Earth

Most people think of water as existing in only one of three phases: Solid ice, liquid water, or gas vapor. But matter can exist in many different phases--ice, for example, has more than ten known phases, or ways that its atoms can be spatially arranged. The widespread use of piezoelectric materials, such as microphones and ultrasound, is possible thanks to a fundamental understanding of how an external force, like pressure, temperature, or electricity, can lead to phase transitions that imbue materials with new properties.

A new study finds that a metal oxide has a "hidden" phase, one that gives the material new, ferroelectric properties, the ability to separate positive and negative charges, when it is activated by extremely fast pulses of light. The research was led by MIT researchers Keith A. Nelson, Xian Li, and Edoardo Baldini, in collaboration with Andrew M. Rappe and Penn graduate students Tian Qiu and Jiahao Zhang. The findings were published in Science.

Their work opens the door to creating materials where one can turn on and off properties in a trillionth of a second with the flick of a switch, now with much better control. In addition to changing electric potential, this approach could be used to change other aspects of existing materials--turning an insulator into a metal or flipping its magnetic polarity, for example.

"It's opening a new horizon for rapid functional material reconfiguration," says Rappe.

The group studied strontium titanate, a paraelectric material used in optical instruments, capacitors, and resistors. Strontium titanate has a symmetric and nonpolar crystal structure that can be "pushed" into a phase with a polar, tetragonal structure with a pair of oppositely charged ions along its long axis.

Nelson and Rappe's previous collaboration provided the theoretical basis for this new study, which relied on Nelson's experience using light to induce phase transitions in solid materials along with Rappe's knowledge in developing atomic-level computer models.

"[Nelson is] the experimentalist, and we're the theorists," says Rappe. "He can report what he thinks is happening based on spectra, but the interpretation is speculative until we provide a strong physical understanding of what happened."

With recent improvements in technology and additional knowledge gained from working with terahertz frequencies, the two chemists set out to see if their theory, now more than one decade old, held true. Rappe's challenge was to complement Nelson's experiments with an accurate computer-generated version of strontium titanate, with every single atom tracked and represented, that responds to light in the same manner as the material being tested in the lab.

They found that when strontium titanate is excited with light, the ions are pulled in different directions, with positively charged ions moving in one direction and negatively charged ions in the other. Then, instead of the ions immediately falling back into place, the way a pendulum would after it's been pushed, vibrational movements induced in the other atoms prevent the ions from swinging back immediately.

It's as if the pendulum, at the moment that it reaches the maximum height of its oscillation, is diverted slightly off course where a small notch holds it in place away from its initial position.

Thanks to their strong history of collaboration, Nelson and Rappe were able to go back and forth from the theoretical simulations to the experiments, and vice versa, until they found experimental evidence that showed that their theory held true.

"It's been a really awesome collaboration," says Nelson. "And it illustrates how ideas can simmer and then return in full force after more than 10 years."

The two chemists will collaborate with engineers on future applications-driven research, such as creating new materials that have hidden phases, changing light-pulse protocols to create longer-lasting phases, and seeing how this approach works for nanomaterials. For now, both researchers are excited about their results and where this fundamental breakthrough could lead to in the future.

"It's the dream of every scientist: To hatch an idea together with a friend, to map out the consequence of that idea, then to have a chance to translate it into something in the lab, it's extremely gratifying. It makes us think we're on the right track towards the future," says Rappe.

Even single-celled organisms desire partners every now and then.

Leishmania - single-celled parasites that cause infections of the skin and internal organs - have long been known to multiply asexually, like bacteria. But occasionally, researchers have found hybrid parasites that carry genetic material from more than one strain - or even more than one species - of Leishmania, suggesting that some kind of genetic mixing is going on.

Now, researchers at Washington University School of Medicine in St. Louis and the National Institutes of Health (NIH) have found that the hybrid Leishmania parasites can mate with one another to produce fertile offspring that carry genes from both parents - signs of a true sexual reproductive cycle. The researchers hope to use their genetic remixing as a tool to find genes involved in virulence in Leishmanial disease.

"What we want to know is why one strain causes a mild form of disease and another causes a lethal form, or how the parasites evade the immune response," said co-senior author Stephen Beverley, PhD, a professor of molecular microbiology at the School of Medicine. "By generating offspring with different characteristics, we can identify the genes that cause severe disease or immune resistance. That could be a step toward better treatment or prevention."

The findings are available online in PLOS Genetics.

More than 1 million people in tropical countries contract Leishmania every year through the bites of infected sand flies. Most people develop disfiguring - but not life-threatening - skin lesions at the sites of the bites. But if the parasite spreads to the internal organs, it causes a disease known as visceral leishmaniasis that kills more than 30,000 people every year.

Beverley and colleagues, including longtime collaborator and co-senior author David Sacks, PhD, the chief of the intracellular parasite biology section at the National Institute of Allergy and Infectious Diseases at the NIH, uncovered hints in 2009 that the parasites could mate and produce hybrid progeny that carried a mix of genes from both parents.

The existence of hybrids alone isn't proof of a true sexual cycle. The Missouri mule, for example, a hybrid of a donkey and a horse, is strong and vigorous but sterile. Scientists need to be able to study a second generation to identify the genes involved in causing disease or interfering with a person's immune response. To find out whether the hybrid parasites were fertile, co-senior author Sacks, Beverley and colleagues, including co-first authors Ehud Inbar, PhD, a former research fellow at NIH, and Jahangheer Shaik, PhD, a bioinformatics specialist at the NIH, analyzed the inheritance patterns of matings involving hybrid offspring.

Since parasites mate only within a sand fly's gut, the researchers created hybrid offspring by feeding sand flies a mixture of two Leishmania strains. People normally carry exactly two copies of each of our 23 chromosomes, but the number of copies of Leishmania chromosomes can vary. Typically, most of their chromosomes are found in matched pairs, but a few chromosomes may be present in three or more copies. In previous work, the researchers found that hybrid progeny inherit two copies of most chromosomes, one from each parent. But if their parents carried extra copies of a particular chromosome, the hybrid parasites could inherit a third, fourth or even fifth copy.

To test whether the hybrid parasites were fertile, the researchers fed sand flies a hybrid parasite mixed with either one of its parental strains or an outside strain. They found that the hybrid parasites produced their own offspring, and the offspring typically inherited one chromosome from each parent, as expected for true sexual reproduction. The offsprings' chromosomes also showed extensive signs of genetic recombination - meaning that bits of DNA from one parent's chromosome had been switched with bits of DNA from the other parent's chromosome - another marker of true sexual reproduction.

By studying the hybrid parasites and their recombined progeny, the researchers will be able to map the location on chromosomes of genes involved in causing disease and resisting the immune response. Such a genetic map will aid efforts to understand why some strains cause worse disease than others, and how to bolster the immune response to the parasites.

"The good news is we generated offspring with new genetic combinations, which are perfect for our purposes," Beverley said. "The less good news is we could only obtain a handful, which were enough to establish their fertility, but not quite enough to make a high-resolution map of virulence genes."

The researchers are now trying to figure out why hybrid parasites so rarely succeed at mating.

"If you're a microbe and you have a winning genetic combination that allows you to thrive, you're going to reproduce asexually most of the time, because why mess with a good thing?" Beverley said. "But even so, you might want to mix things up a bit from time to time, just to see if a new genetic combination can be even more successful. So microbes have mechanisms in place to reshuffle their genetic material via sexual reproduction, but also mechanisms to prevent too much reshuffling so that they can maintain winning genetic combinations and limit inbreeding. If we can find out what it is that is limiting mating of our experimental hybrid parasites, we will likely uncover something new about the biology of reproduction. Even better, we may be able to twist it to our own purposes and learn how to create super-fertile hybrid parasites. And then we can use them to find out what we need to know about how they cause disease."

KNOXVILLE, Tenn. - Higher temperatures and mixing glyphosate with dicamba lead to increased atmospheric concentrations of dicamba, according to scientists with the University of Tennessee Institute of Agriculture.

Tom Mueller and Larry Steckel, both professors in the UT Department of Plant Sciences, examined dicamba measurements following an application to soil inside a humidome. The dicamba formulations examined were diglycolamine (Clarity) and diglycolamine + VaporGrip (XtendiMax). Both formulations were applied as a mixture with glyphosate (Roundup PowerMax), and XtendiMax was also applied alone. Applications were made across a range of temperatures and monitored for 60 hours. Researchers then used air samplers to collect dicamba from the atmosphere within the humidome.

According to study results, as expected, more dicamba was detected in the humidome as the temperature increased, with the largest gains coming when temperatures exceeded 85 degrees. Results also showed that across temperature ranges, the addition of glyphosate to dicamba formulations increased detectable dicamba air concentrations by 3 to 9 times compared to dicamba alone.

"Greater dicamba detections at higher temperatures are consistent with previous findings, and also correlate with increased complaints of off-target dicamba injury during late June and July," says Mueller.

"That glyphosate is a contributor to dicamba volatility is not as widely accepted, but our data shows the addition of glyphosate to a dicamba spray solution increased dicamba detection in the atmosphere which would point to increased volatilization."

According to Mueller, the most plausible explanation for the increased detection of dicamba was that glyphosate lowered the solution pH thereby resulting in more dicamba being in acid form, which is known to increase dicamba volatility. With increased volatility comes increased potential for off-target movement of the herbicide and injury to non-dicamba-tolerant plants.

Many products containing glyphosate are presently approved to be mixed with dicamba before spray applications. Combining herbicides with different modes of action is a common practice among crop producers to control a wider range of weed species. However, based on Mueller and Steckel's research, UT weed experts are discouraging the addition of glyphosate to XtendiMax, as well as other low-volatile dicamba formulations, Engenia, FeXapan and Tavium.

"Based on this research, we believe glyphosate in the tank mix could be a culprit in why we're seeing some of the drift in fields these past three years," says Steckel.

Dicamba drift has been a hot-button issue in the agricultural community since new and expanded uses for this herbicide were approved in 2017. Off-target dicamba movement, occurring either through physical drift or volatility, has been blamed for the damage of millions of acres of crops, trees and ornamental plants.

In an effort to decrease the potential for dicamba drift through volatilization, several states have implemented dicamba spray cut off dates to correspond with the times of year when temperatures consistently rise above 85 degrees. There is currently no spray cut off date in Tennessee, although UT weed scientists recommend not spraying dicamba--even low-volatile formulations of dicamba--when temperatures exceed 85 degrees.

Those same scientists are also recommending leaving glyphosate out of the dicamba spray mixture.

"Glyphosate is an important herbicide with many uses. Despite the continued evolution of glyphosate-resistant weeds, farmers would be lost without glyphosate, as it still provides excellent and economical control of many troublesome weed species," says Steckel. "These data would suggest it just doesn't belong in a tank mix with dicamba."

Phthalates, one of the most common endocrine disruptors, are commonly used by industry in many plastic products - toys, clothing, baby bottles or even medical equipment - as well as in cosmetics. If guidelines are beginning to be imposed to limit their use, their toxic effect on the endocrine system is worrying. Indeed, the exposure of male foetuses to phthalates can have devastating consequences for the fertility of future individuals by modifying the regulatory elements of the expression of genes responsible for spermatogenesis. However, we are not all equal: researchers at the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG), Switzerland, show that phthalate susceptibility depends largely on the genetic heritage of each individual. These results, to be discovered in PLOS One magazine, raise the question of individual vulnerability as well as that of the possible transmission to future generations of epigenetic changes that should normally be erased during foetal development.

Ariane Giacobino, a researcher in the Department of Genetic Medicine and Development at UNIGE Faculty of Medicine and Associate Assistant Physician at HUG Division of Genetic Medicine, is a specialist in epigenetics (the study of the elements that modify gene expression). In 2015, she observed, by comparing two groups of mice, a very different sensitivity to phthalates, one of the most common endocrine disruptors. "We exposed pregnant females to phthalate doses and studied sperm concentration and quality in their male offspring. If one group had very poor sperm quality, the other group, even though they were exposed to the same doses, would get away with it," explains Ariane Giacobino. Why such a difference?

The researchers reviewed possible epigenetic and genetic causes to determine where the difference between the two groups lays. To do so, they studied all variations of the epigenome and genome of these two groups of mice.

Epigenetic changes that goes down to the next generation

Scientists administered a dose of phthalate to both groups of mice for 8 days between 8 and 18 days gestation. Ludwig Stenz, Junior Lecturer in the Department of Genetic Medicine and Development at UNIGE Faculty of Medicine and first author of this work summarizes their results: "We studied epigenetic and genetic variations in specific portions of the genome, located in the vicinity of genes related to spermatogenesis. This allowed us to identify the exact epigenetic mechanism at work that modulates gene expression upwards or downwards, and thus influences sperm quality and mobility."

The researchers identified hormone-binding sites in the genome of mice vulnerable to phthalates that are not present in the resistant group. This is probably where the endocrine disruptors bind and inactivate these genes. Conversely, the other group presents a protein-binding site in its genome that increases the production of protective elements.

In addition, the researchers observed a worrying phenomenon: not only does the epigenetic effect of phthalates prevent spermatogenesis genes from expressing themselves correctly, but in addition the epigenetic wipe out that usually takes place between generations seems to be no longer completely achieved over the two generations following the individual's exposure.

What about human beings?

This study, funded by the Swiss Centre for Human Toxicology (SCAHT), will now extend to cohorts of men in Switzerland exposed to phthalates. "We currently have no way of knowing to what extent we are -individually or in terms of population - genetically susceptible or not to these epigenetic disruptions, says Ariane Giacobino. We want to have an idea of the proportion of people who are vulnerable to each product. In normative terms, the epidemiological dimension should also be taken into account, as well as possible transgenerational effects. Indeed, if 95% of the population is vulnerable or if only 5% are, the question could be examined differently. In addition, the regional and ethnic dimension should perhaps be taken into account."

Researchers from the University of Notre Dame have developed small drug-targeting molecules that may be hundreds to thousands of times more effective at delivering potent drugs to desired sites of disease, including cancer.

According to the study published in ACS Central Science, a compound was developed from a new material, described as an easily injected hydrogel, which acts as a "homing" cue to attract drug molecules to sites bearing a tumor. By this method, the same sites can also be re-targeted for repeat dosing of chemotherapy or other treatments as needed.

"Common strategies, including several clinically approved therapeutics, use antibodies to direct a drug to its target. While offering biological recognition, these approaches only deliver a very small percentage of the drug to the site where it is needed while the remainder of the drug may circulate in the body for a very long time and cause increased toxicity," said Matthew Webber, assistant professor in the Department of Chemical and Biomolecular Engineering and senior author on the study. "As toxic as chemotherapy is, accurate drug-targeting paradigms are key to improving both the effectiveness of treatment as well as the quality of life for patients."

Instead of large protein-based targeting, Notre Dame researchers opted to use a small molecule. The size of the molecule is intended to improve tissue distribution and enable access to the desired site. In the case that the molecules do not make it to their target, their size also allows them to clear rapidly from the body, helping limit toxicity from chemotherapy.

"Our goal was to think about drug targeting in a new way," said Lei Zou, postdoctoral researcher in chemical and biomolecular engineering and lead author on the study. "This approach has allowed us to create something very different from what is currently available in the market, with the potential to improve the chemotherapy treatment experience for cancer patients."

In 2005, condensed matter physicists Charles Kane and Eugene Mele considered the fate of graphene at low temperatures. Their work led to the discovery of a new state of matter dubbed a "topological insulator," which would usher in a new era of materials science.

"A topological insulator is a material that is an insulator in its interior but is highly conducting on its surface," said UC Santa Barbara assistant physics professor Andrea Young. In two-dimensions, an ideal topological insulator would have "ballistic" conductance at its edges, Young explained, meaning that electrons traveling through the region would encounter zero resistance.

Ironically, while Kane and Mele's work would lead to the discovery of topological insulating behavior in a wide variety of materials, their original prediction -- of a topological insulator in graphene -- has remained unrealized.

At the heart of the trouble is spin-orbit coupling -- a weak effect in which the spin of the electron interacts with its orbital motion aroun the nucleus. Critical to all topological insulators, spin-orbit coupling is exceptionally weak in graphene, so that any topological insulating behavior is drowned out by other effects arising from the surface on which the graphene is supported.

"The weak spin-orbit coupling in graphene is a great pity," said postdoctoral researcher Joshua Island, because in practice things haven't really worked out that well for topological insulators in two dimensions. "The two dimensional topological insulators known to date are disordered and not very easy to work with," Island said. The conductance at the edges tends to diminish rapidly with the distance the electrons travel, suggesting it is far from ballistic. Realizing a topological insulator in graphene, an otherwise highly perfect two dimensional material, could provide a basis for low-dissipation ballistic electrical circuits or form the material substrate for topologically protected quantum bits.

Now, in work published in the journal Nature, Island, Young and their collaborators have found a way to turn graphene into a topological insulator (TI). "The goal of the project was to increase or enhance the spin-orbit coupling in graphene," lead author Island said, adding that attempts have been made over the years with limited success. "A way to do this is to put a material that has a very large spin-orbit coupling in close proximity with the graphene. The hope was that by doing that your graphene electrons will take on this property of the underlying material," he explained.

The material of choice? After studying several possibilities, the researchers settled on a transition metal dichalcogenide (TMD), consisting of the transition metal tungsten and the chalcogen selenium. Similar to graphene, tungsten diselenide comes in two-dimensional monolayers, bound together by van der Waals forces, which are relatively weak and distance-dependent interactions between atoms or molecules. Unlike graphene, however, the heavier atoms of the TMD lead to stronger spin-orbit coupling. The resulting device feature's graphene's ballistic electron conductance imbued with the strong spin-orbit coupling from the nearby TMD layer.

"We did see a very clear enhancement of that spin-orbit coupling," Island said.

"By adding spin-orbit coupling of just the right type, Joshua was able to find that this in fact leads to a new phase which is almost topologically insulating," Young said. In the original idea, he explained, the topological insulator consisted of a monolayer of graphene with a strong spin-orbit coupling.

"We had to use a trick only available in graphene multilayers to create the right type of spin-orbit coupling," Young explained about their experiment, which used a graphene bilayer. "And so you get something that approximates two topological insulators stacked on top of each other." Functionally, however, Island's device performs as well as other known 2D topological insulators -- the all-important edge states propagate for at least several microns, much longer than in other known TI materials.

Furthermore, according to Young, this work is one step closer to building an actual topological insulator with graphene. "Theoretical work has since shown that a graphene trilayer, fabricated in the same way, would lead to a true topological insulator."

Most importantly, the devices realized by Island and Young can be easily tuned between a topological insulating phase and a regular insulator, which does not have conducting edge states.

"You can route these perfect conductors around wherever you want," he said, "And that's something nobody's been able to do with other materials."

Osaka, Japan - In eukaryotic cells, the nucleus is walled off from the rest of the cell by the nuclear envelope. All transport into and out of the nucleus occurs via cylindrical channels called nuclear pore complexes (NPCs) that penetrate the nuclear envelope. Each NPC is made up of eight repeating protein complexes containing at least 30 different types of proteins, called nucleoporins (Nups). These complexes fit together like the wedges of an orange, leaving a channel in the middle through which proteins, RNA, and signaling molecules can be transported.

The Nups at either end of the NPC form ring-like structures that frame the openings of the channel. So far, all work in eukaryotic cells has suggested that these outer rings are identical, comprising equal numbers of nine or ten different Nups linked together in repeating Y-shaped structures.

But in a study published this week in PLoS Genetics, a team lead by researchers from Osaka University and National Institute of Information and Communications Technology (NICT) found that the "one size fits all" theory may not hold true.

"We wanted to take a closer look at the NPCs of fission yeast, Schizosaccharomyces pombe", says lead author of the study Haruhiko Asakawa at Osaka University. "Like other eukaryotes, S. pombe has a conserved set of Nups, but unlike these other species, the outer ring structures are made up of unequal numbers of the different types of proteins."

And while the researchers were expecting some differences, they weren't quite prepared for the completely divergent structures revealed by using high-powered immunoelectron and fluorescence microscopes. By carefully tracking the locations of the different proteins, they made their startling discovery.

"It's like S. pombe has completely thrown the rule book out the window," laughs senior author Tokuko Haraguchi at NICT. "We found that the proteins that make up the outer ring structures were arranged asymmetrically. Rather than having identical structures, the nuclear outer ring comprised only two types of Nups, with the seven remaining Nups all part of the cytoplasmic outer ring structure."

Interestingly, the researchers found that the asymmetrical ring structure was essential for normal cell growth in S. pombe.

"This diversity in the outer ring structures may provide clues as to how the nuclear pore is formed, along with insights into the structure and function of the cell nucleus from an evolutionary point of view," says Asakawa. "We also hope that our findings will help us to better understand the mechanisms of diseases caused by abnormal nuclear pore proteins, which in turn may lead to new treatment strategies."

The cell contains transcripts of the genetic material, which migrate from the cell nucleus to another part of the cell. This movement protects the genetic transcripts from the recruitment of "spliceosomes". If this protection does not happen, the entire cell is in danger: meaning that cancer and neurodegenerative diseases can develop. Researchers at the University of Göttingen and the University Medicine Centre Göttingen have demonstrated the underlying mechanism in the cell. The results were published in the journal Cell Reports.

Human cells are made up of the following: a cell nucleus, which contains the genetic material in the form of DNA; and the cytoplasm, where proteins are built. In the cell nucleus, the DNA that contains the blueprint for the organism is rewritten into another form, messenger RNA, in order to transport the information so that these instructions can be used for protein production. Separated from the original transcript, the proteins can then be produced in the cytoplasm. The separation is important because the messenger RNA is not immediately usable; rather, a precursor (pre-messenger RNA) has to be produced that still contains areas that have to be removed before the messenger RNA reaches the cytoplasm. If these areas are not removed beforehand, then shortened or dysfunctional proteins are produced, which is dangerous for the cell.

The molecular machinery that cuts these areas out of the messenger RNA are the spliceosomes. They contain proteins and another type of transcripts of the DNA, the snRNA. The snRNA is not translated into proteins like messenger RNA, but together with the proteins, forms the molecular machinery: the spliceosome. In human cells, the snRNA of the spliceosomes also moves into the cytoplasm. In other organisms, such as baker's yeast, which is often used as a model organism in research, scientists had thought that the snRNA of the spliceosomes never left the cell nucleus. The reason for the evolutionary development to export snRNA before incorporation into the spliceosomes of human cells was also a mystery.

"Our experiments show that in fact the snRNA of the spliceosomes also migrates into the cytoplasm in yeast," said Professor Heike Krebber, Head of the Department of Molecular Genetics at the Institute for Microbiology and Genetics at the University of Göttingen. In a second step, the researchers answered the question as to why the messenger RNA of the spliceosomes actually moves into the cytoplasm. It was unclear because the spliceosomes' task is to cut out individual RNA regions and this takes place back in the cell nucleus. The team of researchers manipulated the yeast by genetic experiments so that the precursors of snRNA no longer changed in the cytoplasm. The observation: "The spliceosomes attempt to work with the precursors, the unfinished snRNA, and this cannot function as it's supposed to," said Krebber. "This is the reason that healthy cells must first send the precursors of messenger RNA out of the cell nucleus immediately after their production: it is to prevent them from being used by the developing spliceosomes. This basic understanding is important in order to identify the underlying cause of the development of diseases.

CAMBRIDGE, MD (JUNE 12, 2019)--Ecologists from the University of Maryland Center for Environmental Science and the University of Michigan are forecasting a large Chesapeake Bay "dead zone" in 2019 due to well-above-average river flows associated with increased rainfall in the watershed since last fall.

"The forecast this year reflects the high levels of precipitation that have been observed across the Bay's watershed," said report co-author Jeremy Testa of the University of Maryland Center for Environmental Science. "The high flows observed this spring, in combination with very high flows late last fall, are expected to result in large volumes of hypoxic and anoxic water."

The bay's hypoxic (low oxygen) and anoxic (no oxygen) zones are caused by excess nutrient pollution, primarily from agriculture and wastewater. The excess nutrients stimulate an overgrowth of algae, which then sinks and decomposes in the water. The resulting low oxygen levels are insufficient to support most marine life and habitats in near-bottom waters, threatening the bay's crabs, oysters and other fisheries.

This summer's Chesapeake Bay hypoxic or "dead zone," an area of low oxygen that can kill fish and other aquatic life, is expected to be about 2.1 cubic miles, while the volume of water with no oxygen is predicted to be between 0.49 and 0.63 cubic miles during early and late summer.

The predicted volumes are larger than the dead zone observed during the summer of 2018 and would be among the four largest in the past 20 years. Measurements of the Chesapeake Bay's dead zone go back to 1950, and the 30-year mean maximum dead zone volume is 1.74 cubic miles.

"The forecast is not surprising considering the near-record high flows in 2018 that have continued into 2019," said Bruce Michael, director of the Resource Assessment Service at the Maryland Department of Natural Resources. "That said, bottom dissolved oxygen concentrations are improving over the long-term in Maryland's portion of the Chesapeake Bay, indicating our efforts to reduce nutrient pollution throughout the entire watershed are improving water quality conditions, helping to support fish, shellfish and our aquatic resources."

The Maryland Department of Natural Resources will conduct bimonthly Bay water quality monitoring cruises June through August to track Bay summer hypoxia. Results from each monitoring cruise will be available on the Department's Eyes on the Bay website at http://eyesonthebay.dnr.maryland.gov/eyesonthebay/index.cfm

The University of Maryland Center for Environmental Science's Chesapeake Bay Report Card released earlier this spring gave the Bay a grade of "C" in 2018, in part due to the extreme precipitation. Spring rainfall plays an important role in determining the size of the Chesapeake Bay "dead zone." This year, exceptionally high spring rainfall and streamflow is transporting nitrogen to tidal waters in amounts above the long-term average, according to the U.S. Geological Survey, which provides the nitrogen-loading estimates used to generate the annual hypoxia forecast.

In spring 2019, the Susquehanna River delivered 102.6 million pounds of nitrogen into the Chesapeake Bay. The Potomac River, as measured near Washington, D.C., supplied an additional 47.7 million pounds of nitrogen, according to USGS. This is well-above long-term averages of 80.6 million pounds from the Susquehanna and 31.8 million pounds from the Potomac. Loads from the Susquehanna have not been this high since 2011.

"Managing estuarine responses to changing conditions on the landscape continues to be one of the nation's environmental challenges," said Joel Blomquist, hydrologist for the U.S. Geological Survey (USGS). "The science partnership in the Chesapeake Bay is setting the standard for supporting environmental managers with observation-based science."

"This year's forecast is for the fourth largest dead zone in the past 20 years, illustrating that more work needs to be done," said University of Michigan aquatic ecologist and report coauthor Don Scavia. "The Chesapeake Bay dead zone remains considerably larger than the reduction goals, and we'll never reach those targets unless more is done to reduce nutrient pollution."

The bay outlook is based on models developed at the University of Michigan and the University of Maryland Center for Environmental Science, with funding provided by the National Oceanic and Atmospheric Administration and data generated by the United States Geological Survey and Maryland Department of Natural Resources.

Throughout the year, researchers measure oxygen and nutrient levels as part of the Chesapeake Bay Monitoring Program, run by the Maryland Department of Natural Resources and the Virginia Department of Environmental Quality. This year's findings will be released in the fall.

Canadian researchers followed their intuition that a drug initially intended for heart failure could be effective in treating cancer. Those efforts have borne fruit, as demonstrated by their work published in the Journal of Experimental and Clinical Cancer Research.

"Some drugs designed for certain therapeutic indications can be used for other diseases; this is called drug repositioning. Since these drugs have already passed the critical approval stages in toxicology, preclinical safety, pharmacokinetics, etc., they represent a real advantage in initiating new clinical trials more quickly," says Elodie M. Da Costa, a doctoral student at Université de Montréal and first author of the study.

"Here, we observed for the very first time the anticancer and epigenetic properties of proscillaridin A - a cardiotonic used to treat heart failure or cardiac arrhythmia - in leukemias in children expressing the MYC gene. When subjected to mutations or overexpression, this gene induces uncontrolled cell proliferation, thus promoting the development of cancer," explains Elodie M. Da Costa.

Currently, no effective treatment is approved to target this type of alteration in leukemias. This approach therefore represents a promising avenue for developing strategies to inhibit the MYC gene and its oncogenic partners.

To achieve these results, the research team used various advanced techniques in molecular biology, next-generation sequencing and pharmacology to evaluate the efficacy and mechanism of action of this drug in the treatment of leukemias. The team observed that the molecule preferentially attacks leukemic stem cells, which drive the spread of the disease.

"Each cancer is unique, and to increase the chances of survival, precision medicine is a promising way forward by developing patient-specific therapeutic strategies," says Noël J.M. Raynal, researcher at CHU Sainte-Justine and professor at Université de Montréal. "It is therefore essential to analyze the different characteristics of each cancer in genomic, epigenetic and proteomic terms in order to identify optimal therapies. Research on drug repositioning opens a new path toward innovative therapeutic options in the treatment of cancer. "

Leukemia, a relentless battle

Over the past few decades, the survival rate of patients with pediatric leukemias has improved significantly. However, some patients remain resistant to current therapies and two-thirds of patients have significant long-term side effects related to the toxicity of treatments (metabolic and neurological disorders, and sometimes secondary cancers).

"In the medium term, we hope to complete the preclinical characterization of this drug to eventually initiate clinical trials. Our ultimate goal is to identify more specific and less toxic therapeutic strategies for children with leukemia characterized by the MYC gene in order to improve survival rates and quality of life," notes Elodie M. Da Costa. "CHU Sainte-Justine is a leader in North America in cancer care and research and we are proud to contribute to the advancement of knowledge in this field," adds Noël J.M. Raynal.

According to Canadian Cancer Society statistics, leukemias are the most commonly diagnosed cancers in children aged 0 to 14 years and account for about 32% of childhood cancers in Canada. Leukemia is the second leading cause of childhood cancer death in Canada. The proto-oncogene MYC is deregulated in nearly 80% of leukemias.

Persistent poverty affects one in five children in the UK, and is associated with poor physical and mental health in early adolescence, suggests research published online in the Archives of Disease in Childhood.

Child poverty is rising in the UK. In 2016-17, 30% (4.1 million) children were reported to be living in poverty, up from 27% in 2010-11, and the proportion is projected to rise further over the next five years. By 2023-24, the proportion of children living in relative poverty is on course to hit 37%, affecting an extra 1.1 million children.

Persistent poverty is associated with poorer mental, social, and behavioural development in children, as well as worse educational outcomes, employment prospects, and earning power into adulthood.

What's less clear is whether specific patterns of exposure to poverty have different effects on adolescent physical and mental health.

To explore this further, a team of UK researchers from the University of Liverpool and University College London analysed data on 10,652 children from the UK Millennium Cohort Study, a large nationally representative sample of babies born between 2000 and 2002 who have been tracked throughout childhood.

Poverty (defined as less than 60% of average household income) was measured at 9 months, and at 3, 5, 7, 11 and 14 years of age.

Mental health was measured using a recognised questionnaire; physical health was measured by obesity (BMI); and parents were asked to report any longstanding illness when their child was 14.

Almost one in five (19.4%) children experienced persistent poverty across all time points, whereas more than 60% (62.4%) of children never did. A further 13.4% of children experienced poverty in early childhood (between 9 months and 7 years), while the remaining 5% experienced it in late childhood (11 to 14 years).

After adjusting for mother's education and ethnicity, the researchers found that compared with children who never experienced poverty, any period of poverty was associated with worse physical and mental health in early adolescence.

In particular, those in persistent poverty had a 3 times higher risk of mental ill health, a 1.5 times greater risk of obesity, and nearly double the risk of longstanding illness than children who had never been poor.

Poverty in early childhood was also associated with a higher risk of obesity in adolescence than in late childhood, while mental ill health and longstanding illness were more strongly associated with poverty in late childhood.

Although this is an observational study, and it is challenging to establish causality, other evidence suggests that poverty does indeed have a causal effect, leading to many aspects of poor child health. What's more, some measures were based on parents' self-report, so may not have been completely accurate, while missing data may also have affected the results, say the researchers.

But they point out that this is a large, nationally representative study, rich in data on family characteristics, added to which the findings are consistent with those of other similar studies.

They warn that the impact of rising levels of poverty on children's mental health "is likely to have profound implications for social policies and their associated social costs, given mental health tracks from early life to adulthood."

And they call for "a renewed commitment" by the UK government to prioritise ending child poverty. Health professionals "are well-placed to argue that policies and services in the UK should fulfil our moral and legal responsibility to ensure that every child is able to achieve their full potential," they suggest.

Professor David Taylor-Robinson, University of Liverpool's Department of Public Health and Policy, said: "As a child health doctor, it is baffling to me that we let an exposure as toxic as child poverty wash over such a large proportion of the children in this country. Our analysis shows that urgent action is needed to reduce child poverty if we want to secure healthy futures for kids in the UK."

Many important natural products such as antibiotics, immunosuppressants, or anti-cancer drugs are produced by microorganisms. These natural products are often small peptides, which in several cases are too complex for a chemical synthesis in the laboratory. In the microbial producers of these drugs, the drugs are generated with the help of the NRPS enzymes in a manner similar to a modern automobile factory: at each station, additional parts are added to the basic structure until finally a complete automobile leaves the factory. In the case of NRPS, a specific amino acid is incorporated and processed at each station (module) so that in the end, peptides emerge that can be linear, cyclic or otherwise modified, and which can also carry unusual amino acids.

Although the basic principles of NRPS have been known for a long time, it was previously hardly possible to modify these enzymes in an easy and efficient way that also allows the complete assembly of fully artificial enzymes leading to new-to-nature peptides. While in the past NRPS modification usually led to a dramatic drop in the production titre of the desired modified peptides, the Molecular Biotechnology research group of Professor Helge Bode already published a new method in 2018 that avoided this drawback. The group has now further optimized this method allowing the easy production of new peptides in excellent yield.

"We use fragments of natural NRPS systems from different bacteria as building blocks that we connect to each other using specific assembly points we have identified," Andreas Tietze and Janik Kranz explain the research approach they developed as part of a larger team in the Bode group. "The yields are comparable to the natural production of the non-modified natural products and the new methods also enable the simple production of peptide libraries, which was not possible before".

The method is so well established, beginners can use it to produce new peptides after a short training period. But to get to this point was a long way. "Following the first promising experiments by Kenan, my PhD student at the time, we worked for a long time on the project with a major part of my group until we were certain that our method fulfilled the requirements of a robust and easily reproducible engineering method," Bode states. "Thanks to the LOEWE priority programmes MegaSyn and Translational Biodiversity Genomics, we had the necessary personnel and financial support, and could concentrate completely on the project."

The next step is to modify the first clinically relevant drugs with this method and produce them in microorganisms applying biotechnology methods. The conditions for this are good - Bode was only recently awarded one of the renowned ERC Advanced Grants from the European Research Council in order to further optimize the methods over the next five years.

Six different colour morphs of the elusive Asiatic golden cat have been discovered in Northeast India - with the findings being hailed as "an evolutionary puzzle" - as the world's greatest number of different coloured wild cat species in one area are reported.

The Indian scientists from international conservation charity ZSL (Zoological Society of London) and UCL discovered the colour morphs, during a wide-scale camera trapping study covering both community forests and protected areas across Dibang Valley, Northeast India.

The study, published on 7 June 2019 in the Ecological Society of America's journal, Ecology aimed to uncover a greater understanding of human-wildlife interactions in the region but discovered a group of entirely different-looking animals on their camera traps - with an inkling they were all the exact same species.

The finding is said to spark more questions than it answers. However, understanding how this remarkable phenomenon takes hold in a population, may help scientists grasp how quickly species can adapt and evolve to changing environments. This would advise scientists of the resilience of the species to climate change or habitat degradation and destruction.

Colour morphs are not classed as different subspecies as they may live in the same area and even interbreed. However, if differences in their behaviour prevented them from interbreeding - this could represent the beginning of the evolutionary process into separate subspecies. A more well-known example of a colour morph is the melanistic (dark coloured) morph (aka black panther) of the common leopard (Panthera pardus).

Within the six colour morphs recorded, an entirely new colour morph was also found in one of the community-owned forests. The now named "tightly-rosetted" morph after the leopard-like rosettes tightly spaced on their gray coat, now sits alongside the already known: cinnamon, melanistic, gray, golden, and ocelot (due to its ocelot-like markings) types.

ZSL scientists believe that the wide variation displayed in the cat's coats provides them with several ecological benefits. It enables them to occupy different habitats at different elevations - from wet tropical lowland forests to alpine scrubs - and provides camouflage while hunting different prey such as tropical pheasants or Himalayan pika (a small mountain-dwelling rabbit-like mammal).

Colour morphs are thought to arise from random genetic mutations and take hold in the population through natural selection. In this region, scientists suspect that the phenomenon is driven by competition with other big cats such as tigers (Panthera tigris) and clouded leopards (Neofelis nebulosa). Being melanistic in the misty mountains during nocturnal hunts, for example, may mean they are better concealed from their prey; making them more efficient predators.

Dr Sahil Nijhawan, the India-based lead author and British Academy Fellow at ZSL's Institute of Zoology and UCL said: "According to evolutionary theory, if a colour morph is not beneficial for a species survival - over time, it should die out in the population. The fact that we have so many different colour morphs persisting in Dibang Valley shows there must be some ecological advantages to the variety of colours.

"We now know Dibang Valley hosts the world's most diverse range of colour morphs of a wild cat species ever reported in one site, but we are only just starting to understand this rare ecological phenomenon. We need more studies that shed light on such unique adaptations and the benefits they provide to species, especially in a world where they must adapt quickly."

Giant petrels will be "temporary" winners from the effects of climate change in the Antarctic region - but males and females will benefit in very different ways, a new study shows.

The study, by experts from the University of Exeter and the British Antarctic Survey (BAS), is one the first to analyse how different sexes of the same species could be affected by changing conditions through global warming.

The research shows that giant petrels - known colloquially as "stinkers" - will benefit from an increased number of warm weather anomalies in the region, while changes to wind patterns across the Antarctic and the southwest Atlantic will also improve their ability to forage at sea.

However, the research reveals that the benefits are different for the male of the species, compared to females.

It shows that the males - as the larger and heavier sex - would benefit more by dominating access to carrion on land and by traveling much less far from the colony when foraging at sea.

Females, on the other hand, are likely to benefit from stronger winds which will help them fly and forage at sea with less effort, and from retreating sea ice increasing the extension of open waters suitable for foraging.

Crucially, however the study also suggests that any increase in longline fishing (and resulting mortality on fishing gear - termed bycatch) could harm their survival.

Few studies have examined how different sexes of a species could be affected by changing conditions, and the researchers say this means the impacts could be underestimated if sex-specific effects are not included.

"It is really difficult - but really important - to measure how the sexes of a species will respond to environmental changes, especially in species with strong sexual size dimorphism, like the giant petrels," said lead author Dr Dimas Gianuca, of the University of Exeter and BAS. "Petrels are going to do relatively well due to the changes we expect to see in this region. The increased winds and other changes in the environment will be good for them. However, any future increase in longline fishing - which may well result in a greater risk of bycatch - is likely to impair the survival of females, which forage further north than males and, consequently interact more with poorly managed longline fishing in subtropical waters."

The study analysed 15 years of monitoring data on giant petrel survival and breeding collected by BAS at Bird Island, South Georgia, and projected the likely consequences of future environmental change and fishing.

Though petrels appear to be climate change "winners" in the coming decades, the researchers warn this could be temporary.

"Although warm conditions may benefit giant petrels, in the long term, persistent warm anomalies can lead to broader ecosystem disruptions in Antarctic food webs, and potentially further reduction in krill stocks. This would lead to further population declines of South Georgia Antarctic fur seals and other species on which male giant petrels depend for food during the breeding season, therefore it will be bad for petrels too," said Dr Richard Sherley, of the University of Exeter.

Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy. If scientists could put a "homing beacon" in tumors, they could attract these medicines and reduce side effects caused by the drugs acting on healthy cells. Now, researchers have made a hydrogel that, when injected near tumors in mice, recruits drugs to shrink the tumor with fewer side effects. They report their results in ACS Central Science.

Scientists have tried to target chemotherapy drugs to tumors by attaching antibodies that bind to proteins expressed on the cancer cells' surfaces. However, less than 1% of the administered drug actually ends up at the tumor site. Matthew Webber and colleagues decided to take a different approach: using cucurbituril to target therapies to a tumor. Cucurbituril is a pumpkin-shaped molecule that can capture certain other chemicals within its central cavity. If the researchers could inject cucurbituril near a tumor, and then attach targeting chemicals to chemotherapy drugs, they might be able to retain the drugs at the tumor site through these interactions. Then, the abnormally acidic microenvironment of the tumor would rupture the linkage between the drug and the targeting chemical, unleashing the therapy to kill cancer cells.

To test their approach, the researchers first injected a hydrogel containing cucurbituril under mice's skin. They attached a dye to the targeting molecule so they could easily track it, and then injected that into the mice's bloodstream. They found that 4.2% of the injected dye ended up in the hydrogel, which is much higher than previously reported antibody approaches. The mice quickly excreted the majority of the dye that was not bound to the hydrogel. When the team injected the hydrogel adjacent to tumor xenografts in mice and then administered the cancer drug doxorubicin attached to the targeting molecule, the mice's tumors showed much slower growth, and the mice had fewer side effects than those given unmodified doxorubicin. The hydrogel persisted in the mice's body for more than 45 days, which could allow repeated doses of chemotherapy drugs, or the use of different drugs with the same targeting molecule, the researchers say.