Why pandemic swine flu causes more severe symptoms than seasonal flu

London, September 11 (ANI): Scientists at Imperial College London have warned that pandemic swine flu can infect cells deeper in the lungs than seasonal flu can.

They write in a research paper that this may help understand why people infected with the pandemic strain of swine-origin H1N1 influenza are more likely to suffer more severe symptoms than those infected with the seasonal strain of H1N1.

The researchers have also stressed the need for monitoring the current pandemic H1N1 influenza virus for any changes in the way it infects cells, which may make infections more serious.

Generally, influenza viruses infect cells by attaching to bead-like molecules on the outside of the cell, known as receptors. If a virus cannot find its specific receptors, it cannot get into the cell.

Seasonal influenza viruses attach to receptors found on cells in the nose, throat and upper airway, enabling them to infect a person’s respiratory tract.

In the current study, the researchers have found that pandemic H1N1 swine flu can also attach to a receptor found on cells deep inside the lungs, which can result in a more severe lung infection.

They say that the pandemic influenza virus’s ability to stick to the additional receptors may explain why the virus replicates, and spreads between cells more quickly.

“Most people infected with swine-origin flu in the current pandemic have experienced relatively mild symptoms. However, some people have had more severe lung infections, which can be worse than those caused by seasonal flu. Our new research shows how the virus does this – by attaching to receptors mostly found on cells deep in the lungs. This is something seasonal flu cannot do,” Nature Biotechnology quoted Professor Ten Feizi, from the Division of Medicine at Imperial College London, as having writte in the research paper.

The researchers found that pandemic H1N1 influenza bound more weakly to the receptors in the lungs than to those in the upper respiratory tract, which is why most people infected with the virus have experienced mild symptoms.

However, the researchers are concerned that the virus could mutate to bind more strongly to these receptors.

“If the flu virus mutates in the future, it may attach to the receptors deep inside the lungs more strongly, and this could mean that more people would experience serious symptoms. We think scientists should be on the lookout for these kinds of changes in the virus so we can try to find ways of minimising the impact of such changes,” said Prof. Feizi.

“Receptor binding determines how well a virus spreads between cells and causes an infection. Our new study adds to our understanding of how swine-origin influenza H1N1 virus is behaving in the current pandemic, and shows us changes we need to look out for,” added Prof. Feizi.

The financial assistance for the study came from the Wellcome Trust, the Medical Research Council and the Engineering and Physical Sciences Research Council. (ANI)

Ex-Mossad head says ‘Netanyahu agreed to Golan pullout’

Jerusalem, Sep.10 (ANI): Former Mossad head Danny Yatom has claimed that Prime Minister Binyamin Netanyahu agreed to withdraw Israeli troops from the entire Golan Heights during his first term in exchange for a peace deal with Syria and the normalization of ties between Jerusalem and Damascus. Yatom told Israel Radio that the proof for his claim was a document that appears in his new book, in which Ron Lauder, Netanyahu’s special envoy for talks with Syria at the time, reported the prime minister’s agreement to then-US president Bill Clinton.

The former Mossad chief said that although Netanyahu’s agreement didn’t bind him now, 11 years later, “he has to admit” that he did agree to withdraw from the territory.

Environmental Protection Minister Gilad Erdan (Likud), however, told the radio station that the prime minister had not agreed to such a pullout and had repeated it on numerous occasions.

According to the Jerusalem Post, Yatom also told Army Radio on Wednesday night that only a military strike would stop Iran from attaining nuclear arms status. (ANI)

BJP announces list for assembly by elections

New Delhi, Aug 22 (ANI): The Bharatiya Janata Party (BJP) on Saturday announced the list of candidates to the by elections to be held at four states of Bihar, Delhi, Gujarat and Madhya Pradesh.

Party General Secretary Ananth Kumar released the list of 11 candidates to the media in the national capital.

Kumar said party’s central election committee has authorized party president Rajnath Singh to decide the candidates for remaining six seats of Bodha Gaya, Begusarai, Aurai, and Bihar, Tendukeva in Madhya Pradesh and Jasden and Danta in Gujarat.

The BJP nominated party’s Minority Morcha National Secretary Mohd Irfan Ahmed for the Ohkhla seat in Delhi State Assembly.

The list stated:

Delhi – Dwaraka _ Pradyumna Singh Rajput, Okhla – Mohmd Irfan hmed

Bihar: Wahishwar Nagar (Reserve) Sanjay Paswan, Ramgarsh – Abhay ingh, Chinpur-Brij Kishore Bind,

Gujarat : Dhoraji – Jaisukhbhai Tesia, Kodihar- Natwar Singh Wala, Chotila-Varshmbhai Khurani, Sami -Bhairosingh Rathore, Dehagaon – Kalyan Singh Chouhan,

Madhya Pradesh Gohad- Sur Jatav Master (ANI)

Scientists use titanium dioxide nanoparticles to kill cancer cells, sparing healthy ones

Washington, August 20 (ANI): Scientists in America have developed a way to target brain cancer cells using inorganic titanium dioxide nanoparticles bonded to soft biological material.

This achievement is a result of the joint efforts of scientists from the U.S. Department of Energy’s (DOE) and the University of Chicago’s Brain Tumor Center.

Thousands of people die from malignant brain tumours every year, and the tumors are resistant to conventional therapies.

The researchers say that their nano-bio technology may eventually provide an alternative form of therapy, which targets only cancer cells and does not affect normal living tissue.

“It is a real example of how nano and biological interfacing can be used for biomedical application. We chose brain cancer because of its difficulty in treatment and its unique receptors,” said scientist Elena Rozhkova with the DOE’s Argonne National Laboratory.

The novel approach relies upon a two-pronged approach.

The researchers describe titanium dioxide as a versatile photoreactive nanomaterial that can be bonded with biomolecules.

When linked to an antibody, they say, nanoparticles recognize and bind specifically to cancer cells.

When focused visible light is shined onto the affected region, the researchers add, the localized titanium dioxide reacts to the light by creating free oxygen radicals that interact with the mitochondria in the cancer cells.

Mitochondria act as cellular energy plants, and when free radicals interfere with their biochemical pathways, mitochondria receive a signal to start cell death.

“The significance of this work lies in our ability to effectively target nanoparticles to specific cell surface receptors expressed on brain cancer cells,” said Dr. Maciej S. Lesniak, Director of Neurosurgical Oncology at University of Chicago Brain Tumor Center.

“In so doing, we have overcome a major limitation involving the application of nanoparticles in medicine, namely the potential of these agents to distribute throughout the body. We are now in a position to develop this exciting technology in preclinical models of brain tumours, with the hope of one day employing this new technology in patients,” Lesniak added.

Using X-ray fluorescence microscopy at Argonne’s Advanced Photon Source, the researchers have also found that the tumours’ invadopodia, actin-rich micron scale protrusions that allow the cancer to invade surrounding healthy cells, can be also attacked by the titanium dioxide.

The researchers have thus far carried out tests on cells in a laboratory setting, but animal testing is planned for the next phase.

Results show an almost 100 percent cancer cell toxicity rate after six hours of illumination, and 80 percent after 48 hours.

Also, since the antibody only targets the cancer cells, surrounding healthy cells are not affected, unlike other cancer treatments such as chemotherapy and radiotherapy.

Rozhkova said that a proof of concept is demonstrated, and other cancers can be treated as well using different targeting molecules.

The expert, however, admits that the research is presently in the early stages. (ANI)

Scientists identify how meningitis bacteria invade the brain

Washington, Aug 19 (ANI): Scientists in the U.S. have discovered that a specific protein on the surface of a common bacterial pathogen allows the bacteria to leave the bloodstream and enter the brain, initiating the deadly infection known as meningitis.

The new finding may lead to the development of improved vaccines to protect those most vulnerable, including young infants and the elderly.

“Streptococcus pneumoniae, commonly known as pneumococcus, is responsible for half the cases of bacterial meningitis in humans,” said the study’s senior author, Victor Nizet, MD, professor of paediatrics and pharmacy at the University of California, San Diego’s School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences.

Meningitis develops when bacteria penetrate the “blood-brain barrier.”

The blood-brain barrier, comprised of a single layer of highly specialized microvascular endothelial cells, prevents most large molecules from entering into the cerebrospinal fluid, preserving an optimal biochemical environment for brain function.

The research team examined the functions of a protein known as NanA in order to discover how an entire bacterium can breech the blood-brain barrier and gain access to the central nervous system.

NanA is produced by all strains of pneumococcus and displayed prominently on the bacteria’s outer surface.

Through genetic manipulations, the researchers were able to remove the entire NanA protein, or just specific sections of the molecule, from the pathogen.

They found that while normal pneumococci were able to bind, enter and penetrate through human brain microvascular endothelial cells, mutant bacteria lacking the NanA protein -or those expressing only a truncated version of the protein – largely lost these abilities.

Conversely, when the full-length pneumococcal NanA protein was cloned and expressed on the surface of a nonpathogenic laboratory strain, the transformed bacteria gained the ability to bind and enter the same endothelial cells.

Satoshi Uchiyama, MD, a postdoctoral fellow in the Nizet Laboratory and lead author on the study, said: “Our tissue culture studies showed that the NanA protein was both necessary and sufficient for bacterial penetration of the blood brain barrier endothelial cells.”

“After infecting mice intravenously, we also found that far fewer NanA-deficient bacteria left the bloodstream and entered the brain, in comparison to mice infected with the normal pneumococcus,” Uchiyama added.

NanA is best known as an enzyme that cleaves and releases the sugar molecule known as sialic acid, which is present in abundance on the surface of all human cells.

While this enzymatic activity played a small part in promoting NanA-mediated blood-brain barrier interactions, a much stronger role was identified for the outer tip of the protein.

This tip seems to directly attach to the brain microvascular endothelial cells and then stimulate them to take in the pneumococcus.

According to Nizet, because NanA is expressed on the surface of all pneumococcal strains, it is an attractive candidate to include in a universal protein-based vaccine against pneumococcal infection.

The study is available online in the Journal of Experimental Medicine. (ANI)

Natural organic matter plays key role in making mercury toxic to living creatures

Washington, August 19 (ANI): Scientists have found that naturally occurring organic matter in water and sediment appears to play a key role in helping microbes convert tiny particles of mercury in the environment into a form that is toxic to most living creatures.

According to Duke University environmental engineers, this finding is important because it could change the way mercury in the environment is measured and therefore regulated.

This particularly harmful form of the element, known as methylmercury, is a potent toxin for nerve cells. When ingested by organisms, it is not excreted and builds up in tissues or organs.

In a series of laboratory experiments, Amrika Deonarine, a graduate student in civil and environmental engineering at Duke’s Pratt School of Engineering, found that organic matter and chemical compounds containing sulfur – known as sulfides – can readily bind to form mercury sulfide nanoparticles.

Since they are more soluble than larger particles, these nanoparticles may be the precursors to a process known as methylation.

“When the organic material combines with the mercury, it prevents the particle from accumulating with other mercury particles and growing larger,” said Deonarine.

“Since the mercury remains in a nanoparticle size, it can easily collect on the surface of microbes where any mercury that dissolves can be taken in by the microbes,” she said.

“Without the organic matter, the mercury sulfide nanoparticles would grow too large and become insoluble, thus reducing the availability of mercury for microbial methylation,” she added.

It is while inside the microbe that the mercury is converted into the harmful methylmercury form, according to the researchers.

These reactions can only take place in cold water environments with little to no oxygen, such as the zone of sediment just below the bottom of a body of water.

Other such anaerobic environments can also be found in waste water and sewage treatment systems, the researchers said.

Mercury is extremely toxic and can lead to kidney dysfunctions, neurological disorders and even death. In particular, fetuses exposed to methylmercury can suffer from these same disorders as well as impaired learning abilities.

There are many ways mercury gets into the environment, with the primary sources being the combustion of coal, the refining of such metals as gold and other non-ferrous metals, and in the gases released during volcanic eruptions. (ANI)

How toxic various sizes of Alzheimer’s clusters can be to brain’s nerve cells

Washington, August 12 (ANI): In a breakthrough that may pave the way for an effective treatment for Alzheimer’s disease, scientists at the University of California-Los Angeles (UCLA) have created various sizes of clusters in their lab, which exactly match the clusters of the amyloid ß-protein (Aß) protein that form in the brains of those affected with the disease.

The researchers say that their work has shown that the ability of these grape-like clusters to kill nerve cells in the brain, scientifically known as toxicity, increases dramatically as they increase in size.

They say that though the larger clusters are more toxic than smaller ones, the larger formations are relatively rare.

Given that smaller versions are numerous, the researchers say, they are an inviting target for the development of new therapeutic drugs.

“We now have the best understanding yet of what types of toxic A-beta structures we should target with new classes of therapeutic drugs,” said senior author David Teplow, a professor of Neurology at UCLA.

The researchers have found that the larger the cluster, the greater the toxicity, but they also found that the increase in toxicity with these clusters is not linear.

“Clusters that contain two Aß molecules are more toxic than a single Aß molecule, and those with three molecules are more toxic that those with two,” said Teplow.

He pointed out that clusters composed of two Aß molecules are three-fold more toxic than the simple monomer compound, but those made of three molecules and four four molecules are more than 10-fold more toxic than are monomers.

This suggests that the larger, more toxic clusters should be the target for scientists trying to stop Alzheimer’s.

But Teplow notes that the relative amounts of the smaller clusters are far greater than that of the bigger clusters, and are, in total, more toxic.

So in an Alzheimer’s brain, the larger clusters are relatively rare, he said.

“Think of the molecules being wrapped in very weak Velcro. So a number of molecules can bind together to form large clusters, but they break apart very easily,” he said.

Having developed a process in the lab to be able to make pure forms of these Aß clusters of specific size will enable detailed study of their structures to show where every atom is.

“This will make development of drugs much easier and likely more successful,” he said. (ANI)

Why H1N1 flu spreads from person to person less effectively than other flu viruses

Washington, July 3 (ANI): Scientists in the US have come up with an genetic explanation for why the new H1N1 “swine flu” virus has spread from person to person less effectively than other flu viruses.

A collaborative team of researchers from the Massachusetts Institute of Technology (MIT) and the Centers for Disease Control and Prevention have found that the H1N1 strain, which circled the globe this spring, has a form of surface protein that binds inefficiently to receptors found in the human respiratory tract.

“While the virus is able to bind human receptors, it clearly appears to be restricted,” says Ram Sasisekharan, the Edward Hood Taplin Professor and director of the Harvard-MIT Division of Health Sciences and Technology (HST) and the lead MIT author of the paper.

He points out that that restricted binding, along with a genetic variation in an H1N1 polymerase enzyme, which was first reported about three weeks ago in Nature Biotechnology, explains why the virus has not spread as efficiently as seasonal flu.

However, flu viruses are known to mutate rapidly, so there is cause for concern if H1N1 undergoes mutations that improve its binding affinity.

“We need to pay careful attention to the evolution of this virus,” says Sasisekharan.

For their study, the researchers compared the new H1N1 strain to several seasonal flu strains, including some milder H1N1 strains, and to the virus that caused the 1918 flu pandemic.

They found that the new strain is able to bind to the predominant receptors in the human respiratory tract, known as umbrella-shaped alpha 2-6 glycan receptors.

However, binding efficiency varies between flu strains, and that variation is partly determined by the receptor-binding site (RBS) within the hemagglutinin protein.

The researchers found that the new H1N1 strain’s RBS binds human receptors much less effectively than other flu viruses that infect humans.

They also observed that the new H1N1 strain spreads inefficiently in ferrets, which accurately mimics human influenza disease including how it spreads or transmits in humans.

When the ferrets were in close contact with each other, they were exposed to enough virus particles that infection spread easily. However, when they were kept separate and the virus could spread only through airborne respiratory droplets, the illness spread much less effectively.

Sasisekharan says that this is consistent with the transmission of this virus seen in humans so far, considering that most outbreaks have occurred in limited clusters, sometimes within a family or a school but not spread much further.

“One of the big payoffs of long-term investments in carbohydrate biology and chemistry research is an understanding of the relationships between cell surface carbohydrate structure and viral infectivity. Tools developed in building such understanding help in the response to events like the recent H1N1 outbreak,” said Jeremy M. Berg, director of the National Institute of General Medical Sciences of the National Institutes of Health, which partly funded the research.

The researchers also pinpointed a second mutation that impairs H1N1′s ability to spread rapidly.

While recent studies have shown that a viral RNA polymerase known as PB2 is critical for efficient influenza transmissibility, the new H1N1 strain does not have the version of the PB2 gene necessary for efficient transmission.

A research article describing the study has been published in the online edition of the journal Science. (ANI)

New plasma torch may improve root canal treatment, reduce infection rates

Melbourne, June 24 (ANI): Scientists at the University of Southern California (USC) have come up with the world’s smallest plasma torch that may one day make root canal treatment faster and less painful, besides reducing the chance of infection after the procedure.

“Our goal is to guarantee that you won’t have to see a doctor for a follow-up visit,” ABC Science quoted says Professor Chunqi Jiang Jiang, who has reported this work in the online edition of the journal Plasma Processes and Polymers, as saying.

“One problem is that between 8 per cent and 10 per cent of patients have an infection post-operation. This is intended to eliminate the chance of an infection,” the researcher added.

Plasma, or ionized gas, is one of the four basic states of matter, the other three being solid, liquid and gas.

The researchers reveal that the trick to creating plasma at room temperature is to pulse it. They say that a continuous stream of plasma very quickly heats up the surrounding air.

According to them, pulsing the plasma allows the tiny electrons in it to heat up and move around, while keeping the much larger and heavier atom nucleus from heating up.

“If you have a piece of paper with bacteria on it and you apply cold plasma to it, the paper won’t burn but the bacteria will die,” says Professor Mounir Laroussi, of Old Dominion University in Virginia, who has studied the effect of cold plasmas for years.

“Cold plasma can kill bacteria on a variety of surfaces such as teeth or skin,” Laroussi adds.

The researchers say that upon being used in the mouth, the free electrons of plasma create single atoms of pure oxygen, ozone and other reactive forms of oxygen, all of which search for other atoms to bind with in the organic biofilms inside decayed teeth.

Biofilms are basically walled colonies of bacteria. In the human body, they can trigger the onset of an infection, and even protect the harmful bacteria from the most powerful antibiotics.

The researchers have revealed that cool, pulsed and purple plasma takes about five to ten minutes to clear an infected tooth of biofilms as compared to bleach, the conventional method for cleaning an infected tooth, which takes 30 minutes.

While about 10 per cent of patients treated with bleach are still infected, tests using the plasma torch on a few dozen human teeth have shown no signs of infection.

The plasma torch is also not as expensive as laser systems that are used as high-tech solutions to biofilms.

While laser systems costing up to 25,000 dollars, the plasma torch could retail for as little as 1,000 dollars, provided it passes official clinical trials.

Laroussi, who used to test cold plasmas effect on teeth, skin and wound healing, says that the trick to regulatory acceptance and commercialisation is ensuring that only harmful cells are killed.

“We can kill bacteria on teeth and on wounds. But we have to ensure that we are not creating a worse problem in nearby healthy cells as well,” says Laroussi.

Initial tests have shown that surrounding healthy tissue remains intact, although more testing is needed to definitively prove this.

Meanwhile, the USC researchers are concentrating on getting the funding necessary to continue with their research. (ANI)

Killing Mehsud would deal a body-blow to Pak Taliban’s effectiveness: Experts

Washington, June 23 (ANI): The Pakistan Army has claimed that its Swat offensive has been successful with scores top Taliban leaders being killed, but the fate of Swat Taliban chief Mullah Fazalullah and the Tehreek-e-Taliban (TTP) chief Baitullah Mehsud is still under wraps.

Now, the Pakistan security forces have shifted their focus on South Waziristan, the stronghold of Mehsud, and the region where the warlord is believed to be hiding, as experts consider that if Mehsud is nabbed, a large quota of the menace of terrorism would die down in times to come.

Mehsud, who has been blamed for carrying out several devastating terror attacks in Pakistan, including the brazen assassination of former Prime Minister Benazir Bhutto, holds a legendry status among the militants, and if the military is successful in sanitizing him, it would mean a severe blow to the extremists, a report in The Christian Science Monitor said.

Experts believe that Mehsud is the prime force that has been able to bind the different sections among the Taliban together, and if he falls the extremists could also fall apart reducing the formidable threat they currently pose, the report said.

“He (Mehsud) is the center of gravity in the war on terror. If you could take out the leadership, it would be a great force multiplier for Pakistan,” said Mahmood Shah, a security analyst and former security chief of Pakistan’s tribal areas.

It would take another four to five years for any other Talibani commander to reach the heights of Mehsud and carry on working on his (Mehsud’s) aims of crippling whole of Pakistan, it went on to add.

“For another individual to step in and gain that stature would take four to five years,” said a senior journalist, Mahmood Shah.

However, analysts also believe that simply capturing or killing Mehsud would not serve the purpose, as Taliban would have to be rooted out completely to quell extremism completely in the region, the report added.

“It (Pakistan government) would have to kill or capture the entire Pakistani Taliban leadership,” said Rifaat Hussain, a security analyst at the Quaid-i-Azam University in Islamabad. (ANI)

How obesity increases diabetes risk

London, June 22 (ANI): Scientists at the Salk Institute for Biological Studies have discovered how obesity makes a person more prone to diabetes, and why thin people can become insulin-resistant.

Led by Dr. Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology, the study has shown how a condition known as ER (endoplasmic reticulum) stress triggers abnormal glucose production in the liver, an important step on the path to insulin resistance.

ER stress is induced by a high fat diet, and is overly activated in obese people.

In healthy people, a “fasting switch” only flips on glucose production when blood glucose levels run low during fasting.

“The existence of a second cellular signalling cascade-like an alternate route from A to B-that can modulate glucose production, presents the potential to identify new classes of drugs that might help to lower blood sugar by disrupting this alternative pathway,” Nature magazine quoted Montminy as saying.

However, not all obese people become insulin resistant, and insulin resistance occurs in non-obese individuals, which led researchers to suspect that fasting-induced glucose production was only half the story.
“When a cell starts to sense stress a red light goes on, which slows down the production of proteins. This process, which is known as ER stress response, is abnormally active in livers of obese individuals, where it contributes to the development of hyperglycemia, or high blood glucose levels. We asked whether chronic ER stress in obesity leads to abnormal activation of the fasting switch that normally controls glucose production in the liver,” said Montminy.

A transcriptional switch called CRTC2 turns on glucose production.

Normally, CRTC2 sits outside the nucleus waiting for the signal that allows it to slip inside and do its work and after entering the nucleus, it teams up with a protein called CREB and together they switch on the genes necessary to increase glucose output.

In insulin-resistant mice, however, the CRTC2 switch seems to get stuck in the “on” position, and the cells start churning out glucose like sugar factories in overdrive.

But when the conditions of ER stress were mimicked in mice, CRTC2 moved to the nucleus but failed to activate gluconeogenesis, and instead switched on genes important for combating stress and returning cells to health.

On closer inspection, the researchers found that in this scenario CRTC2 did not bind to CREB, but instead joined forces with another factor, called ATF6a.

However, it was found that the more ATF6a is bound to CRTC2, the less there is for CREB to bind to.

“This clever mechanism ensures that a cell in survival mode automatically shuts down glucose production, thus saving energy,” said a co-author of the study.

The researchers then found the levels of ATF6a to go down when ER stress was chronically activated, compromising the cells’ survival pathway and favouring the glucose production pathway.

Hyperglycemia wins in conditions of persistent stress.

“Our study helps to explain why obese people have a stronger tendency to become diabetic. When ER stress signaling is abnormal glucose output is actually increased,” said a co-author.

“It is possible that mutations in the highly conserved CRTC2 lead to a predisposition to inappropriate gluconeogenesis,” said Montminy.

The study has been published in the advance online edition of the journal Nature. (ANI)

Now obesity increases diabetes risk

London, June 22 (ANI): Scientists at the Salk Institute for Biological Studies have discovered how obesity makes a person more prone to diabetes, and why thin people can become insulin-resistant.

Led by Dr. Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology, the study has shown how a condition known as ER (endoplasmic reticulum) stress triggers abnormal glucose production in the liver, an important step on the path to insulin resistance.

ER stress is induced by a high fat diet, and is overly activated in obese people.

In healthy people, a “fasting switch” only flips on glucose production when blood glucose levels run low during fasting.

“The existence of a second cellular signalling cascade-like an alternate route from A to B-that can modulate glucose production, presents the potential to identify new classes of drugs that might help to lower blood sugar by disrupting this alternative pathway,” Nature magazine quoted Montminy as saying.

However, not all obese people become insulin resistant, and insulin resistance occurs in non-obese individuals, which led researchers to suspect that fasting-induced glucose production was only half the story.

“When a cell starts to sense stress a red light goes on, which slows down the production of proteins. This process, which is known as ER stress response, is abnormally active in livers of obese individuals, where it contributes to the development of hyperglycemia, or high blood glucose levels. We asked whether chronic ER stress in obesity leads to abnormal activation of the fasting switch that normally controls glucose production in the liver,” said Montminy.

A transcriptional switch called CRTC2 turns on glucose production.

Normally, CRTC2 sits outside the nucleus waiting for the signal that allows it to slip inside and do its work and after entering the nucleus, it teams up with a protein called CREB and together they switch on the genes necessary to increase glucose output.

In insulin-resistant mice, however, the CRTC2 switch seems to get stuck in the “on” position, and the cells start churning out glucose like sugar factories in overdrive.

But when the conditions of ER stress were mimicked in mice, CRTC2 moved to the nucleus but failed to activate gluconeogenesis, and instead switched on genes important for combating stress and returning cells to health.

On closer inspection, the researchers found that in this scenario CRTC2 did not bind to CREB, but instead joined forces with another factor, called ATF6a.

However, it was found that the more ATF6a is bound to CRTC2, the less there is for CREB to bind to.

“This clever mechanism ensures that a cell in survival mode automatically shuts down glucose production, thus saving energy,” said a co-author of the study.

The researchers then found the levels of ATF6a to go down when ER stress was chronically activated, compromising the cells’ survival pathway and favouring the glucose production pathway.

Hyperglycemia wins in conditions of persistent stress.

“Our study helps to explain why obese people have a stronger tendency to become diabetic. When ER stress signaling is abnormal glucose output is actually increased,” said a co-author.

“It is possible that mutations in the highly conserved CRTC2 lead to a predisposition to inappropriate gluconeogenesis,” said Montminy.

The study has been published in the advance online edition of the journal Nature. (ANI)

Now, a quicker, cheaper SARS virus detector

Washington, May 30 (ANI): Scientists at the University of Southern California have developed a quicker and cheaper breed of electronic detectors for viruses like SARS and other biological materials, which may prove very helpful in the battle against epidemics.

Project leaders Zhongwu Chou and Mark Thompson point out that the basic nanotube and nanowire biosensors consist of a piece of synthetic antibody attached to a nanowire that’s attached to an electrical base, immersed in liquid.

If the protein to which the antibody binds is present in the liquid, it will bind to these antibodies, immediately creating a sharply measurable jump in current through the nanowire.

However, according to the researchers, their new design uses two new elements.

Firstly, it takes advantage of bioengineered synthetic antibodies-which are much smaller versions of the natural substances that are designed to bind with a specific protein and only that protein.

And secondly, it uses indium oxide (In2O3) nanowires instead of silicon and other materials previously tried.

The study has shown that unlike silicon, the metal oxides do not develop “an insulating native oxide layer that can reduce sensitivity.”

Thus, the resulting device can detect its target molecules with a sensitivity as great as the best alternative modes, do so more rapidly and without use of chemical reagents.

It is also potentially considerably cheaper than alternatives.

“We believe that nanowire bisensor devices functionalized with engineered proteins … can have important applications ranging from disease diagnosis to homeland security,’ wrote the authors.

The system could be useful in helping to establish certain important parameters for two-part biological systems like the antibody/target protein pair.

The protein the prototype system detects is the SARS (severe acute respiratory syndrome) virus n-protein, which infected more than 8,000 people in 2002-2003, killing nearly 10 percent of them.

The study has been published in ACSNano. (ANI)

New approach may pave way for effective HIV vaccine

Washington, May 23 (ANI): Using gene transfer technology, scientists have developed a new approach to overcome the biggest hurdle in the development of an effective HIV vaccine.

The researchers used gene transfer technology, which produces molecules that block infection, to successfully protect monkeys from infection by a virus closely related to HIV-the simian immunodeficiency virus, or SIV-that causes AIDS in rhesus monkeys.

“We used a leapfrog strategy, bypassing the natural immune system response that was the target of all previous HIV and SIV vaccine candidates,” Nature magazine quoted study leader Dr. Philip R. Johnson, chief scientific officer at The Children’s Hospital of Philadelphia, as saying.

Johnson developed the novel approach over a ten-year period, but warned that many hurdles still remain before the technique could be translated into an HIV vaccine for humans.

Most attempts at developing an HIV vaccine have used substances aimed at stimulating the body’s immune system to produce antibodies or killer cells that would eliminate the virus before or after it infected cells in the body. But, the approach has not been proved fruitful until now.

However, the approach used in the current study was divided into two phases-in the first phase, researchers created antibody-like proteins (called immunoadhesins) that were specifically designed to bind to SIV and block it from infecting cells.

After it was proven to work against SIV in the laboratory, DNA representing SIV-specific immunoadhesins was engineered into a carrier virus designed to deliver the DNA to monkeys.

The researchers chose adeno-associated virus (AAV) as the carrier virus because it is a very effective way to insert DNA into the cells of a monkey or human.

In the second part of the study, the team injected AAV carriers into the muscles of monkeys, where the imported DNA produced immunoadhesins that entered the blood circulation.

After a month of administrating the AAV carriers, the immunized monkeys were injected with live, AIDS-causing SIV.

It was found that the majority of the immunized monkeys were completely protected from SIV infection, and all were protected from AIDS, unlike a group of unimmunized monkeys, who were infected by SIV, and two-thirds died of AIDS complications.

“To ultimately succeed, more and better molecules that work against HIV, including human monoclonal antibodies, will be needed,” said Johnson and his co-authors.

The study has appeared in the online version of Nature Medicine. (ANI)

New approach may pave way for effective HIV vaccine

Washington, May 18 (ANI): Using gene transfer technology, scientists have developed a new approach to overcome the biggest hurdle in the development of an effective HIV vaccine.

The researchers used gene transfer technology, which produces molecules that block infection, to successfully protect monkeys from infection by a virus closely related to HIV-the simian immunodeficiency virus, or SIV-that causes AIDS in rhesus monkeys.

“We used a leapfrog strategy, bypassing the natural immune system response that was the target of all previous HIV and SIV vaccine candidates,” Nature magazine quoted study leader Dr. Philip R. Johnson, chief scientific officer at The Children’s Hospital of Philadelphia, as saying.

Johnson developed the novel approach over a ten-year period, but warned that many hurdles still remain before the technique could be translated into an HIV vaccine for humans.

Most attempts at developing an HIV vaccine have used substances aimed at stimulating the body’s immune system to produce antibodies or killer cells that would eliminate the virus before or after it infected cells in the body. But, the approach has not been proved fruitful until now.

However, the approach used in the current study was divided into two phases-in the first phase, researchers created antibody-like proteins (called immunoadhesins) that were specifically designed to bind to SIV and block it from infecting cells.

After it was proven to work against SIV in the laboratory, DNA representing SIV-specific immunoadhesins was engineered into a carrier virus designed to deliver the DNA to monkeys.

The researchers chose adeno-associated virus (AAV) as the carrier virus because it is a very effective way to insert DNA into the cells of a monkey or human.

In the second part of the study, the team injected AAV carriers into the muscles of monkeys, where the imported DNA produced immunoadhesins that entered the blood circulation.

After a month of administrating the AAV carriers, the immunized monkeys were injected with live, AIDS-causing SIV.

It was found that the majority of the immunized monkeys were completely protected from SIV infection, and all were protected from AIDS, unlike a group of unimmunized monkeys, who were infected by SIV, and two-thirds died of AIDS complications.

“To ultimately succeed, more and better molecules that work against HIV, including human monoclonal antibodies, will be needed,” said Johnson and his co-authors.

The study has appeared in the online version of Nature Medicine. (ANI)

New sponge-like material beneficial for the environment

Washington, May 18 (ANI): A team of chemists has designed a new sponge-like material that can remove mercury from polluted water, easily separate hydrogen from other gases and is a more effective catalyst than the one currently used to pull sulfur out of crude oil.

Hydrodesulfurization is a widely used catalytic chemical process that removes sulfur from natural gas and refined petroleum products, such as gasoline and diesel and jet fuels.

Without the process, which is highly optimized, people would be burning sulfur, which contributes to acid rain.

Scientists have tried to improve hydrodesulfurization, or HDS, but have made no progress. Many consider it an optimized process.

Now, the Northwestern researchers, in collaboration with colleagues at Western Washington University, report that their material is twice as active as the conventional catalyst used in HDS, while at the same time being made of the same parts.

The material, cobalt-molybdenum-sulfur, which is black, brittle and freeze-dried, is a new class of chalcogels, a family of material discovered only a few years ago at Northwestern.

Chalcogels are random networks of metal-sulfur atoms with very high surface areas.

The new chalcogel is made from common elements, is stable when exposed to air or water and can be used as a powder.

This is the first report of chalcogels being used for catalysis and gas separation.

Mercouri G. Kanatzidis, Charles E. and Emma H. Morrison, Professor of Chemistry in the Weinberg College of Arts and Sciences, and doctoral student Santanu Bag made this catalyst using a method different from that of the conventional catalyst.

The Northwestern material is a gel made of cobalt, nickel, molybdenum and sulfur that then is freeze-dried, producing a sponge-like material with a very high surface area.

It is this high surface area and the material’s stability under catalytic conditions that make the cobalt-molybdenum-sulfur chalcogel so active.

The researchers also demonstrated that the new chalcogel soaks up toxic heavy metals from polluted water like no other material.

The chalcogel removed nearly 99 percent of the mercury from contaminated water containing several parts per million.

Mercury likes to bind to sulfur, and the chalcogel is full of sulfur atoms.

In addition to being a better HDS catalyst and a mercury sponge, the chalcogel also is very effective at gas separation.

The researchers showed that the material easily removes carbon dioxide (CO2) from hydrogen, an application that could be useful in the hydrogen economy. (ANI)

Personalised cancer treatment comes closer to reality

London, May 18 (ANI): Researchers at the University of California, San Diego School of Medicine have announced the development of an efficient system for delivering siRNA into primary cells, which may one day lead to personalized cancer treatment.

“RNAi has an unbelievable potential to manage cancer and treat it,” Nature magazine quoted Dr. Steven Dowdy, Howard Hughes Medical Institute Investigator and professor of cellular and molecular medicine at UC San Diego School of Medicine, as saying .

“While there’s still a long way to go, we have successfully developed a technology that allows for siRNA drug delivery into the entire population of cells, both primary and tumor-causing, without being toxic to the cells,” he added.

The researcher has revealed that his study focussed on the potential for a small section of protein called peptide transduction domain (PTD), which has the ability to permeate cell membranes, as a delivery mechanism for getting siRNAs into cancer cells.

In their previous work, he and his colleagues had generated over 50 “fusion proteins” using PTDs linked to tumour-suppressor proteins.

“Simply adding the siRNAs to a PTD didn’t work, because siRNAs are highly negatively charged, while PTDs are positively charged, which results in aggregation with no cellular delivery,” Dowdy said.

He said that his team solved the problem by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA’s negative charge.

According to him, this allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm, where it specifically targets mRNAs from cancer-promoting genes and silences them.

With a view to testing the PTD-DRBD fusion protein’s ability to deliver siRNA, the researchers generated a human lung cancer reporter cell line. They used green and fluorescent protein and analysed the cells using flow cytometry analysis.

Their efforts enabled them to determine the magnitude of RNA inhibitory response and the percentage of cells undergoing this response.

They found that the entire cellular population underwent a maximum RNAi response. Similar results were obtained in primary cells and cancer cell lines.

“We were subsequently able to introduce gene silencing proteins into a large percentage of various cell types, including T cells, endothelial cells and human embryonic stem cells. Importantly, we observed no toxicity to the cells or innate immune responses, and a minimal number of transcriptional off-target changes,” said Dowdy.

The researchers are of the opinion that the RNAi methods can be continually tweaked to combat new mutations, a way to overcome a major problem associated with current cancer therapies.

“Such therapies can’t be used a second time if a cancer tumor returns, because the tumor has mutated the target gene to avoid the drug binding. But since the synthetic siRNA is designed to bind to a single mutation and only that mutation on the genome, it can be easily and rapidly changed while maintaining the delivery system – the PTD-DRBD fusion protein,” said Dowdy. Cancer is a complex, genetic disease that is different in every patient. This is still in early stages, but I believe the siRNA-induced RNAi approach to personalized cancer treatment is the only thing on the table,” Dowdy added.

The study has been published in the advance on-line edition of the journal Nature Biotechnology. (ANI)

Now, a home kit for men to monitor reproductive status post vasectomy

Washington, May 14 (ANI): Men, who don’t know when to stop using contraceptive methods after vasectomy, can now resort to a medical home test kit based on a protein discovered at the University of Virginia Health System, called SpermCheck Vasectomy.

The new product line could revolutionize the way men around the world monitor their reproductive status.

“The SpermCheck family of products is intended for use by men on both sides of the fertility equation – those who don’t want to father children and those who do,” said Dr. John C. Herr, inventor of SpermCheck technology who is professor of cell biology.

SpermCheck Vasectomy is based on antibodies that bind to SP-10, a protein discovered in Herr’s laboratory, and is the only FDA approved immunodiagnostic test for monitoring sperm after vasectomy.

The device looks and functions much like a home pregnancy test.

It measures SP-10, which is present at constant levels in each sperm head, and enables men to quickly and accurately monitor their post-vasectomy sterility.

Such monitoring is important because sperm can remain in the male reproductive tract for weeks or months after a vasectomy.

Thus, to avoid unexpected pregnancies, vasectomized men must practice birth control until their sperm count falls below fertility levels.

According to Herr, at-home privacy, convenience and affordability of SpermCheck Vasectomy will boost post-operative monitoring and make it easy for couples to accurately determine when contraception methods are no longer needed. (ANI)

White blood cells move like millipedes to get to the site of infection or injury

Washington, May 5 (ANI): Weizmann Institute scientists have shown that white blood cells move like millipedes in order to get to the site of infection or injury.

Professor Ronen Alon and his research student Ziv Shulman, who led the study, say that their finding contrasts the current opinion about the movement of the immune system “soldiers”, according to which they advance like inchworms.

The researcher say that rather than sticking front and back, folding and extending to push itself forward, the immune cell creates numerous tiny ‘legs’ no more than a micron in length – adhesion points, rich in adhesion molecules (named LFA-1) that bind to partner adhesion molecules present on the surface of the blood vessels.

They say that tens of these legs attach and detach in sequence within seconds, allowing them to move rapidly while keeping a good grip on the vessels’ sides.

Using scanning and transmission electron microscopes, the researcher produced images that showed that upon attaching to the blood vessel wall, the white blood cell legs “dig” themselves into the endothelium, pressing down on its surface.

The researchers found that the shear force created by the blood flow was necessary for the legs to embed themselves. Without the thrust of the rushing blood, the white blood cells couldn’t sense the exit signals or get to the site of the injury.

According to them, the results of the current study explain previous findings that the blood’s shear force is essential for the white blood cells to exit the blood vessel wall.

The present study suggests that shear forces cause their adhesion molecules to enter highly active states.

In future studies, the scientists plan to check whether it is possible to regulate aggressive immune reactions-such as in autoimmune diseases-by interrupting the “digging” of immune cell legs into the endothelium.

They will also study whether cancerous blood cells metastasise through the blood stream using similar mechanisms in order to exit the blood vessels and enter different tissues. (ANI)

Lupus patients ‘have decreased sense of smell’

Washington, May 01 (ANI): A new study had found that patients with systemic lupus erythematosus (SLE) have a decreased sense of smell.

SLE is an autoimmune disease that sometimes involves the central nervous system in a condition known as neuropsychiatric SLE (NPSLE).

The sense of smell is a complex process of the central nervous system that involves specific areas of the brain.

Research in mice has shown that NPSLE-like symptoms and olfactory impairment might be induced by autoimmune mechanisms that target specific areas of the brain, but this has not been explored.

The new study, led by Yehuda Shoenfeld of Chaim Sheba Medical Center in Tel-Hashomer, Israel, involved 50 SLE patients and 50 age and sex-matched controls.

Researchers evaluated three levels of olfactory function: threshold (identifying a stick with an odour from among sticks that didn’t have an odour); discrimination (differentiating between two smells); and identification of a smell from among four options. The three scores were combined to form a total TDI score.

The results showed that significant olfactory deficits in the SLE patients compared with the controls. SLE patients showed a decrease in olfactory function in both the threshold and discrimination tests.

Also, the study found that patients with more active disease and past NPSLE manifestations had significantly lower TDI scores.

Previous study in mice has shown that injection of antibodies linked to NPSLE manifestations induced olfactory deficit and that these antibodies can bind and penetrate cells in limbic areas of the brain, which are associated with the sense of smell.

Also, magnetic resonance imaging has recently shown limbic system involvement in SLE patients.

“Although the exact mechanism of olfactory impairment has yet to be elucidated, the possibility of an immune-mediated mechanism is intriguing,” the authors said.

The study was published in the May issue of Arthritis and Rheumatism. (ANI)