EKF Diagnostics has acquired Separation Technology, Inc. (STI), the Florida based manufacturer of in vitro diagnostics devices for hematology testing from Thermo Fisher Scientific, Inc. This acquisition complements EKF’s existing offering in the hemoglobin testing market place, which includes Hemo Control (also sold as HemoPoint H2 in USA and Asia). Notably, STI’s primary instrument is the UltraCrit hematocrit measurement device which is FDA-cleared for blood donor screening. STI develops, manufactures and markets specialty IVD devices including ultrasound instruments and tabletop centrifuges for the hematology testing market. STI also has an in-house engineering capability, including product design, production support and new product development. STI’s UltraCrit is the first and only hematocrit/hemoglobin device to use ultrasound technology. The hematocrit reading is displayed automatically in about 30 seconds and provides a hematocrit value that allows for standardization for all collections, including whole blood, apheresis and double red cell collections. UltraCrit uses reagentless cuvettes, a major point of differentiation between different analysers.

EKF Diagnosticswww.ekfdiagnostics.com

A newly identified difference between the brains of women and men with multiple sclerosis (MS) may help explain why so many more women than men get the disease, researchers at Washington University School of Medicine in St. Louis report.
In recent years, the diagnosis of MS has increased more rapidly among women, who get the disorder nearly four times more than men. The reasons are unclear, but the new study is the first to associate a sex difference in the brain with MS.
Studying mice and people, the researchers found that females susceptible to MS produce higher levels of a blood vessel receptor protein, S1PR2, than males and that the protein is present at even higher levels in the brain areas that MS typically damages.
‘It was a ‘Bingo!’ moment – our genetic studies led us right to this receptor,’ said senior author Robyn Klein, MD, PhD. ‘When we looked at its function in mice, we found that it can determine whether immune cells cross blood vessels into the brain. These cells cause the inflammation that leads to MS.’
An investigational MS drug currently in clinical trials blocks other receptors in the same protein family but does not affect S1PR2. Klein recommended that researchers work to develop a drug that disables S1PR2.
MS is highly unpredictable, flaring and fading at irregular intervals and producing a hodgepodge of symptoms that includes problems with mobility, vision, strength and balance. More than 2 million people worldwide have the condition.
In MS, inflammation caused by misdirected immune cells damages a protective coating that surrounds the branches of nerve cells in the brain and spinal column. This leads the branches to malfunction and sometimes causes them to wither away, disrupting nerve cell communication necessary for normal brain functions such as movement and co-ordination.
For the new research, Klein studied a mouse model of MS in which the females get the disease more often than the males. The scientists compared levels of gene activity in male and female brains. They also looked at gene activity in the regions of the female brain that MS damages and in other regions the disorder typically does not harm.
They identified 20 genes that were active at different levels in vulnerable female brain regions. Scientists don’t know what 16 of these genes do. Among the remaining genes, the increased activity of S1PR2 stood out because researchers knew from previous studies that the protein regulates how easy it is for cells and molecules to pass through the walls of blood vessels.
Additional experiments showed that S1PR2 opens up the blood-brain barrier, a structure in the brain’s blood vessels that tightly regulates the materials that cross into the brain and spinal fluid. This barrier normally blocks potentially harmful substances from entering the brain. Opening it up likely allows the inflammatory cells that cause MS to get into the central nervous system.
When the researchers tested brain tissue samples obtained from 20 patients after death, they found more S1PR2 in MS patients’ brains than in people without the disorder. Brain tissue from females also had higher levels of S1PR2 than male brain tissue. The highest levels of S1PR2 were found in the brains of two female patients whose symptoms flared and faded irregularly, a pattern scientists call relapsing and remitting MS.
Klein is collaborating with chemists to design a tracer that will allow scientists to monitor S1PR2 levels in the brains of people while they are living. She hopes this will lead to a fuller understanding of how S1PR2 contributes to MS. Washington University School of Medicine

Using next generation DNA sequencing, Dartmouth scientists have identified potentially actionable mutations in cancers of the appendix. When specific mutations for a cancer type are identified, patients can be treated with chemotherapy or other targeted agents that work on those mutations.
Little is known about the molecular biology of two types of appendix tumours, low-grade appendiceal mucinous neoplasm (LAMN) and adenocarcinoma, but both can lead to pseudomyxoma peritonea (PMP), a critical condition in which cancerous cells grow uncontrollably along the wall of the abdomen and can crush digestive organs.

Dartmouth pathologists studied 38 specimens of LAMN and adenocarcinoma tumors (some of which had progressed to PMP) from their archives to look for shared genetic errors that might be responsible for the abnormal cell growth. Tissue samples were sequenced using the AmpiSeq Hotspot Cancer Panel v2, which pathologists had verified for the clinical screening of mutations in 50 common cancer-related genes for which treatments exist. This was the first study making use of a multigene panel in appendiceal cancers to support the use of potential targeted therapies.

‘We routinely use this molecular profiling approach on all of our lung adenocarcinomas, melanomas, colon cancers, and gliomas,’ said Gregory Tsongalis, PhD, principal investigator for the study and director of Molecular Pathology at Dartmouth-Hitchcock Norris Cotton Cancer Center. He says examining an individual tumour profile has the potential to significantly alter patient outcome in a positive way.

KRAS and GNAS mutations were the most common alterations identified in the study. Twelve distinct abnormalities were mapped to the KRAS gene. Additional mutations were identified (i.e., AKT1, APC, JAK3, MET, PIK3CA, RB1, and STK11 for LAMN and TP53, GNAS, and RB1 for adenocarcinoma) in the four sample types studied. Seven of these mutations were shared by more than one group, which suggests there is some molecular similarity.

‘These findings suggest that tumours of the appendix, although rare and very aggressive, are distinct entities and have subclasses of disease within each category that are different from each other based on their mutation profile,’ said Tsongalis. ‘New therapeutic approaches may be able to target those pathways that are mutated in these tumour types.’

This laboratory research has the potential to change clinical practice if physicians now develop treatment plans to target the identified genetic mutations. ‘Our success in the Dartmouth-Hitchcock Medical Center Department of Pathology at the Norris Cotton Cancer Center is attributed to our multidisciplinary approach to these discoveries, which truly allow us to bring scientific findings from the bench to the bedside,’ said Tsongalis. Norris Cotton Cancer Center at Dartmouth-Hitchcock

Prostate cancer is a leading cause of cancer-related death in men in the United States. The development and progression of the disease depend on the actions of male sex hormones called androgens, which bind to the androgen receptor to activate signalling pathways involved in cell growth and survival. Therefore, there is a strong need to identify novel drug targets to alter androgen-receptor signalling and treat this often deadly disease.

Sanford-Burnham researchers have discovered that a protein called NWD1 affects androgen-receptor signalling to control the growth of prostate cancer cells. ‘A very limited number of proteins have been shown to specifically and exclusively affect androgen-receptor signalling, so our findings represent a major advance in the field,’ said lead study author Ricardo Correa, Ph.D., staff scientist at Sanford-Burnham. ‘NWD1 could represent a new biomarker for predicting patient prognosis as well as a therapeutic target for a novel class of prostate cancer drugs.’
High levels of androgens are critical for the growth of prostate cancer cells in early disease stages, and one major type of therapy focuses on inhibiting androgens. But over time, prostate cancer cells often respond to hormone therapy by expressing high levels of the androgen receptor, allowing these castration-resistant cells to grow even when androgen levels are low. Castration-resistant prostate cancer is an advanced form of the disease associated with poor survival rates. However, both early and advanced stages of prostate cancer depend on androgen-receptor signalling, highlighting the value of targeting this pathway for treating a broad range of patients.

While searching for novel modulators of androgen-receptor signalling, Correa and his team became interested in the nucleotide-binding domain and leucine-rich repeat (NLR) family of proteins. These proteins are involved in recognising pathogens and cell-injury signals and activating immune-defence pathways, but they have also been implicated in a variety of cancers. In particular, the researchers were intrigued by an NLR-related protein called NWD1, which was previously identified in zebrafish but had not yet been analyzed in humans.

In the new study, Correa and his colleagues found that the expression of the human NWD1 gene was very high in prostate tissue and other parts of the male reproductive system. Moreover, NWD1 expression was higher than normal in human prostate cancer cell lines, especially in castration-resistant and highly metastatic cell lines. Similarly, NWD1 protein levels were higher than normal in advanced-stage and castration-resistant prostate tumour tissue from patients.

Taken together, the findings suggest that NWD1 could be a potential prostate cancer biomarker because high levels of the protein are associated with malignant progression. ‘We believe that NWD1 could represent a promising biomarker because changes in NWD1 expression happen at stages where the levels of prostate-specific antigen (PSA), a protein that is widely used to screen men for prostate cancer, are not very accurate in the clinic,’ Correa said.
In addition to its potential use for predicting patient prognosis, NWD1 could represent a promising therapeutic target. When the researchers inhibited the activity of the NWD1 gene in prostate cancer cells, they noticed a drop in androgen-receptor levels as well as a decrease in cell growth and survival. On the other hand, an increase in NWD1 activity led to a rise in androgen-receptor levels in these cells.

Their experiments also shed light on the molecular mechanisms by which NWD1 affects androgen-receptor signalling. NWD1 silencing fed the activity of cancer-related genes such as PDEF (prostate-derived epithelial factor), which is known to bind to androgen receptors and belongs to a family of proteins that regulate cell growth and survival. Moreover, a protein called sex-determining region Y (SRY), which controls sex determination during fetal development, affected the activity of the NWD1 gene. Thus, the findings not only reveal a novel molecular pathway involved in prostate cancer, but also suggest that drugs targeting NWD1 could eventually become a new class of treatments for the disease. Sanford-Burnham

Findings should help narrow the search for genetic contributions of autism and suggest new routes for therapy
‘Aha’ moments are rare in medical research, scientists say. As rare, they add, as finding mice with Mohawk-like hairstyles.
But both events happened in a lab at NYU Langone Medical Center, months after an international team of neuroscientists bred hundreds of mice with a suspect genetic mutation tied to autism spectrum disorders.
Almost all the grown mice, the NYU Langone team observed, had sideways,’overgroomed’ hair with a highly stylised centre hairline between their ears and hardly a tuft elsewhere. Mice typically groom each other’s hair.
Researchers say they knew instantly they were on to something, as the telltale overgrooming — a repetitive motor behaviour — had been linked in other experiments in mice to the brain condition that prevents children from developing normal social, behavioural, cognitive, and motor skills. People with autism, the researchers point out, exhibit noticeably dysfunctional behaviours, such as withdrawal, and stereotypical, repetitive movements, including constant hand-flapping, or rocking.
Now and for what NYU Langone researchers believe to be the first time, an autistic motor behaviour has been traced to specific biological pathways that are genetically determined.
The findings, says senior study investigator Gordon Fishell, PhD, the Julius Raynes Professor of Neuroscience and Physiology at NYU Langone, could with additional testing in humans lead to new treatments for some autism, assuming the pathways’ effects as seen in mice are reversible.
In the study, researchers knocked out production in mice of a protein called Cntnap4. This protein had been found in earlier studies in specialized brain cells, known as interneurons, in people with a history of autism.
Researchers found that knocking out Cntnap4 affected two highly specialized chemical messengers in the brain, GABA and dopamine. Both are so-called neurotransmitters, chemical signals released from one nerve cell to the next to stimulate similar sensations throughout the body. GABA, short for gamma-aminobutyric acid, is the main inhibitory neurotransmitter in the brain. It not only helps control brain impulses, but also helps regulate muscle tone. Dopamine is a well-known hormonal stimulant, highly touted for producing soothing, pleasing sensations.
Among the researchers’ key findings was that in Mohawk-coiffed mice, reduced Cntnap4 production led to depressed GABA signalling and overstimulation with dopamine. Researchers say the lost protein had opposite effects on the neurotransmitters because GABA is fast acting and quickly released, so interfering with its action decreases signalling, while dopamine’s signalling is longer-acting, so impairing its action increases its release.
‘Our study tells us that to design better tools for treating a disease like autism, you have to get to the underlying genetic roots of its dysfunctional behaviours, whether it is overgrooming in mice or repetitive motor behaviours in humans,’ says Dr. Fishell. ‘There have been many candidate genes implicated in contributing to autism, but animal and human studies to identify their action have so far not led to any therapies. Our research suggests that reversing the disease’s effects in signalling pathways like GABA and dopamine are potential treatment options.’
The U.S. Centers for Disease Control and Prevention estimate that one in 68 American children under age 8 has some form of autism, with five times as many boys as girls suffering from the spectrum of disorders.
As part of their study, researchers performed dozens of genetic, behavioural, and neural tests with growing mice to isolate and pinpoint where Cntnap4 acted in their brains, and how it affected chemical signalling among specific interneuron brain cells, which help relay and filter chemical signals between neurons in localised areas of the brain.
They found that Cntnap4 in mature interneurons strengthened GABA signalling, but did not do so in younger interneurons. When researchers traced where Cntnap4 acted in immature brain cells, Dr. Fishell says tests showed that it stimulated ‘a big bolus of dopamine.’
As part of testing to confirm the hereditary link among Cntnap4, the two pathways, and grooming behaviours, researchers exposed young mice with normal levels of Cntnap4, who did not groom each other, to mature mice with and without Cntnap4. Only mature mice deficient in Cntnap4 preened the hairstyle on other mice. Further tests in young mice without Cntnap4 showed that other, mature mice with normal amounts of Cntnap4 largely let them be, without any particular grooming or hairstyle. EurekAlert