The researchers from University College London studied a group of genes that have previously been linked to an increased risk of disease in the arteries. They studied data from nearly 4,000 men and women from across Europe, comparing their genes, their artery thickness and their artery health.

The scientists, led by BHF Professor Steve Humphries, believe they have pinpointed the gene in the group that is associated with an increased risk of a heart attack or stroke in women, but not in men.

Called BCAR1, the gene they identified is involved in many processes in the body that are affected by the female sex hormone oestrogen. The researchers believe that a high risk version of the BCAR1 gene – the GG version – when combined with a woman’s naturally occurring high oestrogen levels, could lead to the increased risk of cardiovascular disease compared with the low risk version – the AA version. Men with the GG version of the BCAR1 gene do not seem to be affected.

Over the five-year study, women with the high risk BCAR1 gene – around a third of those studied – had an increased risk (6.1%) of having a heart attack, stroke or diseased blood vessels compared with those with the low risk version of the gene (2.5%).

Heart disease is the major cause of heart attack and someone has a heart attack in the UK every three minutes. Understanding what puts people at risk of heart attacks is an important part of finding ways to prevent them and potentially treat people with medication to lower their risk of having a heart attack. British Heart Foundation

Researchers at UT Southwestern Medical Center have identified a second role for a class of RNA-binding proteins, revealing new insights about neurological diseases and conditions associated with this protein such as autism, epilepsy, and certain types of cancer.

“These data should promote a re-evaluation of those diseases to see if this new function that we’ve identified contributes to those defects,” said senior study author Dr. Michael Buszczak, Associate Professor of Molecular Biology and with the Hamon Center for Regenerative Science and Medicine at UT Southwestern.

The study indicates that RNA-binding fox (Rbfox) proteins oversee translation of messenger RNA, or mRNA, into proteins. Using the fruit fly Drosophila as a model, researchers showed that the Rbfox1 protein, in particular, has this regulatory role.

Rbfox1 proteins were known to play a key role in splicing together coding portions of genes called exons to form mRNA, which is subsequently translated to form proteins. Splicing largely takes place within the nucleus of cells, where many Rbfox1 proteins are found. But there are also variants of Rbfox1 proteins found in the cytoplasm – the portion of the cell outside the nucleus – and the function of those cytoplasmic proteins had not been understood. 

“We found that cytoplasmic Rbfox1 represses the production of specific proteins,” Dr. Buszczak said.

The lead author of the study, UT Southwestern Molecular Biology graduate student Arnaldo Carreira-Rosario, found that Rbfox1 binds to specific elements at the ends of mRNA molecules, preventing these mRNAs from being translated into proteins. If Rbfox1 proteins are lost and mRNA is no longer repressed, that could lead to aberrant growth of cells, or cancers.

The researchers found that cytoplasmic forms of Rbfox1 were required for germ cell development in Drosophila. “Without this protein, the germ cells are blocked in a very specific stage of differentiation and just linger there. They can’t differentiate into mature eggs,” said Dr. Buszczak, an E.E. and Greer Garson Fogelson Scholar in Medical Research.

This block leads to sterility in female Drosophila and, in other contexts, can result in an inappropriate proliferation of cells, which underlies cancer.

Work by co-author Dr. Mani Ramaswami of Trinity College Dublin in Ireland points to a link between the newly identified function of Rbfox1 proteins and neuronal development and function, which could have important implications for a number of the neuronal disorders linked to disruption of Rbfox1.

“The idea is that loss of Rbfox1 causes disease by disrupting protein expression, not RNA splicing,” Dr. Buszczak said. “If this interpretation is correct, then it has implications for how one would develop therapeutics to treat the disease in question.” UT Southwestern Medical Center

A gastric cancer risk screening study will be organized in Chinese healthcare centres by the China Health Promotion Foundation. The foundation is a public organization, managed by the Chinese Ministry of Health.
The multi-centre study will be conducted by fifty to one hundred primary healthcare units. The screening of about half a million 40-80-year-old asymptomatic persons will be tested with GastroPanel biomarkers, delivered by Biohit Oyj. The parties have agreed not to disclose the value of the contract. Data collection and analysis, including evaluation, are planned to be finalized at the end of 2016. The sample collection has started in the summer of 2015.
GastroPanel is a non-invasive blood test for stomach health. The test diagnoses Helicobacter pylori infection and atrophic gastritis, caused by H. pylori infection or autoimmune disease. These results can be used to assess whether asymptomatic patients have an increased risk of gastric or esophageal cancer, peptic ulcer disease or risk of vitamin B12-, calcium-, magnesium- and iron malabsorption and if further examinations or treatments are needed.
According to CEO Liu Feng, Biohit Biotech (Hefei) Co., Ltd, ’The most important risk factors for stomach cancer are H. pylori infection and atrophic gastritis, which often are asymptomatic, and can be accurately detected by GastroPanel biomarkers used for this population-based screening. Early detection of risk groups is important for the effective prevention of gastric cancer.’
CEO Semi Korpela, Biohit Oyj said: ‘This is an outstanding opening for GastroPanel biomarkers in the screening of asymptomatic subjects to identify the risk groups for gastric cancer and vitamin B12 malabsorption among other things. Gastric cancer is the leading cause of cancer related mortality in China. The use of the very informative GastroPanel for the screening of gastric cancer risk offers the possibility of prevention and early detection of stomach cancers. Based on correct diagnosis, screening reduces sick leaves and loss of labour input, as well as self-medication with its associated risks. Early detection of risk conditions for gastric cancer and vitamin and mineral deficiencies saves healthcare costs and human suffering as well.’

www.biohithealthcare.cominvestor.relations@biohit.fi

University of Utah chemists devised a new way to detect chemical damage to DNA that sometimes leads to genetic mutations responsible for many diseases, including various cancers and neurological disorders.

“We are one step closer to understanding the underlying chemistry that leads to genetic diseases,” says Cynthia Burrows, distinguished professor and chair of chemistry at the university. “We have a way of marking and copying DNA damage sites so that we can preserve the information of where and what the damage was.”

Jan Riedl, a University of Utah postdoctoral fellow and the study’s first author, says 99 percent of DNA lesions – damage to the chemical bases known as A, C, G and T that help form the DNA double helix – are repaired naturally. The rest can lead to genetic mutations, which are errors in the sequence of bases and can cause disease. The new method can “identify and detect the position of lesions that lead to diseases,” he says.

Burrows says: “We are trying to look for the chemical changes in the base that can lead the cell to make a mistake, a mutation. One of the powerful things about our method is we can read more than a single damaged site [and up to dozens] on the same strand of DNA.”

The chemists say their new method will let researchers study chemical details of DNA lesions or damage. Such lesions, if not repaired naturally, accumulate over time and can lead to mutations responsible for many age-related diseases, including colon, breast, liver, lung and melanoma skin cancers; clogged arteries; and neurological ailments such as Huntington’s disease and Lou Gehrig’s disease.

“A method capable of identifying the chemical identity and location in which lesions appear is crucial for determining the molecular etiology [cause] of these diseases,” Burrows and colleague write in their study.

The new method for finding DNA lesions combines other, existing techniques.

First, the researchers find the damage and cut it out of the DNA the same way a cell does naturally, using what is called “base excision repair,” the discovery of which won a Nobel Prize in Chemistry this year for Tomas Lindahl, a scientist in England.

Second, an “unnatural base pair” is inserted at the snipped-out DNA damage site to label it. Instead of natural base pairs C-G and A-T, the Utah chemists used a so-called third or unnatural base pair invented by chemists at the Scripps Research Institute in California. Burrows says her study demonstrates the first practical use of that invention.

Third, the DNA with the damage site labelled by an unnatural third base pair is then amplified or copied millions of times using a well-known existing method called PCR, or polymerase chain reaction. Burrows says the new study’s key innovation was to use base excision repair to snip out the damage and then to insert the unnatural base pair at the damage site, making it possible to make millions of copies of the DNA – a process that normally would be prevented by the damage.

Fourth, another chemical label, named 18-crown-6 ether, is affixed to the unnatural base pair on all the DNA strands, which are then read or sequenced using a kind of nanopore sequencing developed a few years ago by Burrows and Utah chemist Henry White. Such sequencing involves determining the order and location of bases on a DNA strand – including damage sites labell ed by unnatural bases – by passing the strand through a molecule-size pore or nanopore.

People are born with their genome or genetic blueprint of 3 billion base pairs, “and then stuff happens,” Burrows says. “There’s damage from oxidative stress due to inflammation and infection, too much metabolism, or environmental chemicals.”

The new method seeks “molecular details that define how our genome responds to what we eat and the air we breathe, and ends up being healthy or not,” she says. University of Utah

Genes that act as brakes to stop the development of an aggressive form of leukaemia have been identified by researchers. Their findings offer fresh insights into how to tackle the disease and could lead to new therapies that prevent relapses.

Scientists have found that two molecules – Hif-1alpha and Hif-2alpha – work together to stop the formation of leukemic stem cells in an aggressive type of blood cancer called Acute Myeloid Leukaemia (AML). The cancer occurs when production of new blood cells by the bone marrow goes awry. This leads to the formation of leukemic stem cells, which fuel the disease and provide a constant flow of abnormal leukaemia cells.

The University of Edinburgh study shows that blocking Hif-2alpha – or both Hif-1alpha and Hif-2alpha – accelerates the development of leukaemia.  The findings are surprising because previous research had suggested that blocking Hif-1alpha or Hif-2alpha may stop leukaemia progression.

Researchers say that their new results suggest that therapies designed to block these molecules may have no impact or could even worsen disease.
Conversely, designing new therapies that promote the activity of Hif-1alpha and Hif-2alpha could help to treat AML or stop the disease from recurring after chemotherapy. University of Edinburgh