Earth

Underwater melting of tidewater glaciers is occurring much faster than previously thought, according to a new study by researchers at Rutgers and the University of Oregon.

The findings, which could lead to improved forecasting of climate-driven sea level rise, are based on a new method developed by the researchers that for the first time directly measures the submarine melting of tidewater glaciers.

The study appears in the July 26 issue of the journal Science.

"Tidewater glaciers around the globe -- in Greenland, Alaska, Antarctica and beyond -- are retreating and raising sea levels globally," said study co-author Rebecca Jackson, an oceanographer at Rutgers University-New Brunswick. "Submarine melting has been implicated as a trigger for this glacier retreat, but we have had no direct measurements of melting, let alone how it might vary in time. In our study, we show that the prevailing theory for melt significantly underestimates melt rates. These results suggest a stronger coupling between the ocean and glacier than previously expected, and our work provides a path forward to improving our understanding of how the ocean impacts glaciers."

In the National Science Foundation-funded project, the scientists studied the underwater melting of the LeConte Glacier, a tidewater glacier in Alaska, from 2016-2018. Most research on the underwater melting of glaciers around the world has relied on theoretical modeling, measuring conditions near the glaciers and then applying theory to predict melt rates, but this theory had never been directly tested, said lead author Dave Sutherland, a professor in the UO's Department of Earth Sciences.

The team of oceanographers and glaciologists used sonar to scan the glacier's underwater face; downstream measurements of currents, temperature and salinity to estimate the meltwater flow; radar to measure the glacier's speed above water; time-lapse photography to detect iceberg calving; and weather station data to measure the surface melt from the glacier. They then looked for changes in melt patterns between the August and May measurements.

"We found that melt rates are significantly higher than expected across the whole underwater face of the glacier -- in some places 100 times higher than theory would predict," Jackson said. "We also find, as expected but never shown, that melt rates are higher in summer than in spring, and that variations in melt rates across the terminus cause overcutting and undercutting."

While the study focused on one tidewater glacier, the new approach should be useful to researchers who study melting at other tidewater glaciers around the world, which would help to improve projections of global sea level rise.

"The fact that we show the existing theory it is wildly inaccurate at one glacier - the only glacier where we can make a robust comparison between theory and observations - should lead us to be very skeptical of its current use in studying any tidewater glacier," Jackson added. "Our results also align with several recent studies of other glaciers that have indirectly suggested that theory under-predicts melting. Our observations prove this in a robust way and contribute to a growing body of research that suggests that we need to revisit our basic assumptions about what controls underwater melting at glaciers around the world."

Sutherland said: "Future sea level rise is primarily determined by how much ice is stored in these ice sheets. We are focusing on the ocean-ice interfaces because that's where the extra melt and ice is coming from that controls how fast ice is lost. To improve the modeling, we have to know more about where melting occurs and the feedbacks involved."

Oxytocin is widely referred to as the love hormone and plays an important role in the regulation of social and maternal behavior. In recent years, the oxytocin system in the brain has received tremendous attention as key to new treatments for many mental health disorders, such as anxiety, autism spectrum disorders and postpartum depression. New research led by a biologist and his students at LSU have discovered a group of cells that are activated by oxytocin in one area of female mouse brains that are not present in the same area in male mouse brains.

"Many researchers have attempted to investigate the difference between the oxytocin system in females versus males, but no one has successfully found conclusive evidence until now. Our discovery was a big surprise," said Ryoichi Teruyama, LSU Department of Biological Sciences associate professor, who led this study published in PLOS ONE.

The oxytocin receptor cells are present in the brain area thought to be involved in the regulation of maternal behavior. Moreover, the expression of oxytocin receptors in these cells are only present when estrogen is also present. These imply that these cells are involved in inducing maternal behavior. In addition, it confirms what many recent human studies have shown: there is a connection between an altered expression of oxytocin receptors and postpartum depression.

Postpartum depression contributes to poor maternal health and has negative effects on a child's development. A number of studies have found that children of depressed mothers are at risk for a wide range of cognitive, emotional, behavioral and medical problems. Therefore, postpartum depression is a major public health concern that has significant adverse effects on both mother and child. About 10 to 20 percent of women experience postpartum depression after childbirth.

This new discovery that occurred at LSU opens doors to potential new treatments and drugs for postpartum depression targeting oxytocin receptor cells.

"I think our discovery could be universal to all mammals that exhibit maternal behavior, including humans," Teruyama said.

Student researchers

Study co-author Ryan LeBlanc from Denham Springs was an undergraduate student researcher at LSU whose work was instrumental to this discovery. However, he had little previous research experience before joining Teruyama's lab.

Teruyama recalled that when LeBlanc first approached him to be his mentor, he asked him about his hobbies. LeBlanc said he liked to build plastic models of battleships.

"I certainly don't know much about battleship plastic models, but anyone who can assemble 500 to 2,000 plastic parts into models must be persistent, focused and exceedingly careful. I accepted him gladly thinking he is going to find something extraordinary, and I was right," Teruyama said.

LeBlanc took on the tedious task of finding and marking the exact location of thousands of oxytocin receptor cells with a red pen. He spent more than a month identifying the cells, which was instrumental to this discovery.

Specialized immune cells protect against obesity by regulating the diverse communities of intestinal bacteria in mice, according to a new study, which shows how changes in gut microbiota can influence the development of metabolic disorders. The results suggest the potential for new microbiome-based therapies for obesity and other metabolic diseases. Obesity, a common metabolic syndrome affecting the health of nearly two billion people worldwide, has been linked to a variety of factors including genetics, diet, behavior and most recently, the host's microbiome. Studies in mice have revealed differences in the gut microbiota composition in lean and obese animals, which can predispose a mouse to obesity. Moreover, transplanted microbiota of obese humans can confer metabolic defects into otherwise healthy animals. Building on previous research, which identified the immune system as a key factor in regulating the composition of the microbiome, Charisse Petersen and colleagues discovered that specialized immune cells called T follicular helper (TFH) cells shield mice from obesity by promoting the production of immunoglobulin A (IgA) antibodies by B cells in the gut. Genetically altered mice with defective TFH cell development produced little IgA. This resulted in symptoms of metabolic syndrome, including fat accumulation and insulin resistance, which are characteristics of human metabolic disease. According to Petersen et al., dysfunctional IgA production impeded the colonization of Clostridia bacterial species, allowing the expansion of Desulfovibro bacteria. Clostridia and Desulfovibro, respectively, suppress and enhance the expression of genes that direct the absorption of dietary lipids. In a related perspective, Yuhao Wang and Lora Hopper write that "the Petersen et al.'s findings beautifully illuminate how immune system defects can lead to metabolic disease."

Researchers at University of Utah Health have identified a specific class of bacteria from the gut that prevents mice from becoming obese, suggesting these same microbes may similarly control weight in people. The beneficial bacteria, called Clostridia, are part of the microbiome -- collectively trillions of bacteria and other microorganisms that inhabit the intestine.

Published online in the journal Science on July 25, the study shows that healthy mice have plenty of Clostridia -- a class of 20 to 30 bacteria -- but those with an impaired immune system lose these microbes from their gut as they age. Even when fed a healthy diet, the mice inevitably become obese. Giving this class of microbes back to these animals allowed them to stay slim.

June Round, Ph.D., an associate professor of pathology at U of U Health, is the study's co-senior author along with U of U Health research assistant professor W. Zac Stephens, Ph.D. Charisse Petersen, Ph.D., a graduate student at the time, led the research.

"Now that we've found the minimal bacteria responsible for this slimming effect, we have the potential to really understand what the organisms are doing and whether they have therapeutic value," Round says.

Results from this study are already pointing in that direction. Petersen and colleagues found that Clostridia prevents weight gain by blocking the intestine's ability to absorb fat. Mice experimentally treated so that Clostridia were the only bacteria living in their gut were leaner with less fat than mice that had no microbiome at all. They also had lower levels of a gene, CD36, that regulates the body's uptake of fatty acids.

These insights could lead to a therapeutic approach, Round says, with advantages over the fecal transplants and probiotics that are now being widely investigated as ways to restore a healthy microbiota. Therapeutics such as these, that are based on transferring living microbiome to the gut, won't work for everyone due to differences in diet and other factors that influence which bacteria can survive and thrive.

The current study found that one or more molecules produced by Clostridia prevented the gut from absorbing fat. The next step is to isolate these molecules and further characterize how they work to determine whether they could inspire focused treatments for obesity, type 2 diabetes, and other related metabolic disorders.

"These bacteria have evolved to live with us and benefit us," Petersen says. "We have a lot to learn from them."

A Good Defense Is the Best Offense

Finding that mice with a compromised immune system couldn't help but become obese was a discovery that almost didn't happen. Serendipity brought Petersen into the lab at the right time to see that mice genetically engineered to lack myd88, a gene central to the immune response, were "as fat as pancakes." She had let the rodents age longer than usual, revealing an unappreciated link between immunity and obesity.

Still, the observation didn't answer the question why the animals became overweight.

Based on previous research she had carried out in the Round lab, she suspected the microbiome was involved. She had helped demonstrate that one role of the immune system is to maintain balance among the diverse array of bacteria in the gut. Impairing the body's defenses can cause certain bacterial species to dominate over others. Sometimes, the shift negatively impacts health.

Following a similar logic, Petersen and colleagues determined that the obesity observed in immune-compromised mice stemmed from the failure of the body's defense system to appropriately recognize bacteria. These mice produced fewer of the antibodies that ordinarily latch onto the microbiome like target-seeking missiles. This change made the gut less hospitable for Clostridia, leading to more fat absorption and excessive weight gain. Over time, the mice also developed signs of type 2 diabetes.

Round points out that research by others have shown that people who are obese similarly lack Clostridia, mirroring the situation in these mice. There are also some indications that people who are obese or have type 2 diabetes may have a suboptimal immune response. The hope is that understanding these connections will provide new insights into preventing and treating these pervasive health conditions.

"We've stumbled onto a relatively unexplored aspect of type 2 diabetes and obesity," Round says. "This work will open new investigations on how the immune response regulates the microbiome and metabolic disease."

What defines a "good life" in your 30s?

The exact answer probably depends on the person, but most people could agree on some general themes: good physical and mental health, solid relationships, and a steady job or good education. Being financially responsible and involvement in your community or civic life also help make life better.

Now University of Washington researchers have found that that "good life" in adulthood can start in grade school, by teaching parents and teachers to build stronger bonds with their children, and to help children form greater attachments to family and school. In a study of more than 800 adults throughout their 30s -- a group the researchers have followed since they were fifth-graders at Seattle elementary schools in 1985 -- the people who reported better health and socioeconomic status were, consistently, those whose parents and teachers had received lessons aimed at building stronger bonds with their children decades ago.

The researchers know of no other study of a program provided during elementary school that has followed participants for this long. Participants in the longitudinal study, known as the Seattle Social Development Project, have responded to surveys over the years about health, lifestyle, even the parenting of their own kids. Such research requires participants who will stick with a study over a big stretch of their lives, and nearly 90% of them have done just that.

The latest study involved coming up with broad measures of health and functioning in adulthood, surveying participants on specific issues related to those measures, and comparing participants whose teachers and parents received the bonding interventions during elementary school with those who didn't.

"These early elementary-school interventions seek to make kids' current lives better both in and out of school," said Rick Kosterman, a principal investigator with the Social Development Research Group, part of the UW School of Social Work. "But can we actually get kids on a different life trajectory that lasts beyond elementary school? In fact, we found enduring effects, where they're having an overall better experience in adulthood."

The prevention curriculum, called Raising Healthy Children, was created by UW social work professors J. David Hawkins and Richard Catalano. The lessons, for use by parents and teachers, focused on enhancing children's opportunities for forming healthy bonds in grades 1 through 6 and providing them with social skills and reinforcements. Teachers and parents of children in some classrooms of the 18 participating Seattle elementary schools used the curriculum in the 1980s, while those in other classrooms did not have access to it.

Many of the concepts are teaching tools and parenting tips that are well-known today: reinforcing positive behaviors; setting expectations for making responsible choices; and promoting positive social interaction at school through group projects and seating arrangements. Table groups in the classroom facilitate cooperation and learning from one another, for example, while at home, parents can "catch" their child being good and offer praise. With older children, parents can discuss issues such as smoking so that standards for healthy behavior are established before the teen years.

For the new follow-up study, published in late spring in Prevention Science, Kosterman devised a list of nine measurable aspects of life for people in their 30s: physical health; mental health; health maintenance behaviors (such as exercise and sleep); low sex-risk behavior; low rates of substance abuse; friendships and relationships; socioeconomic status (income, education, homeownership); responsibility (employment, managing finances); and civic engagement. The team then used surveys and in-person physical evaluations to determine participants' health and successful functioning in adult life.

In a comprehensive test of effects that combined all nine indicators of a healthy and successful adult life, those from intervention classrooms when in elementary school reported significantly better outcomes than those from comparison classrooms through their 30s. Specific areas of significant improvement included fewer symptoms of mental health disorders, more engagement in health maintenance behaviors, and overall better health and socioeconomic success. On the remaining measures, the intervention group scored better on each one, though not as dramatically, compared with the control group.

It's hard to attribute results that manifest decades later directly to the curriculum, said Hawkins, a co-author on the new study. But the changed behaviors of their teachers and parents during the elementary grades likely had a snowball effect, leading to positive relationships and responsible decision-making in adulthood.

"We worked to build healthier relationships -- we call it social bonding -- between teachers and students, and parents and children. The larger question was, if we do all these things, will it turn into a prosocial, healthy lifestyle?" Hawkins said. "We didn't know we would see these results so much later in life."

In analyzing the data, researchers examined factors that tend to negatively affect health outcomes: whether a child grew up in poverty, was raised by a single parent, or born to a teenager. Participants who were born to a mother under age 20 were found to have a substantially lower quality of life on several of the measures, especially in the areas of socioeconomic status, physical health and substance abuse. The intervention effects the researchers found persisted even after controlling for these effects of being born to a teen mother.

"The most important thing we've learned is to provide opportunities for kids to have positive social involvement," Hawkins said. "Make sure your kids have the opportunity to engage with you as a parent. Play with them, hold them; don't just sit on your phone when you're with them.

"When kids feel bonded to you, they're less likely to violate your expectations. And you are likely to be setting them up to have better lives long into the future."

Kosterman and his team have applied for funding to conduct further research on the group, now in their mid-40s, in midlife. "More studies are needed that test childhood interventions and follow participants through the 30s and beyond," Kosterman added, "but we are encouraged that these findings suggest that lasting change for important outcomes is possible."

New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works. The findings potentially pave the way for better cancer treatments and revolutionary new drugs that could vastly improve human health in the twilight years.

The work, from Assistant Professor of Chemical Engineering and Materials Science Nick Graham and his team in collaboration with Scott Fraser, Provost Professor of Biological Sciences and Biomedical Engineering, and Pin Wang, Zohrab A. Kaprielian Fellow in Engineering, was recently published in the Journal of Biological Chemistry.

"To drink from the fountain of youth, you have to figure out where the fountain of youth is, and understand what the fountain of youth is doing," Graham said. "We're doing the opposite; we're trying to study the reasons cells age, so that we might be able to design treatments for better aging."

What causes cells to age?

To achieve this, lead author Alireza Delfarah, a graduate student in the Graham lab, focused on senescence, a natural process in which cells permanently stop creating new cells. This process is one of the key causes of age-related decline, manifesting in diseases such as arthritis, osteoporosis and heart disease.

"Senescent cells are effectively the opposite of stem cells, which have an unlimited potential for self-renewal or division," Delfarah said. "Senescent cells can never divide again. It's an irreversible state of cell cycle arrest."

The research team discovered that the aging, senescent cells stopped producing a class of chemicals called nucleotides, which are the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent, or aged.

"This means that the production of nucleotides is essential to keep cells young," Delfarah said. "It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly."

Graham's team examined young cells that were proliferating robustly and fed them molecules labeled with stable isotopes of carbon, in order to trace how the nutrients consumed by a cell were processed into different biochemical pathways.

Scott Fraser and his lab worked with the research team to develop 3D imagery of the results. The images unexpectedly revealed that senescent cells often have two nuclei, and that they do not synthesize DNA.

Before now, senescence has primarily been studied in cells known as fibroblasts, the most common cells that comprised the connective tissue in animals. Graham's team is instead focusing on how senescence occurs in epithelial cells, the cells that line the surfaces of the organs and structures in the body and the type of cells in which most cancers arise.

Graham said that senescence is most widely known as the body's protective barrier against cancer: When cells sustain damage that could be at risk of developing into cancer, they enter into senescence and stop proliferating so that the cancer does not develop and spread.

"Sometimes people talk about senescence as a double-edged sword, that it protects against cancer, and that's a good thing," Graham said. "But then it also promotes aging and diseases like diabetes, cardiac dysfunction or atherosclerosis and general tissue dysfunction," he said.

Graham said the goal was not to completely prevent senescence, because that might unleash cancer cells.

"But then on the other hand, we would like to find a way to remove senescent cells to promote healthy aging and better function," he said.

Graham said that the team's research has applications in the emerging field of senolytics, the development of drugs that may be able to eliminate aging cells. He said that human clinical trials are still in early stages, but studies with mice have shown that by eliminating senescent cells, mice age better, with a more productive life span.

"They can take a mouse that's aging and diminishing in function, treat it with senolytic drugs to eliminate the senescent cells, and the mouse is rejuvenated. If anything, it's these senolytic drugs that are the fountain of youth," Graham said.

He added that in order for successful senolytic drugs to be designed, it was important to identify what is unique about senescent cells, so that drugs won't affect the normal, non-senescent cells.

"That's where we're coming in--studying senescent cell metabolism and trying to figure out how the senescent cells are unique, so that you could design targeted therapeutics around these metabolic pathways," Graham said.

LOUISVILLE, Ky. - Researchers at the University of Louisville have developed an easily reproducible system that enables them to keep slices of human hearts alive for a longer period of time, allowing more extensive testing of new drugs and gene therapies.

This new biomimetic culture system mimics the environment of a living organ through continuous electrical stimulation and oxygenation, maintaining viability and functionality of the heart segments for six days. Previous culture systems maintained functional heart slices for no more than 24 hours. The extended viability time will enable improved preclinical testing of new drugs for effectiveness and toxicity.

"This new method maintains fully functional human heart slices for six days in the culture environment. This facilitates testing efficacy of heart failure therapeutics and cardiotoxins on human heart tissue with no need for a living human," said Tamer M. A. Mohamed, Ph.D., who led the research.

The system provides access to the complete 3D multicellular system that reflects the heart's functional and structural condition in a living person.

"This system will save time and costs of clinical trials during phase one research, which includes testing for toxicity and proof of efficacy," Mohamed said. "In addition to drugs, we have demonstrated the system's effectiveness in testing gene therapy."

The optimized medium for sustaining the heart tissue slices is described in an article published online last week in Circulation Research, a publication of the American Heart Association. It will appear in the August 30, 2019, print and online issue. Along with Mohamed, the research was conducted by Qinghui Ou, B.Sc., Riham R.E. Abouleisa, Ph.D., and others at UofL, along with colleagues in California, Colorado, the United Kingdom, Germany and Egypt. UofL has a provisional patent application on this technology.

WOODS HOLE, Mass. -- Animals have an intimate and important connection with the microbial populations (microbiomes) that live inside their bodies. This holds for the behaviorally sophisticated cuttlefish, whose microbiome, it turns out, contains only two different kinds of bacteria.

In a collaboration led by Marine Biological Laboratory (MBL) scientist Jessica Mark Welch, scientists characterized the microbiome of the European common cuttlefish, Sepia officinalis, an animal whose impressive camouflage skills and behavior have long been studied. They published their findings in this month's issue of mSystems.

The project began when Roger Hanlon of the MBL and Jack Gilbert of University of California, San Diego, chose the cuttlefish to look for a connection between the gut microbiome and behavior. However, they first needed to identify the microbes present.

"Not much is known about the microbiomes of cephalopods (cuttlefish, squid and octopus), other than a famous symbiosis between the bobtail squid and Vibrio bacteria in its light organ," says Mark Welch.

Holly Lutz, a postdoctoral scientist from Gilbert's lab, examined microbial populations from the cuttlefish's digestive tract, gills, and skin. She found that the cuttlefish microbiome has just two families of bacteria: Vibrionaceae and Piscirickettsiaceae. By comparison, humans have hundreds of different kinds of bacteria in the gut microbiome alone.

The simplicity of the cuttlefish microbiome came with other surprises. Tabita Ramírez-Puebla, a postdoctoral scientist at the MBL, fluorescently probed the bacteria to reveal their organization under the microscope. "It turned out that most of the microbes were in the esophagus, an unusual place to find the most dense community of microbes," says Mark Welch.

Bacteria in the Vibrio family include some species that cause disease, but others form symbiotic relationships with their hosts, such as in the bobtail squid. "It's interesting that we find those Vibrios in association with the cuttlefish. It suggests that there is a long-term evolutionary relationship between Vibrios and marine invertebrates," says Mark Welch.

While Vibrio species are sometimes found in the gastrointestinal tract of fish, the findings hint at an expanded range of organisms and body sites associated with Vibrio. It's possible that Vibrio species in the esophagus serve as a reservoir of bacteria that seed the cuttlefish gut, bringing along enzymes that can aid in digestion. Or Vibrio colonization of the esophagus (and the rest of the animal) may be pathogenic or opportunistic.

Understanding the microbiome of cuttlefish can help aquariums care for these animals. "We need to know how to keep them healthy and knowing something about their microbiome is very useful," says Mark Welch. For example, antibiotic treatment can alter an animal's microbiome, causing unintended consequences elsewhere in the animal. In their study, the scientists treated cuttlefish with enrofloxacin, an antibiotic commonly used by aquarium veterinarians. They found enrofloxacin had no effect on the cuttlefish microbiome.

WASHINGTON -- A research team, led by investigators from Georgetown University Medical Center and Fudan University in China, have devised a very promising non-invasive and individualized technique for detecting and treating bladder cancer.

The method uses a "liquid biopsy" - a urine specimen - instead of the invasive tumor sampling needed today, and a method developed and patented by Georgetown to culture cancer cells that can reveal the molecular underpinnings of each patient's unique bladder cancer.

Their study, published in Protein & Cell, sets forth a cost-friendly, simpler and painless technique that can determine the best treatment for each person's bladder tumor, monitor the progress of that treatment, predict or detect cancer recurrence early, and identify new drugs that are sorely needed for this common cancer.

Bladder cancer is the most common urologic cancer in China and is the top 10 most common cause of cancer death in the U.S, leading to approximately 17,000 deaths in 2018. Currently no method is available to predict which patients will respond to therapy - and, apart from new and limited use of immunotherapy, treatment regimens for bladder cancer have not improved and survival rates have not increased in the last 30 years.

In addition, because cancer comes back in more than 60% of patients within two years after initial diagnosis, almost all patients need long-term intrusive, uncomfortable, expensive cystoscopy which makes bladder cancer the costliest cancer (per case) of all cancer types, according to study investigators.

"This is the first study to show, using patient samples, that a 'living liquid biopsy' from urine can help determine treatment. This work also suggests that we might be able to grow and test cancer cells for treatment from other 'living biomarkers' found in blood and saliva. We are just at the beginning of this new diagnostic innovation," says the study co-senior author, Xuefeng Liu, MD, professor of pathology and oncology and member of the Center for Cell Reprogramming at Georgetown University and Georgetown Lombardi Comprehensive Cancer Center.

The other co-senior author is Yongjun Dang, PhD, a professor from Fudan University in China. The lead author is Shuai Jiang, MD, a urologist also from Fudan University.
"This study, and Dr. Liu's earlier work demonstrates the great potential liquid biopsies offer for real time precision medicine to diagnose and treat bladder cancer," says Dang.

The ability to use a patient's urine to grow cells is a transformational innovation from Georgetown called "conditional reprogramming" or CR. Patient-derived cells using CR can grow indefinitely without genetic manipulation, says Liu. Before this technique, which is less than a decade old, normal cells could not grow in lab culture, and cancer cells acquired numerous genetic mutations using previous culturing techniques. In the short time that investigators worldwide have been using CR, the method has been proven very useful in basic and clinical research in many kinds of cancers, the National Cancer Institute Office of Cancer Genomics is also developing conditional reprogrammed cells using the Georgetown method as a next generation human cancer model.

"Functional analyses using patient-derived models such as CR are urgently needed for precision oncology," Liu says. Currently, the percentage of U.S. patients with cancer who benefit from genome-driven oncology treatment is less than 10%, he adds.

Liquid biopsies could displace the current method of analyzing a patient's tumor to help direct treatment. The authors say new research suggests that liquid biopsies provide equally accurate and dynamic clinical information and can capture the complex genetic mutational profile of primary and metastatic tumors. Urine is one of the most convenient, painless and cheapest sources of liquid biopsies - and because urine is stored in the bladder until released, it readily provides the cancer cells needed for bladder cancer CR.

This study, published as a "rapid report," compares tumor biopsies from 70 patients with individual urine specimens - both processed through CR cultures (CRC). Primary cells isolated from urine and tumor samples both rapidly formed CRC and representative three-dimensional compact spheroids. The overall success rate of culturing urine CRC was about 84%.

"Similarly, the analysis of the mutation ratio for both patient tissue and corresponding CRC confirmed that both single nucleotide variants and DNA insertions and deletions were retained during the culturing," says Liu.

This means that a patient's urine produced cancer cells that molecularly matched their cancer tissue sample. "We also identified some mutations not identified in the original tumor biopsies, suggesting that the urine cell cultures better reflect overall tumor diversity than a single biopsy," he says. "The CRC technique may also expand our understanding of how low frequency mutations help lead to bladder cancer development and progression. Overall, CRC cultures may identify new actionable drug targets and help explain why this cancer is so often resistant to treatment."

After determining that the urine colonies and tumor tissue samples had matching molecular characteristics and genetic alterations, the researchers tested urine-based CRC cancer cells with 64 clinical oncology drugs. They found that, overall, the urine-based cancer cells were resistant to more than half of the drugs. And they discovered that many of the urine cancer cells were highly sensitive to one of the drugs, bortezomib, which is currently being tested for a different GU tumor, urothelial cancer.

Investigators also showed that as tumors progress, they change to become more molecularly diverse. "In our study, we can obtain urine samples at any time before and after treatment, which provides the possibility to obtain real-time pathological conditions," Liu says. In fact, for some patients, researchers compared urine-based CRC-based drug sensitivities with a patient's clinical responses to traditional treatment as well as to CT and PET follow-up images. They discuss how this analysis on seven patients matched the patient's clinical history and their urine-based CRC findings, "which confirms and supports use of urine conditional reprogramming in clinical practice," the researchers say.

"We successfully built up a novel, convenient model of CRCs that faithfully retains the molecular characteristic and genetic landscapes of the original tumor," the study authors write. "The high success rate and rapid proliferation of urine CRCs imply they are suitable for large-scale drug testing."

Liu adds that the proven ability to form 3-D tumor spheroids from CRC will allow them to study the tumor microenvironment that contributes to cancer treatment, resistance, and progression. "This novel in vitro bladder cancer system opens us new avenues for predicting patient-specific drug responses and turning the promise of personalized medicine into a reality," he says.

WASHINGTON -- Insect infestation is becoming an increasingly costly problem to the forestry industry, especially in areas experiencing increased droughts and hot spells related to climate change. A new terahertz imaging technique could help slow the spread of these infestations by detecting insect damage inside wood before it becomes visible on the outside.

"Our approach could be used to detect early-stage insect infestation on the trunks of trees, in imported wood or on wood products in an early infestation stage," said research team member Kirsti Krügener, from HAWK University of Applied Science and Arts in Germany. "This could help keep out damaging insects from other countries and stop infestation before it spreads throughout a forest."

In the Optical Society journal Applied Optics, the researchers report how they used terahertz time-of-flight tomography to noninvasively identify wood samples with otherwise invisible damage from the typographer beetle, which infects spruce and other coniferous trees in Europe. They were also able to reconstruct the internal structure of wood samples.

"Detecting the boreholes of wood-destroying insects is typically done by manually inspecting the wood, and the infected area of the forest to be removed is then estimated," said Krügener. "To our knowledge, this is the first time a technical method has been used to detect insect boreholes."

Incorporating the new approach into a portable instrument could allow assessment of individual trees in a forest so that only infested trees would need to be removed. Because it does not damage the sample being imaged, the technique might also be useful for investigating mummies, studying and restoring art or for quality control in industry.

Seeing beneath the surface

The terahertz region of the electromagnetic spectrum lies between microwave and infrared regions. It is used for applications such as the full-body scanners found in many airports because it doesn't harm people or materials being examined and can see through materials such as clothing, plastics and plant material.

Terahertz time-of-flight tomography works much like ultrasonic measurement in that each interface within the wood sample reflects a certain amount of the terahertz radiation that is detected and analyzed in respect to its time-dependent order. Each subsurface tunnel made by the insects leads to a new interface on which the radiation is reflected.

"An infested sample will reflect more terahertz radiation than one that is not infected because there will be fewer interfaces," said Krügener. "In addition, the individual reflected terahertz signals can be used to form a picture of an entire area so that the inner structure of infested wood can be visualized."

Beyond flat surfaces

Although terahertz time-of-flight tomography has been used for almost 20 years, until recently it could only be applied to flat samples. Two years ago, the researchers developed new procedures to use a robotic arm to scan an arbitrarily shaped sample point by point while keeping the emitter-receiver-head perpendicular to, and at defined distance from, the sample surface.

The researchers applied those methods to image wood samples with both known and unknown inner structures. They compared the results to conventional tomographic techniques and found that the inner structure reconstructed from terahertz signals matched well with what can be achieved with X-ray or computed tomography. They were able to distinguish between infested and non-infested samples by detecting typographer beetle burrows that were up to 1 centimeter beneath the wood's surface.

"The depth resolution of the terahertz measurements is higher than that of conventional x-ray techniques and comparable to micro-CT," said Krügener. "However, unlike micro-CT, the terahertz system can be used with any size sample."

The researchers are now working to improve the speed of the measurement and data analysis and also develop more complex data analysis to make the method more practical for detecting infested wood. They also want to develop a portable instrument that could be used in the field.

Structures inside rare bacteria are similar to those that power photosynthesis in plants today, suggesting the process is older than assumed.

The finding could mean the evolution of photosynthesis needs a rethink, turning traditional ideas on their head.

Photosynthesis is the ability to use the Sun's energy to produce sugars via chemical reactions. Plants, algae, and some bacteria today perform 'oxygenic' photosynthesis, which splits water into oxygen and hydrogen to power the process, releasing oxygen as a waste product.

Some bacteria instead perform 'anoxygenic' photosynthesis, a version that uses molecules other than water to power the process and does not release oxygen.

Scientists have always assumed that anoxygenic photosynthesis is more 'primitive', and that oxygenic photosynthesis evolved from it. Under this view, anoxygenic photosynthesis emerged about 3.5 billion years ago and oxygenic photosynthesis evolved a billion years later.

However, by analysing structures inside an ancient type of bacteria, Imperial College London researchers have suggested that a key step in oxygenic photosynthesis may have already been possible a billion years before commonly thought.

The new research is published in the journal Trends in Plant Science.

Lead author of the study, Dr Tanai Cardona from the Department of Life Sciences at Imperial, said: "We're beginning to see that much of the established story about the evolution of photosynthesis is not supported by the real data we obtain about the structure and functioning of early bacterial photosynthesis systems."

The bacteria they studied, Heliobacterium modesticaldum, is found around hot springs, soils and waterlogged fields, where it performs anoxygenic photosynthesis. It is very distantly related to cyanobacteria, the main bacteria that performs oxygenic photosynthesis today.

It is so distantly related that it last had a 'common ancestor' with cyanobacteria billions of years ago. This means that any traits the two bacteria share are likely to also have been present in the ancient bacteria that gave rise to them both.

By analysing the structures that both H. modesticaldum and modern cyanobacteria use to perform their different types of photosynthesis, Dr Cardona found striking similarities.

Both structures contain a site that cyanobacteria and plants exclusively use to split water - the first crucial step in oxygenic photosynthesis.

The evolution of cyanobacteria is usually assumed to also be the first appearance of oxygenic photosynthesis, but the fact that H. modesticaldum contains a similar site means that the building blocks for oxygenic photosynthesis are likely much more ancient than thought, as old as photosynthesis itself, and therefore could have arisen much earlier in Earth's history.

Dr Cardona also suggests that this might mean oxygenic photosynthesis was not the product of a billion years of evolution from anoxygenic photosynthesis, but could have been a trait that evolved much sooner, if not first.

Dr Cardona said: "This result helps explain in fantastic detail why the systems responsible for photosynthesis and oxygen production are the way they are today- but for it to make sense it requires a change of perspective in the way we view the evolution of photosynthesis.

"Under the traditional view - that anoxygenic photosynthesis evolved first and was the only type for about a billion years or more before oxygenic photosynthesis evolved - these structures should not exist at all in this type of bacteria."

Coral reefs are delicate ecosystems that are particularly sensitive to human influences such as climate change and environmental pollution. Even if the warming of the earth does not exceed 1.5 to 2 degrees Celsius - a limit set by the International Panel of Climate Change (IPCC) - more than 70 percent of coral reef ecosystems are likely to be lost, resulting in an economic and ecological catastrophe.

How do corals adapt to changing environmental conditions? How can we protect corals? Christian Voolstra, Professor of Genetics of Adaptation in Aquatic Systems at the University of Konstanz, assigns great importance to bacteria and other microorganisms. He emphasizes that no animal or plant lives alone - they are constantly interacting with bacteria and other microbes. Researchers call this a metaorganism - a tribute to the notion that all animal and plant hosts interact closely with their associated microbes. Corals are particular illustrative examples of metaorganisms, given that their association with photosynthetic microbial algae allows them to live like sessile plants. Since corals are bound to the place they settle, they have no choice but to adjust to the local environmental conditions. Bacteria and other microorganisms help with this by playing roles in the nutrition, metabolism and immune defence of a coral.

Different studies have shown that corals are associated with various bacteria that assumingly perform different functions. The following question, however, remained to be answered: Do the bacterial communities vary with prevailing environmental conditions or do they stay the same? Researchers have observed both cases. Based on this knowledge, the research team led by Professor Voolstra investigated two species of coral they believed to have considerable differences in terms of their strategies for associating with bacteria: The species Acropora hemprichii, assumed to flexibly associate with bacteria, and the species Pocillopora verrucosa that harbours highly consistent bacterial communities, irrespective of environmental differences. Their experiment was carried out over a period of 21 months in a marine ecosystem that is greatly affected by human activities: the Red Sea near Jeddah in Saudi Arabia. In order to investigate changes in coral associated bacterial communities that are exposed to stress, the researchers transplanted fragments of the same coral colonies into marine environments exposed to varying degrees of human influence. Using coral fragments from the same colony ensured that the samples had identical genetic material and that any changes could only be the result of environmental conditions.

"We could show that some corals respond flexibly to changing environmental conditions by associating themselves with certain bacteria, while other corals looked the same everywhere," explains Professor Voolstra. In their study, the researchers were able to confirm their hypothesis that there are generalists among corals who are flexible and versatile, and that other species are specialized and consistent in their association with bacteria. The generalists' ability to adapt provides cause for optimism because evolutionary adaptation processes would take far too long to allow coral to cope with the rapid changes brought about by climate change. By associating with new bacteria, the corals are able to react much faster ? these changes became apparent after only a few months. Furthermore, by transplanting the coral back into its original environment, the researchers discovered that the associated bacterial communities were able to return to their original state, thus recovering.

The example of Pocillopora verrucosa also shows that specialised corals can implement a successful survival strategy. "We must remember that the species we examined are those that have survived the tremendous changes of the past decade ? thus, both types of corals harbour successful strategies," emphasizes Voolstra. This study shows that corals take advantage of the symbiotic relationship with bacteria in different ways. The research results contribute to the further development of coral probiotics - a method by which corals are specifically exposed to bacteria that help corals to adapt to changing conditions. The aim is to enhance the corals' resilience to the extreme and rapid changes to their natural habitats and to prevent reefs from going extinct.

Abandoning exotic pets is an ethical problem that can lead to biological invasions that threaten conservation of biodiversity in the environment. An article published in the journal Biological Invasions, whose first author is the researcher Alberto Maceda Veiga, from the Biodiversity Research Institute of the University of Barcelona (IRBio), reveals that the release of invasive species in the environment has not been reduced despite the regulation that prohibits the possession of these species since 2011.

Other participants in the study, which goes over the regulation of the national catalogue of exotic invasive species, are Josep Escribano Alacid, from the Natural Science Museum of Barcelona, Albert Martínez Silvestre and Isabel Verdaguer, from the Amphibians and Reptiles Recovery Centre of Catalonia (CRARC), and Ralph Mac Nally, from the University of Canberra (Australia).

From buying impulsively to abandoning exotic pets

The study shows that, from 2009 to 2011, more than 60,000 exotic animals causing trouble to the owners were recorded in the northern-eastern area of Spain, but these figures do not correspond completely to the animals that were abandoned. "The main reason people abandon their pets is because they buy impulsively, and some of these species can easily reproduce once they are released", says Alberto Maceda, member of the Department of Evolutionary Biology, Ecology and Environmental Sciences of the University of Barcelona.

"In general, people get an animal very easily when it is young and cute, but when it grows up and causes trouble, they abandon it. Not all people do what it takes regarding the responsibilities of having a pet, it's a responsibility that lasts many years for those animals who live long, such as turtles".

Laws that do not stop this crime: abandoning exotic animals

Since 2011, a law prohibits the trade, possession and transport of exotic species in Spain. The regulation has been effective to stop shops from selling species of crabs, fish, reptiles and amphibians that are listed in the regulation, but it has not prevented people from abandoning invasive species, the study warns.

"Apart from the species listed in the regulation, there are many others that are abandoned in the natural environment or are left in animal centers", notes Maceda. "The worst problem, however, lies in the exotic species that were commercialized massively years ago. This is the case of the known Florida turtles, which are really small at first, but when they grow, they are usually abandoned. The study shows that the legislative response takes a long time to make any effect regarding the release of invasive species which were sold years ago in this country. These measures are not very effective once the invasive species is distributed around the territory".

Although the law served to stop those species from being sold, "abandoning animals is another crime, and there is not any current legislation to solve this problem". "We cannot ignore -he insists- that releasing any pet in the environment is a risk, apart from not being ethical, and therefore, it has to stop", stresses the researcher.

Fighting for animal wellbeing and promoting a responsible possession of animals

Improving biosafety measures in livestock stabling centers, changing commercial criteria for the species and training buyers to promote a responsible possession are measures that could help reduce the abandoning rate. "It is necessary to create a record of owners, apart from making more educational campaigns. One option could be to require a certificate for the owner's training, as well as the use of microchips and special licenses to have certain species at home, and avoid the free access to species we know that could bring trouble to the owners".

According to the authors, importation of exotic species should be regulated, since nowadays it is only debated on when there is scientific evidence of a risk of biological invasion, or when there is risk of extinction for a species. In short, it would be necessary to list the species owners can have at home.

Not all exotic pets in the environment have been abandoned

Experts warn that prohibiting certain species can generate a response in the market that can promote the commerce of other animals with the same problems. A revealing example is the prohibition of the trade of the red-eared slider (Trachemys scripta elegans), which was introduced in the market of other freshwater turtles that brought similar problems to the buyers.

Also, not all exotic pets get to the environment for being abandoned. In some cases, the reason is a lack of biosafety measures -disinfection of waste waters, etc.- in companies that stable exotic species. Also, some legislative measures from the past have been controverted for the conservation of the environment: for instance, releasing mosquitofish -one of the most dangerous invasive species worldwide- to control the local populations of mosquitos.

"Regarding environmental problems, we have to be more proactive than reactive, and we are usually reactive. Pets -invasive or not- cannot be uncontrolled in the natural environment, let alone abandoned. Among other negative effects, they can hunt native species, and alter the natural hábitat and can bring diseases that can persist in the native fauna even when the animal with the disease has already disappeared", concludes Maceda.

The 3D analysis of crystal structures requires a full 3D view of the crystals. Crystals as small as powder, with edges less than one micrometer, can only be analysed with electron radiation. With electron crystallography, a full 360-degree view of a single crystal is technically impossible. A team of researchers led by Tim Gruene from the Faculty of Chemistry at the University of Vienna modified the holder of the tiny crystals so that a full view becomes possible. Now they presented their solutions in the journal „Nature Communications".

Typically, crystallographers use X-rays to examine their samples. Size, however, matters greatly for X-ray structure analysis: Crystals with edges less than 50 to 100 micrometres are too small to produce a measurable signal. "Electron crystallography is a quite recent development. We demonstrated to our chemist colleagues that we can analyse crystals with edges less than 1 micrometre - this includes many crystals which escape 3D structure determination so far", Tim Grüne says, who is member of the Department of Inorganic Chemistry and head of the Centre for X-ray Structure Analysis.

Limited View

Electrons interact with matter much stronger than X-rays. Submicrometre sized crystals produce characteristic diffraction images when they are irradiated with electrons. These provide the data for structure analysis. However, the sample holder prevents a full 360 degree rotation: Currently only one rotation axis is available, and the metal bars necessary to stabilise the delicate cannot be penetrated by the electrons. Only a rotation of about 75 degrees is possible in either direction. „This gives us a maximum of 300 degree valuable data, which leads to an erroneous structural analysis", says Gruene. He and his colleagues from ETH Zurich and from PSI came up with a neat trick to solve the problem.

Their study presents two solutions to circumvent the problem: They prepared the sample holder so that crystals can be viewed from all sides. One sample holder contains dozens of crystals, more than enough to complete the data and provide an undistorted 3D view.

Tricking the Carrier

A simple, readily available means disturbs the carrier material, an ultrathin carbon layer, with a fine brush. According to Gruene "as a consequence, individual segments of the carbon layer curl up - like when you touch the fruit of touch-me-not. The crystals stick to the curls and achieve a random orientation. One can comfortably select several individual crystals from very different views".

The second solution covers the carbon carrier with nylon fibres. „The surfaces resembles a forest covered chaotically with tree logs", Tim Grüne says. This again leads to many random orientations of the crystals when they are deposited on the sample holder. However, the nylon fibres are deposited with electrospinning, which requires an additional apparatus and is a bit more complex than stroking it with a brush.

"Neat and simple"

Both measures provide data sets from the crystals with a complete 3D structural analysis. This type of combining data sets is common practice in protein crystallography, but much less common in chemical crystallography. Tim Grüne explains, "Our work exploited the fact that data merging works likewise for chemical compounds as it does for proteins. We only needed 5 crystals in both cases to complete the data".

„We did not avoid the problem, but demonstrated how to reveal the hidden faces of the crystals to the electron beam. Both solutions are surprisingly simple and can be realised without much effort", says Tim Grüne.

Synapses between nerve cells in the brain undergo constant remodeling, which is the basis of learning. An Ludwig-Maximilians-Universitaet (LMU) in Munich team has now traced the molecules that direct remodeling and shown that they circulate in the living cell like running sushi.

The human brain is like a long-term construction site - there's always something else to be done. This is certainly true of synapses, the functional links between nerve cells, which are constantly being strengthened, attenuated or demolished. Indeed, this process termed synaptic plasticity is the basis of our ability to store and recall information - in other words, to learn. The instructions for the synthesis of necessary components, which are encoded in molecules known as messenger RNAs (mRNAs), are delivered to the specific synapses that need them by a specialized transport system. But how the blueprints reach their destinations is poorly understood. In order to learn more about the underlying mechanisms, cell biologist Professor Michael Kiebler and his group at the LMU Biomedical Center have now followed the transport of individual mRNAs to specific synapses. Their analysis shows that the same mRNA can be presented to potential addresses several times - a system which the researchers compare to running sushi, the use of an 'endless' conveyor belt to enable patrons to pick and choose from the delicacies on offer.

In order to serve the extensive network of synapses on a typically elongated process termed dendrite, the mRNAs must be transported from the nucleus in the cell body to the terminal branches at the end of the process. To monitor this process, the LMU team used cell cultures derived from neurons isolated from the hippocampus of the rat, which serves as a model for the human hippocampus. "We labelled specific mRNAs in living cells with a fluorescent dye, which enabled us to track their progress in real time," Kiebler explains. "This approach permitted us to determine, for the first time, whether or not a given molecule is delivered directly to a particular synapse, and whether different mRNAs are handled differently in this respect. In one case, we were able to follow how an mRNA entered one of the spine-like processes extended by a dendrite," he says. "Dendrites act as antennas that receive inputs from synapses on other cells." The observations revealed that one and the same mRNA may repeatedly circulate back and forth between the cell body and the nerve processes - like sushi wending its way between the tables in a restaurant - until it finds a synapse that needs it.

Certain recognition sequences located in the segment of the mRNA that follows the stop codon (which marks the end of the protein-coding blueprint) serve as both the postage stamp and the address to direct the molecule to ensure that the molecule reaches the right region of the cell. "We have also demonstrated that, if the postage stamp is left intact, transport from the cell body to the neural processes is more effective and the mRNA is brought closer to the synapse than when it has been removed," says Kiebler. In addition, RNA-binding proteins such as Staufen2 play an important role in the regulation of mRNA transport by this cellular sorting system. Earlier studies had previously shown that Staufen2 is capable of binding several different mRNAs - so that the same mechanism can distribute distinct mRNAs. In addition, the new report confirms early results which had suggested that uptake of the mRNA by the synapse depends on both the nature of the binding protein and the level of activity of the synapse. Taken together, the new data provide further details on the mechanisms underlying the delivery of proteins to synapses, and will have an impact on future efforts to understand the molecular basis of synaptic plasticity in mammals.