#Stop copying protein to knock out flu virus The Influenza a virus makes a protein that helps it outwit one of the body natural defense mechanisms.
When an influenza virus infects a human cell, it uses some of the host cellular machinery to make copies of itself,
FAST-SPREADING EPIDEMICS The need for new antiviral drugs against the influenza virus is great.
Because flu vaccines are not 100 percent effective, antiviral drugs play an important role in fast-spreading epidemics.
Yet Influenza a viruses are developing resistance to antiviral drugs currently in use. Krug and his team discovered that the viral NS1 protein is associated often,
#New clues to why RSV sends babies to the hospital Researchers have pinpointed a viral protein that plays a major role in making respiratory syncytial virus (RSV) the most common cause of hospitalization in children under one
and potential treatments for an infection that strikes nearly all children before they reach the age of three
and causes severe disease in 3 percent of infected children. RSV infection leads to the hospitalization of between 75,000 and 125,000 babies under one year of age in the United states every year.
Globally RSV is the second-leading cause of infant mortality due to infectious disease behind only malaria. ee known for a long time that RSV has increased an propensity,
compared to other respiratory viruses, for causing obstruction and inflammation in the narrowest airways of the infant lung,
leading to severe bronchiolitis, says Raymond Pickles, associate professor of microbiology and immunology. ut what wee now shown is that RSV has increased an ability to cause airway obstruction because, during an RSV infection,
the virus expresses a specific RSV-encoded nonstructural protein, or NS2, in epithelial cells, causing the cells to shed from the airway lining and into the airway lumen.
and its effect on epithelial-cell shedding that makes RSV by far the most common cause of bronchiolitis in otherwise healthy young children.
and other common respiratory viruses that might account for the increased disease caused by RSV, Pickles says. e compared the ability of RSV
which compose the lining of the lung airway. ut comparing these consequences of infection did not provide hints as to why RSV and PIV3 produced such differences in disease severity.
though, that the epithelial cells infected by RSV looked very different during infection compared to those infected by PIV3.
They found that infection of the narrowest airways of the lung by PIV3 alone caused moderate levels of inflammation,
but after infection by PIV3 expressing RSV NS2, the epithelial cells lining the narrow airways were shed rapidly into the airway lumen.
what has been found in human infants who had died because of RSV infection. Pickles says convinced that the RSV NS2 gene is a major driver for the well-recognized increased ability of RSV to cause lung disease, especially in the extremely narrow small airways of human infants.
Pickles is now on the trail of a human biomarker that would tell doctors if an RSV-infected infant is at greater risk of developing severe lung disease.
A biomarker would be key in the development of a needed diagnostic tool and would aid clinical trials that aim to develop anti-RSV therapeutics.
TOO SICK TO SEND HOME? hen young children arrive at the hospital with an RSV infection,
it challenging and frustrating to guess which children you can safely send home, versus those you should admit to the hospital
because they might require supportive care in an intensive care unit, says Michelle Hernandez, a pediatric immunologist. ny information that will help us make these decisions not only helps us ensure that we provide the best care for these kids,
but also helps us use health care resources more wisely. Using animal models, Pickles has already found candidate molecular biomarkers that indicate
if the epithelial cells in the tiniest airways are expressing the RSV NS2 protein. He is now initiating studies to look for the same biomarkers in human infants infected with RSV f we can find biomarkers informing us that the most vulnerable parts of the lung have already been infected by RSV,
then it could be possible to identify much more quickly the children at more risk for developing severe lung disease
and to get those babies in a treatment protocol at an earlier time, he says.
Thwarting this shedding effect wouldn stop infection or stifle the typical symptoms of RSV infection
which are the most likely to be obstructed by cells shed during infection. This would lead to a less severe infection and fewer hospitalizations.
Suppressing the effects of the RSV NS2 protein may also allow our immune system more time to deal with the RSV infection before the small airways become clogged with cells shedding from the lining of the airway,
Pickles says. hese are questions we are aiming to answer in studies already underway
#Gastric banding treats diabetes in overweight people Gastric banding can play a vital role in the treatment of type 2 diabetes in people who are overweightot just those who are obese.
Monash University researchers found that weight loss surgery (gastric banding) for overweight people with diabetes had a profound impact on the illness. his is randomized the first controlled trial demonstrating that treatment of type 2 diabetes
in overweight people by substantial weight loss is safe and hugely beneficial, says Professor Paul Orien from Monash University Centre for Obesity Research and Education (CORE).
this study indicates a potentially attractive path for the overweight person with diabetes and for those providing the care.
The study, published in the Lancet Diabetes and Endocrinology, looked at people who suffered diabetes
The connection between excessive body weight and diabetes is well known, but while the benefits of weight loss for obese people suffering type 2 diabetes have been well document,
it has not been clear if those who were overweight would enjoy the same benefits.
The study enrolled 50 people with diabetes who were overweight but not obese, with a body mass index between 25 and 30. e provided a comprehensive program of multidisciplinary care to all of the participants,
Orien explains. he surgery was conducted as an outpatient procedure with no significant adverse effects. We were pleased to see was that after two years into the trial,
more than half of the banded group were in remission of their diabetes while only eight percent of the non banded group were in remission.
The results showed a strong relationship between the amount of weight loss and remission of diabetes
clearly showing that successful ways of reducing weight such as gastric banding should have a high priority in the treatment of diabetes e
Although cleft palate is one of the most common birth defects in children, affecting approximately one in 1, 500 live human births in the United states,
Bannasch explains that common breeding practices have made the dog a unique animal model to help understand the genetic basis of naturally occurring birth defects.
Children born with cleft palate may develop hearing loss and difficulties with speech and eating. They also may be increased at risk for neurological deficits.
The Center for Companion Animal health at the School of veterinary medicine and the National institutes of health supported the research
#Scientists find off switch for scleroderma Researchers have identified a signaling pathway that switches on scleroderma,
a rare and sometimes fatal disease that causes skin and other tissue to thicken. There is currently no cure for the condition.
The team also says they have found the chemical compounds that can turn the switch off. ur findings provide a new approach to developing better treatment options where few have existed,
says Richard Neubig, chairperson of the department of pharmacology and toxicology in the College of Osteopathic Medicine at Michigan State. here are two kinds of scleroderma, localized and systemic,
with the latter often proving to be life threatening, Neubig says. his research shows that by inhibiting this main signaling pathway,
we can block fibrosishe thickening of tissue that occurs with the disease. Localized scleroderma affects the skin and causes a loss of flexibility.
Systemic sclerosis can spread throughout the body, hardening organs such as the lungs, heart, gut, and kidneys.
Scleroderma is an autoimmune disorder. It estimated 300,000 Americans suffer from the disease with about one-third of those having the systemic form.
Localized scleroderma patients usually live normal lifespans. Yet about half of systemic patients especially with widespread skin involvement and internal organ fibrosis, will see their lives cut short.
Scleroderma many pathways he majority of drug treatments that exist today for fibrosis basically look at reducing just the inflammation,
says Dinesh Khanna, associate professor of internal medicine at the University of Michigan. here are other drugs that block one or two of the signaling pathways that cause the disease,
but scleroderma has many of these pathways. Published in the Journal of Pharmacology and Experimental Therapeutics, the new research could significantly change the quality of life for scleroderma patients
and greatly increase the lifespan of systemic patients, Neubig says. ur research shows promise for the development of a new drug that can reverse the fibrosis process by flipping the main switch on all of the signaling pathways.
By validating this core switch as a viable drug target, we can now continue our work to improve the chemical compounds
so they will work with doses that are appropriate for people. It definitely promising. A donation from Jon and Lisa Rye, a Michigan family who has experienced the effects of scleroderma,
and the family crowdfunding site, the Scleroderma Cure Fund, helped support the research h
#Anticancer drug reverses schizophrenia symptoms in teen mice An experimental anticancer drug appears to reverse schizophrenia-related behavior
and restore some lost brain cell function in young mice with a rodent version of the illness,
researchers say. The compound, called FRAX486, appears to halt an out-of-control biological runingprocess in the schizophrenic brain that unnecessarily destroys important connections among brain cells,
according to a new study published online in the Proceedings of the National Academy of Sciences. y using this compound to block excess pruning in adolescent mice,
we also normalized the behavior deficit, says study leader Akira Sawa, professor of psychiatry and behavioral sciences at Johns hopkins university School of medicine. hat we could intervene in adolescence
and still make a difference in restoring brain function in these mice is intriguing. FRAX486 is a PAK inhibitor,
one of a class of drugs shown in animal experiments to confer some protection from brain damage due to Fragile X syndrome,
an inherited disease in humans marked by mental retardation. There also is some evidence, experts say, that PAK inhibitors can be used to treat Alzheimer disease.
And because the PAK protein itself can initiate cancer and cell growth PAK inhibitors have also been tested for cancer.
Working with mice that mimic schizophrenia and related disorders, the researchers were able to partially restore disabled neurons
so they could connect to other nerve cells. The findings in adolescent mice are an especially promising step in efforts to develop better therapies for schizophrenia in humans,
researchers say, because schizophrenia symptoms typically appear in late adolescence and early adulthood. Schizophrenia is a chronic,
severe mental disorder that affects about one in 100 people, the National institute of mental health says. Patients may experience hallucinationsften hearing nonexistent voicesnd delusions
and they may not make sense when they speak. Among other problems, they may also appear agitated
or have cognitive problems such as difficulty focusing or issues with working memory. MISSING SPINES The researchers began their study by chemically turning down expression in their mice of a gene known as Disrupted-in-Schizophrenia 1. DISC1,
as it is called, makes a protein that appears to regulate neurons in the cerebral cortex responsible for igher-orderfunctions, like information processing.
In studies of rodent brain cells, the researchers found that a DISC1 deficit caused deterioration of vital parts of the neuron called spines
which help neurons communicate with one another. Reduced amounts of DISC1 protein also impact the development of a protein called Kalirin-7 (KAL7),
which is needed to regulate another protein called Rac1. Without enough DISC1, KAL7 can adequately control Rac1 production and the development of neuronal spines.
Sawa cautions that it has not yet been shown that PAK is elevated in the brains of people with schizophrenia.
There is a neuropsychiatric phenomenon in which any organism will react less to a strong, startling sound when they have first been primed by hearing a weaker one.
In schizophrenia the first noise makes no impact on the reaction to the second one.
and appeared to be safe for the animals. rugs aimed at treating a disease should be able to reverse an already existing defect as well as block future damage,
Grants from the National institutes of health, the Stanley Foundation, the RUSK Foundation, the S-R Foundation, the National Alliance for Research on Schizophrenia and Depression, Johns Hopkins Medicine Brain science Institute, the Maryland
#DNA sequencing reveals six new forms of blindness Scientists have discovered six new forms of inherited blindness,
which multiple members were blind from birth due to conditions such as Leber congenital amaurosis, cone-rod dystrophy,
is driving a diagnostic revolution in inherited eye diseases. s the cost of sequencing comes down,
the greater understanding of the biology of vision gained from such studies also informs the search for new forms of therapy,
Inglehearn says. ince new therapies are often specific to particular forms of inherited blindness, it is essential for each patient to know which condition they have,
helping to test the new therapies and potentially benefiting from them themselves. A grant from the National Eye Research Centre, together with funding from other sources, supported the research s
#Melanoma in families linked to mutations in one gene The discovery that mutations in a specific gene are responsible for a hereditary form of melanoma could make it easier to detect and treat,
are extremely likely to develop melanoma, new research shows. These mutations deactivate the POT1 gene. his finding significantly increases our understanding of why some families have a high incidence of melanoma,
says Tim Bishop of the School of medicine at the University of Leeds and a senior co-author of the study published in Nature Genetics. ince this gene has previously been identified as a target for the development of new drugs, in the future,
it may be possible that early detection will facilitate better management of this disease. ith this discovery we should be able to determine who in a family is at risk,
Known genetic mutations account for approximately 40 percent of all occurrences of inherited forms of melanoma. The team set out to identify the hereditary mutations that account for the other 60 percent by sequencing part of the genome of 184 patients with hereditary melanoma caused by unknown mutations.
They found that the inactivation of POT1 caused by these mutations leads to longer and potentially unprotected telomeres
The team found that there were also cases of other cancer types in families with these hereditary mutations such as leukemia
and brain tumors. ur research is making a real difference to understanding what causes melanoma and ultimately therefore how to prevent
and treat melanoma and is a prime example of how genomics can transform public health, says Julia Newton Bishop,
co-senior author from the University of Leeds. his study would not have been possible without the help
and patience from the families that suffer from these devastating, inherited forms of melanoma. Cancer Research UK and the Wellcome Trust Sanger Institute funded the work.
Source: University of Leed e
#To study bipolar disorder, start with skin Scientists investigating what makes a person vulnerable to bipolar disorder took skin cells from people with the condition
and ultimately turned them into neurons. The team then compared those neurons to cells taken from people without bipolar.
The comparison revealed very specific differences in how these neurons behave and communicate with each other,
and identified striking differences in how the neurons respond to lithium, the most common treatment for bipolar disorder.
Already, we see that cells from people with bipolar disorder are different in how often they express certain genes,
But wee only just beginning to understand what we can do with these cells to help answer the many unanswered questions in bipolar disorder origins
and Mcinnis, a professor in the department of psychiatry, are co-senior authors of the new paper published in the journaltranslational Psychiatry.
Mcinnis, who sees firsthand the impact that bipolar disorder has on patients and the frustration they and their families feel about the lack of treatment options,
says the new research could take treatment of bipolar disorder into the era of personalized medicine. Not only could stem cell research help find new treatments,
very specific differences emerged between the cells derived from bipolar disorder patients and those without the condition.
the new findings support the idea that genetic differences expressed early during brain development may have a lot to do with the development of bipolar disorder symptomsnd other mental health conditions that arise later in life, especially in the teen and young adult years.
and receivednd the new cell lines will make it possible to study this effect specifically in bipolar disorder-specific cells.
the neurons made from bipolar disorder patients also differed in how they were ddressedduring development for delivery to certain areas of the brain.
This supports the emerging concept that bipolar disorder arises from a combination of genetic vulnerabilities. The researchers are already developing stem cell lines from other trial participants with bipolar disorder,
though it takes months to derive each line and obtain mature neurons that can be studied.
Researchers were interested in using mice without the FAT10 gene to study its role in sepsis
a devastating and sometimes fatal inflammatory response to infection. FAT10 belongs to a family of genes that act as recyclers of cellular proteins
Since older mice and humans are more susceptible to sepsis, some mice were left to age.
then this could be a potential target for new therapies, Canaan says. The immune system response that produces inflammation is crucial in warding off infections. hus it has short-term beneficial effects on survival
but for the long term we may pay a price in a sort of evolutionary tradeoff. Researchers from Stanford, Tufts University,
#Math that predicts glucose paves way for artificial pancreas A mathematical model can predict with more than 90 percent accuracy the blood glucose levels of individuals with type 1 diabetes up to 30 minutes before a change
in levels. any people with type 1 diabetes use continuous glucose monitors, which examine the fluid underneath the skin,
The team tested the accuracy of its model using an FDA-approved UVA/Padova simulator with 30 virtual patients and five living patients with type 1 diabetes.
The results appeared online in the Journal of Diabetes Science and Technology. DYNAMIC DEPENDENCIES e learned that the dynamic dependencies of blood glucose on insulin dose
if chemo kills liver cancer New 3d scans of liver cancer quickly show if chemotherapy is working,
precisely measuring living and dying tumor tissue, researchers report. The findings are the first roof of principlethat 3d MRI technology accurately measures tumor viability and death.
Researchers hope to prove that the technology, when used before and after chemotherapy, is faster and better than current tools for predicting patient survival.
Liver cancer kills nearly 20,000 Americans each year, and is much more prevalent outside the United states,
where it is among the top-three causes of cancer death in the world. ur high-precision 3d images of tumors provide better information to patients about
whether chemoembolization has started to kill their tumors so that physicians can make more well-informed treatment recommendations,
says Jean-Francois Geschwind, interventional radiologist at Johns hopkins university and the project senior scientist. A series of studies involved 140 patients with either primary liver cancers or metastatic tumors that were caused by cancers spreading from elsewhere in the body.
The patients underwent chemoembolization, chemotherapy aimed directly at a tumor. Dead and live tissue Unlike standard methods to assess tumor response, based on two-dimensional images and tumor size,
the 3d technology distinguishes between dead and live tissue, giving an accurate assessment of tumor cell death.
The new technology builds on standard two-dimensional imaging and uses computer analytics to evaluate the amount of so-called contrast dye absorbed by tumor tissue.
The dye is injected into patients before their MRI scan to enhance image production. Researchers say live tissue will absorb more dye than dead tissue, affecting image brightness,
which can also be measured for size and intensity. Geschwind, a professor of radiology, says that knowing the true extent of tumor response to chemoembolization is particularly important for patients with moderate to advanced disease,
whose liver tumors might initially be too large or too numerous to surgically remove. In the first study, researchers compared the standard imaging method and the newly developed technology in 17 Baltimore men and women with advanced liver cancer.
All were treated with surgery or liver transplantation after chemoembolization. Low error margin The research team used existing MR analysis techniques
as well as the new 3d method, to compare the radiologistsanalyses with pathologic review of tumor samples after therapy and surgical removal.
The error margin of the new 3d image analysis, they say, was low (at up to 10 percent)
when predicting the amount of dead tumor tissue found by pathologists. The standard 2d method deviated by as much as 40 percent from actual values.
In a series of additional studies, researchers used the standard and new imaging techniques to analyze the MRI scans of more than 300 liver tumors in some 123 other men and women
also from the Baltimore region. All patients were treated at Johns Hopkins Hospital between 2003 and 2012,
and each received pre-and post-chemoembolization MRI scans to assess the effects of therapy on the tumors.
The 3d technology improved accuracy removes a lot of the guesswork that now goes into evaluating treatment outcomes,
so radiologists can provide almost instantaneous treatment advice. Geschwind and colleagues plan further software refinements to the new approach before training more physicians to use it.
and whether these therapy choices help people live longer. The software used in the MRI scans was developed at Johns Hopkins and at Philips Research North america.
The findings were presented at a recent San diego meeting of the Society of Interventional Radiology. The french Society of Radiology, Philips Research North america, the National institutes of health,
and the Rolf W. Günther Foundation for Radiology and Radiological Sciences helped support the study.
Source: Johns Hopkin J
#Microbes could expand how doctors use ultrasound The addition of nanoscale organisms could potentially expand the range of medical conditions diagnosed with noninvasive ultrasound.
The technology opens the door to a variety of potential imaging applications where the nanometer size is advantageous,
such as labeling targets outside the bloodstream, detecting tumors, and monitoring the gastrointestinal system. To create the nanoscale organisms,
with several unique properties making them especially useful in biomedical applications. BETTER THAN MICROBUBBLES Previously, most ultrasound imaging agents were based on small gas bubbles,
and scientific research were included in the study such as agricultural pests vectors of disease and pollinators. This study provides a foundation for future study of insects.
They are of immense ecological economic and medical importance and affect our daily lives from pollinating our crops to vectoring diseasessays lead author Bernhard Misof with the Zoological Research Museum Alexander Koenig in Bonn Germany. e can only start to understand the enormous species richness
Copsin belongs to the group of defensins a class of small proteins produced by many organisms to combat microorganisms that cause disease.
The human body also produces defensins to protect itself against infections. They have been found for example on the skin and in the mucous membranes.
For Aebi the main focus of this research project was not primarily on applications for the new substance. hether copsin will one day be used as an antibiotic in medicine remains to be seen.
while humans have been using antibiotics in medicine for just 70 years with many of them already becoming useless due to resistance?
In addition to being used as an antibiotic in medicine it may also be possible to use copsin in the food industry as well.
This is because copsin kills many pathogens including Listeria a type of bacteria that can cause severe food poisoning
and other medical professionals measure and improve the diets of children and adults alike. here is great interest in the development of objective biomarkers of dietary intake especially biomarkers that can be measured noninvasivelysays coauthor Susan T. Mayne professor of epidemiology at Yale university
and a developer of the device. ur earlier studies demonstrated a correlation between skin carotenoids
Diets rich in fruit and vegetables have been linked to important health outcomes including reductions in cardiovascular disease type 2 diabetes and some forms of cancer.
Brenda Cartmel a senior research scientist and lecturer at the Yale School of Public health is a co-author of the paper along with researchers from the USDA/Agricultural research service Grand Forks Human nutrition Research center and the University of Utah.
and has been shown to cause cancer. ecause biochar can be produced from various waste biomass including agricultural residues this new technology provides an alternative and cost-effective way for arsenic removalsays Bin Gao associate professor of agricultural
Discovering its secrets may lead to better synthetic collagen for tissue engineering and cosmetic and reconstructive medicine.
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