Researchers at the University of Pittsburgh have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge the existing dogma about how neurons that release the chemical signal dopamine communicate, and may have important implications for many dopamine-related diseases, including schizophrenia, Parkinson’s disease and addiction.
Neurons communicate with one another by releasing chemicals called neurotransmitters, such as dopamine and glutamate, into the small space between two neurons that is known as a synapse. Inside neurons, neurotransmitters awaiting release are housed in small sacs called synaptic vesicles.
“Our findings demonstrate, for the first time, that neurons can change how much dopamine they release as a function of their overall activity. When this mechanism doesn’t work properly, it could lead to profound effects on health,” explained the study’s senior author Zachary Freyberg, M.D., Ph.D., who recently joined Pitt as an assistant professor of psychiatry and cell biology. Freyberg initiated the research while at Columbia University.
When the researchers triggered the dopamine neurons to fire, the neurons’ vesicles began to release dopamine as expected. But then the team noticed something surprising: additional content was loaded into the vesicles before they had the opportunity to empty. Subsequent experiments showed that this activity-induced vesicle loading was due to an increase in acidity levels inside the vesicles.
“Our findings were completely unexpected,” said Freyberg. “They contradict the existing dogma that a finite amount of chemical signal is loaded into a vesicle at any given time, and that vesicle acidity is fixed.”
The team then demonstrated that the increase in acidity was driven by a transport channel in the cell’s surface, which allowed an influx of negatively charged glutamate ions to enter the neuron, thus increasing its acidity. Genetically removing the transporter in fruit flies and mice made the animals less responsive to amphetamine, a drug that exerts its effect by stimulating dopamine release from neurons.
“In this case, glutamate is not acting as a neurotransmitter. Instead it is functioning primarily as a source of negative charge, which is being used by these vesicles in a really clever way to manipulate vesicle acidity and therefore change their dopamine content,” Freyberg said. “This calls into question the whole textbook model of vesicles as having fixed amounts of single neurotransmitters. It appears that these vesicles contain both dopamine and glutamate, and dynamically modify their content to match the conditions of the cell as needed.”
In the future, the team plans to look more closely at how increases in vesicle acidification affect health. A number of brain diseases are characterized by abnormal dopamine neuron signalling and altered levels of the neurotransmitter.
“Since we have demonstrated that the balance between glutamate and dopamine is important for controlling the amount of dopamine that a neuron releases, it stands to reason that an imbalance between the two neurotransmitters could be contributing to symptoms in these diseases,” said Freyberg.
University of Pittsburghhttp://tinyurl.com/y7laad5d

ClearLLab reagents are the first to receive Food and Drug Administration (FDA) clearance (via the De Novo Process) to market them in the US.  They deliver the first preformulated, IVD antibody cocktails for leukemia and lymphoma immunophenotyping in the clinical lab. For clinical laboratories it means they no longer have to develop their own laboratory developed test (LDT), a technically demanding, manual, time-consuming, and potentially error-prone process. Previously, labs would have had to make and validate their own antibody cocktails.  ClearLLab reagents simplify and standardize the process.
 ‘FDA allows marketing of test to aid in the detection of certain leukemias and lymphomas’ with the FDA confirming that the test ‘provides consistent results to aid in the diagnoses of these serious cancers’.  The FDA evaluated data from a multi-site clinical study which compared panel results to alternative detection methods.
Dr Mario Koksch, Vice President and General Manager of Beckman Coulter’s Cytometry Business Unit said: “Flow cytometry is a powerful tool for the detailed and fast analysis of complex populations, with the technique becoming increasingly valuable to the clinical hematology laboratory. “Clearance to market the first IVD L&L reagents in the US has opened the door to the expansion globally of our clinical reagent and instrument portfolio.”  
ClearLLab reagents deliver fast and accurate qualitative identification of various hematolymphoid cell populations by immunophenotyping on the FC500 flow cytometer.  With the reliability of a standardized kit and protocols, the preformulated combinations offer LEAN-focused benefits which reduce manual preparation and validation time, accelerate sample preparation time, improve workflow, streamline lab inventory management and provide confidence in the accuracy and reliability of results.
As Dr Koksch added: “The routine use of ready-to-use ClearLLab reagents delivers greater efficiency and cost savings.  Preformulated antibody combinations enable the lab to avoid the potential errors of manual antibody cocktail preparation, with the reassurance of standardized reporting to international guidelines.”
ClearLLab reagents follow the 2006 Bethesda International Consensus Recommendations on the Flow Cytometric Immunophenotypic Analysis of Hematolymphoid Neoplasia. They are compatible with the World Health Organization (WHO) 2016-revised classification of myeloid neoplasms and acute leukemia.  WHO, in collaboration with the European Association for Hematopathology and the Society for Hematopathology, recently made important changes to the classification of these diseases. These included new criteria for the recognition of some previously described neoplasms as well as clarification and refinement of the defining criteria for others. www.beckman.com

In an effort to provide customers with expanded, more comprehensive solutions for molecular testing, Siemens Healthineers has announced a new strategic relationship with Fast-track Diagnostics (FTD) that includes the addition of FTD’s broad range of CE-marked kits and multisyndromic panels to the menu of the Siemens Healthineers VERSANT kPCR Molecular System. The addition of FTD’s broad menu of kits and panels – which cover conditions from respiratory to gastroenteritis to central nervous system (CNS) and childhood infections – increases the breadth of Siemens Healthineers’ complete molecular testing solution, ensuring leading-edge performance from extraction through detection and increasing workflow efficiency for molecular labs of all sizes.
 “Over the past 24 months, Siemens Healthineers has made significant advancements in the delivery of molecular diagnostic applications and services,” says Fernando Beils, Head of Molecular Diagnostics, Siemens Healthineers. “We continue to strengthen and broaden our Molecular System by offering a comprehensive, scalable solution for accurate diagnosis and monitoring to our customers worldwide through our alliance with Fast-track Diagnostics.”
The VERSANT kPCR Molecular System, an established market player in molecular testing for HIV and Hepatitis, will now feature over 75 assays, consolidating testing for the infectious disease spectrum in a single molecular ecosystem.
“The VERSANT kPCR Molecular System is perfectly suited to our wide range of assays, which means laboratories can now diagnose nearly any infectious disease in one workflow,” says Bill Carman, CEO of Fast-track Diagnostics.
In offering customers the option of a single, consolidated system with a broad menu and virtually open platform, Siemens Healthineers enables healthcare providers to meet their current challenges, especially as an increasing push towards a value-based healthcare philosophy relies heavily on increased productivity and streamlined workflows. With this in mind, Siemens Healthineers has made its growth and enhancement within the molecular diagnostics space a key priority for its business strategy moving forward. www.siemens.com/healthineerswww.fast-trackdiagnostics.com

Following the presentation to the European market at EuroMedLab in Athens and to the US market at AACC 2017 of the Thermo Scientific Cascadion SM Clinical Analyser bringing together the ease of use of clinical analysers with the selectivity and sensitivity of liquid chromatography-tandem mass spectrometry (LC-MS/MS), the company will now seek CE marking  followed by FDA approval.
“This is a marvelous development, and it is really quite outstanding. It will fulfill the needs of many laboratories,” said Professor Brian Keevil, consultant clinical scientist and head of the Clinical Biochemistry Department, University Hospital of South Manchester NHS Foundation Trust, UK, after viewing a demonstration during EuroMedLab 2017.
The Cascadion system was designed and built using Thermo Fisher products and technologies combined with its industry-leading expertise in mass spectrometry.  Featuring turnkey operation, the Cascadion analyser is designed to be used by laboratory staff with no specialized training.
James Nichols, PhD, medical director, Chemistry and Point of Care Testing, Vanderbilt University Medical Center, added, “For much of what we do in terms of chromatography and mass spectrometry, we need very highly skilled and experienced medical technologists. The Cascadion analyser is relatively maintenance-free and because it includes specially designed reagent kits, there is not a lot of interaction required with the technology.”
After previewing the Cascadion analyser, Michael Vogeser, senior physician and professor of laboratory medicine, University Hospital of Munich, stated “About 70% of all physician’s decisions are based on laboratory tests so the impact on laboratory testing is huge and this completely new technological approach is of enormous value to mankind.” www.thermofisher.com/Cascadion