Washington, October 21 (ANI): Johns Hopkins scientists have found that sugar plays a significant role in how cells work, paving the way for new therapies for a number of diseases like diabetes, neurodegeneration, and cancer.

The researchers say that sugar may be as influential as phosphate in putting the proteins in cells on and off.

The conventional wisdom was that the job of turning proteins on and off fell to phosphates, which did so by fastening to and unfastening from proteins, a process called phosphorylation.

The latest research paper by the Johns Hopkins team suggests that sugar also plays a role in regulating phosphorylation itself.

The team say that the new switches form yet another potential target for manipulation by drugs.

"Like dark matter in the cosmos, it's hard to find even though it's very abundant," says Dr. Gerald Hart, the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine, referring to the sugar O-GlcNAc that carries out GlcNAcylation.

The researcher revealed that it was with the aid of new technologies that they could measure the extent to which the addition of sugar to proteins affects phosphorylation.

Of 428 sites on which phosphate was being added to, and taken off of proteins, all responded in some way to increased O-GlcNAc: 280 decreased phosphorylation and 148 increased phosphorylation.

"The influence of sugar is striking. The presence of O-GlcNAc causes the enzymes that add the phosphate to do something different, and this cross-talk itself can modify proteins," Hart says.

Given the association of both sugar and phosphate modifications with the working of cells, according to the researchers, they are fundamental to understanding and eventual control of the molecular processes that underlie many diseases.

"With regard to cancer, diabetes and Alzheimer's, most people in the world today have been studying the yang (phosphorylation) but not the yin (GlcNAcylation). There's another whole side that people were unaware of where diabetes diagnostics and cancer therapies could be targeted," says Hart. (ANI)

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Washington, October 21 (ANI): A leading European scientist has revealed that his new research has provided significant insights into how proteins in human cells interact and "talk" to one another, and thereby led to a better understanding of how medications work.

Giulio Superti-Furga, a professor at the Centre for Molecular Medicine of the Austrian Academy of Sciences, hopes that such insights may result in more effective therapies.

"Most of the time the mechanism of action of drugs is ill understood and we often do not even know the primary target of the drugs we swallow daily. We do not know how these drugs work at the molecular level, and side effects can have serious consequences," he said.

For his research, Prof. Superti-Furga uses a 'proteomics' approach to understanding precisely how certain proteins that are key drug targets organise themselves in the cell, and how they make complex interactions with often dozens of other proteins.

"Proteomics is a way of joining the dots together to give us the bigger picture," he said.

His team has been investigating a particular enzyme, a tyrosine kinase called Bcr-Abl, which is involved in leukaemia.

The researchers has revealed that a drug is available that acts on the enzyme, but it eventually loses its efficiency as patients become resistant to it.

"We need to understand the relationship between the drug and the target. Can we understand the 3-d protein as a molecular machine much better?" he said.

Superti-Furga's lab in Vienna has used a range of proteomics techniques to isolate the enzyme, and dissect its constituent parts.

They have discovered that the protein exists as a complex of some 46 separate components, and operates as a giant molecular machine, with each part in close communication with the others.

"It is clear that tyrosine kinase inhibitors do not simply inhibit the enzyme, but rather remodel the machine. So drugs do not simply ablate things, they interfere with the equilibria of networks. If we can understand how these proteins interact, in the future people might say we should target this pathway or that network'; by targeting multiple nodes we will be able to maximise the good side effects against the bad side effects," the researcher said.

The team say that their main objective is to develop methods to understand how the human body can recognise invading foreign genetic material, from bacteria or viruses for example, and distinguish it from its own, innate genetic material.

They hope that their work will provide important insights into how the body defends itself against invading organisms.

Superti-Furga made a presentation of his team's work at the European Science Foundation's 3rd Functional Genomics Conference in Innsbruck, Austria, held on 1-4 October. (ANI)

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Washington, Oct 21 (ANI): Heart failure patients are at an increased risk of fractures, which includes debilitating hip fractures, according to a group of researchers.

Canadian researchers have reported in Circulation: Journal of the American Heart Association that heart failure patients are at higher risk for fractures than other heart patients and should be screened and treated for osteoporosis.

The study found that one year after an emergency room visit, 4.6 percent of heart failure patients experienced a fracture compared to only 1 percent of other heart patients. The one-year rate for hip fractures was 1.3 percent for heart failure patients compared to only 0.1 percent for other heart patients.

After researchers adjusted for other risk factors, heart failure patients had four times the risk of fracture and 6.3 times the risk of hip fracture as patients with heart attacks, chest pain or rhythm disturbances.

"This is the first study to link heart failure patients to a higher risk of fractures," said Justin A. Ezekowitz, M.D., senior author of the study and director of the Heart Function Clinic and assistant professor of medicine at the University of Alberta in Canada.

Heart failure and osteoporosis share common risk factors such as older age, female sex, smoking and type-2 diabetes.

The study included 16,294 patients with heart disease presenting at emergency rooms in Alberta, Canada from 1998 to 2001. Slightly more than 2,000 patients, average age 78, presented with a new diagnosis of heart failure.

The primary outcome was fracture requiring hospital admission at one year follow-up that was not due to trauma or other disease.

Researchers excluded patients with hospitalization for heart failure two years prior to the ER visit and patients with conditions known to modify fracture or fall risk.

Researchers ascertained prescription medication use based on database claims 60 days prior to and 60 days after the emergency room visit. The use of bisphosphonates and other osteoporosis medications was higher in the non-heart failure control group. But even when researchers excluded these patients, the risk of fracture was of similar magnitude.

Even after adjusting for medications known to affect the bones, dosages and co-morbidities, heart failure patients had a fourfold higher risk of fracture, Ezekowitz said. he reasons for this remain unclear, Ezekowitz said.

"It may be that heart failure patients aren't getting enough calcium or vitamin D," the expert added. (ANI)

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Washington, Oct 21 (ANI): The typical Western diet, which includes red meat, fried foods, dairy products and salty snacks, is responsible for 30 per cent of the world's heart attacks, according to a study of dietary patterns in 52 countries.

The study has been reported in Circulation: Journal of the American Heart Association.

Researchers identified three dietary patterns in the world: Oriental, which include higher intake of tofu, soy and other sauces; Prudent, which includes higher intake of fruits and vegetables; and Western, which includes higher intake of fried foods, salty snacks, eggs and meat.

The Prudent diet was associated with a lower heart attack risk than the Oriental, researchers said.

"The objective of this study was to understand the modifiable risk factors of heart attacks at a global level," said Salim Yusuf, D.Phil., the study's senior author.

Researchers analyzed the INTERHEART study, which documents the association of various risk factors and the risk of heart attack in about 16,000 participants in 52 countries. Here, they analyzed 5,761 heart attack cases and compared them to 10,646 people without known heart disease (controls).

The researchers created a dietary risk score questionnaire for heart attacks patients, based on 19 food groups and adjusted it for dietary preferences for each country. rained medical personnel interviewed the heart attack patients and the control group. The questionnaires included healthy food items (such as fruits and vegetables) and unhealthy food items (such as fried foods and salty snacks).

"A simple dietary score, which included both good and bad foods with the higher score indicating a worse diet, showed that 30 percent of the risk of heart disease in a population could be related to poor diet," said Romania Iqbal, Ph.D., lead author of the study.

After adjusting for known risk factors, researchers found: people who consumed the Prudent diet of more fruits and vegetables had a 30 percent lower risk of heart attack compared to people who ate little or no fruits and vegetables; people who consumed the Western diet had a 35 percent greater risk of having a heart attack compared to people who consumed little or no fried foods and meat; and the Oriental pattern showed no relationship with heart attack risk.

Researchers said that while some components of the Oriental pattern may be protective, others such as the higher sodium content of soy sauces, may increase cardiovascular risk, neutralizing any relationship. (ANI)

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