How parasites influence evolution of immune genes

Washington, May 26 (ANI): It’s the parasites that make the immune proteins in the body to adapt themselves to turn into inflammatory defenders, says a population genetics study.

Conducted by a team of researchers in Italy, the study also suggested that parasites also influence some of those genes to turn into risk factors for intestinal disorders.

Usually parasite-driven selection leaves a footprint on our DNA in the form of mutations known as “single nucleotide polymorphisms” (SNPs).

Making sure that genetic variation (in the form of multiple SNPs) is maintained within certain immune genes over time helps ensure that the host can fend off different infections in different environments.

In the study, researchers led by Matteo Fumagalli, sift through 1,052 SNPs in genes that code for immune proteins called interleukins from roughly 1000 people worldwide.

Out of the 91 genes assessed, 44 were found to have signatures of evolutionary selection, which meant that the genetic variation was neither due to chance nor to the migration of populations over time.

And some of that variation was linked with the diversity of parasites that live alongside humans.

The data revealed that having lots of different parasites around has shaped the evolution of our interleukin genes.

Generally, parasitic worms appear to have had a more powerful influence on certain interleukin genes than smaller microbes such as viruses, bacteria, and fungi.

But it doesn’t surprise senior author Manuela Sironi, because worms typically evolve slower than bacteria or viruses, giving their human hosts time to adapt in response.

Some of the genes that were shaped by worm diversity made perfect sense, as the proteins they encode help generate the precise type of immune response required to rid the body of worms.

However, other genes seemed to be influenced more by the diversity of viruses, bacteria, and fungi than by that of worms.

The results of the study will appear in an upcoming issue of the Journal of Experimental Medicine. (ANI)

Scientists unravel cow genome

Washington, Apr 24 (ANI): An international team of scientists has successfully sequenced cow’s genome, thus paving the way for more sustainable food production.

A research team involving 300 researchers from 25 countries spent six years mapping and analysing the genetic make-up of a Hereford cow, named L1 Dominette.

The findings of this study provide the means to select animals with a smaller environmental footprint, particularly animals with less greenhouse gas emissions.

“The bovine genome is more similar to that of humans than mice or rats at all levels, from genomic DNA rearrangements, to shared genes and identity of their protein sequences” said Evgeny Zdobnov, one of the lead analysts from the project and a researcher at the University of Geneva and the Swiss Institute of Bioinformatics.

He added, “The finding that about 75percent of human genes are well conserved across mammals is striking. The bovine genome gives us further insight into human biology, allowing us to highlight the loss or gain of certain gene families in hominoids.

The majority of the genes in the former group can encode several different proteins through a mechanism called alternative splicing.

“The sequencing of the cow genome allowed us to determine that this diversification mechanism is more evolutionary conserved than previously thought”, said Alexandre Reymond, the leader of the analysis.

In cattle biology, chromosomal rearrangements have an influence on the genes involved in the processes of immunity, lactation, digestion and metabolism.

These changes could help explain the amazing ability of cattle to efficiently convert low-quality forage into energy-dense meat and milk, processes long exploited by man.

The study appears in journal Science. (ANI)

Drug to prevent exercise-induced arrhythmias identified

London, Mar 30 (ANI): Vanderbilt University Medical Center researchers have found that a drug can prevent potentially lethal arrhythmias caused due to exercise or stress, called CPVT.

Patients with CPVT experience abnormally rapid heart rates (tachycardia), usually during exercise or stress, and are at risk for fainting and cardiac arrest.

“It’s potentially a breakthrough in the treatment of this rare syndrome,” Nature quoted Bjorn Knollmann, M.D., Ph.D., associate professor of Medicine and Pharmacology, as saying.

For a long time, researchers have been studying the molecular defects that trigger arrhythmias and knew that the disorder is caused by mutations in two genes that encode calcium-handling proteins- the ryanodine receptor and calsequestrin.

In 2006, the group discovered these mutations allows calcium to “leak” out of its storage containers inside heart cells and cause arrhythmias at the cellular level.

The researchers developed a mouse model for CPVT (by eliminating the calsequestrin gene) and proposed using the model to study medications and interventions for the disorder.

When they tried flecainide, a clinically available anti-arrhythmic that is used to treat atrial fibrillation, it gave positive results.

In isolated heart cells, flecainide blocked the ryanodine receptor and the calcium “leak” (the underlying molecular defect in CPVT), and it completely prevented ventricular arrhythmias in the mouse model of CPVT.

“So we knew that this established drug specifically targets the disease mechanism in CPVT,” said Knollmann.

They then tested the drug in two patients, and found that, flecainide (combined with a beta blocker in the boy) prevented exercise-induced ventricular arrhythmias in both patients.

The patients have taken flecainide for more than six months now and are living normal lives.

The study was published in Nature Medicine. (ANI)

Gene that suppresses skin cancer growth identified

London, March 30 (ANI): Scientists at the National Institutes of Health (NIH) in the U.S. have announced the discovery of a gene that suppresses tumour growth in melanoma, the deadliest form of skin cancer.

The finding was made as part of a systematic genetic analysis of a group of enzymes implicated in skin cancer, and many other types of cancer.

According to the analysis, one-quarter of human skin cancer tumours had mutations in genes that code for matrix metalloproteinase (MMP) enzymes.

The researchers believe that their findings may pave the way for more individualized cancer treatment strategies, where MMP and other key enzymes play a functional role in tumour growth and spread of the disease.

They even say that their study may help understand why drugs designed to treat cancer by blocking MMP enzymes have not been very successful as yet.

During the current study, the team led by researchers from the National Human Genome Research Institute (NHGRI) have found that MMP-8 actually serves as a tumour suppressor gene in melanoma, which is why may not be wise to block all MMPs in skin cancer patients with mutation in this gene.

The researchers say that a better approach may be to look for drugs that restore or increase MMP-8 function, or for drugs that block only those MMPs that are truly oncogenes-genes that encode proteins involved in normal cell growth.

“This research is an illustrative proof of concept that shows the value of genomic strategies for understanding cancer and possible therapies,” Nature magazine quoted Dr. Eric Green, NHGRI Scientific Director, as saying.

“It is gratifying to see that genomic technologies are guiding scientific discovery, advancing cancer research, especially melanoma research,” Green added.

While experimenting on mice, the researcher observed that when they injected the animals with cells expressing normal MMP-8, they would not develop skin ulcers.

However, when the mice were injected with cells expressing mutated MMP-8, they went on to develop ulcerations and metastases in their lungs.

A research article on the gene discovery has been published in the journal Nature Genetics. (ANI)

Computer learning-electrical stimulation combo may give paralysed people better muscle control

Washington, March 19 (ANI): A University of Florida researcher that paralysed people can be enabled to control their limbs in more precise and life-like manner by combining computer learning technology with electrical stimulation, a simple technique that has been in use for decades to prompt muscles to contract.

Warren Dixon, an associate professor of Mechanical and Aerospace Engineering, agrees that his research is still exploring the fundamentals, but insists that his progress so far suggests computer-adapted electrical stimulation could one day be ready to help scores of stroke and cord injury sufferers annually.

“It’s an adaptive scheme to do electrical stimulation more efficiently, with less fatigue and more accuracy,” said Dixon, explaining that existing techniques did little more than apply a set current to a designated muscle.

He points out that stroke sufferers who work at regaining the ability to walk often unconsciously drag their toes, causing them to stumble.

He says that this problem can be solved by making a wearable, pacemaker-sized device that would deliver just the right stimulation to the calf at just the right moment in a person’s gait, lifting the toe just enough to avoid a stumble and walk naturally.

The researcher reckons that the device would adapt to individuals, adjusting itself to weight, activity and diet.

According to him, such a device might even act as a kind of robotic therapist to the patient, guiding him or her in the proper action while very slowly backing off its own electrical input.

Dixon concedes that the current state-of-the-art rehabilitation devices show the potential. He, however, adds that such devices only apply a predetermined and relatively high voltage to a designated muscle, which means that while the muscle may move, it can easily fatigue, becoming less responsive and sore.

He and his graduate students are developing methods aimed at improving that model using techniques of “adaptive learning”, or giving a computer the ability to learn from a patient’s actions and reactions and adjust its muscular stimulation accordingly.

“We start with a desired trajectory, we do the leg extension, encode that in a computer and measure the motion. Then we develop control methods to intelligently stimulate the muscle to make it behave the way it should,” Dixon said.

His recently authored a paper accepted in the IEEE Transactions on Neural Systems and Rehabilitation Engineering, and its publication is anticipated for this summer. (ANI)

Unexpected outcomes key to human learning

Washington, March 14 (ANI): Psychologists and neuroscientists at the University of Pennsylvania say that unexpected outcomes play a significant role in human learning.

Describing their study in the journal Science, the researchers revealed that they used a computer-based card game and microelectrodes to observe neuronal activity of the brain.

They said that their study suggested that neurons in the human substantia nigra (SN) play a central role in reward-based learning, modulating learning based on the discrepancy between the expected and the realized outcome.

“This is the first study to directly record neural activity underlying this learning process in humans, confirming the hypothesized role of the basal ganglia, which includes the SN, in models of reinforcement including learning, addiction and other disorders involving reward-seeking behavior,” said lead author Kareem Zaghloul, postdoctoral fellow in neurosurgery at Penn’s School off Medicine.

“By responding to unexpected financial rewards, these cells encode information that seems to help participants maximize reward in the probabilistic learning task,” the researcher added.

Previous studies on animal models suggested that learning occurs when dopaminergic neurons, which drive a larger basal ganglia circuit, are activated in response to unexpected rewards and depressed after the unexpected omission of reward.

The researchers explain this by giving the example that a lucky win is more likely to be retained than a probable loss.

“Similar to an economic theory, where efficient markets respond to unexpected events and expected events have no effect, we found that the dopaminergic system of the human brain seems to be wired in a similar rational manner — tuned to learn whenever anything unexpected happens but not when things are predictable,” said Michael J. Kahana, senior author and professor of psychology at Penn’s School of Arts and Sciences.

Working in collaboration with Associate Professor Gordon Baltuch, Zaghloul and Kahana used microelectrode recordings obtained during deep brain stimulation surgery of Parkinson’s patients to study neuronal activity in the SN, the midbrain structure that plays an important role in movement, as well as reward and addiction.

The researchers said that the patients showed impaired learning from both positive and negative feedback in cognitive tasks due to the degenerative nature of their disease, and the decreased number of dopaminergic neurons.

They analysed the recordings to determine whether responses were affected by reward expectation, and asked the participants to choose between red and blue decks of cards presented on a computer screen, one of which carried a higher probability of yielding a financial reward than the other.

If the draw of a card yielded a reward, a stack of gold coins was displayed along with an audible ring of a cash register and a counter showing accumulated virtual earnings. But where the draw did not yield a reward, or no choice was made, the screen turned blank and participants heard a buzz.

“This new way to measure dopaminergic neuron activity has helped us gain a greater understanding of fundamental cognitive activity,” said Baltuch, director of the Penn Medicine Center for Functional and Restorative Neurosurgery. (ANI)