EKF Diagnostics, the global in vitro diagnostics company, announces that it is expanding the distribution of its Procalcitonin LiquiColor Test into Eastern Europe, Middle East and APAC regions. Procalcitonin (PCT) is a marker for bacterial infection and sepsis, a condition that has grown in awareness in recent years. PCT is now widely recognized as an important adjunct marker in sepsis diagnosis which aids in the differentiation between viral and bacterial infections. Sepsis can quickly develop into severe sepsis and septic shock – conditions associated with signs of end-stage organ damage and hypotension. At this stage, risk of death is high and increases drastically the longer the initiation of treatment is delayed. However, if a patient receives antimicrobial therapy within the first hour of diagnosis, their chances of survival are close to 80%. This short window is therefore often referred to as ’the golden hour.’ EKF’s Stanbio Chemistry PCT assay can be used in conjunction with other tests, to rapidly assess initial severity of sepsis within the golden hour.  As it provides quantitative results within ten minutes, it helps physicians to monitor treatment and track improvements over time. The test is CE-marked and will shortly receive FDA approval. It is an open-channel immunoturbidimetric assay that can run with multiple sample types, providing a cost effective solution for many hospital laboratories. “We have started to see significant interest in Asia Pacific for PCT. Here we are working closely with three major distributors covering the Philippines, Indonesia and Vietnam to introduce PCT into hospitals,” said Trevor McCarthy, EKF’s Sales Manager. “As awareness about the severity of sepsis and the importance of early detection grows, we anticipate more and more interest globally in this product. FDA approval will help us build our brand, both in the Asian market and further afield.”
www.ekfdiagnostics.com

Fungal infections are a serious health risk. They can be harmful especially to patients whose immune system is compromised through illness or chemotherapy. A team working at the Technical University of Munich (TUM) has discovered an important mechanism in the body’s defences against fungi. The discovery explains, among other things, why people with certain genetic variations are more susceptible to fungal infections.

To fight pathogens such as viruses, bacteria and fungi, the body has a complex security system. The widespread notion of white blood cells operating as the ‘body police,’ tracking down and incapacitating invaders, falls far short of adequately describing how the immune system actually works. Before the body’s defence response gets started, complex chains of biochemical reactions occur at the molecular level. The scientists studying a certain immune reaction are often not yet aware of all links in these chains.

This is true, for example, in the case of the innate immune response to certain fungi studied by the team under Professor Jürgen Ruland, who holds the chair in Clinical Chemistry and Pathobiochemistry at TUM. It was known that the reaction began with protein elements known as C-type lectin receptors of blood and tissue cells recognizing certain molecules on fungus cells and triggering the chain reaction, also known as a signal pathway. It has also been known for some time that the protein CARD9 plays an important role in this chain. Only when CARD9 is present is it possible for the body to trigger an immune response that destroys the fungus cells.

Jürgen Ruland and his team demonstrated that before CARD9 can perform its role in the chain, molecules known as Vav proteins must be active. Three of these proteins occur in the human body: Vav1, Vav2 and Vav3. If all three are deactivated, the body is particularly susceptible to fungus infections even if CARD9 is present. As signal molecules, the Vav proteins play a role in various processes, including immune responses. ‘Previously, however, the functions of the Vav proteins were understood mainly as part of the acquired or adaptive immune system. Their functions in the innate immune response, which is the focus of our work, remain largely unexplored,’ explains Dr. Susanne Roth, the first author of the study. As the name suggests, the acquired immune response means that the body learns to fight off certain substances only in the course of a person’s life. By contrast, the substances resisted by the innate immune response are genetically determined before birth.

The researchers were also able to use patient data to demonstrate the importance of Vav proteins for innate immunity: A certain genetic variation was disproportionately represented among a group of people suffering from candidiasis, a yeast infection. The variation causes the protein Vav3 to occur in a slightly modified form. It was the absence of Vav3 that had the strongest impact on the immune response in past experiments.

The newly discovered role of the Vav proteins could be used in the future to design diagnostic approaches. ‘It would be conceivable to develop a risk profile for chemotherapy patients,’ says Jürgen Ruland. He suggests that genetic analysis could be used to determine which patients might be more susceptible to fungal infections.

EurekAlert www.eurekalert.org/pub_releases/2016-12/tuom-ieo121916.php

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/

A study of people from an isolated village in the Netherlands reveals a link between rare variants in the gene NKPD1 and depressive symptoms. The study, led by co-first authors Najaf Amin, PhD, of Erasmus University Medical Center in the Netherlands and Nadezhda Belonogova of the Russian Academy of Sciences in Novosibirsk, Russia, helps researchers understand the molecular pathology of the disease, which could eventually improve how depression is diagnosed and treated.
Genetics play a strong role in risk for depression, but the identification of specific genes contributing to the disorder has eluded researchers. "By sequencing all of the DNA that codes for mRNA and ultimately, proteins, Dr. Amin and colleagues found a single gene that may account for as much as 4% of the heritable risk for depression," said Doctor John Krystal, Editor of Biological Psychiatry.
To identify the gene, the researchers assessed data from the Erasmus Rucphen Family study, which was composed of a collection of families and their descendants living in social isolation until the past few decades. In a population like this, genetic isolation leads to an amplification of rarely occurring variants with little other genetic variation, providing a more powerful cohort for the discovery of rare variants. Nearly 2,000 people who had been assessed for depressive symptoms were included in the analysis.
Using whole-exome sequencing to examine portions of DNA containing genetic code to produce proteins, Amin and colleagues found that several variants of NKPD1 were associated with higher depressive symptom scores. The association between depressive symptoms and NKPD1 were also replicated in an independent sample of people from the general population, although the replication sample highlighted different variants within NKPD1.
"The involvement of NKPD1 in the synthesis of sphingolipids and eventually of ceramides is interesting," said Dr. Amin, referring to the predicted role of NKPD1 in the body. Altered sphingolipid levels in blood have been associated with depression and have been proposed as a therapeutic target for major depressive disorder.
"We are the first to show a possible genetic connection in this respect," said Dr. Amin, adding that this implies that such a therapy might be beneficial for patients carrying risk variants in the NKPD1 gene.
As with other psychiatric disorders, depression lacks genetic or biochemical markers to aid diagnosis and treatment of the disorder. According to Dr. Amin, moving depression treatment into the era of precision and personalized medicine will require a transition to objective and unbiased measurements where patients are stratified based on the molecular pathology of the disease. "NKPD1 may be one such molecular mechanism," she said.

ScienceDaily
www.sciencedaily.com/releases/2017/04/170404090027.htm

Using state-of-the-art molecular biology and statistical approaches, researchers at Dartmouth’s Norris Cotton Cancer Center (NCCC) have identified the functional role of two distinct DNA modifications in glioblastoma (GBM) tissues. The signature of one of these pattern disruptions in particular, 5hmC, had a particularly strong association with patient survival.

Glioblastoma (GBM) is a rare but deadly type of cancer that originates in the brain. Roughly 12,000 new cases are confirmed in the U.S. each year and its highly infiltrative nature renders it particularly difficult to treat.

One of the distorted molecular features of GBM is faulty epigenetic regulation. The epigenome involves modifications to DNA that dictate which genes are turned off and on within a particular cell-type. Defects here are known to contribute to cancer and current methods to predict brain tumour patient prognosis are based on epigenetic tumour subtypes. However, the epigenome is complex and there are recently discovered epigenetic marks that remain understudied in GBM.

Led by Cancer Center Member, Brock Christensen, PhD, Associate Professor of Epidemiology at Dartmouth’s Geisel School of Medicine, researchers broke new territory by analysing the profile of multiple DNA modifications, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5-hmC), in a set of 30 glioblastomas in collaboration with clinicians at NCCC. ‘An intense interest has emerged in detailing the functional role of distinct DNA modifications in both healthy and disease tissues,’ said Christensen. ‘Here, we uncovered that specific DNA 5mC and 5hmC patterns are disrupted in GBM and uniquely characterize the molecular switches of the genome known as ‘enhancers.’ Importantly, we discovered that 5hmC signatures had a particularly strong association with patient survival.’

Previous technical limitations prohibited scientists from simultaneously studying high-resolution 5mC and 5hmC levels in a cancer genome. The Dartmouth study utilizes state-of-the-art molecular biology and statistical approaches, including the Dartmouth Discovery Computing Cluster and Nano String nCounter technology, to identify the levels of the distinct DNA modifications across the critical regions of the genome. ‘Together, our work reveals more about the powerful influence of the epigenome in cancer and highlights the distinct functional role of 5hmC,’ explains Christensen.

Norris Cotton Cancer Center www.eurekalert.org/pub_releases/2016-11/dmc-drb112316.php