Researchers from MIT`s Koch Institute of Integrative Cancer Research including two of Indian origin have presented a novel approach to developing a dengue therapy using mutated antibodies.

According to a study by the International Research Consortium on Dengue Risk Assessment, Management and Surveillance, up to 390 million people are infected with the dengue virus each year. For most people the mosquito-borne virus causes flulike symptoms, including fever, headache and joint pain. But for some, particularly children, the virus can develop into the far more serious dengue hemorrhagic fever, causing severe blood loss and even death.

Despite the threat posed by the disease, developing a vaccine against dengue has so far proved challenging, according to Ram Sasisekharan, the Alfred H. Caspary Professor of Biological Engineering at MIT. That`s because dengue is not one virus but four different viruses, or serotypes, each of which must be neutralized by the vaccine.

Protecting people from only one or some of the four viruses could cause them to develop the more severe form of dengue if they later become infected with one of the other serotypes, in a process known as antibody-dependent enhancement, Sasisekharan explained.

"That was the motivation for carrying out our study, to generate a fully neutralizing antibody that works for all four serotypes," he stated.

This transmission electron micrograph depicts a number of round, dengue virus particles.

Efforts to develop a therapeutic antibody for dengue are focused on a part of the virus called the envelope protein.

"This is a very critical protein that allows the virus to latch on to the appropriate receptor within the host, to infect them, replicate and spread," Sasisekharan said.

The envelope protein contains two regions of interest, known as the loop and the "A" strand. Research teams have previously attempted to engineer an antibody that targets the loop region of the virus protein, as this is known to be able to attack all four serotypes if targeted in the right way.

However, the antibodies that target the loop region tend to have low potency, meaning they are unable to completely neutralize the virus. This increases the risk of more severe secondary dengue infection.

So a team led by Sasisekharan decided instead to look for antibodies that target the "A" strand region of the protein. Such antibodies tend to have much higher potency, but they are unable to neutralize all four serotypes.

The researchers chose as their model an antibody known as 4E11, which has been shown in tests to neutralize dengue 1, 2 and 3, but not dengue 4.

"We wanted to see if we could get good neutralizing activity to dengue 4, and also tweak the antibody to increase the potency associated with the other subtypes," Sasisekharan said.

The researchers mined existing antibody-antigen complexes to analyze the physical and chemical features that play an important role in their interaction, such as hydrogen bonding and ionic attraction. Taking a statistical approach, they then ranked these features in terms of their importance to each of the antibody-antigen interactions.

This significantly narrowed the number of possible changes, or mutations, the researchers needed to make antibody 4E11 in order to improve its ability to neutralize all four viruses, in particular dengue 4.

"So rather than random screening, we used a statistically driven approach so we knew the regions to focus on, and what things we had to change," Sasisekharan said.

As a result, the researchers came up with 87 possible mutations, which they were able to reduce to just 10 changes after further investigation.

When they tested their mutated antibody on samples of the four dengue serotypes in the laboratory, they found it had a 450-fold increase in binding to dengue 4, a 20-fold increase in binding for dengue 2, and lesser improvements in binding for dengue 1 and 3, Sasisekharan noted.

The researchers have developed a novel computational method for predicting protein-protein interaction that captures the essential chemical and physical features of interacting surfaces, asserted Subhash Vasudevan, an associate professor in the Emerging Infectious Diseases Program at the Duke-NUS Graduate Medical School in Singapore.

"By learning and validating data from numerous three-dimensional structures of interacting antibody and protein complexes, the researchers gained valuable insights that enabled them to redesign a dengue virus envelope antibody to improve its binding by an astounding 450-fold," Vasudevan said.

"The cross-reactive and pan-dengue neutralizing antibody was protective against all four serotypes in cell culture and in an animal model of infection," he added.

The MIT researchers are now preparing for potential preclinical trials, and hope to be ready to test the antibody on humans within the next two to three years. In the meantime, they are also investigating other targets for their immunotherapy approach, including the influenza virus.

A paper describing the study results was published in the Proceedings of the National Academy of Sciences.

Your skin can be a crucial early-warning system for a range of health problems, according to doctors.

They said signs of brittle bones, diabetes and vitamin deficiencies may surface on skin before other symptoms appears, the Huffington Post reported.

A study of 114 recently postmenopausal women found that deep wrinkles on the face and neck could indicate an increased risk for broken bones.

The reason is that women with such wrinkles were more likely to have lower bone density in areas like the hips, spine and heels.

Estrogen promotes the production of the protein collagen, which your skin and bones both rely on to maintain density. So as a woman`s level of estrogen declines in menopause, said Dr. Ronald Young, co-director of the Menopause Center at Texas Children`s Pavilion for Women in Houston, "collagen in the skin is depleted, which means the skin isn`t as firm and elastic, and wrinkles develop."

Deeper, worsening wrinkles are a sign that the body is producing less collagen, which often means bone density is decreasing as well.

The worse the wrinkles, the lesser the bone density, added lead researcher Lubna Pal, a Yale School of Medicine associate professor.

"This relationship was independent of age or of factors known to influence bone mass," Pal noted.

If you discover thick, dark, velvety patches on folds of skin on your neck, armpit or groin, doctors suggest a blood test to check for diabetes.

These patches, known as acanthosis nigricans, could be benign or a normal side effect of obesity, but they also could be a sign of diabetes, said dermatologist Janet Lin of Baltimore`s Mercy Medical Center.

Thyroid gland is responsible for hormones that, among other functions, regulate your body temperature, metabolism and nervous system as well as the health of skin, hair and nails.

Signs that your thyroid isn`t performing properly-it can be either overactive or underactive-tend to appear first on your skin, typically on the back of your upper arms and the back of your fingers.

At first the skin just seems rough or bumpy, like a mild rash, according to naturopath Alan Christianson of Phoenix.

But if the thyroid continues to be out of whack, other areas can be affected, he said, such as the legs, scalp and neck. An underactive gland could result in hair loss, brittle nails or dry, flaky skin.

If any such things happen, schedule a physical with your internist and ask for a thyroid function test, the doctors said.

Again dull, dry skin or complexion could indicate an omega-3 deficiency, Christianson said, because its absence can slow your natural exfoliation cycle, also potentially leading to dryness or dandruff.
Supplements are one option to restore omega-3, but the best way to correct the deficiency is through diet.

The American Heart Association recommends eating a 3- to 4-ounce serving of oily fish twice a week. Flaxseeds, walnuts and soybeans can also help maintain omega-3 levels , it said.

Low levels of melatonin, a hormone regulating the sleep-wake cycle, may increase the risk of Type 2 diabetes in women, a new study has warned.

US researchers found that women who had low levels of melatonin at night had twice the risk of developing Type 2 diabetes over a 12-year period compared with women who had high melatonin levels.
The link between low melatonin levels and Type 2 diabetes held even after the researchers took into account other factors that could increase the risk of diabetes, such as age, weight, physical activity levels and sleep duration.

However, the study only found an association, and cannot prove that low melatonin levels cause Type 2 diabetes, website MyHealthNewsDaily reported.

The findings raise the question of whether increasing people`s melatonin levels, through supplements or prolonged exposure to darkness, could decrease diabetes risk, said study researcher Dr Ciaran McMullan, of Brigham and Women`s Hospital in Boston.

The new study involved 370 women who developed Type 2 diabetes between 2000 and 2012 (but did not have the condition before the study`s start), and 370 women who didn`t develop diabetes.

Urine samples were collected in the morning as a way to measure melatonin levels produced overnight.

Factors that can lower melatonin levels include: sleep disturbances, short sleep duration, working the night shift and taking certain drugs, such as beta-blockers, said Dr John Forman, also of Brigham and Women`s Hospital.

The study included mostly white women, so it`s not clear if the results apply to men or to other ethnic groups, the researchers said.

Since more research is needed to confirm the findings, it`s too early to recommend that people start taking melatonin to reduce their diabetes risk, Forman said.

The study appears in the Journal of the American Medical Association.

Global population data spanning the years from 1900 to 2010 have enabled researchers to predict that the number of people on Earth will stabilise around the middle of the century, a report has said.

The results, obtained with a model used by a research team from the Autonomous University of Madrid, coincide with the UN`s downward forecasts.
According to United Nations` estimates, the world population in 2100 will be within a range between 15.8 billion people according to the highest estimates, high fertility variant- and 6.2 billion according to the lowest, low fertility variant, a figure that stands below the current 7 billion.

A mathematical model developed by a team from the Autonomous University of Madrid (UAM) and the CEU-San Pablo University, both from Spain, seems to confirm the lower estimate, in addition to a standstill and even a slight drop in the number of people on Earth by the mid-21st century.

The population prospects between 1950 and 2100 provided by the UN were used to conduct the study, published in the journal `Simulation`.

Mathematical equations that are used in scientific fields, such as condensed matter physics, were then applied to this data.

The model`s S-shaped sigmoid curve reflects this situation with an inflection point in the mid-1980s when the speed at which the population is growing starts to slow down until it stabilises around 2050.

The data also reflected the downward trend in the UN`s series of prospects.

"Overpopulation was a spectre in the 1960s and 70s but historically the UN`s low fertility variant forecasts have been fulfilled," Felix F. Munoz, UAM researcher and co-author of the project. highlighted.

In an important step forward in the fight against HIV, scientist at Duke University have recorded the body`s own "training manual" for successfully attacking HIV, a finding that may turn out to be useful in developing vaccines.

The research team's study is based on a patient in Africa who had a rapid diagnosis, about four weeks after being infected with the virus. However, it was found that his immune system started to an antibody named CH 103 that could neutralize bout 55 percent of all known HIV strains.

As per the study, published in the journal Nature, the super antibody was not produced in one step. Rather it was the product of the war of the immune system and HIV trying to out-evolve each other.
Using cutting edge genetic analyses tools, the scientists' pieced together each of the steps that culminated in the production of CH103 it was like a training manual for the immune system.

Human body develops antibodies to fight off infections, but HIV mutates rapidly in defense against the onslaught. Only 20 Percent of HIV patients develop them naturally. This study, however, has given an insight into how broadly neutralizing antibodies progress.
"What we were able to do was map out the arms race of both virus and antibody, and in doing so we have now a map," Prof Barton Haynes, a leader of the research from Duke University, told the BBC.

"This is the first time we`ve been able to see the actual road map."

This research could help scientists make a vaccine that would mimic the antibodies` evolution and ward off HIV.