their history rather than unpreserved jumps in anatomy."

Co-author Jenny Greenwood, also from the University of Bristol's School of Earth Sciences, wanted to dig deeper. She wanted to work out which of the many proposed genetic mechanisms drove the evolution of animal body plans.

Jenny said: "We did this by collecting data on the different genomes, proteins, and regulatory genes, that living animal groups possess. The differences in anatomical designs correlate with regulatory gene sets, but not the type or diversity of proteins. This indicates that it is the evolution of genetic regulation of embryology that precipitated the evolution of animal biodiversity."

Co-author Kevin Peterson from Dartmouth College (USA), added: "Our study confirms the view that continued gene regulatory construction was a key to animal evolution."

CAMBRIDGE, MA -- One of the most common complications of sickle-cell disease occurs when deformed red blood cells clump together, blocking tiny blood vessels and causing severe pain and swelling in the affected body parts.

A new study from MIT sheds light on how these events, known as vaso-occlusive pain crises, arise. The findings also represent a step toward being able to predict when such a crisis might occur.

"These painful crises are very much unpredictable. In a sense, we understand why they happen, but we don't have a good way to predict them yet," says Ming Dao, a principal research scientist in MIT's Department of Materials Science and Engineering and one of the senior authors of the study.

The researchers found that these painful events are most likely to be produced by immature red blood cells, called reticulocytes, which are more prone to stick to blood vessel walls.

Subra Suresh, president of Singapore's Nanyang Technological University, former dean of engineering at MIT, and the Vannevar Bush Professor Emeritus of Engineering, is also a senior author of the study, which appears in Proceedings of the National Academy of Sciences the week of Sept. 3. The paper's lead authors are MIT postdoc Dimitrios Papageorgiou and former postdoc Sabia Abidi.

Simulating blood flow

Patients with sickle cell disease have a single mutation in the gene that encodes hemoglobin, the protein that allows red blood cells to carry oxygen. This produces misshapen red blood cells: Instead of the characteristic disc shape, cells become sickle-shaped, especially in low-oxygen conditions. Patients often suffer from anemia because the abnormal hemoglobin can't carry as much oxygen, as well as from vaso-occlusive pain crises, which are usually treated with opioids or other drugs.

To probe how red blood cells interact with blood vessels to set off a vaso-occlusive crisis, the researchers built a specialized microfluidic system that mimics the post-capillary vessels, which carry deoxygenated blood away from the capillaries. These vessels, about 10-20 microns in diameter, are where vaso-occlusions are most likely to occur.

The microfluidic system is designed to allow the researchers to control the oxygen level. They found that when oxygen is very low, or under hypoxia, similar to what is seen in post-capillary vessels, sickle red cells are two to four times more likely to get stuck to the blood vessel walls than they are at normal oxygen levels.

When oxygen is low, hemoglobin inside the sickle cells forms stiff fibers that grow and push the cell membrane outward. These fibers also help the cells stick more firmly to the lining of the blood vessel.

"There has been little understanding of why, under hypoxia, there is much more adhesion," Suresh says. "The experiments of this study provide some key insights into the processes and mechanisms responsible for increased adhesion."

The researchers also found that in patients with sickle cell disease, immature red blood cells called reticulocytes are most likely to adhere to blood vessels. These young sickle red cells, just released from bone marrow, carry more cell membrane surface area than mature red blood cells, allowing them to create more adhesion sites.

"We observed the growth of sickle hemoglobin fibers stretching reticulocytes within minutes," Papageorgiou says. "It looks like they're trying to grab more of the surface and adhere more strongly."

Patient predictions

The researchers now hope to devise a more complete model of vaso-occlusion that combines their new findings on adhesion with previous work in which they measured how long it takes blood cells from sickle cell patients to stiffen, making them more likely to block blood flow in tiny blood vessels. Not all patients with sickle cell disease experience vaso-occlusion, and the frequency of attacks can vary widely between patients. The MIT researchers hope that their findings may help them to devise a way to predict these crises for individual patients.

"Blood cell adhesion is indeed a very complex process, and we had to develop new models based on such microfluidic experiments. These adhesion experiments and corresponding simulations for sickle red cells under hypoxia are quantitative and unique," says George Karniadakis, a professor of applied mathematics at Brown University and a senior author of the study.

NASA-NOAA's Suomi NPP satellite captured an infrared image of Potential Tropical Cyclone Six that shows the storm is not as "stretched out" as it was the previous day. Despite its lack of organization, a Tropical Storm Warning is in effect for the Cabo Verde Islands of Santiago, Fogo, and Brava.

Tropical storm conditions expected over the southern Cabo Verde islands later today, Aug. 31.

NASA-NOAA's Suomi NPP satellite flew over Potential Tropical Cyclone Six on Aug. 30 at 11:18 p.m. EDT (Aug. 31 at 0318 UTC). The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard NASA-NOAA's Suomi NPP satellite provided a visible image that showed the circulation is gradually becoming less elongated. Satellite data revealed that there is still relatively little deep convection near the estimated center of circulation. A few strong storms were found where cloud top temperatures were as cold as or colder than minus 70 degrees Fahrenheit (minus 56.6 degrees Celsius).

The National Hurricane Center said that "Most of the convection remains confined to the monsoon trough southwest of the center, where low-level convergence is strongest. Therefore, the system is not quite yet being designated as a tropical cyclone."

At 8 a.m. EDT (1200 UTC), the disturbance was centered near latitude 13.7 degrees north and longitude 21.8 degrees west. The system is moving toward the west-northwest near 12 mph (19 kph), and this motion at a slightly faster forward speed is expected to continue for the next three to four days. On the forecast track, disturbance is expected to move near or over the southern Cabo Verde Islands as a tropical storm later today and tonight.

Maximum sustained winds are near 35 mph (55 kph) with higher gusts. Strengthening is forecast during the next several days, and the disturbance is expected to become a tropical storm later today or Saturday.

NHC said "Environmental conditions are favorable for the system to become a tropical cyclone later today."

For updated forecasts, visit: http://www.nhc.noaa.gov

Genetic mutations in a form of non-small cell lung cancer (NSCLC) may drive tumor formation by blurring cells' perception of key growth signals, according to a new laboratory study published August 31, 2018 in Science. The research, led by UC San Francisco researchers, could have important implications for understanding and ultimately targeting the defective mechanisms underlying many human cancers.

Healthy cells rely on the central Ras/Erk growth signaling pathway (also known as the Ras/MAPK pathway) to interpret external cues about how and when to grow, divide, and migrate, but defects in how these messages are communicated can cause cells to grow out of control and aggressively invade other parts of the body. Such mutations are found in the majority of human cancers, making treatments for Ras/Erk defects a "holy grail" of cancer research.

Decades of study have led scientists to believe that Ras/Erk-driven cancers occur when mutations cause one or more components of the pathway to get stuck in a pro-growth state. Researchers have labored to develop targeted treatments that flip these broken switches back off, but so far most have failed to make it through clinical trials. Now, using a high-throughput technique developed at UCSF that allows scientists to take control of Ras/Erk signaling using pulses of light, and then quickly read out resulting genomic activity, researchers have made a surprising discovery about this extensively studied pathway.

Optogenetics -- in which light-sensitive proteins are genetically engineered into cells in order to make them respond to pulses of light -- has been a transformative laboratory technique in neuroscience, allowing researchers to control and study electrical activity patterns within networks of neurons with exquisite precision. By using the same approach to explore patterns of chemical communication within individual cells, the new research has revealed that some Ras/Erk mutations may trigger cancer by altering the timing, rather than the intensity, of cellular growth signals. The new study also shows that this blurring of signal timing may explain why some targeted drugs designed to shut off defective Ras/Erk signaling can paradoxically activate the pathway instead potentially raising the risk of new tumor formation.

"This new technique is like a diagnostic instrument that we hook up to a diseased cell, which lets us stimulate and interrogate the cell with many light-based stimuli to see how it responds," said UCSF synthetic biologist Wendell Lim, PhD, one of the study's senior authors. "Using this approach, we were able to identify cancer cells that have certain defects in how they process signals, behaviors that lead to cell proliferation in response to signals that normally are filtered by the cell circuits."

UCSF medical oncologist and cancer biologist Trever Bivona, MD, PhD, and Princeton molecular biologist Jared Toettcher, PhD, formerly a postdoctoral researcher in Lim's lab, were co-senior authors of the new study. The study's lead author was Lukasz Bugaj, PhD, of the University of Pennsylvania, also formerly a postdoctoral researcher in Lim's lab.

Optogenetics Reveals Corruption of Cellular Growth Signaling by Mutations, Drugs

The Ras/Erk pathway is complex, but at its core is a cascade of four proteins -- Ras, Raf, Mek, and Erk -- that activate one another like a chain of falling dominoes in response to growth signals from outside the cell. Ras sits at the cell membrane and receives incoming signals, then passes them along to Raf and Mek, which process and amplify them, until finally Erk (also called MAP Kinase or MAPK) transports the signal into the cell nucleus, where it can activate the appropriate genetic programs.

Previously, researchers had little understanding of how the timing of growth signals impacted cells' behavior. To address this question, the new research made use of a novel optogenetic tool which was developed by Toettcher as a post-doc in the Lim lab. This tool, OptoSOS, can be engineered into cells to trigger Ras activity in response to precisely timed pulses of light.

To track cells' responses to different patterns of Ras activation, the researchers engineered the OptoSOS system into multiple lines of healthy and cancerous cells, and placed different groups of these cells into an array of small wells in a laboratory dish. By illuminating this dish with a specially designed device -- dubbed the optoPlate -- the team was able to rapidly stimulate hundreds of different experimental groups of cells with a variety of test patterns, and simultaneously read out their responses under a microscope.

These techniques revealed that healthy cells respond selectively to long-lasting growth signals, while ignoring signals that flicker on and off -- presumably considering them to be irrelevant "noise." In contrast, the researchers found that certain non-small cell lung cancer (NSCLC) cell lines appear to misinterpret these intermittent noisy signals as stronger, sustained signals, triggering excessive growth and tumor formation.

"Cancer biologists expect oncogenic mutations to turn a pathway on to a constant, high level," Toettcher said."Our work shows that there is a second option, where mutant cells can still sense external inputs but alter the dynamics of their response."

This misreading of signals appears to occur because of a specific type of mutation in the protein B-Raf corrupts the timing of incoming growth signals, the researchers found, causing short pulses of Ras activation to reverberate for longer within an affected cell -- similar to how the "sustain" pedal on a piano causes individual notes to be drawn out and blur together.

When the researchers activated Ras in healthy cells with a brief pulse of OptoSOS stimulation, Erk would turn on and off again with only about a two-minute lag. In contrast, in B-Raf mutant cells, it took Erk activity 20 minutes to dissipate following OptoSOS stimulation, and further experiments showed that this resulted in activation of downstream genetic programs associated with cell growth and proliferation.

The researchers also showed that some targeted cancer drugs that are intended to shut down overactive components of the Ras/Erk signaling pathway may blur the fidelity of signaling much as B-Raf mutations do. Specifically, they found that vemurafenib and SB590885 -- part of a class of drugs called paradox activating B-Raf inhibitors -- significantly slowed how long it took Ras/Erk activity to shut off following OptoSOS stimulation, which could help researchers understand these drugs' known risk of triggering new tumor formation in patients.

"This research teaches us about a previously underappreciated dimension to oncogenic signaling and suggests that the timing of growth signaling could play an important role in a wider variety of human cancers," Bivona said. "There may be future diagnostic and therapeutic opportunities that leverage the ability to detect aspects of signal corruption on a functional level that are not apparent by merely sequencing the cancer genome with the descriptive approaches that are currently standard in the field."

Lim added, "We can now use interrogative tools like optogenetics to achieve a much more quantitative and systematic understanding of how cellular circuits work and how they break. This approach may be able to help us uncover what goes wrong in many diseases involving malfunctioning decision-making circuits in cells, ranging from cancer to autoimmunity."

The Mediterranean diet as a secret of long life for elderly. These are the conclusions of a study by the Department of Epidemiology and Prevention of the I.R.C.C.S. Neuromed, in Molise, Italy, published in the British Journal of Nutrition. Researchers analyzed the relationship between the traditional Mediterranean diet and mortality in a sample of more than 5,000 people over 65 years of age participating in the Moli-sani Study and followed-up for 8 years.

In addition to data from the Moli-sani Study participants, Italian researchers also analyzed other epidemiological studies published in several Countries, for a total of 12,000 subjects. Results clearly indicate that the Mediterranean diet is an authentic life-saving shield, able to significantly reduce the risk of mortality in elderly people. This effect is maintained despite the Mediterranean diet has changed considerably over the years, with pantries full of supermarket products and with a lifestyle very different from the one followed by original Mediterranean farmers.

"The novelty of our research is to have focused our attention on a population over 65 years old - says Marialaura Bonaccio, epidemiologist at the Department and first author of the study - We already knew that the Mediterranean diet is able to reduce the risk of mortality in the general population, but we did not know whether it would be the same specifically for elderly people. Now data from Moli-sani Study clearly show that a traditional Mediterranean-like diet, (rich in fruit, vegetables, fish, pulses, olive oil and cereals, low in meat and dairy products, with moderate wine consumption during meals), is associated with 25% reduction of all-cause mortality. This effect remains also if we consider specifically cardiovascular or cerebrovascular mortality".

"Besides data from the Moli-sani population - explains Licia Iacoviello, head of the Laboratory of Molecular and Nutritional Epidemiology at Neuromed Institute and professor at the University of Insubria, Varese - we analysed the results from six other studies conducted on people aged over 65 in other Countries, involving a total of twelve thousand people. Through the technique of meta-analysis, we could confirm that a higher adherence to the Mediterranean diet lowers overall mortality risk in a dose-response, progressive, way. In other words, the more you follow the Mediterranean diet, the greater the gain in terms of mortality risk reduction".

The foods that, in the context of a Mediterranean-type dietary model, are able to offer greater protection, include a high consumption of monounsaturated fats (widely present in extra virgin olive oil) and fish, but also a moderate consumption of alcohol, preferably during meals.

"Our research considers nutrition as a whole, but it is still interesting to understand which foods mainly contribute to the 'driving' effect of the Mediterranean diet - explains Bonaccio - Our data confirm what has already been observed in numerous epidemiological and metabolic studies, namely that a moderate consumption of alcoholic beverages, if inserted in a Mediterranean food context, is a protective factor for our health ".

"We think that our data launch an important message in terms of public health. - says Giovanni de Gaetano, director of the Department - With the progressive aging of the world population, we know that, in a few years, people over 65 will represent about a quarter of Europeans. It is therefore necessary to study and identify those modifiable factors that can guarantee not only a long lifespan, but also an acceptable quality of life. We use to say that we must add life to years, not just years to life. Our study is a robust basis to encourage a healthy diet model inspired by the principles of the Mediterranean diet, even among older people ".

CORVALLIS, Ore. - The reintroduction of wolves into Yellowstone National Park is tied to the recovery of aspen in areas around the park, according to a new study.

The study was published today in the journal Ecosphere.

This is the first large-scale study to show that aspen is recovering in areas around the park, as well as inside the park boundary, said Luke Painter, a wildlife ecologist at Oregon State University and lead author on the study. Wolves were reintroduced to the park in 1995. The study shows their predation on elk is a major reason for new growth of aspen, a tree that plays an important ecological role in the American West.

Wolves are culling the elk herd, adding to the effects of bears, cougars, and hunters outside the park, which means less elk are browsing on aspen and other woody species. The presence of wolves has also resulted in most of the elk herd spending winter outside of the park, Painter said. Before wolf restoration, even when elk numbers were similarly low, most of the elk stayed in the park.

"What we're seeing in Yellowstone is the emergence of an ecosystem that is more normal for the region and one that will support greater biodiversity," Painter said. "Restoring aspen in northern Yellowstone has been a goal of the National Park Service for decades. Now they've begun to achieve that passively, by having the animals do it for them. It's a restoration success story."

Elk numbers in northern Yellowstone have declined from a high of nearly 20,000 in 1995 - the year wolves were restored to the park - to 7,579 counted over two days in January by biologists with Montana Fish, Wildlife, and Parks and Yellowstone National Park.

The study answers the question of whether the return of wolves to Yellowstone could have a cascading effect on ecosystems outside the park, Painter said, where there is much more human activity such as hunting, livestock grazing, and predator control. There has also been skepticism surrounding the extent and significance of aspen recovery, he said.

"We show that the recovery of aspen is real and significant, though patchy and in early stages, and occurring throughout the region where elk population densities have been reduced," he said. "Also important is that the regional distribution of elk has changed, and not just their number, and this is reflected by young aspen growing taller in winter ranges in and near the park. Meanwhile, elk densities have increased farther from the park. Other factors besides wolves affected elk, but wolves played an essential role in these changes."

The researchers surveyed aspen from 2011-2015 in three winter ranges in the Yellowstone region. They compared that data to aspen surveys in 1997-98 in the park's Northern Range, Gallatin National Forest Northern Range, and the Sunlight/Crandall Range, which provided a baseline for aspen conditions when wolves were beginning to colonize these areas.

They found that if elk densities were greater than about four elk per square kilometer, aspen were heavily browsed and suppressed. Elk densities in the Yellowstone region were generally greater than this prior to wolf reintroduction. With high elk densities, starvation was common and elk ate whatever was available, but with lower elk densities their effects are not so uniform, allowing for a patchy reduction in browsing and release of young aspen to grow taller.

"Our findings represent another piece of the puzzle as we're trying to understand the role of predation in the ecology of the Rocky Mountain region," Painter said. "Much of the research ecologists have done has been in the absence of non-human predators. Before the reintroduction of wolves, most experts didn't think it was going to make much difference for aspen. Wolves didn't cause aspen recovery all by themselves, but it is safe to say it would not have happened without them."

Neisseria gonorrhoea continues to show high levels of resistance to azithromycin across the European Union and European Economic Area, according to the 2016 results of the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP). This threatens the effectiveness of the currently recommended dual therapy regimen for gonorrhoea. Overall, the rates of resistance to cefixime, ceftriaxone and azithromycin have remained stable when compared to recent years.

The main antibiotics currently recommended for gonorrhoea treatment in Europe, so-called third generation cephalosporins, are the last remaining options for effective first-line antimicrobial single therapy. As susceptibility of Neisseria gonorrhoea to these antimicrobials had decreased in the past, the European treatment guidelines suggest the addition of azithromycin to the basic course of the cephalosporins ceftriaxone or cefixime.

In order to monitor the continued effectiveness of this treatment regimen, countries of the European Union and European Economic Area (EU/EEA) participate in Euro-GASP sentinel surveillance programme. Each year they submit isolates to test susceptibility of Neisseria gonorrhoeae to the antibiotics commonly used to treat gonorrhoea.

In 2016, 25 EU/EEA countries collected and tested 2 660 gonococcal isolates showing stable rates of resistance against cefixime (2.1%), ciprofloxacin and azithromycin (7.5%) compared with 2015. No isolates with resistance to ceftriaxone were detected compared with one in 2015, five in 2014 and seven in 2013.

While the absence of ceftriaxone resistance among the tested isolates in 2016 is encouraging, the persistent level of resistance to azithromycin is of concern as it threatens to reduce the effectiveness of the recommended dual therapy with ceftriaxone and azithromycin.

Among those patients for whom information on their treatment course was reported in 2016, 86% were administered ceftriaxone and more than half received combined treatment with azithromycin. The use of two antimicrobials for gonorrhoea treatment has likely contributed to increased susceptibility to ceftriaxone. However, Euro-GASP data completeness for the variable 'treatment used' has still some way to go overall with just 37% in 2016.

Minimising the threat of untreatable gonorrhoea

With more than 75 000 reported cases in 2016, gonorrhoea is the second most commonly notified sexually transmitted infection (STI) in the EU/EEA countries. Apart from these reports, many more asymptomatic infections are know to occur.

Successful gonorrhoea treatment with antibiotics not only reduces the risk of complications such as pelvic inflammatory disease, ectopic pregnancies, infertility or increased HIV transmission in some settings. Combined with regular testing to diagnose and treat infections at an early stage, it also serves as one of the main public health strategies in order to reduce further transmission.

In light of limited alternatives to the current combination therapy introduced in 2012, ECDC launched a regional response plan to control multidrug-resistant gonorrhoea to minimise the threat of drug-resistant gonorrhoea in Europe. ECDC is currently revising the plan, also following recent reports of extensively drug resistant gonorrhoea strains that reached Europe.

Even low doses of toxic chemicals in the environment pose a significant risk to cardiovascular health, according to a report in today's edition of The BMJ, led by researchers at the University of Cambridge. The researchers have also challenged the omission of environmental risk factors such as toxic metal contaminants in water and foods from the recent World Health Organization report on non-communicable diseases (NCDs).

In recent decades, exposures to environmental toxic metals such as arsenic, copper, lead, cadmium and mercury, have become a global public health concern. Although often naturally occurring, these contaminants have made their way into water supplies and, via irrigation, into the food chain. For example, in Bangladesh, deep wells were introduced in the Ganges Delta to draw water clear of bacterial and viral pathogens, but this inadvertently led to exposure to toxic metals.

Concern has often focused on the toxicity or carcinogenic properties of the metals, particularly at high doses. However, there is increasing evidence to suggest that heavy metals may have other adverse effects on health - including cardiovascular disease such as heart disease and stroke - even at lower levels of exposure, which might be prevalent in many parts of the world, including the UK and the US.

To interpret the available evidence, a team led by researchers at Cambridge's Department of Public Health and Primary Care carried out a systematic review and meta-analysis of published studies covering 350,000 unique participants from 37 countries.

The results of the study showed that exposure to arsenic, lead, cadmium and copper - but not mercury - was associated with an increased risk of coronary heart disease and cardiovascular disease.

"It's clear from our analysis that there's a possible link between exposure to heavy metals or metalloids and risk of conditions such as heart disease, even at low doses - and the greater the exposure, the greater the risk," says Dr Rajiv Chowdhury, the study's first author. "While people shouldn't be overly worried about any immediate health risk, it should send a message to policymakers that we need to take action to reduce people's exposure."

Worldwide, those at greatest exposure of arsenic, lead, cadmium and copper were around 30% to 80% more likely to develop cardiovascular disease than those at lowest exposure.

The report is important, say the researchers, because it highlights the need to tackle this environmental and public health problem, one which disproportionately affects people in low and middle income countries, though may still affect those in higher income countries. Interventions need not be costly, they stress; for example, cheap, scalable technologies (e.g. environmentally-friendly water filters) or behavioural interventions (e.g. rinsing practices of rice and vegetables prior to cooking) are currently being tested to reduce exposures at the household level.

Additionally, in a letter published at the end of June, Dr Chowdhury and colleagues expressed their disappointment that the earlier WHO report by the Independent High-Level Commission on non-communicable diseases published in June did not include exposure to heavy metals as a key contributing factor. Writing in the Lancet, the authors said: "Unfortunately, this globally important report had a major omission: recognising the detrimental role of environmental risk factors, beyond the conventional behavioural factors (tobacco and alcohol use, physical inactivity, and unhealthy diet), in enhancing global NCD burden and health inequality."

Dr Chowdhury and colleagues recently also received £8.1 million from the UK Research Councils' Global Challenges Research Fund to set up a long-term programme (called CAPABLE) to further investigate environmental factors of cardiovascular diseases and to help inform preventative strategies.

Researcher profile: Dr Rajiv Chowdhury

2006 was a year of "life-changing events" for Dr Rajiv Chowdhury: not only did he receive a Commonwealth scholarship to study for a masters at Cambridge, but his wife also gave birth to their baby daughter.

Rajiv grew up in Bangladesh, where he studied medicine before moving to Cambridge for his masters. This made him acutely aware of the challenges facing low-income countries. "I could see for myself the massive inequalities, the huge burden of disease, the poor infrastructure, lack of resources..." he says. But it was his encounter with non-communicable diseases (NCDs) - conditions such as heart disease, cancer and type 2 diseases - that was to have particular relevance to his current work.

Following his masters, Rajiv went on to receive a Gates Cambridge scholarship to support his PhD in epidemiology - the first Gates Cambridge scholar from Bangladesh. He now studies the role played by both environmental factors (such as toxic metals, diet, etc.) and genetic factors in influencing the risk of chronic NCDs.

Rajiv's particular interest involves working closely with researchers in low-income countries such as Bangladesh, Sri Lanka and Malaysia - as well as being the principal investigator on several international research projects, he is also Scientific Director for CAPABLE (Cambridge Programme to Assist Bangladesh in Lifestyle and Environmental risk reduction), funded through the Global Challenges Research Fund.

"I hope that our work will lead to the establishment of the largest NCD scientific cohort study in Bangladesh," he says. "We're aiming for it to recruit over 150,000 participants. This should help us generate some effective solutions to reduce the impact of environmental risk factors which affect many hundreds of millions of people worldwide."

Rajiv says he has learned a lot from both his mentors and peers during his time at Cambridge. "Cambridge offers one of the most intellectually stimulating environments in the world for scientific endeavours," he says. "I have come across some of the brightest minds in biomedical science here who have changed my life and the way I perceive research."

Sea level rise and extreme weather events have become harsh realities for those living along the world's coasts. The record-breaking hurricanes of the past decade in the United States have led to staggering tolls on coastal infrastructure and communities, leading many local governments to consider the benefits of natural coastal barriers.

In a landmark study titled "Warming accelerates mangrove expansion and surface elevation gain in a subtropical wetland" a team of Villanova University biologists have documented that coastal wetlands in the southeastern United States are responding positively to rising temperatures both in their growth and in their ability to build soil to keep pace with sea level rise.

Published August 29 in the British Ecological Society's Journal of Ecology, the study's results are a ray of sunshine in the climate change forecast. Members of the research team included Glenn A. Coldren, J. Adam Langley, and Samantha Chapman, from Villanova University's Department of Biology, Villanova, PA and Ilka C. Feller of The Animal-Plant Interaction Lab, Smithsonian Environmental Research Center, in Edgewater.

The Villanova research team's two-year experiment, funded by grants from the National Aeronautics and Space Administration (NASA), was performed at the Kennedy Space Center (KSC) within the Merritt Island National Wildlife Refuge (MINWR) on Merritt Island. The KSC was an ideal location to conduct the research being situated at the intersection of two wetland biomes, salt marshes and mangroves. The implications for the KSC are serious since coastal wetlands and sand dunes help protect NASA's $5.6 billion low-lying infrastructure against rising seas.

The large-scale warming experiment was conducted in place in the MINWR using large passive warming chambers to increase both marsh and mangrove ecosystem air temperatures. The Villanova researchers found that experimental warming both doubled plant height and accelerated the transition from marsh to mangrove.

Mangroves are woody trees with more complex roots than their grassy marsh plant counterparts. When subjected to temperatures similar to those that will occur in a warmer future, mangrove plots showed increased surface elevation which is a measure of the wetland's ability to build soil and keep pace with sea level rise.

"Our study provides some evidence that the ongoing reshuffling of species on earth's surface could allow for some adaptation to the same global changes that are causing them," says Chapman. "Conserving and restoring our coastal wetlands can help humans adapt to climate change."

With their unique structure and migration to higher latitudes caused by climate change, mangroves may help coasts keep pace with sea level rise and combat severe weather events like hurricanes. Expansion of these natural barriers in areas like the Kennedy Space Center may enhance the sustainability of coastal communities as they face accelerating sea-level rise in a warmer future.

"The study links the growth of individual plants, and particularly their roots, to the survival of an entire ecosystem. The long-term strength of the mangrove effects we identified may determine what the maps of our southeastern coastlines look like in the future," says Langley. "This mangrove effect could benefit coastal wetlands around the world."

"Our experiment highlights the impact multiple interacting aspects of climate change, such as warming and sea level rise, can have on the outcome of species invasions resulting from climate change -- and on the capacity of those communities to protect shorelines," concluded Coldren.

Scientists at Hollings Cancer Center at the Medical University of South Carolina have found that some cells can divide without a molecule that was previously thought necessary. Their results, published online in the July 2018 issue of Genes and Development, explain how liver cells can regenerate after injury and may help us understand how cancer arises and how cancer cells evolve to have additional mutations, which accelerates growth and spread.

Authors on the paper included Gustavo Leone, Ph.D., director of Hollings Cancer Center and a Grace E. DeWolff Endowed Chair in Medical Oncology, and Takayuki Okano-Uchida, Ph.D. One of the areas of focus in Leone's lab is studying how normal cells divide to better understand the process in cancer cells, which can divide rapidly and spread.

Uchida explained that cell division is necessary during periods of growth, such as embryonic development, and to replace dead or damaged cells. A key component of cell division is to accurately copy each chromosome providing identical DNA to each cell produced, termed DNA replication. Errors that occur during this process can result in cells with abnormal copies of chromosomes or deleterious mutations which can lead to cancer.

"We are multicellular organisms," said Uchida. "To make multicellular organisms, it is important to copy cells, so DNA replication is very important to us."

To divide properly and ensure accurate DNA replication, the cell must start this process at a specific location on each chromosome, called the 'origin of replication'. The entire process of firing these origins to start DNA replication, like the starting up of engines at the beginning of a car race, is highly regulated by a group of molecules called the 'origin replication complex' that binds to a certain place on the DNA within each chromosome and helps the cell recognize where to start DNA replication. This complex helps each cell make a precise copy of its DNA before it divides, and thus ensures that all cells have a perfect genome.

Uchida and colleagues found while the majority of cells need a part of the origin recognition complex, called ORC1, to copy their DNA, cells of the liver and placenta do not need ORC1. These cells are a rare type that routinely copy their DNA but do not divide, resulting in a larger cell with twice the normal amount of DNA. This process, termed an endocycle, can occur multiple times creating a cell with many times the normal amount of DNA.

The researchers found that in the liver, ORC1 is expressed at high levels in dividing cells. However, researchers found as the animal model ages and more liver cells start to endocycle, ORC1 levels drop indicating that ORC1 may not be needed to replicate DNA in endocycling cells. In order to test this idea, ORC1 was deleted in liver cells, and it was found that without OCR1, liver cells started to endocycle much sooner.

"This finding is extremely relevant because it is generally accepted that ORC1 is essential for all forms of DNA replication," Uchida said.

In their future research, Leone and Uchida are focusing on the role of ORC1 and abnormal DNA replication in cancer cells. Cancer cells use processes similar to the endocycle to grow rapidly and become resistant to therapy, according to Uchida. In fact, certain cancers have very low levels of ORC1 but are able to grow rapidly without it. "The catch is, that we think that by replicating DNA without ORC1, cells accumulate more mutations than normal, which could of course fuel cancer growth and progression."

Uchida acknowledges that these results in mice may not extend to humans, and that question is also behind the team's next steps, which is testing their results in human liver cell lines.

"In this paper, we show that ORC1 is essential for mouse development," said Uchida. "It should be the same in human development, but we really do not know yet."

BIRMINGHAM, Ala. - A shortage of organs for transplantation -- including kidneys and hearts -- means that many patients die while still on waiting lists. So, research at the University of Alabama at Birmingham and other sites has turned to pig organs as an alternative.

Using gene-editing, researchers have modified such organs to prevent rejection, and research with primates shows the modified pig organs are well-tolerated.

An added step is needed to ensure the safety of these inter-species transplants -- sensitive, quantitative assays for viruses and other infectious microorganisms in donor pigs that potentially could gain access to humans during transplantation.

The U.S. Food and Drug Administration requires such testing, prior to implantation, of tissues used for xenotransplantation from animals to humans. It is possible -- though very unlikely -- that an infectious agent in transplanted tissues could become an emerging infectious disease in humans.

In a paper published in Xenotransplantation, Mark Prichard, Ph.D., and colleagues at the University of Alabama at Birmingham have described the development and testing of 30 quantitative assays for pig infectious agents. These assays had sensitivities similar to clinical lab assays for viral loads in human patients. After validation, the UAB team also used the assays on nine sows and 22 piglets delivered from the sows through caesarian section.

"Going forward, ensuring the safety of these organs is of paramount importance," Prichard said. "The use of highly sensitive techniques to detect potential pathogens will help to minimize adverse events in xenotransplantation."

"The assays hold promise as part of the screening program to identify suitable donor animals, validate and release transplantable organs for research purposes, and monitor transplant recipients," said Prichard, a professor in the UAB Department of Pediatrics and director of the Department of Pediatrics Molecular Diagnostics Laboratory.

The UAB researchers developed quantitative polymerase chain reaction, or qPCR, assays for 28 viruses sometimes found in pigs and two groups of mycoplasmas. They established reproducibility, sensitivity, specificity and lower limit of detection for each assay. All but three showed features of good quantitative assays, and the lower limit of detection values ranged between one and 16 copies of the viral or bacterial genetic material.

Also, the pig virus assays did not give false positives for some closely related human viruses.

As a start to understanding the infectious disease load in normal healthy animals and ensuring the safety of pig tissues used in xenotransplantation research, the researchers then screened blood, nasal swab and stool specimens from nine adult sows and 22 of their piglets delivered by caesarian section.

Mycoplasma species and two distinct herpesviruses were the most commonly detected microorganisms. Yet 14 piglets that were delivered from three sows infected with either or both herpesviruses were not infected with the herpesviruses, showing that transmission of these viruses from sow to the caesarian-delivery piglet was inefficient.

Prichard says the assays promise to enhance the safety of pig tissues for xenotransplantation, and they will also aid evaluation of human specimens after xenotransplantation.

The UAB researchers say they subsequently have evaluated more than 300 additional specimens, and that resulted in the detection of most of the targets. "The detection of these targets in pig specimens provides reassurance that the analytical methods are functioning as designed," said Prichard, "and there is no a priori reason some targets might be more difficult to detect than others with the methods described here."

Your teenage daughter gets into a shouting match with another kid at school. It turns out that it may have started over something as simple as not understanding one another's tones of voice. Recently published research in the Journal of Nonverbal Behavior shows that the ability to understand what someone is feeling based on their tone of voice can be challenging in mid-adolescence (between 13-15 years of age). While adults are able to accurately read a range of emotions in the voices of teens, and the opposite also holds true, teens are far less able to understand what is going on with their peers, particularly when it comes to tones of voice which express anger, meanness, disgust, or happiness.

"Our results suggest that teenagers have not yet reached maturity in either their ability to identify vocal emotions, or to express them," said Michele Morningstar, the first author on the paper, who conducted the research while completing her Ph.D. in Psychology at McGill University. "This means that teenagers face quite a challenge in their social spheres: they must interpret poorly expressed cues with immature recognition skills. Understanding how we learn emotional communication skills will be important to help teenagers who struggle socially."

Reading inflections to decode a speaker's feelings

The researchers played a total of 140 recordings made by child and adult actors to 50 teens between 13-15 years old and to 86 adults between the ages of 18-30. The recordings were of neutral phrases such as "I can't believe you just did that" which could be expressed with various intonations to convey different feelings. Participants of all ages were asked to select the emotion being conveyed in each recording, choosing from five basic emotions (anger, disgust, fear, happiness, and sadness) and from social expressions of affiliation (friendliness) or hostility (meanness).

The results showed a clear divide at a couple of different levels. The adults had no trouble, generally, reading the emotions of their peers, and had relatively few problems discerning the emotions of the teens. Teens, on the other hand, could read the emotions of the adults without difficulty, but struggled to understand the expressions of their peers. Morningstar's earlier research suggests that one reason for that may be that teens' are less able than adults to produce recognizable emotions with their voices. Adults' greater skill at recognizing emotion may become more apparent when trying to decode these more challenging signals.

"Parents shouldn't get too discouraged by these findings," adds Melanie Dirks, the senior author on the paper. "Although what we showed is that it takes longer for teens to recognize and identify the feelings of others than had previously been thought to be the case, our research suggests that it may just be a matter of brain development- that things will come with time."

This study was made available online in January 2018 behind a paywall ahead of final publication in print in June 2018.

AUSTIN, Texas -- Researchers at The University of Texas at Austin have developed a new approach to treating cancer using enzyme therapy.

The enzyme, PEG-KYNase, does not directly kill cancer cells but instead empowers the immune system to eradicate unwanted cells on its own. PEG-KYNase is designed to degrade kynurenine, a metabolite produced by numerous tumors that suppresses the immune system. The UT team's findings were published in a recent issue of Nature Biotechnology.

A healthy, fully functioning immune system can combat the spread of cancer cells and eliminate tumors by itself. However, tumors have evolved in multiple ways to suppress the immune system, leading to the growth and metastasis of cancer cells.

"Our immune system constantly polices the body and normally recognizes and eliminates cancerous cells," said Everett Stone, research assistant professor in the College of Natural Sciences' Department of Molecular Biosciences and co-author of the study. "Kynurenine acts as a roadblock to immune cells that impedes normal surveillance; our drug removes this obstacle."

Enzymes have been used in specific treatments before, to treat cancers such as leukemia for example, but this is the first time one has been designed to take on the role of immune checkpoint inhibitor. The researchers are confident this approach could prove effective in treating a variety of different cancers.

The team, led by Stone and professor George Georgiou in the Cockrell School of Engineering, developed an enzyme therapy that stimulates a human immune system abnormally suppressed by cancer cells, unleashing the body's power to fight back against the disease.

Their next step is to initiate clinical trials to test the safety and efficacy of the enzyme.

"Our work presents a new therapeutic approach to overcoming the suppression of the immune system by cancer cells," said Georgiou, who is a professor in the Cockrell School's chemical and biomedical engineering departments, the College of Natural Sciences' molecular biosciences department and Dell Medical School's oncology department. "By relieving immune suppression, the immune system becomes primed to kill cancer cells and eradicate tumors."