Researchers have identified a novel mutation that may be associated with prostate cancer in African American men, according to a new study.

Scientists have long known that a huge variety of DNA mutations can lead to cancer. Some proteins can repair DNA mutations, but when repair proteins are mutated themselves, cancer may arise. Knowing which mutations are linked to which cancer types helps scientists develop new targeted treatments and detection strategies.

To improve knowledge of mutations associated with prostate cancer, Alice Walker of The University of North Texas, and colleagues searched for relevant mutations in genes that code for a family of DNA repair proteins known as AlkBH.

The researchers ran two separate datasets of DNA sequences through a software program called HyDn-SNP-S, which had previously been developed by members of the team. The software allowed them to compare DNA sequences of AlkBH family proteins from healthy genomes, to those found in genomes derived from prostate cancer tumours. In both datasets, a mutation in the gene that codes for a protein called ALKBH7 was significantly associated with prostate cancer in African American men.

Next, the researchers used computer simulations to investigate how the ALKBH7 mutation, R191Q, would affect the protein’s structure. They found that the mutation might cause a structural change that significantly decreases the ability of the protein to perform its normal role. Spectroscopy experiments with actual protein samples confirmed these predictions.

According to study co-author G. Andrés Cisneros of the University of North Texas, the next steps for research are further experimental exploration of how the R191Q mutation is related to prostate cancer, as well as investigation of potential new avenues for detection and treatment based on the mutation.

‘Scanning the DNA of individuals in the target population for this mutation could help indicate those with a higher risk of developing prostate cancer before symptoms are evident,’ Walker says.

EurekAlertwww.eurekalert.org/pub_releases/2017-02/p-nmm021617.php

New research suggests that GlycA, a newly identified blood marker, and C-reactive protein both independently predict major adverse cardiac events, including heart failure and death. Patients who have high levels of both biomarkers are at especially high risk.
 
That’s the finding of researchers from the Intermountain Medical Center Heart Institute in Salt Lake City, who teamed with LipoScience Laboratories to examine the markers to see if the two proteins, each previously linked to inflammation, are independent or related and whether either or both can identify patients at elevated risk for cardiovascular events.
 
The research grew out of an earlier analysis that paired plasma samples collected as part of the Intermountain Heart Collaborative Study with an assay developed by LipoScience that uses nuclear magnetic resonance technology to measure, among other things, the particle numbers in low-density lipoprotein (LDL) cholesterol, often called “bad” cholesterol. While scanning the plasma samples with the nuclear magnetic resonance technology, LipoScience had detected the GlycA and determined it to be a novel marker of inflammation.
 
Early research by the Intermountain Medical Center Heart Institute team showed that GlycA can predict heart attack risk; inflammation makes it more likely cholesterol plaques will rupture.
 
GlycA didn’t predict coronary artery disease nearly as well, said Brent Muhlestein, MD, co-director of cardiology research at Intermountain Medical Center and the study’s lead author.
 
C-reactive protein has already been shown to accurately predict adverse heart events and coronary artery disease, so the researchers wondered if the two are independent of each other, or if GLycA just offers another way to measure the effects of CRP.
 
Using the same plasma samples — part of more than 30,000 DNA samples collected over the course of 25 years by the Intermountain Medical Center Heart Institute— the researchers compared the value of both GlycA and CRP in predicting future heart attacks, strokes, or death.
 
For the study, nearly 3,000 patients undergoing coronary angiography were followed, two-thirds of them male. Sixty-five percent of them had been diagnosed with coronary artery disease, 42 percent with acute coronary syndrome, and 26 percent with diabetes.
 
“The correlation between GlycA and CRP was only modest,” said Dr. Muhlestein. “Some patients had a high level of one and a low level of the other and vice versa. But the two proteins independently predicted future risk, and if you had both, it was the worst scenario completely. It tells us that GlycA is perhaps something important.”
 
How important will be the focus for future research. Dr. Muhlestein said his research team would like to identify exactly what GlycA is, what it does, and the underlying physiology of its connection to inflammation.

Intermountain Medical Center Heart Institute
intermountainhealthcare.org/news/2017/03/people-who-have-high-levels-of-two-cardiac-markers-at-high-risk-of-heart-failure-and-death/

An algorithm based on levels of metabolites found in a blood sample can accurately predict whether a child is on the Autism spectrum of disorder (ASD), based upon a recent study. The algorithm, developed by researchers at Rensselaer Polytechnic Institute, is the first physiological test for autism and opens the door to earlier diagnosis and potential future development of therapeutics.
 
“Instead of looking at individual metabolites, we investigated patterns of several metabolites and found significant differences between metabolites of children with ASD and those that are neurotypical. These differences allow us to categorize whether an individual is on the Autism spectrum,” said Juergen Hahn, lead author, systems biologist, professor, and head of the Rensselaer Department of Biomedical Engineering. “By measuring 24 metabolites from a blood sample, this algorithm can tell whether or not an individual is on the Autism spectrum, and even to some degree where on the spectrum they land.”
 
Big data techniques applied to biomedical data found different patterns in metabolites relevant to two connected cellular pathways that have been hypothesized to be linked to ASD: the methionine cycle and the transulfuration pathway. The methionine cycle is linked to several cellular functions, including DNA methylation and epigenetics, and the transulfuration pathway results in the production of the antioxidant glutathione, decreasing oxidative stress.
 
Autism Spectrum Disorder is estimated to affect approximately 1.5 percent of individuals and is characterized as “a developmental disability caused by differences in the brain,” according to the Centers for Disease Control and Prevention. The physiological basis for ASD is not known, and genetic and environmental factors are both believed to play a role. People with ASD “may communicate, interact, behave, and learn in ways that are different from most other people.” According to the CDC, the total economic costs per year for children with ASD in the United States are estimated between $11.5 billion and $60.9 billion. Research shows that early intervention can improve development, but diagnosis currently depends on clinical observation of behavior, an obstacle to early diagnosis and treatment. Most children are not diagnosed with ASD until after age 4 years.

Rensselaer Polytechnic Institute
news.rpi.edu/content/2017/03/16/blood-test-autism

An overactive molecular signal pathway in the brain region of the amygdala can lead to obsessive-compulsive disorder (OCD). A research team from Würzburg has established this connection.
Some people have an extreme fear of dirt or bacteria. As a result, they may develop a habit of compulsive washing and repeatedly cleaning their hands or body. They are trapped in a vicious circle, as the fear of new contamination returns quickly after washing. Sufferers see no way out. They are even incapable of changing their behaviour when the excessive washing has led to skin irritation or damage. 
Around two percent of the general population suffer from some kind of obsessive-compulsive disorder (OCD) at least once in their life. The disorder is characterised by persistent intrusive thoughts which the sufferers try to compensate for by repetitive ritualized behaviour. 
Like depression, eating disorders and other mental diseases, OCD is treated with antidepressants. However, the drugs are non-specific, that is they are not tailored to the respective disease. Therefore, scientists have been looking for new and better targeted therapies that have fewer side effects.
Professor Kai Schuh from the Institute of Physiology at the Julius-Maximilians-Universität (JMU) Würzburg (Germany) and his team explore the underlying causes of obsessive-compulsive disorder in collaboration with the JMU’s Departments of Psychiatry and Neurology. 
"We were able to show in mouse models that the absence of the protein SPRED2 alone can trigger an excessive grooming behaviour," Schuh says. He believes that this finding is crucial as no clear trigger for this type of disorder has been identified until now. Previous research pointed to multiple factors being responsible for developing OCD. 
Occurring in all cells of the body, the protein SPRED2 is found in particularly high concentrations in regions of the brain, namely in the basal ganglia and the amygdala. Normally, the protein inhibits an important signal pathway of the cell, the so-called Ras/ERK-MAP kinase cascade. When it is missing, this signal pathway is more active than usual.
"It is primarily the brain-specific initiator of the signal pathway, the receptor tyrosine kinase TrkB, that is excessively active and causes the overshooting reaction of the downstream components", biologist Dr. Melanie Ullrich explains.
Administering an inhibitor to attenuate the overactive signal cascade in the animal model improves the obsessive-compulsive symptoms. Moreover, the JMU research team was able to treat the OCD with an antidepressant, similarly to standard therapy in humans. 
"Our study delivers a valuable new model that allows the disease mechanisms to be investigated and new therapy options for obsessive-compulsive disorders to be tested," Professor Schuh says. 
The recently discovered link between OCDs and the Ras/ERK-MAP kinase cascade also opens up new targets for therapy. Drugs that inhibit this cascade are already available and some of them are approved for human treatment.
According to Melanie Ullrich, these are cancer drugs, as overactivation of the Ras/ERK-MAP kinase cascade is also a frequent trigger of cancer: "So we are wondering whether such drugs could also be effective in the treatment of obsessive-compulsive disorders and whether they are beneficial in terms of side effects."

University of Würzburg
www.uni-wuerzburg.de/en/sonstiges/meldungen/detail/artikel/ursache-fuer-zwangsstoerungen-entdeckt-1/