Earth

Microscopic marine plants flourish beneath the ice that covers the Greenland Sea, according to a new study in the Journal of Geophysical Research: Oceans. These phytoplankton create the energy that fuels ocean ecosystems, and the study found that half of this energy is produced under the sea ice in late winter and early spring, and the other half at the edge of the ice in spring.

The researchers pioneered new technology and methods to make this discovery. About 4,000 oceanographic instruments called Argo floats are currently bobbing around the global ocean, moving between the deep sea and surface as they take vital measurements such as water temperature and salinity. This study used some of the first floats equipped to navigate icy waters and measure biogeochemical properties like nutrient concentrations and phytoplankton biomass. The floats sampled in the difficult conditions around and below the Greenland Sea ice continuously for four years, giving the researchers an unprecedented and invaluable look at this previously impenetrable region.

"These floats gave us the opportunity to gather data through the annual cycle and across multiple years, which is crucial for understanding this changing region," said Paty Matrai, Bigelow Laboratory senior research scientist and study author. "We now have an incredible observational dataset and are able to see the full picture of the phytoplankton community through the seasons."

This new approach represents a breakthrough in studying the Greenland Sea, which has historically been difficult. Extensive sea ice and the long polar night prevent both ships and satellites from capturing the huge amount of biological activity under the ice.

Sampling with floats gave the researchers access to this concealed ecosystem. The data they collected revealed that, once light arrives at these northerly latitudes, half of energy production occurs beneath the sea ice, and the other half occurs at the ice edge. In summer, the phytoplankton communities move deeper in the water to access nutrients - another place that cannot be seen by satellites, but can be sampled by floats. These results suggest that previous studies might have significantly underestimated the amount and productivity of phytoplankton in this region.

"By the time the ice has receded and the water is accessible to boats and satellites, half the annual production has already happened," said Nico Mayot, a postdoctoral researcher at Bigelow Laboratory and first author on the paper. "If you only look at those data, you only have half the story. These float data give us the full story, from winter to summer, and from the surface to the deep ocean."

The Greenland Sea is an important transition zone between the North Atlantic and Arctic oceans, both of which are being profoundly impacted by global climate change. The way it functions and changes may have important consequences for how food webs in these waters evolve.

An accurate picture of the phytoplankton community in this important region opens the door for further study, and the researchers have made the project data available to the global scientific community. The researchers anticipate that the under-ice floats will become a key component of Arctic observation and believe that coupling these data with satellite measurements can make it even more powerful.

"Now we are able to ask a whole set of new questions, like whether this pattern is the same elsewhere in the Arctic Ocean," Mayot said. "Understanding how energy is produced in these rapidly changing environments will allow us to anticipate and plan for the future."

Many cat owners worry about their pets wandering the streets, but perceive cats hunting mice and birds to be unavoidable instinct, researchers at the University of Exeter have found.

Owners often dislike their feline companions' compulsion to catch wildlife but feel unable, or unwilling, to control it.

The researchers interviewed cat owners about their pets' roaming and hunting behaviour, what worried them, and what they felt responsible for.

Hunting, and the resulting corpses on the kitchen floor, were seen as natural behaviour outside owners' control. Those who did want to limit hunting felt this was difficult to achieve without locking cats indoors - and hardly any owners wanted this.

"We found a spectrum of views on hunting, from owners who see it as positive for pest control to those who were deeply concerned about its consequences for wild animal populations," said lead author Dr Sarah Crowley, of the Environment and Sustainability Institute on the University of Exeter's Penryn Campus in Cornwall.

"However, because hunting is a natural cat behaviour, few owners believed they could effectively control this without negatively affecting their cats' welfare."

Cats vary in the amount they hunt, with some catching multiple birds and small mammals every week, while many others stay indoors or rarely lift a predatory paw.

With up to 11 million cats in the UK, some conservationists are nevertheless concerned about the effect even a minority of hunting cats might have on wildlife, especially declining species like house sparrows.

Current methods of preventing cats catching wild prey include fitting them with collars with bells and bright colours, and keeping them indoors at night.

"Cat owners understandably make their pets' health and well-being a priority, and many feel that cats need free access to the outdoors," said Professor Robbie McDonald, head of Exeter's Wildlife Science group, who is leading the research.

"At the same time, having such independent pets creates extra anxieties for owners about both their cats' safety while ranging free, and their impacts on wildlife.

"We are working closely with cat owners and cat welfare organisations. Our aim is to find practical ways of reducing hunting, while enhancing cat health and welfare."

The researchers interviewed 48 cat owners from urban, suburban and rural areas in Cornwall and Oxfordshire.

Sponsorship for the study comes from the independent bird conservation charity SongBird Survival and is overseen by an advisory group comprising veterinarians, cat behaviour and welfare experts, and representatives from SongBird Survival, International Cat Care and the RSPCA.

"We are very concerned about the significant adverse impacts that free-ranging domestic cats can have on our songbirds and other wildlife," said Robert Middleditch, SongBird Survival's Chairman.

"We are therefore delighted to have commissioned this important project, and believe that working with cat owners to find practical solutions, while promoting responsible pet ownership, can benefit both vulnerable wildlife and cats."

Sam Watson, RSPCA cat welfare expert, said: "This is valuable work which helps us to understand pet owners' sense of responsibility towards their cats and any potential impact they could have on wildlife.

"While there is still lots of debate as to whether cats have detrimental effects on wild bird populations, on an individual level predation attempts by cats are likely to cause considerable suffering, so we would welcome any practical solutions which would help to avoid this.

"We hope further study can help find ways to reduce the impact that cats may have on wildlife whilst also maintaining and boosting the welfare of our cats."

The paper, published in the journal People and Nature, is entitled: "Hunting behaviour in domestic cats: an exploratory study of risk and responsibility among cat owners."

Genes contain all the information needed for the functioning of cells, tissues, and organs in our body. Gene expression, meaning when and how are the genes being read and executed, is thoroughly regulated like an assembly line with several things happening one after another.

Researchers at the Centre for Genomic Regulation (CRG) in Barcelona, Spain, in collaboration with scientists at the structural bioinformatics group, University Pompeu Fabra (UPF) and department of molecular epigenetics, Helmholtz Center Munich, Germany, have discovered a new step in this line, which controls the expression of some genes with an important role in cancer. "We observed that breast cancer cells need a particular modification to express a set of genes required for cellular proliferation and tumour progression," explains Priyanka Sharma, CRG researcher and first author of the paper. "This modification allows the enzyme RNA polymerase II to overcome a pausing barrier and to continue to transcribe these genes," adds Sharma, who is a Beatriu de Pinós postdoctoral researcher (cofunded by EU Marie Curie Fellowship) and also received funding from Novartis and the CRG internal call for women scientists (Women Scientists Support Grant - WOSS).

Cancer cells are willing to quickly proliferate so, genes involved in cell division and proliferation are really active and usually highly expressed. Such a precise and meticulous machinery involves many different molecules to properly function. In this case, when all the machinery to express proliferation genes is ready, it still has to wait for a particular modification to go. As in race when runners are asked to be ready, set and go. Here, the polymerase is also ready and set but still needs a final modification to cross the barrier for transcription and go.

"Deciphering every single step and all actors involved in this process is an important achievement in terms of fundamental science. We are now able to better understand how an intricate mechanism of gene regulation actually works and this might be a new target for clinical researchers to study novel therapies for certain types of cancer," states Miguel Beato, CRG group leader and principal investigator in this work.

The work, which has been published in Molecular Cell, describes a novel modification of in the Carboxyl terminal domain of RNA Polymerase II, namely the de-imination of an arginine, by the enzyme PADI2, which allows the polymerase to transcribe genes relevant for cancer cell growth. "Most chemo-therapies are oriented at blocking the activity of enzymes, but we know that PADI2 participates in many different processes involving the nervous system, immune response and inflammation, among others. Thus, inhibiting PADI2 would have multiple side effects. Our results make it possible to target just the particular action of PADI2 on RNA polymerase needed for tumour progression without globally blocking the enzyme," explains Beato.

About one in every 5,000 babies is born without enteric neurons in distal colon resulting in Hirschsprung's disease. Because of the lacking neurons, contents of the gut cannot pass normally resulting in constipation and enlargement of colon.

The condition is treated with a surgical removal of the affected gut part, but the patients remain at high risk of enterocolitis, or inflammation of the gut. This is the major life threatening complication of Hirschsprung's disease.

About half of the Hirschsprung's disease cases are caused by mutations in a gene called RET. RET is a receptor, a large protein molecule, which is located at the surface of the cell to receive signals from other cells. During development, a complex formed by two proteins called GDNF and GFRa1 binds to RET and activates signaling required for normal development of the enteric neurons.

For developing new treatments, animal models of the disease are most often a prerequisite. This work lead by Associate Professor Jaan-Olle Andressoo describes generation and characterization of the first viable mouse model of Hirschsprung's disease and associated enterocolitis with a defect in GDNF/GFRa1/RET signaling thus representing most patients.

This is important because so far animal studies of Hirschsprung's disease have used model systems that represent a minority of the genetic mutations in Hirschsprung's disease.

Using the new mouse model scientists at the University of Helsinki were now able to shed further light on the chronology of events in enterocolitis. They found that mucin producing goblet cells, a specific type of cells responsible for lubricating the inner surface of the gut, may be a potential target for preventative treatment.

Scientists also conclude that reduced expression of GFRa1 can contribute to susceptibility to Hirschsprung's disease. The new mouse model will serve as a useful tool for enhancing understanding of the disease and for defining treatment in the future.

SAN ANTONIO, Texas, USA -- UT Health San Antonio researchers, collaborating with the Mayo Clinic and the Wake Forest School of Medicine, are the first to publish results on the treatment of a deadly age-related disease in human patients with drugs called senolytics. The findings were posted Jan. 4 by the journal EBioMedicine, which is published by The Lancet.

Senolytics target cellular senescence, a process in which damaged cells, rather than dying, persist and become toxic to cells around them. Cellular senescence has been shown to drive multiple age-related diseases, including idiopathic pulmonary fibrosis (IPF), a chronic, irreversible and progressive disease that results in scarring of the lungs. In animal studies, run by Mayo Clinic collaborators James Kirkland, M.D., Ph.D.; Nathan LeBrasseur, Ph.D., M.S., and Tamara Tchkonia, Ph.D., senolytics selectively cleared these toxic cells in mice that model IPF.

A lethal disease for which there are few options

"IPF is a devastating and progressive fibrotic lung disease with a median survival of less than five years in newly diagnosed adults usually over 60 years of age," said Anoop M. Nambiar, M.D., M.S., associate professor of medicine at UT Health San Antonio and founding director of the university's Interstitial Lung Disease Program, one of 60 Pulmonary Fibrosis Foundation Care Centers in the United States. Dr. Nambiar is co-first author of the research manuscript and enrolled 12 of the patients at UT Health San Antonio and the South Texas Veterans Health Care System.

Despite the current availability of two U.S. Food and Drug Administration-approved therapies that may slow down disease progression in some IPF patients, the prognosis remains poor and is worse than for many common cancers, Dr. Nambiar said. Lung transplantation may be lifesaving, but often is only an option for younger, healthier patients. "There remains a significant unmet need for safer and better treatments for patients with IPF," Dr. Nambiar said.

Patients enrolled in Texas, North Carolina

In this first-in-human pilot study, the investigators enrolled 14 older adults diagnosed with stable, primarily mild-to-moderate IPF. Participants were enrolled at both UT Health San Antonio, which served as the primary patient recruitment site, and Wake Forest medical school, which initiated the trial and served as the study coordinating center. "Though small, this pilot study marks a major breakthrough in how we treat age-related diseases such as IPF," said Jamie Justice, Ph.D., assistant professor at Wake Forest medical school, co-lead investigator and corresponding study author. "Here, we've therapeutically targeted a fundamental biological hallmark of aging that is implicated in IPF, and we show early but promising results for the first time in human patients. This small study represents a major paradigm shift in treatment strategy."

Each participant received two senolytic drugs, dasatinib and quercetin (DQ), taken by mouth for three consecutive days each week for three consecutive weeks (nine doses total). All patients were able to comply with this regimen without any discontinuation of the study drugs.

The research team measured clinical laboratory chemistries before and after DQ administration, and performed rigorous symptom questionnaires weekly of health, quality of life and side effects to obtain preliminary evidence of safety and tolerability. The team also evaluated markers of physical function including six-minute walk distance, walking speed, sitting-to-standing repetitions, a frailty index based on clinical laboratory chemistries, and biological assays of senescence-associated proteins secreted by the toxic cells.

Results

The most consistent improvements following senolytic therapy were observed in participants' mobility. The six-minute walk test, timed sitting-to-standing repetitions and other measures were significantly improved after completion of the treatment. The majority of patients exhibited mobility gains of greater than 5 percent. Other physical function markers, including grip strength and pulmonary function testing, did not change.

"No drug therapies, including the available anti-fibrotic drugs, have ever shown to stabilize, let alone improve, an IPF patient's six-minute walk distance," Dr. Nambiar said. "But in this pilot study of DQ, participants' six-minute walk distance improved an average of 21.5 meters.

"We should be cautious about whether this finding is true based upon this small study without a placebo control group," Dr. Nambiar said. "However, this and other results warrant further study in larger randomized, controlled trials."

Preliminary but encouraging

"Cellular senescence is clearly emerging as a main player in aging," said manuscript co-author Nicolas Musi, M.D., professor of medicine at UT Health San Antonio and director of the university's Sam and Ann Barshop Institute for Longevity and Aging Studies. "Previously, no published data existed to demonstrate that drugs targeting cellular senescence could be safely given to older patients, or that they might be used to treat diseases of aging such as IPF. The pilot research we've reported is preliminary but encouraging."

Dasatinib and quercetin are U.S. FDA-approved for other indications. Moreover, they are effective in eliminating senescent cells originating from different cell types.

"This is the same combination of drugs that was shown to improve pathology in animal models of Alzheimer's disease, which our group, including Dr. Miranda Orr at UT Health San Antonio, demonstrated three months ago for the first time," Dr. Musi said. (For background, see Toxic zombie cells seen for 1st time in Alzheimer's.)

Side effects did not discontinue the treatment

The most frequent side effects reported after DQ therapy were mild to moderate in severity, including respiratory symptoms such as cough and shortness of breath, and gastrointestinal discomfort or heartburn. Some patients reported skin irritation or bruising related to tissue biopsies obtained for biological measurement purposes.

Limitations and goals

This pilot study has obvious limitations. First, it was small (14 patients), and substantially larger numbers of research participants are needed to definitively evaluate change in biological markers of cellular senescence. In addition, the study did not enroll a control group of IPF patients who took a placebo rather than the senolytic. "Therefore, any improvements in physical function should be interpreted with caution and require further study," Dr. Nambiar said.

WASHINGTON (Jan. 7, 2019)-A stop sign at an intersection appears to be larger than a parked car across the street. Is our brain playing tricks on us?

Researchers at the George Washington University gained important insights into how the human brain processes information and allocates attention. Their study, "Attention Scales According to Inferred Real-World Object Size," shows people pay attention to objects based on their real-world size, rather than how they are perceived by the eye.

"Since a person can only pay attention to a limited amount of information at a time, our brain uses object size to determine how much attention to allocate to that object," Sarah Shomstein, a professor of cognitive neuroscience at the GW Columbian College of Arts and Sciences, said. "However, the way our eyes perceive an object can be different from its actual size, such as a car appearing large when it is close and small when it is far. Our study has shown for the first time that the brain adjusts attention based on our knowledge of an object's size, not how our eyes view it."

The findings could have significant impacts on many everyday tasks, from a radiologist looking for tumors of various sizes, to an airport security agent tasked with searching for threats hidden in luggage. This study suggests attention allocation can be trained, which could lead to improvements and efficiency in performing such tasks.

To determine whether the human brain differentially allocates attention depending on an object's size, Dr. Shomstein and her team showed participants several images of small and large everyday objects such as a domino or billiards table, but presented them at an identical fixed size. The team measured how long it took participants to identify probe targets that were embedded within object images.

Researchers found that responses were quicker across known smaller real-world sized objects compared to larger ones, even though the space occupied by both objects on the eye was the same.

"If objects are of identical size on your eye, but you know that one of them is smaller--such as a domino nearby versus a pool table far away--you allocate more attention to the smaller item," Dr. Shomstein said. "Your knowledge of the object's size overrides its physical size thereby adjusting how much attention your brain allocates to the objects."

The researchers also showed participants images of everyday objects on a screen and asked them to rate the size of each object on a scale of one to six, one being very small and six being very large. Findings showed a direct correlation between how participants rated the size of each object and how long it took them to respond to target stimuli within the image.

"Your own personal ratings determine how efficient you are going to be at attending to that object," co-author Andrew J. Collegio, a GW alumnus and researcher in Dr. Shomstein's Attention and Cognition Lab, said. "If you think the pool table is really large, then your attention is going to be less focused."

Dr. Shomstein and Dr. Collegio hope these findings will help future researchers predict how effectively people process particular objects as they pay attention to the world around them.

In experiments in rats and human cells, Johns Hopkins Medicine researchers say they have added to evidence that a cellular protein signal that drives both bone and fat formation in selected stem cells can be manipulated to favor bone building. If harnessed in humans, they say, the protein -- known as WISP-1 -- could help fractures heal faster, speed surgical recovery and possibly prevent bone loss due to aging, injury and disorders.

A report on the experiments was published online Oct. 23 in the journal Scientific Reports.

"Our bones have a limited pool of stem cells to draw from to create new bone," says Aaron James, M.D., Ph.D., associate professor of pathology at the Johns Hopkins University School of Medicine, and the study's senior author. "If we could coax these cells toward a bone cell fate and away from fat, it would be a great advancement in our ability to promote bone health and healing."

The regenerative group of cells, known collectively as stem cells, all have the potential to develop into a variety of cell types including those that make up living tissues, such as bones. Scientists have long sought ways to manipulate the growth and developmental path of these cells, in either a living animal or the laboratory, to repair or replace tissue lost to disease or injury.

Previous studies by others, James points out, showed that a particular type of stem cell -- perivascular stem cells -- had the ability to become either bone or fat and numerous studies since then have focused on advancing the understanding of what signaling proteins drive this developmental change.

From past studies of his own, James also knew that the protein WISP-1 plays a key role in directing the stem cells.

In his new experiments, James and his team genetically engineered stem cells collected from patients to block the production of the WISP-1 protein. Looking at gene activity in the cells without WISP-1, they found that four genes that cause fat formation were turned on 50-200 percent higher than control cells that contained normal levels of the WISP-1 protein.

The team then engineered human fat tissue stem cells to make more WISP-1 protein than normal, and found that three genes controlling bone formation became twice as active as in the control cells, and fat driving genes such as peroxisome proliferator-activated receptor gamma (PPARγ) decreased in activity in favor of "bone genes" by 42 percent.

With this information in hand, the researchers next designed an experiment to test whether the WISP-1 protein could be used to improve bone healing in rats that underwent a type of spinal fusion -- an operation frequently performed on people to alleviate pain or restore stability by connecting two of the vertebrae with a metal rod so that they grow into a single bone. An estimated 391,000 spinal fusions are performed in the U.S. each year, according to the U.S. Agency for Healthcare Research and Quality.

"Such a procedure requires a massive amount of new bone cells," says James. "If we could direct bone cell creation at the site of the fusion, we could help patients recover more quickly and reduce the risk of complications."

In their experiments, the researchers mimicked the human surgical procedure in rats, but in addition, they injected -- between the fused spinal bones -- human stem cells with WISP-1 turned on.

After four weeks, the researchers studied the rats' spinal tissue and observed continued high levels of the WISP-1 protein. They also observed new bone forming, successfully fusing the vertebrae together, whereas the rats not treated with stem cells making WISP-1 did not show any successful bone fusion during the time the researchers were observing.

"We hope our findings will advance the development of cellular therapies to promote bone formation after surgeries like this one and for other skeletal injuries and diseases, such as broken bones and osteoporosis," says James.

According to the Office of the Surgeon General, 1.5 million Americans suffer fractures from bone disease every year. James cautions that while transplanting stem cells to affected bones to help them heal is an increasingly popular therapeutic goal, it has not yet been proved safe or effective in humans.

The researchers also plan to explore whether reducing the level of WISP-1 protein in stem cells could preferentially favor the development of fat cells for soft tissue wound healing as well.

Cancerous tumors trick myeloid cells, an important part of the immune system, into perceiving them as a damaged part of the body; the tumors actually put myeloid cells to work helping them grow and metastasize (spread). A research team co-led by scientists at Rush University Medical Center have discovered a potential therapy that can disrupt this recruitment and abnormal function of myeloid cells in laboratory mice. The findings of their latest study were published on Dec. 19 in Nature Communications.

Myeloid cells are a type of white blood cell that kills invaders like bacteria and cancer. "In the cancer context, myeloid cells promote tumor growth and suppress the activity of T cells," says Vineet Gupta, PhD, professor and vice chairperson for research and innovation in the Department of Internal Medicine at Rush Medical College.

Gupta and Judith Varner, PhD, of the Moores Cancer Center at the University of California at San Diego (UCSD) in California, were co-senior corresponding authors on the study. Samia Khan, PhD, a post-doctoral fellow in Gupta's lab; and Michael Schmid, PhD, and Megan Kaneda, PhD, with UCSD, were co-first authors.

Cancer recruit harmful myeloid cells, while suppressing helpful ones

Gupta's research focuses in general on integrins, a type of protein that are cellular receptors and regulate a number of biological processes. In this study, investigators looked at the integrin CD11b, which I present on myeloid cells and normally helps myeloid cell migration and its ability to fight disease.

Here, the researchers found that CD11b promotes development of myeloid cells into one sub-type, the M1 macrophage, that functions appropriately to suppress tumor growth. However, the tumors often suppress CD11b activity that results in development of the myeloid cells into a different type of cell, the M2 macrophage. These cells actually ward off T cells, which are vital to fighting disease, and M2s also secrete growth factors and promote the development of new blood vessels that allow cancer to grow and metastasize.

In previous research, agents developed to activate T cells have been "extremely effective in controlling tumor growth," Gupta says, but that approach, known as immunotherapy, has not resulted in a universal treatment for cancer. The hunt goes on.

Study found that CD11b is critical in regulating myeloid cells

In this study, the team explored how modifying the activity of CD11b affects myeloid cell behavior in the presence of cancer and if that could be used as a novel strategy to treat cancers. Using a small molecule discovered in the Gupta laboratory, Leukadherin-1 (LA-1), which in the body activates CD11b, the researchers developed a therapy that can boost the function of CD11b to promote the disease-fighting M1 type of myeloid cells, helping create a microenvironment at the tumor site where T cells can enter and attack the cancer.

The study used two types of genetically altered mice. One set of experiments was done with otherwise normal mice that lacked CD11b. Transplanted tumors grew much larger in those mice as compared to the tumors in wild-type (normal) mice, suggesting that CD11b restrains tumor growth.

Exploring further the reason for this difference, the team found that CD11b plays a critical role in regulating the polarization of myeloid cells into M1 or M2 macrophages. In the absence of CD11b, most of the myeloids cells in tumors were the M2 sub-type, that help the tumor grow and spread.

Boosting CD11b activity helped reduce tumor growth

In a different experiment, the team used LA-1 to boost CD11b activity beyond its normal levels in wild-type (normal) mice, and discovered that this increase caused a significant reduction in tumor growth in treated animals. Then, to be sure that their pharmacological intervention was directly due to the effects of LA-1 on CD11b, they created a mouse with a "point mutation" (a genetic mutation at a single residue in the CD11b protein sequence) and created a situation in which CD11b was active all the time (which is usually isn't) in the genetically modified animals.

"The boost in CD11b activity in the mouse with the point mutation mimics the one imparted on CD11b in normal mice with administration of LA-1," Gupta says. "The results were the same," Gupta says. In both cases, the tumors shrank dramatically, suggesting CD11b activation as an novel target for cancer immunotherapy.

In this study, LA-1 showed a great deal of promise, although, Gupta says it will be years before a treatment based on this molecule becomes available to patients. The results are very encouraging and will continue to motivate the team to move this novel approach towards developing treatments for patients.

DURHAM, N.C. -- Young people who self-harm are three times more likely to commit violent crime than those who do not, according to new research from the Center for Child and Family Policy at Duke University.

The study also found young people who harm themselves and commit violent crime -- "dual harmers" -- are more likely to have a history of childhood maltreatment and lower self-control than those who only self-harm. Thus, programs aimed at preventing childhood maltreatment or improving self-control among self-harmers could help prevent violent crime, the authors state.

Rates of self-harm -- deliberately harming oneself, often by cutting or burning -- have increased substantially among adolescents in recent years both in the United States and the United Kingdom. In the U.S., roughly one in four teenage girls try to harm themselves and one in 10 teenage boys. In the U.K., the yearly incidence of self-injury among teenage girls has risen by nearly 70 percent in three years.

"We know that some individuals who self-harm also inflict harm on others," said Leah Richmond-Rakerd, lead author of the study. "What has not been clear is whether there are early-life characteristics or experiences that increase the risk of violent offending among individuals who self-harm. Identifying these risk factors could guide interventions that prevent and reduce interpersonal violence."

In the study, published in The American Journal of Psychiatry, Richmond-Rakerd and researchers from Duke and King's College London compared young people who engage in "dual-harm" behavior with those who only self-harm.

Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative U.K. cohort of 2,232 twins born in 1994 and 1995 who have been followed across the first two decades of life. Self-harm in adolescence was assessed through interviews at age 18. Violent offenses were assessed using a computer questionnaire at age 18 and police records through age 22.

"By comparing twins who grew up in the same family, we were able to test whether self-harm and violent crime go together merely because they come from the same genetic or family risk factors," said Terrie E. Moffitt of Duke University, founder of the E-Risk Study. "They did not. This means that young people who self-harm may see violence as a way of solving problems and begin to use it against others as well as themselves."

Researchers also found that those who committed violence against both themselves and others were more likely to have experienced victimization in adolescence. They also had higher rates of psychotic symptoms and substance dependence.

"Our study suggests that dual-harming adolescents have experienced self-control difficulties and been victims of violence from a young age," said Richmond-Rakerd. "A treatment-oriented rather than punishment-oriented approach is indicated to meet these individuals' needs."

Additional recommendations include:

After incidents of self-harm, clinicians should routinely evaluate a person's risk of suicide. Clinicians should also assess a person's risk of committing acts of violence against others.

Improving self-control among self-harmers could help prevent violent crime. Self-harming adolescents should be provided with self-control training, which may reduce further harmful behaviors.

Self-harm and violent crime have largely been studied separately within the fields of psychology, psychiatry and criminology. Interdisciplinary research should be pursued, since it could yield new insights.

Comprehensive AIDS prevention programs in prisons: A review study

In the current issue of Family Medicine and Community Health (Volume 6, Number 4, 2018; DOI: https://doi.org/10.15212/FMCH.2018.0118: , Somayeh Zare, Mehdi Kargar, Jeyran Ostovarfar, Mohammad Hossein Kaveh of the Department of the Health Education and Promotion, School of Health, Shiraz University of Medical Science, Shiraz, Iran discuss how studies show that suitable design of educational programs can affect prisoners' awareness of AIDS. However, it is not easy to study their effectiveness. So the authors posed the question of whether these programs affect significantly the decrease of HIV transmission among prisoners. Counseling and diagnostic testing are not considered as the final goals of these programs, but they help to diagnose and treat AIDS and also provide supportive programs for prisoners and decrease the risk of HIV transmission to them. Condom provision programs have been used effectively in several countries. The studies reviewed indicate that these programs have been supported more than before by officials and prisoners. They also showed if prisoners have access to condoms, they use them in their sexual contacts. The investigations illustrated the importance of NSPs whenever AIDS is prevalent. They lead to lessening of the risk of HIV transmission and also extra expenses for disease therapy. The investigations showed the effectiveness of medical therapy programs related to AIDS. MMT, as one of the most preventive and AIDS control therapies, can be effective whenever it is given appropriately. MMT can diminish the frequency of medicine use and also use of a common syringe. Principally, effective and accessible therapies influence health and safety in prisons. However, few studies have been conducted to determine the impact of decontaminant provision and safe tattooing programs in prisons, so it is not easy to evaluate their effectiveness.

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While a sudden coughing fit is a protective reflex to clear the airway, chronic cough can be caused by multiple factors that must be investigated to determine treatment. Cough is just one of several laryngeal symptoms including hoarseness and dysphoric breathing that can become debilitating. Until recently, the cause of these severe laryngeal symptoms could not be identified in many patients, and the only treatments were to manage them with medication and rehabilitation therapy.

A team of MUSC researchers can now offer these patients some hope. Lucinda Halstead, M.D., associate professor of medicine in MUSC's Department of Otolaryngology: Head & Neck Surgery and medical director of the Evelyn Trammell Institute for Voice and Swallowing, led her team to uncover a new cause for these symptoms and an effective treatment.

"Symptoms like hoarseness may not seem serious, but if you are a singer, teacher or a preacher, or have a job at a call center, it's exhausting to push your voice every day," explained Halstead. "Chronic cough is not just a little throat-clearing. We're talking about a very forceful cough. These people can break ribs or become incontinent from the force. It's very debilitating. They're afraid to go out in public - to church, or a concert, or a restaurant-because it's so disruptive."

When a patient presents with chronic laryngeal symptoms (persisting for more than eight weeks and not improving with standard treatment), physicians follow a step-by-step protocol to look at the most common causes. For example, over 86% of chronic coughs are caused by post-nasal drainage, asthma or gastroesophageal reflux disease.

If a full history and exam do not identify the cause, an otolaryngologist evaluates the larynx. In some patients, this turns up asymmetrical movement of the vocal fold (the vocal cords) or vocal fold paralysis. The cause is usually a lesion or another structure pressing on one of the nerves that activates the vocal fold and swallowing (cranial nerves nine and ten). Because these nerves run from the brain stem through the neck and into the chest, further investigation is needed to pin-point exactly where the compression is occurring.

"The laryngeal exam tells us that the vocal fold is not opening, lengthening or shortening correctly," said Halstead. "For people with vocal fold paralysis, we look right away in the chest and neck. Maybe a mass in the thyroid gland is pressing on a nerve and interfering with the signal. Maybe it's a lesion in the chest or a mass along the carotid sheath that's causing the laryngeal weakness."

But sometimes the cause remains elusive. "If the usual scans don't show anything that could cause it, we usually assume that it had a viral origin-viruses do sometimes cause these problems - or we simply say that the etiology is unknown."

Then, Halstead's team met their index case who would inspire the study that led to their recent discovery. A medical student presented at their clinic with severe difficulty swallowing and "breathy" speech. A laryngeal exam found vocal fold paralysis, but further investigations didn't identify a cause.

"The patient just wasn't going to take, 'I don't know' for an answer and refused to believe we couldn't find an etiology for what was happening," recalled Halstead. "We kept investigating but there were no masses in the neck or chest - everything looked good. So, we went back through the history and saw that the symptoms all started during a bad migraine, which is a vascular event in brain. A migraine wouldn't cause cranial nerve compression, but many blood vessels in the brain can press on these nerves. Based on some vagal nerve symptoms that the patient reported while exercising, we hypothesized that maybe when blood vessels dilated during the migraine, it exacerbated some ongoing vascular compression at the brain stem."

When this was confirmed by MRI, the patient chose to have surgery to move the vessel off the nerve (a procedure similar to what is done to relieve trigeminal neuralgia). It was a success. Partial motion of the paralyzed vocal fold occurred, and swallowing ability was recovered completely.

The team wondered how many of their other patients with unexplained symptoms might also have compression at the brain stem. Could this neurosurgical procedure also help them? They used retrospective chart reviews to identify 149 study candidates and, after extensive work-ups to eliminate all other causes, they found that 33% (49/149) had nerve compression at the brainstem. Their symptoms included dysphonia (51%), chronic cough (39%), dysphoric breathing (6%) and dysphagia (4%). After explaining the potential risks and benefits, 49% elected neurosurgical decompression and 51% chose non-surgical/standard-of-care treatment.

Results showed that surgical decompression significantly improved quality of life on all measures. The change in Voice-Related Quality of Life (V-RQOL) was p=0.02, Reflux Symptom Index (RSI) was p=0.02 and Glottal Closure Index (GCI) was p=0.01. Results comparing surgical and non-surgical groups showed significantly (p=0.02) greater improvement in V-RQOL in the surgical group and trends toward statistical significance on the RSI (p=0.20) and GCI (p=0.17).

42% of the surgical group reported near-complete or complete symptom resolution compared to 8% in the non-surgical group (p=0.008). Over a mean follow-up of three years, non-surgical patients (60%) experienced no significant improvement or worsening symptoms, compared to surgical patients (13%) (p=0.001). Finally, none of the non-surgical patients demonstrated improved laryngeal exam findings, while 43% of surgical patients demonstrated improvements and 29% demonstrated resolution of their laryngeal exam findings.

"Our study shows that when we can't identify a cause for vocal fold weakness based on the standard work up, the next step may be to look at the brain stem," Halstead said. "It's so important that we now have one more thing to look at and one more thing we can offer as definitive treatment."

The team hopes that their findings will benefit more patients soon and that their study might point others to investigate nerve compression at the brain stem as a possible cause for other unexplained symptoms.

Most evolutionary biologists distinguish one species from another based on reproductivity: members of different species either won't or can't mate with one another, or, if they do, the resulting offspring are often sterile, unviable, or suffer some other sort of reduced fitness.

For most of the 20th century, scientists believed that this reproductive incompatibility evolved gradually between species as a by-product of adapting to different ecological circumstances: if two species were geographically isolated, they would adapt differences based on their environment. New research conducted at the University of Rochester, in collaboration with the University of Nebraska, shows, however, that there are more factors at play--specifically the presence of selfish genes called meiotic drive elements, whose flow among species may dictate whether two species converge or diverge. In a new paper published in the journal eLife, the researchers show that sex chromosomes evolve to be genetically incompatible between species faster than the rest of the genetic chromosomes and reveal the factors at play in this incompatibility.

When two members of a species mate and exchange genetic material, this is known as gene flow. When two members of different species mate, however, gene flow is reduced. "Genes from one species simply can't talk to genes from the other species," says Daven Presgraves, a dean's professor of biology at Rochester. Though the genes may work fine on their own genetic background, when they are moved into the genetic background of another species, they have negative effects. "All of the gene copies in you and me work in the human genome. But if we were to take a gene out of you and stick it in a macaw parrot, they haven't seen this sequence before and it might not work together with the other genes. That would compromise some sort of function like fertility."

This is what happened when Presgraves and members of his lab crossed two different species of fruit flies, one from Madagascar and the other from the island of Mauritius. When the two species were crossed, their female hybrid offspring were fertile, but the hybrid male offspring were completely sterile. "One of the steps on the way to complete reproductive isolation is that the XY sex becomes sterile first in that gradual build-up of incompatibility," Presgraves says. In the case of fruit flies, as in human beings, the XY sex is male.

Chromosomes are divided into two types: allosomes, or sex chromosomes, and autosomes, or body chromosomes. Genetic traits linked to an organism's sex are passed on through the sex chromosomes. The rest of the genetic hereditary information is passed on through the autosomes. When the researchers mapped the factors that cause hybrid males to become sterile, they found that there were many more incompatibility factors on the X allosome compared to the autosomes. This means that sex chromosomes become functionally different between species much faster than non-sex chromosomes, Presgraves says. "There's a lot more exchange going on between the autosomes than on the X."

But what is it that makes sex chromosomes accumulate genetic incompatibility faster than the rest of the genome?

The researchers found that a class of "selfish genes" called meiotic drive elements are responsible for making sex chromosomes genetically incompatible at a faster rate. In general, selfish genes are parasites of the genome--they propagate themselves at the expense of other genes. Meiotic drive elements in particular sabotage the rules of typical inheritance: in normal Mendelian inheritance, a gene is transmitted to half the offspring. Meiotic drive elements, however, manipulate reproduction so they can transmit themselves to more than their fair share of the genome. In hybrid male fruit flies, meiotic drive elements usually kill any sperm that don't carry them, leaving only (or mostly) sperm that do carry the meiotic drive elements.

"This could be because multiple meiotic drive elements from both parental species are unsuppressed in hybrids, and their combined action causes sterility," says Colin Meiklejohn, a former postdoctoral student in Presgraves's lab.

In a twist, however, the researchers also found that if meiotic drive elements are able to experience gene flow, they can also help bring species together. During early speciation, when two different species are just beginning to break away from one another, reproductive incompatibility can be incomplete and "leaky"--some part of the genome may still be compatible and exchangeable.

"If two populations are leaky and there is opportunity for gene flow, a selfish gene can leak over into the other population and spread there," Presgraves says. If the species interbreeds and this selfish gene is able to be passed down, instead of becoming incompatible, "that part of the genome will become perfectly exchangeable. In some cases a selfish gene will basically erase the build-up of incompatibilities for a part of the genome."

That is, meiotic drive elements can cause incompatibilities between species if they do not experience gene flow, or they can cause a convergence of the species, if they species does experience gene flow. A major factor in determining whether or not a species is compatible hinges on whether or not there is gene flow between the species, Presgraves says. "Species--even ones that are geographically isolated--are much leakier than we thought."

PHILADELPHIA--Doctors diagnose about 2000 adults with uveal melanoma, a cancer of the eye, every year. In half of cases, the disease metastasizes to the liver. For these patients treatment options are scarce. Researchers at the Sidney Kimmel Cancer Center (SKCC) -- Jefferson Health and the Icahn School of Medicine at Mt. Sinai found that a compound extracted from the Christmas berry primrose plant stops the cancer's growth in preliminary tests. With further testing, the discovery could lead to new therapeutic options for patients with uveal melanoma.

"I'm very optimistic," said Jeffrey Benovic, PhD, Thomas Eakins Endowed Professor of Biochemistry & Molecular Biology at Thomas Jefferson University and an Associate Director with the SKCC, who led the new work. "If the results are confirmed in animal models and eventually humans, it could offer a new way to treat metastatic uveal melanoma patients down the road," he added.

Dr. Benovic and team published their findings in the journal Molecular Cancer Research.

Uveal melanoma (UM) is the most common eye cancer in adults. The cancer forms in melanocytes, the cells that make pigment. Although the condition differs from melanoma of the skin, both cancers are lethal. Uveal melanoma accounts for about 5 percent of all melanoma cases. Surgery or radiation is the go-to treatment for patients with primary UM that has not spread to other parts of the body. But metastases occur in about half of cases. The cancer most often travels to the liver. Once the cancer has spread, patients often only have a year or so to live as no effective therapies yet exist.

The researchers tested whether a compound derived from an ornamental plant in the primrose family known as Ardisia crenata, might be able to fight the disease.

The compound, dubbed FR900359, or simply FR, was discovered 30 years ago from the plant's leaves.

FR works by blocking a particular type of G protein that sits on a cell's membrane, called Gq - an important signaling molecule. But a subset of these proteins are mutated in uveal melanoma, turning on a molecular pathway that leads to cancer growth.

Dominic Lapadula, a graduate student in Dr. Benovic's lab, grew three different types of uveal melanoma cells that have the cancer-spurring mutations in the lab. Then he treated the cells with FR.

"We didn't expect it would work because previous research suggested a related compound called YM-254890 did not inhibit the mutated forms of the proteins found in uveal melanoma," said Dominic Lapadula. "But lo and behold, FR very effectively blocked the growth of the uveal melanoma cells." When the uveal melanoma cells were treated with small amounts of FR, the cells appeared to revert from cancer cells to typical melanocytes. "FR appears to be able to help reset the cells back to their normal state," Dr. Benovic said. "Ideally that's what you want."

Higher doses of FR killed the cells, the researchers report in the new study. The results suggest the compound could be an effective drug to treat uveal melanoma one day.

This study emanated from a team effort within the Cancer Cell Biology and Signaling program in the SKCC in collaboration with Dr. Julio Aguirre-Ghiso at the Icahn School of Medicine at Mt. Sinai. Next, Dr. Benovic would like to repeat the findings in a mouse model of uveal melanoma. To do so, he'll team up with Takami Sato, MD, PhD, Director of the Metastatic Uveal Melanoma Program at Jefferson. The program is one of the only centers dedicated to both research and treatment of the disease.

"I'm hopeful FR and related compounds will reset the cancer cells in the mouse model as it did in the cells we grew in the lab," Dr. Benovic said, "getting it one step closer to testing in humans."

"This outstanding work is part of a larger effort within our Center to develop new strategies for combating uveal melanoma. As one of the few cancer centers specializing in this aggressive cancer type, Dr. Benovic and team work closely with clinical partners within SKCC to fast track discoveries into the translational setting," said Karen E. Knudsen, PhD, Enterprise Director of the Sidney Kimmel Cancer Center.

BUFFALO, N.Y. -- With more than 1.8 million children in the U.S. being treated annually with drugs for attention deficit hyperactivity disorder (ADHD), the possibility that such drugs could damage their hearts has been a significant cause of concern for parents and physicians alike.

Now, the results of a long-term National Institutes of Health (NIH)-funded study published last month in Pediatric Research could allay many of those concerns.

The authors caution that because the study was conducted on primates, the findings are not automatically applicable to humans. However, they have previously published that this primate model reliably shows other side effects similar to what is found in children receiving these medications. Their new findings conclude that chronic exposure to methylphenidate (MPH), a commonly prescribed ADHD drug, is unlikely to increase cardiovascular risks in healthy children.

"The findings are very reassuring in that even high-dose chronic MPH stimulant therapy did not result in any evidence of abnormal structures or function in the hearts of the monkeys," said Steven E. Lipshultz, MD, the study's principal investigator, and senior and corresponding author, who is the A. Conger Goodyear Professor and Chair of the Department of Pediatrics in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. He also is the pediatric chief-of-service at Kaleida Health; medical director, pediatrics services business development, for John R. Oishei Children's Hospital; and president of UBMD Pediatrics.

The research was conducted while Lipshultz was the Batchelor Chair of Pediatrics and director of the Batchelor Children's Research Institute at the University of Miami Miller School of Medicine, and later while he was the Carman and Ann Adams Endowed Chair of Pediatric Research at Wayne State University School of Medicine and Children's Hospital of Michigan.

Sudden cardiac death controversy

The results contribute important evidence to an ongoing controversy about whether or not MPH is associated with sudden cardiac death. A number of studies have reported an increase in sudden cardiac death or other damage to the heart in some children taking the drug or other stimulant therapy for ADHD.

With ADHD and related disorders diagnosed in about 10 percent of all children in the U.S., and with as many as 70 percent of these children receiving stimulant prescription therapy, the question of possible cardiac risks has emerged as a major public health concern, Lipshultz said.

In response, the U.S. Food and Drug Administration (FDA) has issued a "black box warning" on the drug packaging of some prescription stimulants, noting that children with underlying heart disease should use these medications with caution. Canadian authorities temporarily removed a stimulant drug from use only to reintroduce it, based on the small number of sudden cardiac death events identified through voluntary reporting.

"This controversy has persisted without answer," said Lipshultz. "Yet the number of prescriptions for these medications for children with ADHD continues to expand."

For that reason, about a decade ago, Lipshultz was interested to learn of a U.S. government research project involving 30 male rhesus monkeys that had been receiving daily chronic stimulant therapy with MPH. He noted that the monkeys were carefully maintained and ethically cared for at the FDA's National Center for Toxicological Research in Jefferson, Arkansas.

"I thought they could also shed some light on this charged medical issue related to the safety of chronic stimulant therapy with regard to children's heart health," he said.

Long-term testing

With funding from the NIH and FDA, Lipshultz and his colleagues spent several years developing infrastructure to test how the therapy affected the hearts of these monkeys over the long term. Specialized cardiac catheterization and echocardiography labs were developed at the primate center at the National Center for Toxicological Research where a pediatric interventional cardiologist and a specialist in randomized studies, both on temporary leave from their hospital posts, conducted this study.

For five years, the monkeys were continuously treated with therapeutic, super-therapeutic (high doses) or a placebo, using a randomized design, starting when they were about 2 years old. The duration of the study corresponds to what would be a childhood to adulthood span, the researchers said.

"For ethical reasons, this study could not have been done in children," said Lipshultz.

After comprehensive cardiovascular assessment in all the monkeys, there were no statistical differences between the three groups on serum cardiovascular and inflammatory biomarkers, electrocardiograms, echocardiograms, cardiac pathology from endomyocardial biopsies and other clinical parameters.

The single difference of statistical significance was that elevated levels of mean serum myoglobin were found in the lower-dose group. This protein, found in skeletal and cardiac muscle, can be a sign of skeletal muscle injury when found in the serum of humans who have not sustained cardiac injury. Primates in the group receiving high-dose therapy had lower, but still significantly elevated levels.

Because there was no clinical or laboratory evidence of significant cardiac disease in the animals, the authors concluded the elevated myoglobin levels most likely originated in skeletal muscle and were unrelated to a cardiac effect.

In addition to the large population of children being treated with this therapy for ADHD and related disorders, Lipshultz noted that the findings also are good news for child survivors of cancer.

"On a personal level, I have cared for children and adolescents who have survived childhood cancer, who now are experiencing severe learning disabilities as a result of their cancer therapies," he said. "They become my patients because their hearts have been damaged, an unfortunate effect of the successful treatment of their childhood cancer.

"Current recommendations state that children, such as these, with underlying heart disease should avoid chronic stimulant therapy because of the concern that it could further damage their hearts. However, these prescription stimulants often allow these children to do much better with their learning progress, and denying such a useful therapy for theoretical reasons is difficult. The findings that we are reporting demonstrate that these useful medications, in many cases, can be prescribed to these children as well."

One answer to our greenhouse gas challenges may be right under our feet: Soil scientists Oliver Chadwick of UC Santa Barbara and Marc Kramer of Washington State University have found that minerals in soil can hold on to a significant amount of carbon pulled from the atmosphere. It's a mechanism that could potentially be exploited as the world tries to shift its carbon economy.

"We've known for quite a long time that the carbon stored on minerals is the carbon that sticks around for a long time," said Chadwick, co-author of the paper, "Climate-driven thresholds in reactive mineral retention of soil carbon at the global scale," published in the journal Nature Climate Change. How much carbon the soil can take and how much it can keep, he said, are dependent on factors including temperature and moisture.

"When plants photosynthesize, they draw carbon out of the atmosphere, then they die and their organic matter is incorporated in the soil," Chadwick explained. "Bacteria decompose that organic matter, releasing carbon that can either go right back into the atmosphere as carbon dioxide or it can get held on the surface of soil minerals."

Water plays a significant role in the soil's ability to retain carbon, say the researchers. Chadwick and Kramer consulted soil profiles from the National Ecological Observatory Network (NEON) and from a globally representative archived data set for this first-ever global-scale evaluation of the role soil plays in producing dissolved organic matter and storing it on minerals. Wetter climates are more conducive to formation of minerals that are effective at storing carbon, therefore much of the Earth's estimated 600 billion metric tons of soil-bound carbon is found in the wet forests and tropical zones. Arid places, meanwhile, tend to have a "negative water balance" and can thus store far less organic carbon. According to Chadwick, the findings suggest that even a small, strategic change in the water balance could drive greater carbon storage.

"That's not as easy as it sounds, because water is dear," Chadwick said, and in places where a shift in soil moisture could tip the water balance from negative to positive -- like the desert -- there's not enough water to begin with. "So, it doesn't actually make any sense to spread a lot of water out over the landscape because water is hugely valuable," he added.

Climate change is another driver to consider. As the Earth warms, microbial activity increases and, in turn, so does the potential for carbon to be released back into the atmosphere at a greater rate than photosynthesis can draw it out. Increased evaporation due to a warmer climate also decreases the amount of water in the soil available to dissolve and move carbon to minerals deep below the surface.

There is still a lot to investigate and several hurdles to overcome as soil scientists everywhere consider ways to tip the balance of the Earth's soil from carbon source to carbon sink, but according to these researchers, understanding this relatively little-known but highly significant carbon storage pathway is a start.

"We know less about the soils on Earth than we do about the surface of Mars," said Kramer. "Before we can start thinking about storing carbon in the ground, we need to actually understand how it gets there and how likely it is to stick around. This finding highlights a major breakthrough in our understanding."

Among the next steps for the scientists is to date the mineral-stored carbon in the soil to better understand how long these reactive (typically iron and aluminum) minerals can keep carbon out of the air. "Which is really important if we're going to put effort into trying to store carbon in the soil," Chadwick said. "Is it going to stay there long enough to matter? If we put it in and it comes out five years later, it's not solving our problem, and we ought to be barking up a different tree."