Earth

DURHAM , N.C. -- Many people turn to the Internet to find a Mr. or Ms. Right. But lemurs don't have to cyberstalk potential love interests to find a good match -- they just give them a sniff.

A study of lemur scents finds that an individual's distinctive body odor reflects genetic differences in their immune system, and that other lemurs can detect these differences by smell.

From just one whiff, these primates are able to tell which prospective partners have immune genes different from their own. The ability to sniff out mates with different immune genes could make their offspring's immune systems more diverse and able to fight more pathogens, said first author Kathleen Grogan, who did the research while working on her Ph.D. with professor Christine Drea at Duke University.

The results appeared online August 22 in the journal BMC Evolutionary Biology.

Lemurs advertise their presence by scent marking -- rubbing stinky glands against trees to broadcast information about their sex, kin, and whether they are ready to mate.

For the study, Grogan, Drea and colleagues collected scent secretions from roughly 60 lemurs at the Duke Lemur Center, the Indianapolis Zoo, and the Cincinnati Zoo. The team used a technique called gas chromatography-mass spectrometry to tease out the hundreds of compounds that make up each animal's signature scent.

They also analyzed the lemurs' DNA, looking for differences within a cluster of genes called MHC that help trigger the body's defenses against foreign invaders such as bacteria and viruses.

Their tests reveal that the chemical cocktail lemurs emit varies depending on which MHC types they carry.

To see if potential mates can smell the difference, the researchers presented lemurs with pairs of wooden rods smeared with the bodily secretions of two unfamiliar mates and observed their responses. Within seconds, the animals were drawn to the smells wafting from the rods, engaging in a frenzy of licking, sniffing, or rubbing their own scents on top.

In 300 trials, the team found that females paid more attention to the scents of males whose immune genes differed from their own.

MHC genes code for proteins that help the immune system recognize foreign invaders and distinguish "friend" from "foe." Since different genetic versions respond to different sets of foreign substances, Grogan said, sniffing out genetically dissimilar mates produces offspring capable of fighting a broader range of pathogens.

Just because females spent more time checking out the scents of dissimilar males doesn't necessarily make them more likely to have kids together, Grogan said. Moving forward, she and her colleagues plan to use maternity and paternity DNA test results from wild lemurs living in Beza Mahafaly Reserve in Madagascar to see if lemur couples are more different in their MHC type than would be expected by chance.

Similar results have been found in humans, but this is the first time the ability to sniff out partners based on their immune genes has been shown in such distant primate kin, said Grogan, who is currently a postdoctoral fellow at Pennsylvania State University.

"Growing evidence suggests that primates rely on olfactory cues way more than we thought they did," Grogan said. "It's possible that all primates can do this."

A little bit of norovirus - the highly infectious microbe that causes about 20 million cases of food poisoning in the United States each year - goes a long way. Just 10 particles of the virus can cause illness in humans. A team of University of Arizona researchers has created a simple, portable and inexpensive method for detecting extremely low levels of norovirus.

Jeong-Yeol Yoon, a researcher in the Department of Biomedical Engineering; Soo Chung, a biosystems engineering doctoral student who works in Yoon's Biosensors Lab; and Kelly A. Reynolds, Chair of the Department of Community, Environment and Policy in the Mel & Enid Zuckerman College of Public Health, led the project. The team published their results in ACS Omega, the official journal of the American Chemical Society, and Yoon is presenting the research at the ACS Fall 2019 National Meeting & Exposition in San Diego this week.

"Advances in rapid monitoring of human viruses in water are essential for protecting public health," Reynolds said. "This rapid, low-cost water quality monitoring technology could be a transformational tool for reducing both local and global disease burdens."

The National Science Foundation Water and Environmental Technology Center at the UA and Tucson Water both provided funding for this research. While norovirus is often associated with cruise ships, it can also spread quickly through a community via its water supply. It causes about 200,000 deaths globally each year.

Keeping Components Simple

Devices to detect norovirus in small quantities do already exist, but they typically require a laboratory setting with an array of microscopes, lasers and spectrometers that can cost thousands of dollars. To detect norovirus in the field, such as on cruise ships or in municipal water wells, the team decided to use much simpler materials: paper, in the form of microfluidic chips, and a smartphone.

"Paper substrate is very cheap and easy to store, and we can fabricate these chips easily," Chung said. "The fibrous structure of paper also allows liquid to flow spontaneously without using the pumping systems other chips, such as silicon chips, usually require."

However, scientists usually detect contaminants on the chips by measuring the scattering and reflection of light in a sample, and paper's porousness and opacity can cause background scattering that interferes with imaging and makes it difficult to detect very small concentrations of a virus. So, the group developed a new way to detect norovirus, by counting fluorescent beads rather than measuring light intensity.

The process starts with adding potentially contaminated water to one end of a paper microfluidic chip. To the other end, a tester adds tiny, fluorescent polystyrene beads (picture the little white balls inside of a bean bag - these are the same material, but much smaller). Each bead is attached to an antibody against norovirus. If norovirus is present, several of the antibodies attach to each virus particle, creating a little clump of fluorescent beads.

"Norovirus particles are too small to be imaged by a smartphone microscope, and so are antibodies," Yoon said. "But when you have two or three or more of these beads joined together, that indicates that the norovirus is there, causing the beads to aggregate."

These clumps of beads are large enough for a smartphone microscope to detect and photograph. Then, a smartphone app the researchers created counts the number of illuminated pixels in the image to identify the number of aggregated beads, and subsequently, the number of norovirus particles in the sample. That's another advantage of the paper chip: Through capillary action, the groups of beads spread out along the paper, making them easier to count. The most expensive component of the whole device - the smartphone microscope - costs less than $50. It is also simple to use.

"You don't have to be a scientist or an engineer to run the device," Yoon said. "Analysis will be done automatically by the smartphone app, so all you have to worry about is loading a sample of water onto the chip."

In the future, the team hopes to develop methods for detecting norovirus infections in patients even earlier, and to expand their smartphone monitoring platform to detect other hazards, such as potentially cancer-causing chemicals. They also plan to spread the platform's use across the globe, fighting and detecting far-reaching diseases with tools that are just as widespread.

Scientists at USC and UC San Diego have discovered a potential novel target for treating glioblastoma, the deadly brain cancer that took the life of Sen. John McCain and kills 15,000 Americans a year.

The target is the circadian "clock" found within the tumor stem cells, which governs how the tumor grows, multiplies and develops resistance to current treatments.

"We think this is opening the door to a whole new range of therapies," said Steve Kay, Provost Professor of neurology, biomedical engineering and biological sciences at the Keck School of Medicine of USC, who is working with Jeremy Rich, a neuro-oncologist at University of California, San Diego who specializes in malignant brain tumors. "It's a great example of collaboration and convergence."

Kay and Rich report their findings today in Cancer Discovery.

Glioblastoma is rare but nearly always fatal, striking adults in their mid-60s. Average survival is only 15 months. That's because this type of cancer infiltrates surrounding brain tissue, making it impossible to eradicate, even after surgery, radiation and chemotherapy. The tumor comes back, growing from stubborn cancer stem cells left behind.

Now scientists are focusing on a new potential vulnerability in those left-behind stem cells.

Kay is a pioneer in the study of circadian rhythms and the biochemical circadian clocks that regulate hundreds of activities, from sleep to digestion to body temperature.

Circadian clocks are comprised of specific protein molecules that interact in cells throughout the body, controlling how they grow, replicate and repair damage to their DNA. When circadian timing is off in cells, it can cause disease. Biological clocks that run fast or slow can result in disrupted or abnormal circadian rhythms, increasing the risk of developing cancer in some people.

When the team first examined the biological clocks of glioblastoma stem cells in the lab, Kay said the researchers found them "on steroids, on overdrive." The cells' circadian clock was ramping up the cells' metabolism, making the cells stronger and more resistant to treatment and able to divide and multiply rapidly.

In collaboration with Synchronicity Pharma, a San Francisco-based biotechnology company, they used a small-molecule drug to target the proteins in the stem cells' circadian clocks to disrupt their activity. The ramped-up metabolism abated, and the cells quickly died.

"This was a striking, amazing result nobody really predicted," Kay said. Small-molecule drugs can enter cells easily and in this case, cross the blood-brain barrier in mouse models of the disease.

Next, the researchers tested the small-molecule drug in an animal model of glioblastoma. They found the animal models lived longer and the tumor shrank in size.

"This lays the groundwork for us to explore this as a novel therapy for glioblastoma," Kay said. "In the near future, we're going to do more work with animal models of the tumor and compare our new drug with the current standard of care. Perhaps we can one day contribute towards meeting this terrible unmet medical need."

For the past few hundred years, the colorful hair and unique patterns of the so-called "Fancy Mouse" have made them the stars of pet shows in Japan and beyond. Now, scientists have finally revealed the true cause of the genetic mutation responsible for the iconic black pigmentation in the popular East Asian pet.

Their findings were published on August 2, 2019 in Communications Biology.

All mammals possess an "agouti gene," which controls the distribution of melanin pigment that determines the color of hair, skin and eyes. The dominant A allele -- the variant form of a gene that gives rise to specific physical traits -- restricts black pigmentation, and its presence in wild mice results in an "agouti mouse" with a coat comprised of black and yellow banded hairs. "Nonagouti mice," by contrast, possess two a/a alleles due to a hypomorphic mutation of the agouti gene. This mutation causes an almost entirely loss of gene function, resulting in the mouse's coat consisting of only black hair.

In addition to being popular pets, nonagouti mice have been used for a variety of studies into the mechanism and role of pigmentation and the production, storage and distribution of melanin, as well as the link between coat color and behavior.

"Nonagouti mutation is one of the most famous, classical mutations in mouse genetics. Until now, it has been thought that the insertion of a single retrovirus, called VL30, into the gene responsible for expressing hair color is the cause of the nonagouti mutation that results in black coat color in East Asian mice," said study co-author, Tsuyushi Koide, an associate professor in the Mouse Genomics Resource Laboratory at the National Institute of Genetics (NIG), and the Department of Genetics, SOKENDAI (The Graduate University for Advanced Studies) in Japan.

"In our paper, we clarified the true cause of the nonagouti mutation and showed its historical origin. These findings provide a clearer understanding of one of the most well-known mutations in mice," said Koide, who adds that a better understanding of the cause of nonagouti mutation could be useful for many research fields.

In the study, another endogenous retrovirus, known as β4, was found in VL3, and β4, but not VL30, interrupts the agouti gene expression. The researchers used a genome editing technique whereby the genome DNA sequence is efficiently inserted or removed to effect a change or mutation. By using these 'molecular technique' to precisely target and delete the β4 retrovirus located within the VL30 virus on the DNA strand of fertilized mouse eggs that were then inserted into pseudopregnant female mice, the coat color of the neonatal pups was changed from nonagouti (black hairs) to agouti (black and yellow banded hairs). These results show that insertion of a new type of retrovirus β4 into the VL30 retrovirus is the true cause of black coat color, and not the VL30 alone.

After analyzing DNA samples from black (nonagouti) mice as well as a series of wild-derived strains, the researchers also found that the nonagouti trait originated from a line of East Asian mice that were most likely related to Japanese fancy mice.

"We found that the insertion of the β4 retrovirus into VL30 occurred in the lineage of Japanese fancy mice," said Koide. "This mutation was then introduced into a variety of laboratory mice including a standard strain in the early days of mouse genetics."

According to Koide, the insertion of the β4 retrovirus is also found in the gene that causes another type of classical mutation -- piebald coloration -- in mice. "The piebald mutation was also found in the Japanese fancy mice and is known to cause the characteristic black and white piebald pattern," said Koide.

The authors speculated that the β4 retrovirus actively spread within the founder group of Japanese fancy mice. "It will be important to understand when and how β4 was infected into the mouse DNA and the genetic consequences of it amplifying and spreading into several genes that form part of the genetic makeup of the mouse," said Koide.

The discovery of a new quasiparticle is analogous to the discovery of a new molecule, except molecules contain different elements, while quasiparticles are made from fundamental particles and interactions. As each molecule has its own unique properties, so do quasiparticles, and the discovery of a new one brings a range of possible technological applications.

A new quasiparticle named 'polaronic trion', discovered in molybdenum disulphide (MoS2) by a team from the National University of Singapore (NUS), could be used to design an optical modulator for visible light that is controlled by both temperature and electric fields.

The research effort for this breakthrough was led by Professor T Venky Venkatesan, Director of the NUS Nanoscience and Nanotechnology Initiative (NUSNNI), and was published in Advanced Materials on 26 August 2019.

The formation of the new quasiparticle

A quasiparticle is essentially a composite formed due to the interaction of elementary particles. For instance, the coulomb interaction between oppositely charged particles, both electrons and holes, in a semiconductor gives rise to a quasiparticle, known as the 'exciton'. "Recently it was reported that in electron-rich semiconductors, an extra electron can bind to an exciton to form a new quasiparticle called the 'trion'," shared Prof Venkatesan.

In this case, the researchers discovered that when an atomically thin layer of MoS2 is grown on a single crystal of strontium titanate (SrTiO3), the charged trion in MoS2 can further interact with the atomic vibrations of the SrTiO3 lattice to form a new quasiparticle. The nature of this interaction is similar to that between electrons and lattice vibrations (or phonons) in solids, giving rise to another quasiparticle known as a 'polaron'. Hence, they dubbed the new quasiparticle a 'polaronic trion'.

"The polaronic trion can be visualised like a Russian Tea doll, or Matryoshka. Inside the polaronic trion is a bare trion, inside which is an exciton that itself is made from electrons and holes," explained Associate Professor Shaffique Adam, one of the lead authors of the work, who is from the NUS Department of Physics, Yale-NUS College and the Centre for Advanced 2D Materials (CA2DM).

The significance of the polaronic trion

"Trions and excitons in 2D materials like MoS2 are interesting because these can absorb and emit light," said Dr Soumya Sarkar, the first author of the publication who is from NUSNNI and the NUS Graduate School for Integrative Sciences and Engineering. He discovered this phenomenon during his doctoral research under Prof Venkatesan.

He added, "Usually, phonons have energies that are too large to couple with a trion. This is where the SrTiO3 crystal is special because it undergoes a structural phase transition at temperatures below -120°C and gives rise to a particular atomic vibration, the soft mode."

This soft mode has an energy which is of the same order with that of the bare trion, and enables a strong coupling between the trion of MoS2 and SrTiO3 phonons to form the new entity, the 'polaronic trion'. While normal lattice vibrations decrease as the crystal freezes at low temperatures, the soft mode vibration, on the other hand, is highly enhanced, consistent with the observations.

Another important property of this quasiparticle is its sensitivity to electric fields. Dr Sreetosh Goswami from NUSNNI, who is one of the lead authors of this paper, elaborated, "What we are observing here is a many-body interaction and tuning that interaction with an external electric field. This is the Holy Grail in condensed matter physics, and such examples are quite rare."

He continued, "For me, the most exciting part of this entire study is the electric field tunability of polaronic trions by manipulating the soft phonons in SrTiO3. The ability to tune its binding energy by almost 40 meV using a voltage bias is much more than any other that was previously reported, and requires only a meagre amount of external energy."

Theoretically, the coupling is unusual as this is the first observation of such a strong interfacial phonon coupling involving rotational phonons. "We have extended an old result by Feynman and Fröhlich to explain this interaction. In fact, 2D materials interact strongly with their environment and this was crucial to this coupling," added Dr Maxim Trushin, a theoretical physicist at CA2DM who performed all the calculations included in the paper and proposed the quasiparticle picture to explain the observed phenomenon.

Next steps

Dr Sinu Mathew, who initiated the 2D materials effort at NUSNNI under Prof Venkatesan and is a key player in this research, provided a broader picture to this discovery. He said, "90 per cent of the research on 2D materials uses SiO2 or hexagonal boron nitride as substrates. Those might be great to explore quantum properties of 2D materials, but if you want to explore interface interactions, oxide substrates can be far more interesting as they have rich quantum functionalities. In this paper we report the interaction between MoS2 and SrTiO3, but there is a lot more room to explore."

Recently, there has been a lot of excitement regarding exciton-based interconnects. "The polaronic trion is charged and hence it would be easier to guide with applied voltages, thereby making it a key player in this area," concluded Prof Venkatesan. "In fact we have already started observing polaronic trions in other 2D semiconductors and are working to demonstrate a functional device based on this new quasiparticle."

Water is everywhere on Earth, but maybe that just gives it more space to hide its secrets. Its latest surprise, Stanford researchers report Aug. 26 in Proceedings of the National Academy of Sciences, is that microscopic droplets of water spontaneously produce hydrogen peroxide.

The discovery could pave the way for greener ways to produce the molecule, a common bleaching agent and disinfectant, said Richard Zare, the Marguerite Blake Wilbur Professor in Natural Science and a professor of chemistry in the Stanford School of Humanities and Sciences.

"Water is one of the most commonly found materials, and it's been studied for years and years and you would think that there was nothing more to learn about this molecule. But here's yet another surprise," said Zare, who is also a member of Stanford Bio-X.

The discovery was made serendipitously while Zare and his lab were studying a new, more efficient way to create gold nanostructures in tiny water droplets known as microdroplets. To make those structures, the team added an additional molecule called a reducing agent. As a control test, Zare suggested seeing if they could create gold nanostructures without the reducing agent. Theoretically that should have been impossible, but it worked anyway - hinting at an as yet undiscovered feature of microdroplet chemistry.

The team eventually traced those results to the presence of a molecule called hydroxyl - a single hydrogen atom paired with an oxygen atom - that can also act as a reducing agent. That equally unexpected result led Katherine Walker, at the time a graduate student in Zare's lab, to wonder whether hydrogen peroxide - a molecule with two hydrogen and two oxygen atoms - was also present.

To find out, Zare, Walker, staff scientist Jae Kyoo Lee and colleagues conducted a series of tests, the simplest of which involved spraying ostensibly pure water microdroplets onto a surface treated so that it would turn blue in the presence of hydrogen peroxide - and turn blue it did. Additional tests confirmed that water microdroplets spontaneously form hydrogen peroxide, that smaller microdroplets produced higher concentrations of the molecule, and that hydrogen peroxide was not lost when the microdroplets recombined into bulk water.

The researchers ruled out a number of possible explanations before arriving at what they argue is the most likely explanation for hydrogen peroxide's presence. They suggest that a strong electric field near the surface of water microdroplets in air triggers hydroxyl molecules to bind into hydrogen peroxide.

Although the results are something of a basic science curiosity, Zare said, they could have important practical consequences. Hydrogen peroxide is an important commercial and industrial chemical, most often manufactured through an ecologically unfriendly process. The new discovery could help make those methods greener, Zare said, and it could lead to simpler ways to disinfect surfaces - simply spraying water microdroplets on a table or floor might be enough to clean it.

"I think it could be one of the most important things I've ever done," Zare said.

The evolutionary process that occurs when a species colonizes a new environment provides an opportunity to explore the mechanisms underlying genetic adaptation, which is essential knowledge for understanding evolution and the maintenance of biodiversity. An international team of scientists, led by researchers from Uppsala University, Uppsala, Sweden, reports that a single amino acid change in the light-sensing rhodopsin protein played a critical role when herring adapted to the red-shifted light environment in the Baltic Sea. Remarkably about one third of all fish living in brackish or freshwater carry the same change. The study is published today in PNAS.

"The Atlantic and Baltic herring are excellent models for evolutionary studies for two reasons", explains Dr. Leif Andersson from Uppsala University and Texas A&M University who led the study. "Firstly, their enormous population sizes allow us to study the effects of natural selection without the disturbing stochastic changes in the frequency of gene variants that happens in small populations. Secondly, the colonization of the brackish Baltic Sea by herring within the last 10,000 years (following the most recent glaciation) provides an opportunity to study what happens when a species adapts to a new environment."

"We have examined the entire genome in many populations of Atlantic and Baltic herring and find that a single amino acid change in the protein rhodopsin, in which phenylalanine has been replaced by tyrosine, played a critical role during the adaptation to the Baltic Sea," says Jason Hill, scientist at Uppsala University in Uppsala, Sweden, and first author on the paper. This makes a lot of sense since rhodopsin is a light-sensitive receptor in the retina and satellite data show that the Baltic Sea has a red-shifted light environment compared with the Atlantic Ocean, because dissolved organic material absorbs blue light.

"A careful genetic analysis of our data shows that the evolutionary process must have been very rapid. We estimate that the rhodopsin gene variant found in Baltic herring increased in frequency to become the most common variant within only a few hundred years," says scientist Mats Pettersson at Uppsala University.

The amino acids phenylalanine and tyrosine are structurally very similar and only differs by the presence of a hydroxyl (-OH) moiety in tyrosine, so could this change really be so important?

"In fact, the crystal structure of rhodopsin shows that residue 261 is located in the vicinity of the chromophore retinal where light absorption occurs. The presence of tyrosine in Baltic herring rhodopsin makes light absorption red-shifted by about 10 nanometer and can thereby catch more photons in the red-shifted light environment in the Baltic Sea," says Dr. Patrick Scheerer at Charité - Universitätsmedizin Berlin, in Berlin, Germany, and one of the co-authors of the study.

When the scientists analysed the rhodopsin sequence from more than 2,000 fish they found that about one third of all species occurring in brackish or freshwater carry exactly the same genetic change as the Baltic herring whereas nearly all fish living in marine waters have a rhodopsin gene variant with phenylalanine like the Atlantic herring. "It is remarkable that we find the same mutation occur independently and at least 20 times across thousands of fish species, this provides a really striking example of convergent evolution at the molecular level," says Erik Enbody, co-author and post-doctoral fellow at Uppsala University.

"Our hypothesis is that this change in rhodopsin is particularly important during the juvenile stage and that the Baltic herring variant allows fish larvae to better utilise the light environment in the Baltic Sea when searching for food or avoiding predators", explains Leif Andersson. This hypothesis is supported by their finding that both Atlantic salmon and brown trout that always spawn in freshwater but may live most of their life in marine water have tyrosine 261 in rhodopsin like a freshwater fish. In contrast, the European and Japanese eel which both are born in marine waters but live most of their adult lives in freshwater carry phenylalanine 261 like the great majority of marine fish.

PITTSBURGH, Aug. 26, 2019 - Researchers at UPMC Hillman Cancer Center provide the first concrete evidence for the long-held belief that sick mitochondria pollute the cells they're supposed to be supplying with power.

The paper, published this week in the Proceedings of the National Academy of Sciences, involves a causal experiment to kick off a mitochondrial chain reaction that wreaks havoc on the cell, all the way down to the genetic level.

"I like to call it 'the Chernobyl effect' -- you've turned the reactor on and now you can't turn it off," said senior author Bennett Van Houten, Ph.D., professor of pharmacology and chemical biology at the University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center. "You have this clean-burning machine that's now polluting like mad, and that pollution feeds back and hurts electron transport function. It's a vicious cycle."

Van Houten's team used a new technology invented by Marcel Bruchez, Ph.D., of Carnegie Mellon University, that produces damaging reactive oxygen species -- in this case, singlet oxygen -- inside the mitochondria when exposed to light.

"That's the Chernobyl incident," Van Houten said. "Once you turn the light off, there's no more singlet oxygen anymore, but you've disrupted the electron transport chain, so after 48 hours, the mitochondria are still leaking out reactive oxygen -- but the cells aren't dying, they're just sitting there erupting."

At this point, the nucleus of the cell is being pummeled by free radicals. It shrinks and contorts. The cell stops dividing. Yet, the DNA seems oddly intact.

That is, until the researchers start looking specifically at the telomeres -- the protective caps on the end of each chromosome that allow them to continue replicating and replenishing. Telomeres are extremely small, so DNA damage restricted to telomeres alone may not show up in a whole-genome test, like the one the researchers had been using up to this point.

"If you imagine the chromosome as a car, the telomere would be the width of its license plate," said study coauthor Patricia Opresko, Ph.D., professor of environmental and occupational health at the Pitt Graduate School of Public Health and UPMC Hillman.

So, to see the genetic effects of the mitochondrial meltdown, the researchers had to light up those tiny endcaps with fluorescent tags, and lo and behold, they found clear signs of telomeres' fragility and breakage.

Then, in a critical step, the researchers repeated the whole experiment on cells with inactivated mitochondria. Without the mitochondria to perpetuate the reaction, there was no buildup of free radicals inside the cell and no telomere damage.

"Basically, we shut the machine off before it had a chance to do any damage," Van Houten said.

These findings could be used for improving photodynamic cancer therapy, which involves bombarding solid tumors with reactive oxygen species using light delivered with fiber optic cables, Van Houten suggested.

One thing his team discovered in the course of these experiments is that inhibiting ATM -- a protein that signals DNA damage -- magnified the damaging effects of the reactive oxygen species spewed out by the mitochondria. The cells not only shriveled, but also died.

By combining photodynamic therapy with ATM inhibition, it may be possible to design a system that effectively kills cancer cells with light, Van Houten said.

PHILADELPHIA -- French organ transplant centers are far more likely to accept "lower-rated" kidneys, like those from older organ donors, than centers in the United States, according to a first-of-its kind analysis published today in JAMA Internal Medicine. French transplant centers would have transplanted more than 60 percent - about 17,500 kidneys - of the nearly 28,000 deceased-donor kidneys discarded in the United States between 2004 and 2014, according to the research team from Penn Medicine and the Paris Transplant Group.

"These findings highlight the striking disparities in organ acceptance between the two countries and suggest that many of the 90,000 Americans awaiting a kidney transplant could reap major benefits from a more aggressive approach," said study co-author Peter Reese, MD, MSCE, an associate professor of Medicine and Epidemiology in the Perelman School of Medicine at the University of Pennsylvania. "Our study provides fresh evidence that organs from older deceased donors are a valuable, underused resource - particularly for people on the waitlist who otherwise may not receive a transplant at all."

The lack of organs available for kidney transplantation is a major global health problem. In the United States, an estimated 37 million adults have chronic kidney disease and more than 720,000 people have end-stage renal disease, meaning their kidneys have failed, and they require either a transplant or dialysis in order to survive. In July, the Trump administration signed an executive order - shaped, in part, by research published by experts at Penn Medicine - to improve kidney care and increase the number of transplants. In recent years, innovative solutions, including the use of Hepatitis C-infected organs, have helped to increase the supply of transplantable kidneys. Yet, every year, 5,000 Americans die while waiting for a kidney transplant.

To identify best practices for kidney allocation and organ use, researchers analyzed the acceptance and use of deceased-donor kidneys in France and the United States between 2004 and 2014. During that timeframe, centers in the United States discarded about 18 percent of the 156,089 deceased-donor kidneys recovered - about two times as high as the discard rate in France. Researchers found that, over the 10-year-period, transplant
centers in France addressed the need for organs by accepting lower-rated kidneys, such as those from older donors. For example, the average age of a kidney donor in France was 56 years old - 17 years older than the average age of a donor in the United States.

Although donor age is a risk factor for organ failure, studies have shown that kidneys from donors in their 50s or 60s may extend life for transplant candidates, particularly older recipients. Previous research found that transplant candidates older than 65 lived longer if they reduced their wait time by accepting kidneys from an "extended criteria" donor - those older than 60, or older than 50 with comorbidities, such as high blood pressure.

Researchers noted the significant need for viable kidneys suitable for older adults in the United States, where the percentage of transplant recipients older than 60 has increased from 22 percent in 2004 to 32 percent in 2017. More than 35,000 people older than 60 in the United States remain on the waitlist for a kidney. By adopting a similar model to France, the United States could provide more than 10,000 years of life with a functioning kidney transplant to its patients each year.

"This study demonstrates that there is more the U.S. can do to prevent the deaths of thousands of Americans each year who are waiting for a transplant," said coauthor Dr. Alexandre Loupy, nephrologist at the Department of Nephrology and Kidney Transplantation at Necker Hospital in Paris and Head of the Paris Transplant Group. "Our findings reinforce how collaboration between countries can lead to a concrete, new direction on how to help address a global health problem and advance care for wait-listed kidney patients in the United States."

ROCHESTER, Minn. -- Colorectal cancer outcomes may improve by genetically altering an immune-regulatory protein in cancer cells, making the cells more vulnerable to chemotherapy. That's according to new Mayo Clinic research.

The findings, published this month in Oncogene, indicate that increasing the expression of the PD-L1 protein in colorectal cancer cells can improve the effectiveness of chemotherapy.

"These findings, if verified by subsequent research, suggest that the level of tumor cell PD-L1 may be important in drug sensitivity and suggest that enhancing PD-L1 expression may be a potential strategy to improve treatment outcomes in this malignancy," says Frank Sinicrope, M.D., a Mayo Clinic medical oncologist and gastroenterologist. Dr. Sinicrope is co-director of the Gastrointestinal Cancer Program at Mayo Clinic and corresponding author of the study.

PD-L1 is an immune checkpoint protein that interacts with another protein, PD-1, to negatively affect cell functions and enable tumor cells to evade the body's immune system. Research has shown that interrupting the PD-L1/PD-1 interaction can enhance attacks on anti-tumor immunity.

However, the Mayo Clinic study describes another function of PD-L1: its effect on proteins that regulate tumor cell death. Deleting the PD-L1 gene suppressed two proteins that are associated with increased chemotherapy-induced cell death. In contrast, restoring PD-L1 expression reversed the suppression of these proteins.

"We sought to determine the relevance of our findings for PD-L1 in patients with colorectal cancer," Dr. Sinicrope says. "To do so, we utilized the Cancer Genome Atlas database of the National Cancer Institute to examine the association of PD-L1 expression with the survival of patients with colon cancer."

The study found that increased tumor cell PD-L1 expression was associated with better survival among patients expected to have received chemotherapy, which is the standard of care for patients with stage 3 and stage 4 cancers, according to Dr. Sinicrope.

"This suggests a broader role for PD-L1 as a possible predictive biomarker for how patients will respond to cancer treatment, though more research is needed to address this issue," he says.

The study also found that the BRAF oncogene, a gene that can transform a cell into a cancer cell, can regulate the expression of PD-L1. When the BRAF oncogene is mutated, it can increase PD-L1 expression in colorectal cancer cells, according to the study.

"Current therapies targeting PD-L1 are mainly focused on blocking or disrupting its function in tumor cells," says Haidong Dong, M.D., Ph.D., a Mayo Clinic tumor immunologist and co-author of the study. "This work suggests that enhancement of PD-L1 expression in tumor cells may promote the efficacy of chemotherapy, at least in colon cancer. It is an idea-changing discovery that, if validated in clinical trials, would bring more benefit to patients with colon cancer that is resistant to current chemotherapy."

Moving can be tough, but eventually most of us acclimate to new surroundings.

That's true for humans, and research from Washington State University shows it's the same for sage-grouse too.

A team of scientists successfully moved sage-grouse, a threatened bird species in Washington state, from one area of their range to another to increase their numbers and diversify their gene pool. A WSU study on the project in The Journal of Wildlife Management shows relocating the birds is a viable and productive step towards helping their population recover in the state.

"In the first year after moving sage-grouse in, they tended to move around a lot and didn't reproduce as effectively as the native population," said Kyle Ebenhoch, a researcher now working at the U.S. Geological Survey (USGS). "It took them about a year to settle in and get used to their new surroundings."

Ebenhoch, a WSU graduate student during this project, wrote the paper with WSU School of the Environment professors Daniel Thornton, Lisa Shipley, and Jeffrey Manning. Kevin White, a contract wildlife biologist with the Yakima Training Center at Joint Base Lewis-McChord, was also a member of the research team. The training center hosts a population of sage-grouse where the relocation work was done.

An adjustment period

Ebenhoch wanted to investigate how newly introduced sage-grouse would survive and reproduce in order to determine if relocating birds to the area could be a workable way of keeping the species from further decline in Washington.

It turns out, the birds can adjust, though the training center population continued to decline.

"The birds did adjust to their new surroundings, but it didn't stabilize the population," Ebenhoch said. "This can be one tool in our toolbox for helping, but we'll need more research to find other tools as well."

As for how the birds adjust, it's not too far off from a person or family moving to a new state.

"It reminded me of me when I go somewhere new," Ebenhoch said. "When I move to a different area, I know where my home and work are. Over time, I start to find a grocery store, or a barber. My knowledge and home range expand as I get used to the new place. It's basically the same for these birds."

Studying the birds

The relocated birds, brought in from populations in Oregon, Idaho, and Nevada from 2004-2006 and 2014-2016, were fixed with radio-transmitting collars so Ebenhoch and his colleagues could track their movements and see if they survived in their new area.

The researchers also collared several native sage-grouse each year, to serve as a baseline on how much those birds move around and reproduce. That comparison produced conclusions about the one-year adjustment period.

The collars also had a "mortality signal" built in, so researchers would be notified if a bird perished while wearing a collar. This allowed the team to monitor the mortality rate of the native and transplanted birds.

A necessity

Due to several factors, mostly human-caused like agriculture habitat conversion or wildfire, populations of sage-grouse in Washington have shrunk and become fragmented. There are four central and eastern Washington areas where the birds live, but they can't intermix because these areas are too far away from each other. That leads to inbreeding and less genetic diversity at each area, potentially increasing diseases and abnormalities, which are important factors that biologists monitor when conserving rare or declining wildlife.

Ebenhoch hopes the paper, which was his thesis for his Master's degree from WSU, will help policy makers and other wildlife biologists see that relocation can work. Though the paper is specific to Washington sage-grouse, some of the techniques may be suitable for sage-grouse conservation in other states, or even other species.

"This bird is right on the brink of being listed as threatened at the federal level," Ebenhoch said. "We showed that relocation, while disruptive in the short term, can work once the birds acclimate to their new surroundings."

EVANSTON, Ill. --- A new Northwestern University study found that white parents' racial bias awareness was associated with greater willingness to discuss race with their children, along with increased color consciousness and decreased color blindness.

Previous evidence suggests that white parents generally avoid race-related conversations with their children, relying on society to provide explicit education about race. The new study explores the individual difference factors that may be associated with white parents' racial socialization practices.

The results could have potential implications for interventions to reduce racial biases and discrimination in childhood.

The researchers chose to focus on the parents of middle-childhood-aged children (8 to 12 years old) in part because by this age, children have developed an abstract understanding of the concept of race and, therefore, most parents would have had opportunities to discuss race and racism with their child.

When describing these racial discussions, parents who were higher in bias awareness were more likely to use language acknowledging racism (e.g., "Some people think that the color of someone's skin means they are inferior"), and less likely to use language denying racism (e.g., "Some people like to cry racism for everything and ignore the facts").

By not socializing their children about race, the researchers say, white parents may be unintentionally setting their children up to be ignorant to the racial biases and inequalities that persist in society. Moreover, by failing to discuss race with their children, parents may be implicitly endorsing the negative racial messages children are exposed to from society.

"The current findings suggest that, beyond their racial attitudes and interracial contact, it is parents' awareness of their own racial attitudes and biases and their concerns about responding without prejudice that are associated with them talking to their children about race and acknowledging racial biases in society," said Sylvia Perry, lead author of the study and an assistant professor of psychology in the Weinberg College of Arts and Sciences at Northwestern.

Perry's previous research in this area shows that white people who are higher in bias awareness are more likely to internalize feedback suggesting that they hold biases, and that this internalization is associated with an increased desire to support diversity efforts.

"These findings," Perry said, "extend that work to suggest that, not only are these individuals willing to internalize that feedback and acknowledge that biases of all kinds are problematic, but that these tendencies may trickle down to impact how they talk about race and racism with others, including their children."

In the study, parents responded to open-ended questions including, "What would you say if your child asked you about race?" and "Describe how you have discussed recent current events related to race, such as events related to Trayvon Martin, Michael Brown or the Charleston shooting, with your child. If you have not discussed them, describe why you chose not to do so."

Repeated conversations between parents and their children over time could potentially have long-term impacts on the racial attitudes and biases of white children, said Perry, also a faculty associate with the University's Institute for Policy Research.

"This type of intervention strategy would also impact racial attitudes while children are still in the process of developing, which has been referred to as an optimal time for intervention," Perry said. "Moreover, this approach would maximize the impact of interventions, such that training one parent on how to engage in racial socialization has the potential to impact the racial attitudes of several children."

"Bias awareness predicts color conscious racial socialization methods among White parents" published today in the Journal of Social Issues' special issue on "Research on Race and Racism." In addition to Perry, co-authors include Allison L. Skinner, University of Georgia; and Jamie L. Abaied, University of Vermont.

People in England were using balance weights and scales to measure the value of materials as early as the late second and early first millennia BC. This is what Professor Lorenz Rahmstorf, scientist at the University of Göttingen and project manager of the ERC "Weight and Value" project, has discovered. He compared Middle and Late Bronze Age gold objects from the British Isles and Northern France and found that they were based on the same unit of weight. This confirmed the hypothesis of the research team of the project that there was already expertise in using standard weights and measures in many regions of Europe at that time. The results were published in the journal Antiquity.

Until now, it had often been assumed that trade during the Bronze Age in northwestern Europe was primarily socially embedded - for example as in the exchange of gifts. The existence of precise units of measurement, however, enabled people even at that time to compare exact ratios of material values of different goods such as metals, possibly also wool and grain. They were also able to calculate profits, to create currencies and to save up measurable quantities of metal. "Obviously, the exchange was already based on the economic interests of trading partners," explains Rahmstorf, director of the Institute for Prehistory and Early History at the University of Göttingen. "So it is clear we are talking about real trade."

What is surprising about the statistical analysis of the unit of weight that has been identified, is that it is very nicely compatible and possibly even identical with the dominant East Mediterranean weight of that time. This would be an indication that knowledge about standard weights and measures has been widely disseminated and possibly passed on through travelling traders. It was already known that people in the technologically advanced, literate cultures of the Eastern Mediterranean and Western Asia - for example Greece, Egypt or Mesopotamia - used such weights and scales as an aid. However, these findings now indicate that such value measurement systems already existed in many if not all parts of prehistoric Bronze Age Europe. "The results of our research show that we have so far underestimated the complexity of the early commercial transactions during the Bronze Age in Europe," said Rahmstorf. Further information on the "Weight and Value" project can be found at http://www.uni-goettingen.de/de/572018.html.

The origin of gigantic magma eruptions that led to global climatic crises and extinctions of species has remained controversial. Two competing paradigms explain these cataclysms, either by the splitting of tectonic plates at the Earth's surface or by the impacts of hot currents, called mantle plumes, from the planetary interior. A group of geochemists from Finland and Mozambique suggests they have found the smoking gun in the Karoo magma province. Their new article reports the discovery of primitive picrite lavas that may provide the first direct sample of a hot mantle plume underneath southern Africa in the Jurassic period

The great Jurassic lava flows that flooded across southern Africa and parts of East Antarctica prior to the splitting of the Pangea supercontinent make up one of the largest volcanic systems on Earth. The magma eruptions caused global environmental turmoil and the extinctions of species. The rapid origin of this Karoo flood basalt province in southern Africa has been frequently associated with the melting of a large plume that ascended from the deep mantle around 180 million years ago. However, the plume model has lacked confirmation from lava compositions that preserve a geochemical 'plume signature'.

"To our knowledge, the Luenha picrites are the first lava samples that could originate from the plume source that has been previously inferred from various geological and geophysical data on the Karoo province. Therefore they allow compositional analysis of this source," says Sanni Turunen, the leading author and a doctoral student at the Finnish Museum of Natural History, which is part of the University of Helsinki. In the case of the Luenha picrites, named after the research area near the Luenha River, the geochemical compositions indicate a hot magma source that is in many respects different from previously reported magma sources in the Karoo province. They show compositional similarities to magmas formed in other deep mantle plume-related volcanic provinces worldwide.

"It is very important to realise that in huge and complex volcanic systems, such as the Karoo province, large amounts of magmas may be produced from several magma sources", explains Daúd Jamal, professor at the Eduardo Mondlane University, in Mozambique.

"Previous studies of Karoo picrites in Africa and Antarctica by us and by other groups have suggested the generation of magmas in the upper mantle, but our new results indicate plume sources were also involved", adds Jussi Heinonen, an Academy of Finland fellow at the Department of Geosciences and Geography at the University of Helsinki.

Importantly, the Luenha picrites appear to represent the main source of the voluminous flood basalts of southern Africa. "We were fascinated to realise that the Luenha picrites revealed a type of magma source that was recently predicted using lava compositions, but which had not been confirmed by observational evidence", as characterised by Arto Luttinen, senior curator at the Finnish Museum of Natural History. According to the study, the presently available data are compatible with a plume source that has retained the composition of Earth's primitive mantle remarkably well. This is quite unusual because of the 4.5 billion year evolution of the convecting mantle.

Confirmation of the age and evolution of the primitive mantle-like source of the Luenha picrites requires further constraints from future isotopic studies.

"Whatever the exact nature of the Luenha source turns out to be, we feel confident that we have uncovered rocks that help to address the complex origin of large eruptions in new detail", Turunen concludes.

After successfully harvesting 10 eggs from the world's last two northern white rhinos, Najin and Fatu, on August 22nd in Kenya, the international consortium of scientists and conservationists announces that 7 out of the 10 eggs (4 from Fatu and 3 from Najin) were successfully matured and artificially inseminated. This was achieved through ICSI (Intra Cytoplasm Sperm Injection) with frozen sperm from two different northern white rhino bulls, Suni and Saut, on Sunday, August 25th. This is the next critical step in hopefully creating viable embryos that can be frozen and then later on transferred to southern white rhino surrogate mothers.

"We were surprised by the high rate of maturation achieved as we do not get such high rate (comparable to what we get with horse oocytes) with southern white rhino females in European zoos. The semen of Saut was very difficult to work with and to find three live sperms needed for the eggs of Najin we had to thaw two batches of semen. Now the injected oocytes are incubated and we need to wait to see if any viable embryo develop to the stage where it can be cryopreserved for later transfer," said Cesare Galli of Avantea in Cremona (Italy) who led the fertilization procedure. The international research consortium to save the northern white rhino from extinction is led by Thomas Hildebrandt from the Leibniz Institute for Zoo and Wildlife Research (IZW). Avantea is responsible for maturing the egg cells and creating viable embryos, further key project partners are Dvur Kralove Zoo, Ol Pejeta Conservancy and the Kenya Wildlife Service.

The results of possible embryo development are to be announced around September 10th.
The research program (BioRescue) is funded by the German Federal Ministry of Education and Research (BMBF).