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A new study shows that a test physicians commonly used to guide chemotherapy treatment for post-breast cancer surgery patients may also help them decide whether radiation therapy may be of benefit.

Known as the 21-gene recurrence score, the test is a personalized analysis of the activity of 21 genes found in a patient's breast tumor tissue. The score can be used to predict whether, after undergoing surgery, that patient's breast cancer is likely to return in another part of their body, like the bones or lungs, and whether that patient will likely benefit from chemotherapy treatment.

Study results suggest patients with an intermediate or high 21-gene recurrence score are more likely to see their cancer return to the breast and nearby lymph nodes and, thus, could benefit from radiation. Findings appear today in JAMA Oncology. The study was conducted by the SWOG Cancer Research Network, a cancer clinical trials network funded by the National Cancer Institute (NCI), part of the National Institutes of Health, and part of the oldest and largest publicly funded research network in the nation.

The Canadian Cancer Trials Group, with co-sponsorship by the NCI, is enrolling patients on a trial called TAILOR RT, which will confirm whether the recurrence score - all by itself - can identify low risk node positive patients who do not need radiation. Because randomized trials represent the gold standard in clinical research, TAILOR RT results could change the standard of cancer care. Until that data is in, the SWOG findings provide evidence that the recurrence score can be an effective, additional tool - along with tumor size or stage - that physicians can use to determine whether to recommend radiation therapy, particularly for patients whose cancer presentation makes the need for radiation uncertain.

"For a decade, radiation oncologists have been banging on the doors of precision medicine, looking for genomic tools they can use to personalize treatment for their patients," said Wendy Woodward, MD, PhD, lead investigator of the SWOG study and chief of the clinical breast radiotherapy service at the University of Texas M.D. Anderson Cancer Center. "Radiation oncologists want these tools because they can help their patients. Radiation treatment can help wipe out local disease, saving or lengthening a patient's life. And omitting radiation treatment could spare other patients pain, time, and cost."

The 21-gene recurrence score test is sold as the Oncotype DX Breast Recurrence Score and was developed by the California-based company Genomic Health, Inc. In multiple research studies, the test has been proven to predict the likelihood of disease recurrence - and chemotherapy benefit - in patients with invasive, early-stage breast cancer.

The test made international headlines in June 2018 when the results of the Trial Assigning Individualized Options for Treatment, or TAILORx, were released at the annual meeting of the American Society of Clinical Oncology. Results from TAILORx, the largest randomized post-surgery breast cancer trial ever mounted, showed that the test could predict who would, and would not, benefit from chemotherapy.

Woodward and her team wanted to see if the 21-gene recurrence score could also be useful in predicting the local breast cancer recurrence that radiation can prevent. Radiation is much more targeted than chemotherapy, focusing on specific areas in and around the breast.

Woodward was particularly interested in how recurrence scores might help add to the clinical tools that currently guide radiation for patients - especially when the need isn't clear. Breast cancer patients who have undergone mastectomy, have low-risk clinical factors, and cancer-free lymph nodes often do not require radiation treatment after their cancer surgery. However, those with large tumors and cancer in four or more lymph nodes almost definitely get radiation. But what about patients with a more ambiguous presentation - say, a smaller tumor and one to three cancer-positive lymph nodes? Can scores help safely guide radiation decisions?

To find out, Woodward and her team dove into data generated by S8814, a long-closed SWOG trial that compared post-surgery treatments in post-menopausal women with breast cancer. In this randomized trial, postmenopausal women with node-positive breast cancer were randomly assigned to one of three treatments. Physicians recommended radiotherapy based on clinical factors, such as tumor size and the number of lymph nodes that contain cancer.

As part of S8814, 367 patients took the 21-gene recurrence score test. Woodward and her team reviewed all these records to see which patients had radiation therapy and which had what's known as locoregional recurrence (LRR), when cancer returns after treatment close to the site of the original tumor - in this case, the breast, chest wall, or lymph nodes. After winnowing out certain patients, the SWOG team wound up with a pool of 316 patient records. They logged every patient's recurrence score, and also whether and when LRR occurred. In all, after a median of eight years of follow-up, 34 patients went on to have an LRR event - 27 with intermediate or high recurrence scores and seven with low recurrence scores. Regardless of other factors, such as number of cancer-positive lymph nodes, the recurrence score proved to be an independent predictor for LRR.

"We believe these data support using recurrence scores - along with standard clinical factors like age or tumor size - to determine risk of recurrence and radiotherapy decisions for patients," Woodward said. "Our findings are clearly limited, as we had some small patient numbers and looked at data retrospectively. But these results provide additional evidence of the value of this test in node positive patients. And they suggest it might be possible to skip radiation in patients with low recurrence scores and one to three cancer-positive nodes, a question now being rigorously tested in TAILOR RT.

"There are large clinical trials going on looking at radiation care for breast cancer patients, like TAILOR RT, and I encourage people to enroll. The more data we have, the more we'll know how to use this new precision medicine tool."

Low-income people with addiction, especially those with addiction to opioids, may find it hard to access the kind of care they need to recover no matter where they live, a new study suggests.

But treatment for opioid problems is especially scarce in states that may drop people from their Medicaid health insurance rolls -- unless they can show that they're working, in school, have a disability or are medically frail or receiving treatment for substance use disorder.

In addition, the study shows that states with Medicaid work requirements also have higher rates of opioid overdose deaths than other states - suggesting a need for increased overdose prevention efforts.

In a new paper in the Journal of General Internal Medicine, a pair of University of Michigan researchers looks at data from states that have sought or received federal government permission for Medicaid work requirements, and compares it with data from states that haven't.

They find that work requirement states tend to have fewer substance use disorder treatment facilities that offer care for opioid use disorder. They also have fewer health care providers certified to prescribe the medication buprenorphine, one of the most effective opioid addiction treatments.

High stakes, low availability

The researchers say their findings support a call for more access to substance use disorder treatment, and specifically to evidence-based opioid use disorder care, across the country.

But the stakes for patients are higher in work requirement states, because of the challenges to employment for people with these conditions and the potential for people to lose their Medicaid health coverage if they can't find a provider to diagnose or treat their substance use disorder.

Some states with work requirements apply their policy to all Medicaid enrollees, others only to the population covered by the Medicaid expansion program.

Starting in 2018, the Centers for Medicare and Medicaid Services invited states to apply for waivers to the Medicaid statute that would allow changes to their programs designed to increase employment and community engagement by enrollees.

Seventeen states have applied, and nine have received approval, though most of them have put their programs on hold because of a federal court case contesting the legal basis of the work requirement waiver.

All of the seventeen states except Alabama allow Medicaid participants to count substance use disorder treatment as a form of community engagement to fulfill their work requirement and keep their coverage, or to be exempt from the requirement if they have a formal substance use disorder diagnosis.

"Work requirement states are largely treating substance use disorder as a disability, but many want evidence of a diagnosis, or proof that they're taking part in an approved treatment program," says Paul Christine, M.D., Ph.D., the U-M internal medicine resident who led the analysis of data from several national databases to conduct the study. "If they're requiring this as a condition of eligibility, then it's important to know if treatment resources will be available. And it appears that work requirement states have lower addiction treatment availability, especially in states that have approved waivers."

Renuka Tipirneni, M.D., M.Sc., the assistant professor of internal medicine who worked with Christine on the study, has also studied the effects of Medicaid coverage on enrollees' mental and physical health, and ability to work.

"We know that gaining coverage is associated with better health and ability to be a productive part of society, and that losing coverage can have the opposite effect," she says. "States should increase the availability for substance use disorder treatment, and potentially account for the availability of this care when making decisions about Medicaid eligibility and enrollment."

The prevalence of substance use disorder was similar across states with and without Medicaid work requirements. But states with approved Medicaid work requirement waivers had a higher incidence of both overall overdose-related deaths and opioid-related overdose deaths, compared with states with pending or no work requirements

Increasing the availability of medication-based therapy for opioid use disorder is a priority nationwide, the authors say, and in states with Medicaid work requirements, failing to do so may have health and health insurance repercussions for individuals with substance use disorders.

Selective fishing can disrupt the delicate balance maintained between corals and algae in embattled Caribbean coral reefs. Removing large parrotfish, which graze on algae like large land mammals graze on grasses, can allow the algae to overtake the corals, with potentially dire consequences for reef health. New experimental research suggests that maintaining a healthy size distribution of parrotfishes in a sea floor ecosystem through smart fishing practices could help maintain reefs that are already facing decline due to climate change.

A paper describing the research by scientists at Penn State and the University of California, Santa Barbara appears online in the journal Ecological Monographs.

"Coral reefs are incredibly beautiful and intrinsically valuable, but they also protect thousands of miles of coastline and provide habitat for astonishing biodiversity that is the major source of protein for nearly a billion people worldwide," said Andrew A. Shantz, Eberly Research Postdoctoral Fellow at Penn State and the first author of the paper. "Understanding how fishing impacts coral ecosystems will help us to protect this invaluable resource."

The researchers used survey data on parrotfish populations from 282 sites across the Caribbean and compared these sites to protected reefs in the Florida Keys to assess how parrotfish populations are impacted by fishing. Surprisingly, the biomass--the total mass of parrotfish in a region--was not impacted by fishing. Instead the distribution of fish sizes changed. Fishing selectively removes large parrotfish, but the biomass is maintained because many more small parrotfish are able to occupy the region.

"Because biomass remained basically the same in regions where there is heavy fishing, we were interested to see if different sized fish played different ecological roles," said Shantz. "We set up an experiment where we could exclude larger fish from accessing an area to see how changes in the distribution of fish sizes impacted corals and their relationship with algae."

The experiment involved three different enclosures with different sized openings placed on the sea floor around corals in the protected Florida Keys. One enclosure allowed access to fish of any size, the second excluded only the largest parrotfish, and the third excluded large and medium sized parrotfish.

"We found that by excluding large parrotfish, the algae grew four times faster," said Shantz. "By excluding both large and medium parrotfish, the algae grew ten times faster. So even though fishing does not reduce the biomass of the fish, it's the larger fish that keep the algae at bay. Unless we can develop and implement fishing strategies that maintain a healthy distribution of fish sizes--for example, a slot based system with both minimum and maximum size restrictions--the corals in these regions are at risk."

MELBOURNE, Australia - In a promising discovery that could improve the clinical delivery of insulin for people living with diabetes, scientists have developed a non-fibrillating form of human insulin.

Using a novel glycosylation technique, an international research team led by Associate Professor Akhter Hossain from the Florey Institute of Neuroscience and Mental Health, has successfully synthesised an insulin analogue called glycoinsulin that demonstrates the same glucose-lowering effects as native insulin in preclinical studies without fibril formation.

Fibrils can arise when insulin compounds aggregate together forming clumps. For people with diabetes who rely on pump infusions to administer insulin, fibrils pose serious risk in blocking the delivery of insulin which can potentially lead to life threatening under-dosing.

Associate Professor Hossain said that the discovery of glycoinsulin presents a promising solution for patients.

"Not only did our research demonstrate that glycoinsulin does not form fibrils, even at high temperature and concentration, but also that it is more stable in human serum than native insulin. Together these findings could position glycoinsulin as an excellent candidate for use in insulin pumps and a way to improve the shelf life of insulin products," said A/Prof Hossain.

"We now hope to streamline the manufacturing process for glycoinsulin so this compound can be further investigated in larger, clinical studies."

Over 25,000 people in Australia and 350,000 people in the United States use insulin pumps as part of their diabetes management.

In what can cause significant patient burden and medicine wastage, insulin pump infusion sets are required to be replaced every 24 hours to 72 hours to mitigate the occurrence of fibrils. In the USA alone, more than US$1 billion could be saved per year if the usage period for insulin increased from two to six days.

Critical to the success of the study was the engineering of an insulin-sugar complex from egg yolks using a method jointly developed by collaborators, Associate Professor Ryo Okamoto and Professor Yasuhiro Kajihara, from Osaka University, Japan.

Professor John Wade from the Florey Institute of Neuroscience and Mental Health who co-led the research commented on the landmark success of the research.

"Typically, the chemical modification of insulin causes structural destabilisation and inactivation, but we were able to successfully synthesise glycoinsulin in a way that retains its insulin-like helical structure. The result is an almost fully active insulin analogue which has demonstrated near-native binding to insulin receptors in both lab and animal studies."

Diabetes Australia CEO, Professor Greg Johnson, welcomed the research findings saying they had the potential to make life easier for people living with diabetes who use insulin pumps.

"It is nearly 100 years since the discovery of insulin and it's very exciting that we see new discoveries for insulin, and insulin-like molecules, that have the potential to ease the day to day burden and cost for people with diabetes" he said.

While waiting for free firearm storage devices at gun safety events held in sporting goods stores across Washington, nearly 3,000 people filled out a one-page survey asking how they stored guns at home and other household information.

What the participants reported emphasizes the need for these public gun safety events, Seattle Children's and University of Washington researchers say, because 40% of gun owners at the events reported having at least one firearm in their home that was not locked up. In addition, 39% of survey takers indicated they kept a loaded gun at home, and 14% stored all guns unlocked and loaded.

"Even in this population, which clearly had some interest in or awareness of firearm safety, there was a high prevalence of unlocked firearms," said lead author Aisha King, who worked on the study while a graduate student at the UW's School of Public Health and as an intern with Harborview Injury Prevention & Research Center's INSIGHT summer research program.

Furthermore, results of surveys conducted at the events in 10 Washington cities between 2015 and 2018 determined that the presence of children in the home did not make a difference. The study is available online now and is part of the February 2020 edition of the journal Preventative Medicine.

The firearm safety events were put on by Seattle Children's in partnership with UW Medicine's Harborview Injury Prevention & Research Center, public health agencies, local hospitals in each city, community organizations and Safe Kids coalitions.

In addition to taking a survey and receiving a free firearm lockbox or trigger lock, people at the public events received training on safe firearm storage and proper use of storage devices. The events were held in Monroe, Tacoma, Kirkland, Wenatchee, Seattle, Lacy, Mount Vernon, Moses Lake, Silverdale and Federal Way.

"The purpose of the events is to increase the use of safe firearm storage, an evidence-based strategy to reduce firearm related injuries and deaths," said Elizabeth Bennett, co-author and director of community health and engagement at Seattle Children's. "Our goal is to create a comfortable environment to learn about locking up firearms and to have the devices ready to use right away."

Public gun safety events are an effective tool for improving the safety of kids living around firearms, a previous study found, and the events reach an important audience: male gun owners.

This is an important demographic to reach, King said, because men make up the majority of gun owners and typically take responsibility for how guns are stored in the home. When gun safety interventions are held in pediatrician offices or similar clinic settings, most parents or guardians who attend are female.

Importantly, nearly all of the roughly 3,000 who submitted surveys said they planned to use the free safety device within the following week. Storing firearms locked and unloaded, the researchers point out, is associated with a greater-than 70% reduction in risk of unintentional and self-inflicted firearm injuries among young people.

King, who is currently a project coordinator at Columbia University, added that when it comes to firearm storage some adults might think that younger children don't know where the guns are or don't know how to access them, but that is not always the case.

"A lot of times, the kids do know," King said. "Also, guardians might think that training adolescents or older children is enough to keep them safe, that training means they don't have to lock their guns. Unfortunately, a lot of adolescents are at high risk of suicide, and unlocked guns add to that risk - regardless of training."

Salvage logging and re-seeding a forest after a wildfire helps reduce flooding and returns water levels to normal faster, according to a new paper from a Washington State University researcher.

The paper, just published in the journal Hydrological Processes, shows that water levels are still increased up to 40 years after a fire.

"Trees work like straws, pulling water up out of the ground," said Ryan Niemeyer, an adjunct faculty member in WSU's Center for Sustaining Agriculture and Natural Resources (CSANR). "When you remove them, the water has to go somewhere. Flooding is common after a wildfire, as is elevated stream flow in subsequent summers. But seeing that the effect lasts for up to 40 years is a little surprising and certainly a new finding."

Niemeyer wrote the paper with Kevin Bladon at Oregon State University and Richard Woodsmith of Woodsmith Watershed Consulting.

Natural fire starts a long-term experiment

Their research looked at the U.S. Forest Service's Entiat Experimental Forest in north-central Washington, which burned in 1970. The fire likely started from a lightning strike, Niemeyer said.

Three distinct areas of the forest were observed, with two of them having salvage logging done to remove what remained of the burned trees. Those areas were also fertilized and native seeds were dropped on the area. The third area was left untouched.

The fire interrupted a planned logging experiment in the forest, so researchers at the time switched to monitoring the effects of wildfire, said Niemeyer, who grew up hunting and fishing in the Entiat watershed.

The original studies in the early '70s showed that water levels in the watershed increased significantly after the fire. But the measurement equipment was removed after a few years, said the native Washingtonian.

Past decisions impact today

Fast forward to 2004, when a new grant allowed for stream flow monitoring equipment to be re-installed to measure the long-term impact the fire had on water levels. The measurement period was from 2004-11, after which Niemeyer, a hydrologist who is also a post-doctoral researcher at UC-Santa Barbara, and his colleagues spent five years analyzing the data.

After roughly 40 years, only one of the three areas still had water levels above the pre-fire baseline: the section that was left alone to recover.

"If you visit today, you can easily see that area has less mature vegetation compared to the re-seeded sections," Niemeyer said. "The trees in the re-seeded sections are much bigger, and water levels are back to normal."

Increased water levels can be positive and negative, he said. If you want more water coming down a stream for increased access to water for irrigation, for example, then you wouldn't want to salvage any of the logs or re-seed the area.

But that extra water can have other impacts on the land, he said. Trees help hold soil in place when it rains, so erosion is higher in areas that aren't re-seeded. That increases sediment going into the watershed, which can impact fish and other wildlife.

"It's really a complex set of interactions, and each wildfire situation effects water and water usage differently," Niemeyer said. "But now we know how long a fire impacts nearby water, and that those impacts can be reduced faster."

Since it's now been eight years since the sensors were removed, and 15 since they were first re-installed, the researchers are hoping to start another round of monitoring in the area. They plan to write a grant proposal to fund re-installing the sensors to see if, and when, the untouched area returns to normal water levels.

Birds are the best known class of animals, and since 1999, only five or six new species have been described each year on average. Recently, a joint research team from the National University of Singapore (NUS) and the Indonesian Institute of Sciences (LIPI) made a quantum leap in the discovery of cryptic avian diversity by uncovering five bird species and five subspecies new to science.

The team, led by Associate Professor Frank Rheindt from the Department of Biological Sciences at NUS Faculty of Science, found the birds in three small island groups off Sulawesi, Indonesia. The islands are situated in Indonesia's Wallacea region, an archipelago at the interface between the Oriental and Australian biogeographical realms, named after Sir Alfred Wallace, who was the most famous historical collector exploring the area.

The results of the study, which were published in the journal Science on 10 January 2020, provide evidence that our understanding of species diversity of complex areas such as Wallacea remains incomplete even for relatively well-known groups such as birds. The findings also suggest that modern exploration to find undescribed species diversity can be targeted to areas of high promise.

Insights from paleo-climatology and history guided discovery of new taxa

Sea depth is an important and long-neglected factor in determining the distinctness of an island's terrestrial communities. The Earth undergoes periods of glacial-interglacial cycles, leading to the formation of land bridges between shallow islands during ice ages, allowing fauna of the different islands to interbreed. Deep sea islands, which have always been isolated, and high elevation islands are more likely to harbour endemism due to absence of land connections even during glacial cycles.

Guided by this knowledge, Assoc Prof Rheindt and his team concentrated their research efforts on the islands of Taliabu and Peleng, which are located off the north-eastern coast of Sulawesi, as bathymetric data indicate the presence of deep sea between these islands and Sulawesi.

The research team also examined the accounts of historic collectors such as Sir Alfred Wallace, and sought to focus on parts of Wallacea that had received the least coverage by historic collectors, as these areas would hold the highest promise of harbouring undescribed avian diversity.

The islands that the team targeted were characterised by such incomplete historic coverage: Taliabu and its neighbours, together forming the Sula group, were only briefly visited by eight historic collecting expeditions, all of which remained in coastal areas and failed to penetrate the highlands of the interior because of poor accessibility; and Peleng and the remaining islands of the Banggai group were visited along their coastline by only three historic collectors who never ventured far uphill into the interior.

New taxa found

Assoc Prof Rheindt and his team undertook extensive fieldwork in the three remote islands for six weeks, from November 2013 to January 2014, and collected 10 new, long-overlooked avian forms.

By integrating genomic and phenotypic research methodologies, the team successfully described five new songbird species and five new subspecies:

On Taliabu, they found three new species: the Taliabu Grasshopper-Warbler, the Taliabu Myzomela and the Taliabu Leaf-Warbler; as well as three subspecies: the Taliabu Snowy-browed Flycatcher, Taliabu Island Thrush and Sula Mountain Leaftoiler.

On Peleng, two new species - the Peleng Fantail and the Peleng Leaf-Warbler - and a new subspecies - the Banggai Mountain Leaftoiler - were discovered.

On Togian, a new subspecies - the Togian Jungle-Flycatcher - was found.

"Studying the routes and operations of historic collecting expeditions and identifying gaps has been a fruitful approach to pinpoint focal areas in our case. The description of this many bird species from such a geographically limited area is a rarity," shared Assoc Prof Rheindt.

He added, "Going forward, the use of earth-history and bathymetric information could also be applied to other terrestrial organisms and regions beyond the Indonesian Archipelago to identify promising islands that potentially harbour new taxa to be uncovered."

Implications for conservation

During the expedition, the research team found that both Taliabu and Peleng have suffered from rampant forest destruction. There is virtually no primary lowland forest on both islands, and most highland forests have been impacted by some form of logging or forest fires.

"While most of the avifauna we described seems to tolerate some form of habitat degradation and is readily detected in secondary forest and edge, some species or subspecies are doubtless threatened by the immense levels of habitat loss on these islands. As such, urgent, long-lasting conservation action is needed for some of the new forms to survive longer than a couple of decades beyond their date of description," said Assoc Prof Rheindt.

In November of last year, the wildfire that started in California, U.S.A burned areas that amount about the size of Seoul and destructed over 500 buildings for two weeks. In 2018, six fires started simultaneously in southern California and spread out to the neighboring areas, burning total of 405 km2 with 86 fatalities and 200,000 victims for three days. Also, large-scale wildfires often occur in the northern inland of Russia. The forest fire occurred in July 2018 burned the total area of 3,211 km2 which is 5.3 times bigger than the city of Seoul and, the wildfire, in May 2019, started to spread out and burned down even greater land. So far, extensive wildfires such as the mentioned events are believed to be mostly caused by dry wind, however, the recent study explains that global warming is the kindling that starts such fires.

Jong-Seong Kug, a professor of Division of Environmental Engineering at POSTECH and Jin-Soo Kim, a postdoctoral researcher of University of Edinburgh jointly collaborated with Su-Jong Jeong of Seoul National University, Hotaek Park of Japan Agency for Marine-Earth Science and Technology, and Gabriela Schaepman-Strub of University of Zurich and, they identified a cause of wildfires in the permafrost region of southeastern Siberia which is related to the Artic Oscillation. Their research is published on the international journal, Science Advances on the 8th of January.

Permafrost area, where ground remains frozen for two years straight, spans widely in Siberia, Alaska, and North Europe and it takes about 24% of Northern Hemisphere. It is predicted that permafrost was formed in the end of Ice Age, 11 thousand years ago and believed to have bones of ancient animals, plant roots and five hundred billion tons of carbons buried in it. For this reason, carbon release in this region is as important as the carbon release from human's use of fossil fuels when predicting climate change.

The research team analyzed the relationship between the changes in weather conditions and forest fires occurred in the permafrost region of southeastern Siberia. In result, they discovered a fact that the atmospheric ring-like structure at the Arctic pole is disrupted and high pressure in this region abnormally increases temperature in winter which brings snowmelt earlier and dried surface, resulting in fire spreading.

Also, they analyzed large-scale atmospheric conditions of southeastern Siberia where most frequent forest fires occur in the Arctic regions. As a result, they found that the amount of burned area is larger one to two months before the Arctic Oscillation than the peak fire activity season in spring (April to May).

Even bigger problem exists when wildfire occurs in the permafrost area. It releases even more amount of carbon than fires in other regions and this increases the amount of carbon in atmosphere which accelerates Arctic warming. This will raise temperature in the Arctic, causing dried surface which then brings fire spreading and the vicious cycle of wildfire begins again.

In addition, one of the critical emissions of Siberian fire is aerosol such as fine dust. When large-scale wildfire occurs in this region, rapidly increased aerosol transports by westerlies and it impacts on air quality in Canada.

There had been reports describing a correlation between the Arctic Oscillation and the Siberian fire activity, however, there was no research that explained precise principle and mechanism before their research. Furthermore, their study can predict spring fire activities by measuring the Arctic Oscillation index in winter which then can help prevent wildfires.

Professor Jong-Seong Kug emphasized the importance of this study, "Permafrost region in Siberia is very important climatologically. Wildfire in this region is not ignited by anthropogenic activities but rather controlled by climate conditions. Looking at these factors, we can then predict fire activities. Recently, Arctic warming in southeastern Siberia has caused fast snowmelts which then can cause extensive amount of carbon release and acceleration of global warming. Therefore, it is critical to develop fire management policy accordingly."

Ever since antiretroviral treatments against HIV infection were introduced in 1996, scientists have eagerly been hunting for a cure for the disease.

Although drugs can allow people infected with HIV to live normal, healthy lives, people infected by HIV have to take antiretroviral treatments for as long as they live. Little bits of virus can lie dormant in immune cells for years, so that if patients stop taking the drugs, the dormant virus can come out of hiding and re-infect the patient.

And now, as the first people to start taking this treatment are entering middle or old age, doctors are seeing side effects from inflammation that are caused by having even tiny amounts of HIV in your blood. That's yet another reason for developing a cure for the disease.

Now, researchers from the Norwegian University of Science and Technology's (NTNU) Centre of Molecular Inflammation Research (CEMIR) have uncovered a previously unknown way in which the body's immune system can detect and respond to HIV infection -- which could help improve the chances of developing a cure.

Their results have been published in Nature Communications.

To understand exactly what the researchers did requires a refresher course in how HIV actually works inside the body and how the body responds.

When the virus gets into the body, it infects the very cells that the body would use to combat it -- these are called CD4 T helper cells, or CD4 T cells.

Once the T cells are infected, they can't do their part in helping protect the body from other diseases or infections. That's why the illness that people get from HIV infection is called Acquired Immune Deficiency Syndrome, or AIDS.

Someone with full-blown AIDS would have almost no T cells, and they could die of any number of different infections or diseases that wouldn't normally afflict someone with a healthy immune system.

"Today we have treatments that can stop HIV from replicating itself, and the T helper cells can come back," said Hany Zakaria Meås, a postdoc at CEMIR and a co-first author of the article. "You can live a perfectly healthy life, but you have to take medicine your whole life, because the day you stop treating it, the virus will come back."

The virus comes back if antiretroviral therapy is stopped because HIV hides its genetic material inside T cells that are dormant. That means there's always the potential for more virus to appear and wreak havoc.

These reservoirs of virus have spurred a worldwide hunt for ways to shock, or kick the virus out of the cells where it lies dormant.

If the virus that lies dormant in cells could be smoked out into the open, the formally dormant virus could then be killed by the body's immune system or drugs, and that would leave the patient HIV free, and cured, Meås said.

"We need to activate the virus so it can start replicating, and that will make the cell visible to the immune system," he said. "That is the current idea for a cure. We just need to activate cells that are hiding away so we can kill them, while we give medicine that protects cells from infection, because there will be more virus produced."

One such clinical trial in the UK, called the RIVER study, tried this approach but reported last year that the trial did not succeed, he said.

HIV comes in different varieties, and not all varieties are equally able to infect all T helper cells. To infect a cell, the virus has to have to have a specific ligand, which functions like a key, that has to match up on the target cell with the right kind of receptor, or keyhole.

When a T helper cell doesn't have the receptor that matches the ligand on the HIV virus trying to infect the cell, that means the virus can't actively infect that T cell. Instead, the virus can get trapped in a vesicle in the cell called an endosome.

The CEMIR researchers decided to look at what happened with uninfected T helper cells that had trapped HIV in endosomes. The uninfected cell responds to the HIV in the endosome by destroying the contents of the endosome, Meås said.

In the past, researchers have believed that this particular pathway -- HIV being trapped in an endosome of a T helper cell, and the T helper cell destroying the contents of the endosome -- was a kind of dead end for HIV infection. After all, the T helper cell hadn't actually been infected, and the endosome destroyed the virus.

But now CEMIR researchers have found a previously undescribed immune response that results from HIV destruction in the endosome. This response may hold the key to allowing the shock-and-kill approach to work.

What the researchers found was when the endosome destroys the HIV, some of the genetic material is exposed to the T cell, which in turn activates a type of molecule called TLR8. This in turn results in the production of substances called cytokines, which cause inflammation in the body.

One reason this is surprising is that T cells are part of our immune system called the "adaptive" immune system, which responds to specific infectious substances over time.

Our immune system also has an "innate" part, which we are born with, and which provides more general immune protection by recognizing and responding to bits of viruses or bacteria that are common across many different viruses or bacteria.

TLR8 is a part of the body's innate immune system. T cells are part of the adaptive immune system. Generally, it has been thought that these two systems were separate, independent branches.

"In this study we show that a receptor associated with the innate system actually exists and functions in the adaptive immune system," Meås said.

The inflammation caused by the cytokines helps to wake up T cells that had formally been dormant and that contain HIV genetic material, said Markus Haug, a staff scientist at CEMIR and co-first author of the study.

"The T cell detects the virus and produces cytokines, and these cytokines act on cells that are properly infected with HIV and makes them produce more virus. The dormant T helper cells produce virus, and the T cells that were actively producing virus will produce more of it," Haug said.

In other words, the TLR8 signal and cytokine-induced inflammation shock the HIV out of the dormant cells -- where it can be destroyed.

The destruction of HIV by endosomes and the associated inflammation may also be one reason why patients who have been on antiretroviral treatments for decades are now beginning to develop inflammatory diseases more commonly associated with people decades older.

These include dementia, cardiovascular diseases, metabolic syndrome and cancers that aren't related to HIV.

Meås said that the mechanism where endosomes destroy HIV might release enough genetic material to trigger the T cell's innate immune receptors to cause inflammation.

Beyond that, however, the findings do offer hope, said Jan Kristian Damås, a chief attending physician at the Department of Infectious Diseases, St. Olav's Hospital, Trondheim University Hospital and an NTNU professor associated with CEMIR. Damås works with HIV patients and recruited the nine patients whose cells were used as part of the research. He is also an author on the paper.

"Today we have very efficient drugs for suppressing HIV. However, we are not able to eradicate the virus and just weeks after patients stop medication the virus will reappear from virus reservoirs. Researchers and scientists believe that we can find a cure for HIV if we are able to eradicate these reservoirs," Damås said.

"The breakthrough paper by Meås and Haug brings novel insight in mechanisms for reversal of HIV latency, and their findings of TLR8 as an important receptor for HIV in T cells, clearly represent a potential novel therapeutic target for treating HIV. Moreover, their findings may also represent major step forward in vaccine development as TLR8 ligands could be used as vaccine adjuvants that shape the type of T cell responses that is induced by the vaccine."

Vision is a crucial sense for most animals, and vertebrates have evolved a highly adaptable set of opsin genes that generate light-sensitive pigments to decode the retinal image. These opsins include a rod opsin to help see in low light, and four classes of cone opsins to see in bright light and detect colors across the visible light spectrum.

Throughout evolution, these opsins have been altered, lost or duplicated in many species to provide unique adaptations for vision on land, in air and underwater. For example, most birds have retained the full complement of one rod and four cone opsin genes present in the first jawed fishes, and are therefore cone tetrachromats. By contrast, most placental land mammals have lost the SWS2 blue- and RH2 green-sensitive cone opsins, and retained (in addition to the RH1 rod opsin) only the SWS1 violet- and LWS red-sensitive cone opsins, making them cone dichromats. Some primates subsequently duplicated the LWS cone opsin to produce a third cone pigment and develop the trichromacy familiar to humans.

Previous studies have shown that in their transition to the sea, most marine mammals have also lost the SWS1 opsin gene class, to become cone monochromats with their vision mediated by the LWS opsin. The result is nonexistent (or minimal) color vision in seals, dolphins and whales. And deep-diving whales have been found to have subsequently lost all cone classes and retain just the rod pigment, with a potentially dramatic impact on their range of visual sensitivity.

Until now, little has been known about the evolution of vision in cartilaginous fishes, particularly sharks and their genetic cousins, the rays.

"We have characterized the molecular identity of the retinal visual pigments expressed in five species of shark and four species of ray, focusing on shallow-dwelling species known or likely to possess cone photoreceptors, and those filling particular phylogenetic gaps," said corresponding author Nathan Hart.

In his team's new study, they have shown that all cartilaginous fishes, similar to the marine mammals, have lost the SWS1 and SWS2 opsin genes. Sharks and rays do contain both rod and cone photoreceptors; however rays possess two cone opsin genes whereas sharks have only one cone. Sharks therefore were found to have lost the ability to see colors.

"Furthermore, we provided measurements of the spectral characteristics of the visual pigments expressed in nine species of ray and two species of shark," said Hart. "We can now confirm that all the shark species studied to date appear to be cone monochromats but report that in different species the single cone opsin may be of either the LWS or the RH2 class of opsins."

"Broadly speaking, color discrimination may be useful for behaviors such as prey detection, predator avoidance, and mate choice. Given that many ray species spend considerable periods of time resting on or partially buried in the substrate, color vision may instead aid in the detection of approaching overhead predators through either enhancement of visual contrast or elimination of achromatic flicker."

Hart reasons that the ocean environments, and range of light conditions during hunting may have cause many of the unique opsin adaptations for sharks.

"Due to absorption, reflection, and scattering by the water itself and any dissolved or suspended substances, most aquatic habitats are characterized by low visual contrast. Moreover, many sharks are active both night and day and must therefore operate under a wide range of light intensities. It is likely therefore that sharks are often operating close to the threshold of their visual capabilities where the disadvantages of color vision circuitry might be detrimental to survival."

The study has provided the most detailed picture yet of the diversity of opsins expressed in the retinas of elasmobranchs, which includes rays and sharks.

"Our findings are also relevant for understanding the evolution of cone-based chromatic vision across vertebrates. In general, this reversion to cone monochromacy independently in several primarily and secondarily aquatic taxa suggests that color vision is of little value to many large marine predators."

Hart's team also traced an evolutionary time divergence for the opsin genes in the sharks and rays and placed these timelines within the larger context of vertebrate vision evolution.

The five major classes of visual opsin genes present in vertebrates (SWS1, SWS2, RH1, RH2, and LWS) evolved prior to the divergence of the agnathan lampreys from the gnathostomes over 540 Ma.

"It would appear that the SWS1 and SWS2 opsin genes were lost from this lineage following its separation from the bony fishes 460 Ma and prior to the divergence of the holocephalan (chimeras) and the elasmobranchs (sharks, skates, and rays) 420 Ma. Thus, it seems likely that only the RH1, RH2, and LWS opsin genes were retained in ancestral chondrichthyans (cartilaginous fish), with a subsequent gene duplication within the holocephalan lineage giving rise to two copies of the LWS opsin gene in the elephant shark Callorhinchus milii."

Our fat cells, technically referred to as adipocytes, play an essential role in regulating energy balance in our body. "Adipocytes are not merely an energy storage for times of deprivation, but they also release hormones into the blood, regulating our metabolism as well as feelings of hunger and satiety through the brain and other organs. Nevertheless, too much of a good thing causes harm." explained Professor Klingenspor, Chair of Molecular Nutritional Science at the TUM Else Kröner-Fresenius Center.

White, beige or brown - the color of fat cells affects our health

There are different types of fat tissue in our body, which can be categorized according to color. White fat cells are primarily responsible for energy storage. Brown and beige fat cells can convert nutritional energy into heat. This process is referred to as non-shivering thermogenesis - a principle that small mammals and human newborns use to maintain a stable body temperature.

The occurrence and activity of brown and beige fat cells vary among individuals. There is some evidence suggesting that people with a high number of thermogenic fat cells possess a lower risk to develop obesity and associated metabolic disorders. Especially the growth of beige fat cells within white fat tissue may have particular health benefits.

Browning ability of white fat is genetically determined

"We want to understand how thermogenic fat cells develop; so how beige fat cells grow inside white fat tissue," stated Klingenspor. By "browning" the white fat tissue, an energy-storing organ could be partially transformed into an energy-dissipating organ, thereby improving metabolic health.

The development of beige fat cells is controlled by a still largely unknown genetic program. Mouse strains with divergent genetic backgrounds largely differ in their ability to brown the white fat tissue. "By systematically comparing fat cells among these different strains of mice, we were able to discover which genes or regulators might explain the variation in beige cell differentiation - in other words, the growth of beige fat cells", indicated Klingenspor.

New possibilities due to transcriptomics and network analyses

By sequencing all transcripts of a cell using Next Generation Sequencing technology, all gene activities across the entire genome can be registered in a snap-shot.

For the current study, the joint TUM/EPFL team performed a comparative analysis of the transcriptomics of fat cells from genetically divergent mouse strains. The study goes beyond other work in this field in that it not only identifies important individual factors but also relates them to each other in a molecular network.

With this approach, the team could provide a systematic overview over the network of cell-intrinsic regulatory mechanisms that represent the underlying principle for the development of beige fat cells, making them the first team of scientists to achieve this.

"Now we have gathered a unique insight into the genetic architecture driving the molecular mechanisms of beige fat cell development. What we managed to confirm in a cell culture is now to be examined 'in vivo' - so inside a living organism - as our next step," said Klingenspor with respect to avenues for future research.

Cells called corneal keratocytes are innately programmed to come to the rescue if the eye is injured. This natural healing process sometimes fails, however, resulting in scarring and blindness. Scientists are still trying to understand why.

New research by University of Texas at Dallas bioengineer Dr. David Schmidtke aims to help solve that mystery. Schmidtke and his team have demonstrated a technique in the lab for fabricating tiny strands of collagen called fibrils to facilitate further research on the eye's repair process. The method was detailed in a new study published in the December issue of the journal Biomedical Microdevices.

The study was funded in part by a $1.8 million, five-year National Institutes of Health grant that Schmidtke received last summer to develop new ways to study the eye's healing mechanisms -- knowledge that may lead to new therapies and treatments.

"How keratocytes repair tissue and why, in some cases, they leave scar tissue, is not well understood," said Schmidtke, professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science. "We came up with a way to mimic an injury model, so we can look at how the cells respond when there is a wound."

Dr. Matthew Petroll, professor of ophthalmology and chair of the biomedical engineering graduate program at UT Southwestern Medical Center, initially approached Schmidtke for help in finding a new way to study how the patterning and topography of fibrils can influence corneal cell behavior. These threadlike structures are arranged in a crisscross pattern in the eye and serve as a path to guide keratocytes to an injury.

The UT Dallas research draws on Schmidtke's expertise in microfluidic devices, which are palm-sized pieces of transparent plastic that contain small channels about the size of a strand of human hair. He is using these devices to fabricate the fibrils. Schmidtke's research team, which includes undergraduate and graduate students, injects collagen into the channels. The collagen polymerizes as it flows through the channels, resulting in aligned fibrils that are similar in structure to the collagen fibrils that are present in corneal tissue.

Schmidtke is working with Dr. Victor Varner, assistant professor of bioengineering at UT Dallas, who is focusing on how keratocytes sense the level of stiffness or softness in the fibrils with which they interact. The researchers plan to study how fibrils' density, elasticity and dimensionality affect keratocytes. For example, keratocytes behave differently on aligned collagen fibrils compared to randomly oriented collagen fibrils, Schmidtke said.

The research could help develop therapies to reduce corneal scarring and guide efforts to engineer tissue replacements. The models also could be used in other fields where researchers need to study cell patterning and behavior. Schmidtke conducts his research at UT Dallas and in lab space at UT Southwestern.

"The collaboration with UT Southwestern, and having research lab space there, has been a big benefit to applying engineering tools to biomedical questions," he said.

For adult patients with brainstem high-grade gliomas -- one of the rarest and deadliest forms of brain cancer -- surgically removing the entire tumor may add many months or potentially years of survival beyond that offered by radiation and chemotherapy, according to results of a medical records study led by researchers at the Johns Hopkins Kimmel Cancer Center.

The investigators point out that survival for these tumors has remained poor, with a median survival length of eight months after diagnosis in people who only receive a biopsy. However, if total surgical removal is an option for patients, the data in the records studied suggest it could boost this number to a median of 16 months or more.

"Knowing what these surgeries can do could help neurosurgeons, neuro-oncologists and patients have a better sense of what to expect so we can move forward toward better standardized care for these rare and critical tumors," says study leader Debraj Mukherjee, M.D., M.P.H., assistant professor of neurosurgery at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center.

The findings were reported online Oct. 16 in the Journal of Neuro-Oncology.

Every year, about 10,000 patients in the U.S. are diagnosed with high-grade gliomas, aggressive cancers that arise from a brain cell type called glia, which form the "scaffolding" of the organ. Only a small fraction of these cancers form in the brainstem, a core structure critical for nearly all functions necessary for life, such as heart rate, breathing and consciousness.

Because of the vital nature of this region, brainstem high-grade gliomas have traditionally been treated only by chemotherapy and radiation. However, in recent years, Johns Hopkins and several other academic medical centers around the world have been able to safely access tumors through so-called "brainstem safe entry zones," making surgery possible for previously inoperable tumors.

Consequently, a growing number of patients have opted for partial or total removal of their tumors, according to the researchers. But because gliomas are rare, and the availability of surgical treatment relatively recent, it has been difficult to compare treatments, and unclear what kind of survival benefit surgery confers.

To find out, Mukherjee, along with Johns Hopkins Kimmel Cancer Center postdoctoral fellow Adham M. Khalafallah, M.D., M.B.B.Ch., and their colleagues used data from the National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER) database, an extensive collection of information on cancer patients gleaned from registries in 19 geographic regions that cover about 35% of the U.S. population. A search of this database, covering a time span from 1973 to 2015, turned up 103 patients with brainstem high-grade gliomas who underwent either a biopsy (15%) or some surgical intervention (85%) for their tumors. Of those who had surgery, about 19% underwent total surgical removal.

Beyond information on interventions, SEER records included a wealth of other data on these patients, including age, race, marital status, size of their tumor, how far it had spread, if postoperative radiation treatment was done and length of survival after diagnosis.

When the researchers analyzed this information, they found significantly longer survival in patients who had surgery. Compared with the median survival length of eight months after diagnosis in patients who had just a biopsy, those who had a partial resection survived about 11 months, and those who had a gross total resection survived about 16 months. In a fraction of patients who had other factors associated with longer survival, such as younger age and marital status, median survival with a total resection was up to four times higher than patients who only had biopsies.

In the future, Mukherjee adds, it might be possible to boost survival even further by identifying biomarkers that could help personalize which treatments might benefit patients most.

Metals (iron, zinc, nickel, cobalt, etc.) participate in numerous enzymatic reactions and are essential nutrients for bacteria. Inside our organism, these metals are scarcely available, because they are bound to proteins which preserve and transport them to the cells and tissues where they will be used.

During the infection process, bacteria compete with the organism in obtaining these metals. The response to metal starvation is often very virulent, bringing on strategies aimed to increase the supply of these elements. Metal acquisition is often achieved by releasing toxins, proteins that bind metals with high affinity and transporters that introduce these metals into the bacteria. In essence, these are highly sophisticated virulence mechanisms aimed at guaranteeing the support of essential nutrients needed for the bacteria's survival.

A research team led by the Institute of Biotechnology and Biomedicine of the Universitat Autònoma de Barcelona (IBB-UAB) has discovered the regulation and metal uptake systems of Mycoplasma genitalium (Mge). This emerging sexually transmitted pathogen is responsible for several genitourinary diseases and is becoming a superbacterium thanks to its emerging resistance to the antibiotics used against it. Researchers have managed to identify the protein that regulates metal uptake, the Ferric Uptake Regulator (Fur), as well as other proteins responsible for transporting the metals into the microorganism.

"Through transcriptomic and proteomic techniques, we were able to determine the changes in Mge's gene expression in the presence and absence of metals", states Carlos Martínez, lead author of the study. "Moreover, we were able to identify the metals that bacteria require for growth using a mass spectrometry analysis developed by the UAB Analytical Chemistry Unit", explains Sergi Torres, co-author of the study.

"The regulation and metal transport systems identified in Mge represent very attractive therapeutic targets. This study will allow us to develop strategies to block metal acquisition through inhibitors or immunotherapy", says Òscar Quijada, researcher at the IBB-UAB and coordinator of the study.

In fact, researchers have already begun working in this direction, in collaboration with the UAB Department of Biophysics and the Microbiology Units of the Parc Taulí and Vall d'Hebron hospitals.

Scientists from Trinity College Dublin have discovered both how TB puts the brakes on our immune engines and how we can kick-start those engines back into gear - providing hope that improved treatment options could soon be on the horizon.

Although ancient, TB is still the world's deadliest infectious disease. While it is rampant in Africa, the growing problem of antibiotic resistance is posing a significant threat worldwide.

Part of TB's success as a pathogen is because of its ability to infect the cells of our immune system, which are normally tasked with responding to the infection. It infects our lung macrophage cells and then manipulates them to its benefit - creating a safe home for it to hide out unperturbed, sometimes for years.

As part of an SFI-funded Starting Investigator Research Grant, Frederick Sheedy, Ussher Assistant Professor in the School of Biochemistry and Immunology at Trinity, mentored by St James' Hospital TB specialist, Professor Joseph Keane, has been examining how these lung macrophage immune cells fuel the fight against infection.

The work has been at the forefront of showing how the simple sugar glucose is used to promote the macrophages anti-bacterial activities.

In surprising results, published this week in leading international journal Cell Reports, Dr Emer Hackett (a PhD candidate in Professor Sheedy's group) found that persistent infection of these macrophages with TB puts the brakes on the glucose-fuelled engine. This essentially shuts down our natural response to infection, which allows the bacteria to hide out unperturbed.

Specifically, Dr Hackett found a small RNA molecule (which comprises tiny pieces of genetic information) which the bacteria promotes and which targets key enzymes that act as pumps in our immune engines to commit glucose to promote the anti-bacterial response.

When the bacteria promotes this small RNA molecule, which is termed microRNA-21, these enzyme pumps are removed from the engine and glucose is not used in the same way. This then allows the bacteria to escape and thrive.

Although this newly identified pathway is corrupted by the bacteria, the study also yielded some hope for the future.

Professor Sheedy explained:

"We found that when TB-infected cells are treated with a key 'Interferon gamma protein signal' which is normally produced following vaccination, they will remove this microRNA to effectively relieve the brake and restore our normal immune response."

"What is particularly promising from a societal impact perspective is that as well as increasing our knowledge of how TB corrupts our normal immune response to infection, our identification of the microRNA-21 means that scientists should be able to develop improved immunotherapies or vaccine strategies to help in the fight against TB infection."