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Jun 30
3D brain view may help treat Alzheimer's, Parkinson's
In a breakthrough that may help in developing drugs for Alzheimer's and other neurological disorders, researchers have developed a 3D view of an important receptor in the brain.

This receptor allows us to learn and remember, and its dysfunction can result in a wide range of neurological diseases including Alzheimer's, Parkinson's, schizophrenia and depression.

The unprecedented view gives scientists new insight into how the receptor - called the NMDA receptor - is structured.

And importantly, the new detailed view gives vital clues for developing drugs to combat neurological diseases and conditions.

"This is the most exciting moment of my career," said Eric Gouaux, a senior scientist with Oregon Health and Science University in the US.

"The NMDA receptor is one of the most essential, and still sometimes mysterious, receptors in our brain. Now, with this work, we can see it in fascinating detail," he said.

Receptors facilitate chemical and electrical signals between neurons in the brain allowing them to communicate with each other.

The NMDA (N-methyl-D-aspartate) receptor facilitates neuron communication that is the foundation of memory, learning and thought.

Malfunction of the NMDA receptor occurs when it is increasingly or decreasingly active.

The NMDA receptor makeup includes receptor "subunits" - all of which have distinct properties and act in distinct ways in the brain, sometimes causing neurological problems.

Prior to Gouaux's study, scientists had only a limited view of how those subtypes were arranged in the NMDA receptor complex and how they interacted to carry out specific functions within the brain and the central nervous system.

Gouaux's team of scientists created a 3D model of the NMDA receptor through a process called X-ray crystallography.

"This new detailed view will be invaluable as we try to develop drugs that might work on specific subunits and therefore help fight or cure some of these neurological diseases and conditions," Gouaux said.

"Seeing the structure in more detail can unlock some of its secrets and may help a lot of people," he added.

The findings were published online in the journal Nature.

Jun 30
Decline of hearing ability related to gene: Experts
In a path-breaking research which may have implications for those suffering from a decline of their cognitive and hearing abilities, Indian and American experts have established the role of a specific gene in triggering such conditions.

Experts of Sir Ganga Ram Hospital and University of Louisville School of Medicine stated that the MMP-9 gene plays a major role in causing decline of cognitive and hearing functions and removal of the said gene decreases Hyperhomocysteinemia-induced cognitive and hearing dysfunctions.

Hyperhomocysteinaemia (HHcy) is a medical condition arising due to an abnormally high level of homocysteine in the blood, experts said.

"There is a role of MMP-9 in decline of cognitive and hearing functions. The ablation of MMP-9 decreases Hyperhomocysteinemia-induced cognition and hearing dysfunction. This research was carried out on mice but has large implication for humans," said Dr Seema Bhargava, lead author of the research and Senior Consultant, Department of Biochemistry, Sir Ganga Ram Hospital.

MMP-9 gene is a matrix metallopeptidase which helps in wound healing, cell migration, learning, memory and various other functions.

Currently, 45 per cent of adults in India between 45-92 years of age suffer from hearing impairment. Deficiency of Vitamin B-12 and folate (another form of vitamin) and high homocysteine levels have also been associated with impaired hearing in women.

"It is important to identify individuals at risk for HHcy (e.G. Elderly people)... To reduce homocysteine levels, adequate vitamin supplements should be given. However, if HHcy is already present, vitamins will take several months to reduce the concentration of homocysteine.

"Our study has advocated the role of MMP-9 inhibitors by pharmaceutical companies as a therapeutic option," Bhargava said.

The research was published in the May edition of Journal of Molecular Biology Reports.

Jun 28
How organs coordinate their development with body
Believe it or not, during growth our organs do not develop synchronously with the body's development.

Instead, the organs' growth is coordinated with the whole body at distinct 'milestones'.

The development of wings in fruit flies does not progress synchronously with the organism's development, the findings showed.

The study helps explain how an organism facing environmental and physiological perturbations retains the ability to build correct functional organs and tissues in a proportional adult body.

"With this work we propose a new paradigm for thinking about organ-organ and organ-body coordination during development," said Marisa Oliveira from Instituto Gulbenkian de Ciencia in Portugal.

"We suggest that organisms achieve this coordination not by continuous but rather by discrete communication focused on developmental milestones," Oliveira added.

The researchers studied how organ and whole-body development is coordinated, using the fruit fly, Drosophila melanogaster, as a model organism.

The juvenile period in the fruit fly comprises three larval moults, followed by a wandering stage where larvae leave the food and search for a site to begin metamorphosis at a stage called pupariation.

The research team focused on these so-called developmental events to study how the development of wings is coordinated with the whole body of the fruit fly larvae.

The researchers first analysed the expression of six genes involved in the development of wings in normal conditions of growth, that is, at a temperature of 25 degrees Celsius, and generated a detailed staging scheme.

Next, the researchers changed the temperature to affect the growth conditions of the larvae and analysed the rate of wing development compared to the whole-body development.

It is known that flies grow faster at higher temperatures and slower at lower temperatures.

However, the researchers observed that the development of the wings was slower at 29 degrees Celsius, compared to flies growing in normal conditions or flies growing at 18 degrees Celsius.

The study was published in the journal PLOS Genetics.

Jun 28
Early life stress can leave lasting impacts on brain
Researchers have said that for kids, a little bit of stress provides a platform for learning, adapting and coping, however, a lot of it - chronic, toxic stress like poverty, neglect and physical abuse - can have lasting negative impacts.

A team of University of Wisconsin-Madison researchers recently showed these kinds of stressors, experienced in early life, might be changing the parts of developing children's brains responsible for learning, memory and the processing of stress and emotion.

These changes may be tied to negative impacts on behavior, health, employment and even the choice of romantic partners later in life.

Seth Pollak, co-leader of the study and UW-Madison professor of psychology, said, "We haven't really understood why things that happen when you're 2, 3, 4 years old stay with you and have a lasting impact."

For the study, the team recruited 128 children around age 12 who had experienced either physical abuse, neglect early in life or came from low socioeconomic status households.

Researchers conducted extensive interviews with the children and their caregivers, documenting behavioral problems and their cumulative life stress. They also took images of the children's brains, focusing on the hippocampus and amygdala, which are involved in emotion and stress processing. They were compared to similar children from middle-class households who had not been maltreated.

Hanson and the team outlined by hand each child's hippocampus and amygdala and calculated their volumes. Both structures are very small, especially in children, and study lead author and recent UW Ph.D. graduate Jamie Hanson and Pollak say the automated software measurements from other studies may be prone to error.

Indeed, their hand measurements found that children who experienced any of the three types of early life stress had smaller amygdalas than children who had not. Children from low socioeconomic status households and children who had been physically abused also had smaller hippocampal volumes.

The study has been published in the journal Biological Psychiatry.

Jun 27
Having babies later in life may help women live longer
Researchers have claimed that women who embraced motherhood later in their lives have greater odds for surviving to an unusually old age.

In the nested case-control study, which used Long Life Family Study data, 311 women who survived past the oldest fifth percentile of survival (according to birth cohort-matched life tables) were identified as cases, along with 151 women who died at ages younger than the top fifth percentile of survival who were identified as controls.

Looking at the cases of all 462 women, the study found a significant association for older maternal age, whereby women who had their last child beyond age 33 years had twice the odds for survival to the top fifth percentile of survival for their birth cohorts compared with women who had their last child by age 29 years. More specifically, women between the ages of 33 and 37 having their last child had an odds ratio of 2.08. The odds ratio for older women was 1.92.

It was also observed that having more children (identified as three or more) tempered the association between increased maternal age and later survival. Mortality was not assessed for women who had no children.

According to the authors, the fact that numerous studies have documented the same relationship between older maternal age at birth and exceptional survival provides evidence for sustained reproductive fitness, with age as a selective force for genetic variants conducive to longer life.

NAMS Executive Director, Margery Gass, MD said that while this documented relationship was noteworthy, what was more meaningful was that these findings support the need to conduct additional studies that identify the various genetic influences on reproductive fitness, as these could also influence the rate of aging and a woman's susceptibility to age-related diseases.

The study is published online in Menopause, the journal of The North American Menopause Society (NAMS).

Jun 27
Chronic brain damage not as prevalent in NFL players as believed
Researchers have said that chronic brain damage may not be as prevalent in NFL players as thought.

Researchers performed in-depth neurological examinations of 45 retired NFL players, ranging in age from 30-to 60-years old. The analysis included state-of-the-art magnetic resonance imaging (MRI), susceptibility weighted imaging (SWI), diffusion tensor imaging (DTI) along with comprehensive neuropsychological and neurological examinations, interviews, blood tests and APOE (apolipoprotein E) genotyping.

Lead author and neurologist, Ira R. Casson, MD of the Long Island Jewish Medical Center, in New Hyde Park, New York and the Hofstra North Shore-LIJ School of Medicine, Hempstead, New York, said their results indicated that there were brain lesions and cognitive impairments in some of the players; however the majority of the individuals in our study had no clinical signs of chronic brain damage to the degree that has been noted in previous studies.

The players in the study had an average of 6.8 years of playing time in the NFL and reported approximately 6.9 concussions during their time in the league. The majority had normal clinical mental status.

Neuropsychological testing revealed isolated impairments in 11 patients but none suffered dementia. Six players showed symptoms of moderate to severe depression. No players in the study had dysarthria, Parkinson's Disease or cerebellar dysfunction.

An abnormal gene which may predict future cognitive issues such as dementia was present in 38 percent of the players, which is larger than that in the general male population.

Player positions in the study included: 14 linebackers, 9 offensive lineman, 8 defensive lineman, 8 defensive backs, 2 wide receivers, 2 running backs, 1 tight end and 1 who played on both the offensive and defensive line. No NFL quarterbacks were part of the sample.

The study has been published online in the journal Sports Health: A Multidisciplinary Approach.

Jun 26
Why we fear things approaching us
Researchers have found a general tendency for humans to fear things approaching, even if non-threatening.

In our long struggle for survival, we humans learned that something approaching us is far more of a threat than something that is moving away. This makes sense, since a tiger bounding toward a person is certainly more of a threat than one that is walking away.

According to University of Chicago Booth School of Business Professor Christopher K. Hsee, we still have negative feelings about things that approach us - even if they objectively are not threatening.

Hsee explains in order to survive, humans have developed a tendency to guard against animals, people and objects that come near them.

He said that this is true for things that are physically coming closer, but also for events that are approaching in time or increasing in likelihood.

Hsee, along with Chicago Booth doctoral student Yanping Tu, and Zoe Y. Lu and Bowen Ruan of the University of Wisconsin, conducted a battery of eight tests in support of their thesis and found that even nonthreatening objects and beings evoked negative feelings in participants as they came closer.

Even seemingly docile entities, such as deer, had a fear factor attached to them since participants could still attach some uncertainty to a wild animal's behavior.

These initial investigations into approach avoidance are of practical use in a number of areas.

The study has been published in the Journal of Personality and Social Psychology.

Jun 26
Deploying midwives in poor nations could avert millions of maternal and newborn deaths
Researchers have said that a small increase in number of skilled birth attendants in the world's poorest nations could save the lives of a substantial number of women and their babies.

Study leader Linda Bartlett, MD, MHSc, a faculty member in the Department of International Health at the Johns Hopkins Bloomberg School of Public Health, said that even deploying a relatively small number of midwives around each country could have a profound impact on saving maternal, fetal and newborn lives. He said that their study shows that maternal mortality can be prevented, even in the most difficult of places.

In their analysis, researchers found that a 10 percent increase in midwife coverage every five years through 2025 could avert more than a quarter of maternal, fetal and infant deaths in the world's 26 neediest countries such as Ethiopia and Somalia.

The estimates were done using the Lives Saved Tool (LiST), a computer-based tool developed by Johns Hopkins Bloomberg School of Public Health researchers that allows users to set up and run multiple scenarios to look at the estimated impact of different maternal, child and neonatal interventions for countries, states or districts. For this analysis, the tool compared the effectiveness of several different alternatives including increasing the number of midwives by varying degrees, increasing the number of obstetricians, and a combination of the two.

In a separate study of the 58 poorest countries, reported last week in the journal PLOS One, Bartlett and her team used the LiST tool to estimate that 7 million maternal, fetal and newborn deaths will occur in those nations between 2012 and 2015. If a country's midwife access were to increase to cover 60 percent of the population by 2015, 34 percent of deaths could be prevented, saving the lives of nearly 2.3 million mothers and babies.

Bartlett says maternal mortality is the public health indicator with the greatest disparity between developed and developing countries. "With a very functional medical system," she says, "maternal deaths become extremely rare events."

The 58 countries studied account for about 91 percent of maternal deaths worldwide.

The study has been published in the journal Lancet.

Jun 25
Sunscreen that protects DNA from UV rays
Ever heard of a molecular sunscreen? It is a defence mechanism that the molecular building blocks that make up DNA mount to prevent the damage by ultraviolet rays, reveals new research.

The DNA forming molecules absorb ultraviolet light so strongly that sunlight should deactivate them. But a "relaxation response" protects these molecules and the genetic information they encode from UV damage, the researchers said.

The experiment at the Department of Energy's SLAC National Accelerator Laboratory focused on thymine, one of four DNA building blocks.

Researchers hit thymine with a short pulse of ultraviolet light and used a powerful X-ray laser to watch the molecule's response.

A single chemical bond stretched and snapped back into place within 200 quadrillionths of a second, setting off a wave of vibrations that harmlessly dissipated the destructive UV energy.

Researchers had noticed years ago that thymine seemed resistant to damage from UV rays in sunlight, which cause sunburn and skin cancer.

Theorists proposed that thymine got rid of the UV energy by quickly shifting shape.

But they differed on the details, and previous experiments could not resolve what was happening.

"As soon as the thymine swallows the light, the energy is funnelled as quickly as possible into heat, rather than into making or breaking chemical bonds," said lead researcher Markus Guehr from Stanford University in the US.

"It is like a system of balls connected by springs; when you elongate that one bond between two atoms and let it loose, the whole molecule starts to tremble," he explained.

The findings appeared in the journal Nature Communications.

Jun 25
Chemotherapy likely to get less painful
In a major breakthrough that has long term implications for cancer patients, researchers have discovered the pain pathway in chemotherapy and also a potential way to block it.

Saint Louis University professor of pharmacological and physiological sciences Daniela Salvemini found a molecular pathway by which a painful chemotherapy side effect happens and a drug that may be able to stop it.

"The chemotherapy drug paclitaxel is widely used to treat many forms of cancer, including breast, ovarian and lung cancers," said Salvemini.

"Though it is highly effective, the medication, like many other chemotherapy drugs, is frequently accompanied by a debilitating side effect called chemotherapy induced peripheral neuropathy, or CIPN," she added.

In addition to causing suffering to patients, CIPN is often a limiting factor when it comes to treatment.

Salvemini and her colleagues studied paclitaxel, which is also known as Taxol, and discovered that the pain pathway is dependent on activation of S1PR1 in the central nervous system.

This engages a series of damaging neuro-inflammatory processes leading to pain.

By inhibiting this molecule, they found that they could block and reverse paclitaxel-induced neuropathic pain without interfering with the drug's anti-cancer effects.

The study appeared in the Journal of Biological Chemistry.