Knowledge Update

New York, Sep 18 (IANS) Pathogens in the intestinal tract can manipulate mammalian cells to get the oxygen they need and thereby cause harm to the intestinal lining, a study has found.

The study also offers a new insight into developing strategies targeting the metabolism of the intestinal lining to prevent the expansion of harmful bacteria in the gut, a situation that is exacerbated by the overuse of antibiotics.

"The finding is important because it explains how some enteric pathogens can manipulate mammalian cells to get the oxygen they need to breathe," said Andreas Baumler, Professor at the University of California Davis School of Medicine in the study published in the journal Science.

A healthy large intestine is mostly free of oxygen and the beneficial microbes residing there thrive in this anaerobic environment. In contrast, enteric pathogens, such as Escherichia coli, in humans need oxygen to survive.

Baumler's team discovered how these pathogens change the gut environment to favour their own growth.

Enteric pathogens deploy virulence factors that damage the intestinal lining and cause diarrhea. To repair the damage, the body accelerates the division of epithelial cells that form the intestinal lining, which brings immature cells to the mucosal surface. 

These new cells contain more oxygen and wind up increasing oxygen levels in the large bowel, creating an environment that allows gut pathogens like E. coli to outcompete the anaerobic-loving resident microbes.

"The rise of antibiotic-resistant strains of bacteria has become a major public health threat worldwide. As more bacterial strains do not respond to the drugs designed to kill them, the advances made in treating infectious diseases over the last 50 years are in jeopardy," Baumler added.

New York, Sep 18 (IANS) A new study has found evidence that health becomes endangered when ageing cells lose control of rogue elements of DNA called transposons.

Research has shown that a low-calorie diet, a key intervention already known to increase lifespan, dramatically delays the onset of increased transposon activity.

The new study, published in the journal Proceedings of the National Academy of Sciences, strengthens the links that have led scientists to propose the "transposon theory of ageing".

"In this report, the big step forward is towards the possibility of a true causal relationship," said senior author of the study Stephen Helfand, Professor at the Brown University in Providence, at Rhode Island, in the US.

Transposons are rogue elements of DNA that break free in ageing cells and rewrite themselves elsewhere in the genome, potentially creating lifespan-shortening chaos in the genetic makeups of tissues.

As cells get older, prior studies have shown, tightly wound heterochromatin wrapping that typically imprisons transposons becomes looser, allowing them to slip out of their positions in chromosomes and move to new ones, disrupting normal cell function.

Meanwhile, scientists have shown that potentially related interventions, such as restricting calories or manipulating certain genes, can demonstrably lengthen lifespans in laboratory animals.

The new results come from several experiments that are thorough and direct in connecting the dots among weakening heterochromatin, increased transposon expression, ageing and lifespan.

In one set of experiments, the team visually caught transposable elements in the act of jumping around in fruit flies as they aged.

They showed that an anti-HIV drug called 3TC, which inhibits activation of transposons and their movement into new positions in the genome, can restore some lifespan to flies that have a mutation that disables a gene called Dicer-2 which suppresses transposons.

​New York, Sep 18 (IANS) A team of researchers has created three-dimensional lung "organoids" -- laboratory-grown lung-like tissue -- to study diseases, including idiopathic pulmonary fibrosis.

The 3D dimensional drug has been created by coating tiny gel beads with lung-derived stem cells and allowing them to self-assemble into the shape of air sacs found in human lungs.

"While we haven't built a fully functional lung, we have been able to take lung cells and place them in the correct geometrical spacing and pattern to mimic a human lung," said Brigitte Gomperts, Associate Professor, at the University of California, at Los Angeles in the US.

Idiopathic pulmonary fibrosis is a chronic lung disease characterised by scarring of the lungs. The scarring makes the lungs thick and stiff, which over time results in progressively worsening shortness of breath and lack of oxygen to the brain and vital organs. 

To study the effect of genetic mutations or drugs on lung cells, researchers have previously relied on two-dimensional cultures of the cells. But when they take cells from people with idiopathic pulmonary fibrosis and grow them on these flat cultures, the cells appear healthy.

Gomperts and her colleagues, in the study published in the journal Stem Cells Translational Medicine, started with stem cells created using cells from adult lungs. They used those cells to coat sticky hydrogel beads and then they partitioned these beads into small wells, each only seven millimetres across. 

Inside each well, the lung cells grew around the beads, which linked them and formed an evenly distributed three-dimensional pattern. To show that these tiny organoids mimicked the structure of actual lungs, the researchers compared the lab-grown tissues with real sections of human lung.

"The technique is very simple. We can make thousands of reproducible pieces of tissue that resemble lung and contain patient-specific cells," said Dan Wilkinson, researcher at the University of California, Los Angeles.

Moreover, when the researchers added certain molecular factors to the 3D cultures, the lungs developed scars similar to those seen in the lungs of people who have idiopathic pulmonary fibrosis -- something that could not be accomplished using two-dimensional cultures of these cells.

London, Sep 19 (IANS) Individuals suffering from bipolar disorder or depression treated with a hormone best known to boost performance in sportspersons may also improve their cognitive functioning, a study has found.

The hormone erythropoietin (EPO), mostly produced by the kidney, is essential for the production of red blood cells. 

EPO gives the blood a greater capacity to carry oxygen, and is thus used as a performance-enhancing drug by the sportspersons, the study said. 

The findings showed that EPO had beneficial effects on patients' verbal memory, attention span as well as planning ability. 

The EPO-treated patients showed 11 per cent improvement while placebo treated patients improved only by 2 per cent. 

"This effect of EPO on cognition was maintained six-weeks after patients had completed their treatment," said lead researcher Kamilla Miskowiak from University of Copenhagen in Denmark. 

Further, the patients who performed poorly in neuropsychological tests showed remarkably greater cognitive benefits when given EPO. 

"This means that we may be able to target patients for EPO treatment and perhaps other future cognition treatments, based on how they do on neuropsychological tests," Miskowiak added. 

EPO based drugs are safe if patients' red blood cell levels are controlled regularly. 

However, the EPO may not be beneficial for people who smoke or who previously had blood clots or the have high risk of blood clots, the researchers said. 

"EPO may not be ready to be rolled out as a treatment just yet and may not be for everyone," Miskowiak noted.

Around 350 million people suffer from depression, with a further 60 million suffering from bipolar disorder, but the drugs normally used to treat depression and bipolar disorders don't have any major effect on cognition, according to recent reports from the World Health Organisation (WHO).

Currently there is no available effective treatment to target cognitive problems in these patients, the report stated.

"The results of this study, albeit preliminary, gives hope to people suffering from mood disorders and associated neurocognitive symptoms," said Eduard Vieta, Professor at the University of Barcelona Hospital Clinic, in Spain in a comment.

For the study, the team conducted two randomised controlled trials. They assessed cognitive function in 79 patients suffering from depression or bipolar disorder.

Out of these, 40 patients were assigned on EPO for 9-weeks and the remaining 39 were given a placebo. 

They found that EPO had beneficial effects on patients' completion of a range of cognitive tests, including tests on verbal memory, attention span, and planning ability.

Tests showed that this improvement was maintained for at least 6-weeks after treatment finished (the longest follow-up time in the trials).

The results were presented at the European College of Neuropsychopharmacology (ECNP)conference in Vienna, recently.

London, Sep 19 (IANS) Have you ever wondered why we sometimes 'freeze' when we are frightened or under strong emotional stress? This may be because the response to anxiety may include not only the parts of the brain which deal with emotions, as has been long understood, but also movement control centres in the brain.

"This (study) is the first hard proof that strong emotions produce a response in brain areas concerned with movement," said lead researcher Laura Muzzarelli from Vita-Salute San Raffaele University in Milan, Italy.

The findings give us "a possible explanation for some motor inhibition associated with emotional stress", she added.

For the study, a group of Italian and Canadian researchers followed a selection of socially anxious and control group children from childhood to adolescence. 

The researchers tested 150 children who were between ages of eight to nine, for signs of social inhibition.

Some of these were shown to have early signs of social anxiety, and showed an increased tendency to withdraw from social situations. 

They also had more difficulty in recognising emotions, and particularly angry faces.

The anxious children, plus controls, were then followed into adolescence. At the ages of 14-15 they were tested again to see if signs of social anxiety had developed. 

The researchers also used functional MRI brain scans to test how the teenage brains responded to angry facial expressions.

"We found that when presented with an angry face the brain of socially anxious adolescents showed increased activity in the amygdala, which is the brain area concerned with emotions, memory and how we respond to threats," Muzzarelli said.

"Surprisingly, we also found this produced inhibition of some motor areas of the brain, the premotor cortex. This is an area which 'prepares the body for action', and for specific movements," she noted. 

The findings were presented at the ongoing European College of Neuropsychopharmacology (ECNP) conference in Vienna, Austria.

​Washington, Sep 16 (IANS) The 2016 Arctic sea ice cover tied with 2007 for the second lowest yearly minimum on record, according to a new report.

Arctic sea ice appeared to have reached its annual lowest extent on September 10, NASA and the NASA-supported National Snow and Ice Data Center (NSIDC) at the University of Colorado at Boulder reported on Thursday.

At 4.14 million square kilometres, the 2016 Arctic sea ice minimum extent is effectively tied with 2007 for the second lowest yearly minimum in the satellite record. 

"The record makes it clear that the ice is not rebounding to where it used to be, even in the midst of the winter," said Claire Parkinson, main author of the study and a senior climate scientist at NASA's Goddard Space Flight Center in Greenbelt, Maryland

The lowest sea ice extent recorded was on September 17, 2012, when it fell to just 3.39 million square kilometres, CNN reported.

The sea ice cover of the Arctic ocean and surrounding seas helps regulate the planet's temperature, influences the circulation of the atmosphere and ocean, and impacts Arctic communities and ecosystems. 

Arctic sea ice shrinks every year during the spring and summer until it reaches its minimum yearly extent. 

Sea ice regrows during the frigid fall and winter months, when the sun is below the horizon in the Arctic.

This summer, the melt of Arctic sea ice surprised scientists by changing pace several times.

The melt season began with a record low yearly maximum extent in March and a rapid ice loss through May. 

But in June and July, low atmospheric pressures and cloudy skies slowed down the melt.

Then, after two large storms went across the Arctic basin in August, sea ice melt picked up speed through early September, the report said.

"It's pretty remarkable that this year's sea ice minimum extent ended up the second lowest, after how the melt progressed in June and July," Walt Meier, a sea ice scientist with NASA's Goddard Space Flight Center said.

New York, Sep 16 (IANS) In a first study of its magnitude, researchers in the US aim to infuse an antibody into human immunodeficiency virus (HIV)-negative men and transgender individuals to determine whether it will prevent the infection from developing.

The Antibody Meditated Prevention (AMP) study -- led by an Indian-origin scientist -- aims to recruit a combined 2,700 HIV-negative men and transgender individuals whose sexual partners are men -- the highest-risk demographic for HIV infection -- to test the efficacy of antibody VRC01 in the large clinical trial. 

"It is the first study of this magnitude to see whether an antibody infusion can help prevent new HIV infections. If it proves effective, it could potentially pave a way for developing a vaccine for HIV infection," said Shobha Swaminathan, an infectious disease specialist from Rutgers University in New Jersey, US.

The VRC01 antibody was initially detected in an individual who was able to successfully control HIV infection without taking any medications for HIV.

Further, in laboratory tests, VRC01 antibody has shown to be effective against 90 per cent of HIV-1 isolates that were tested, the researchers said. 

Those enrolled will either be given intravenous infusions of VRC01 or a placebo every eight weeks for a total of 10 infusions.

Participants will be closely monitored for approximately 22 months for safety and also to determine whether they have remained HIV-negative.

HIV continues to be a major global public health issue, though the rate of infection has fallen significantly in recent years. 

In 2014, gay and bisexual men accounted for an estimated 83 per cent of all new HIV infections among men in the US, according to the Centers for Disease Control (CDC).

Though the number of new HIV diagnoses fell 19 per cent from 2005 to 2014, certain demographic groups showed increases in the infection, CDC noted. 

"According to CDC estimates, only about 25 per cent of people who are HIV-positive have it under control," says Swaminathan.

​New York, Sep 16 (IANS) Researchers at Harvard Medical School have found how certain tumours develop a taste for fat over sugar and that one way to kill them could be starving them of their life-sustaining fuel.

The findings showed how a mechanism that normally keeps fat burning in check goes awry in some cancers, revving up fat consumption and fuelling tumour growth.

"This really represents a new frontier in looking at the metabolism of cancer," said senior author of the study Marcia Haigis, Associate Professor of Cell Biology.

"Understanding the molecular handle of this pathway is the first step toward translating the basic work into therapy," Haigis said.

Specifically, the study, published in the journal Molecular Cell, found that a protein called prolyl hydroxylase 3 (PHD3) appears to be a key regulator of the delicate balance inside cells that dampens fat burning. 

That protein, the research showed, is abnormally low in certain forms of cancer - a finding that can help lay the ground for development of therapies that work by starving tumours of their fuel.

Two forms of cancer -- acute myeloid leukemia and prostate cancer -- had by far the lowest PHD3 levels, the analysis showed.

To test their hypothesis that these particular cancers needed fats to survive and that PHD3 was a key regulator in the fat-burning process fuelling tumour growth, the researchers restored to normal the levels of PHD3 in a line of cancer cells and in mice. 

The tumours not only stopped growing, they died.

"That was really exciting," Haigis said. 

"We've altered a lot of metabolic pathways in cancer, and this is one of the few pathways we've modulated where we really see the tumours die. They are so dependent on fat oxidation that they die," Haigis noted.

Before this discovery can move ahead to the clinic, she said, more basic research needs to be done, both in animal models and in cancer cells taken from patients, to understand why certain tumours depend on fat.

New York, Sep 16 (IANS) A team of researchers in the US has developed a new inverter that -- despite being smaller and lighter -- improves the fuel-efficiency and range of hybrid and electric vehicles.

Electric and hybrid vehicles rely on inverter components, which are made of the semiconductor material silicon, to ensure that enough electricity is conveyed from the battery to the motor during vehicle operation.

Now researchers at the Future Renewable Electric Energy Distribution and Management (FREEDM) Systems Centre at North Carolina State University have developed an inverter using components made of the wide-bandgap semiconductor material silicon carbide (SiC).

"Our silicon carbide prototype inverter can transfer 99 per cent of energy to the motor, which is about two per cent higher than the best silicon-based inverters under normal conditions," said Iqbal Husain, ABB Distinguished Professor of Electrical and Computer Engineering.

The new SiC-based inverter is able to convey 12.1 kilowatts of power per liter (kW/L) -- close to the US Department of Energy's goal of developing inverters that can achieve 13.4 kW/L by 2020. By way of comparison, a 2010 electric vehicle could achieve only 4.1 kW/L.

"Conventional, silicon-based inverters have likely improved since 2010 but they are still nowhere near 12.1 kW/L," Husain noted in a statement provided by the university.

According to the researchers, they can make an air-cooled inverter up to 35 kW using the new module, for use in motorcycles, hybrid vehicles and scooters.

"The silicon carbide inverters can be smaller and lighter than their silicon counterparts, further improving the range of electric vehicles. And new advances we have made in inverter components should allow us to make the inverters even smaller still," added Husain, who is also the director of the FREEDM Centre. 

The current SiC inverter prototype was designed to go up to 55 kW -- the sort of power you would see in a hybrid vehicle. 

The researchers are now in the process of scaling it up to 100 kW -- akin to what would see in a fully electric vehicle -- using off-the-shelf components, the research paper, to be presented at the IEEE Energy Conversion Congress and Exposition (ECCE), being held from September 18-22 in Milwaukee, US said.

New York, Sep 16 (IANS) It is an immediate, intrinsic response of the hepatitis A virus (HAV)-infected cell that results in liver inflammation, researchers at University of North Carolina at Chapel Hill have discovered.

HAV does not cause chronic liver disease like hepatitis B and C viruses. But in rare cases, it can cause acute liver failure, which is often fatal.

The new findings, published in the journal Science, could lead to new response to control the infection as hepatitis researchers earlier thought that immune cells sent by the body to attack virus-infected cells in the liver cause the acute liver injury.

"The virus evokes a response in the infected cell that activates a pre-programmed cell death pathway," said one of the study authors Stanley Lemon, Professor of Medicine.

"In effect, the cell commits suicide, sacrificing itself along with the virus in an effort to save the host. This results in inflammation within the liver that we recognise as hepatitis," Lemon explained.

Hepatitis A virus is a vaccine preventable form of infectious hepatitis. HAV is found worldwide and is transmitted through ingestion of food and water that is contaminated with the feces of an infected person. 

Symptoms of hepatitis A include nausea, stomach pain, fever, sore throat, headache and diarrhea. 

People infected with HAV may not experience any symptoms, but shed the virus for two to four weeks. During this period, an infected person can pass the virus to others.