Under the banner “GeT Perfect”, Greiner Bio-One has kicked off the European promotion of the Greiner eHealth Technologies Solution – GeT. For this purpose, a modern microsite in German and English has been created. The one page site provides all essential information at a glance. GeT utilizes a flexible modular based software solution whilst applying the advantages of pre-barcoded VACUETTE tubes. The aim is to increase the efficiency of routine procedures in and around the laboratory. This page provides information on events, reference customers as well as study material. Testimonials from reference customers report on their experiences. Advantages of the system and working procedures can be seen in the form of videos and animation. All in all, the user has here a compact version of all initial information required for initiating any further steps.
www.gbo.com/get
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A gene involved in brain development that can lead to severe disability and infant death has been identified by scientists. Mutations in the gene cause profound developmental problems and seizures in young children, researchers have found. Scientists and doctors worked with children with a range of severe problems, including seizures and abnormal brain scans, and discovered that the infants all had mutations in a gene known as PLAA. The researchers have named the condition PLAA-associated neurodevelopment disorder, or PLAAND. By making a mouse with the same mutation as found in patients, the team – led by the University of Edinburgh – showed how this gene had to function properly for the healthy brain to develop. PLAA is essential for signalling cells to clear build-up of damaged proteins, which is crucial for brain cell function, the researchers say. Cells in children with PLAAND have lost this ability and damaged proteins build up, causing severe problems in brain development and at synapses – parts of brain cells that communicate with other cells. Insights learned from the study may enable scientists to uncover new drugs to treat this rare disease. They could also shed light on conditions such as Alzheimer’s disease, in which there is also an issue with damaged protein build up. Pinpointing mutations in this gene that lead to such severe outcomes in the affected children is an important advance. Children affected with PLAAND die before the age of six and most heart-breaking for their families is that they fail to meet any developmental milestones. There is no treatment currently available. In identifying this gene and the processes it controls, we have made significant steps in understanding its role in healthy brain development, which will help us target drug studies in future.
University of Edinburgh www.ed.ac.uk/news/2017/fatal-childhood-disorder-gene
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Following a three-year study of the Arizona State University football program, researchers at the Translational Genomics Research Institute (TGen) have created the largest dataset to date of extracellular small RNAs, which are potential biomarkers for diagnosing medical conditions, including concussions. The study amassed a collection of biomarkers from the ASU student-athletes’ biofluids: blood, urine and saliva. A portion of that information will be used with data from helmet sensors that recorded the number, intensity and direction of head impacts during games and practices from the 2013-16 football teams. TGen researchers are using that combined data to potentially develop new diagnostic and therapeutic tools. "Large datasets – examining different biofluids, isolation methods, detection platforms and analysis tools – are important to further our understanding of the extent and types of extracellular materials present when someone is injured or develops disease," said Dr. Kendall Van Keuren-Jensen, TGen Associate Professor of Neurogenomics and Co-Director of TGen’s Center for Noninvasive Diagnostics, and one of the study’s senior authors. "Concussion safety, protocol and diagnostics are key components of Sun Devil Athletics’ student-athlete welfare program," said Ray Anderson, ASU Vice President for University Athletics. "Our partnership with TGen and the research conducted with these biomarkers will ideally provide doctors, trainers and administrators with a mechanism to proactively safeguard the health of our student-athletes. We are proud and excited to be a part of this ground-breaking study that will significantly expand research in this important area of scientific discovery." Because the data is being published in an open access journal, they are available to aid other researchers studying how to develop tests for the detection and extent of injuries involving everything from automobile accidents to battlefield explosions. Sensors in the ASU student-athlete football helmets were wirelessly connected to a field-level computer as part of the Sideline Response System – a head impact monitoring and research tool developed and deployed by Riddell, a leading provider of helmets to the NFL and major college football teams. TGen researchers used advanced genomic sequencing to identify the biomarkers of extracellular RNA (exRNA), strands of genetic material that are released from cells, and which can be detected in biofluids. TGen sequenced these biomarkers from among 183 blood samples, 204 urine samples and 46 saliva samples derived from among 55 consenting student-athletes, ages 18-25. "The small RNA profile of each biofluid is distinct," the study said. "These data significantly contribute to the current number of sequenced exRNA samples from young healthy individuals." By identifying biofluids associated with healthy individuals, researchers hope to use these as standards for assessing disease and injury: "Establishing a baseline for individuals when they are healthy may provide the most meaningful comparisons when exploring early indicators of disease, severity or outcome," the study said.
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Why do some breast cancers respond to treatment while others resist it? A study led by researchers at the University of North Carolina Lineberger Comprehensive Cancer Center may provide insight into this important question.
The researchers report at the San Antonio Breast Cancer Symposium they have identified biomarkers they believe can be used as part of a larger model to predict how patients with HER2-positive operative breast cancer will respond to the targeted treatment trastuzumab, commercially known as Herceptin, and chemotherapy. “We’re trying to find biomarkers for resistance to trastuzumab treatment and chemotherapy,” said the study’s first author Maki Tanioka, MD, PhD, a postdoctoral research associate at UNC Lineberger. “What’s the cause of response? What’s the cause of resistance? That’s what we are trying to identify in this genomic study.”
Tanioka and his colleagues analysed multiple biologic features of cancer cells from 213 patients treated for HER2-positive breast cancer through a National Cancer Institute cooperative group clinical trial, CALGB 40601. The biologic features included multiple kinds of genetic information such as DNA mutations, DNA copy number and RNA gene expression data. The researchers found that certain gene signatures, and either having too many, or too few, of certain genes were predictive of whether patients responded to treatment, and that combining those two features was the most effective method of predicting response.
Examining features like mutations, amplifications or deletions of genes in tumour cells, the overall subtype of the tumour, as well as indicators of immune responses helped the researchers predict response. The researchers also determined that amplification of a specific chromosome, and a particular gene called MAPK14 on that chromosome, may be a predictor of sensitivity to treatment, while deletions of other genes predicted resistance.
The researchers say the next step is to identify another set of data to validate and broaden their findings.
“HER2-positive breast cancer is genomically heterogeneous,” Tanioka said. “Therefore, we need a model that incorporates all these different features. We are actively seeking a set of patient data that we can use to validate the biomarkers we have identified so we can create a comprehensive predictive model of response to allow us to better tailor treatment.”
University of North Carolina Lineberger Comprehensive Cancer Center http://tinyurl.com/grk84cg
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As more biomarker-based studies open, such testing will increase opportunities to match patients with clinical trials. Nearly three-quarters of patients with advanced cancer could be referred to a potential targeted treatment based on the results of a comprehensive analysis of their tumour’s genetic landscape, a new analysis finds. The study suggests the value of so-called next generation sequencing, a sophisticated method of evaluating the DNA and RNA of a tumour to help direct treatment. In a report on the first 500 patients with advanced solid tumours to go through the University of Michigan Comprehensive Cancer Center’s sequencing program, 72 percent qualified for a clinical trial based on a genetic marker in their tumour. Although not all of those patients were able to enroll in a trial based on other eligibility factors and trial location, the number who did enroll doubled from about 5 percent of patients in 2012 to 11 percent in 2016. Increased trial enrollment occurred as several major national biomarker-based studies opened. “Availability of biomarker trials is crucial for being able to act on these results. Over time, we became better at matching patients to clinical trials as more of these basket trials opened,” says Erin Cobain, M.D., clinical lecturer of haematology/oncology at the University of Michigan Medical School. As part of the sequencing program, patients with stage 4 cancer undergo a biopsy and provide a blood sample to test their normal DNA. Patients also receive genetic counselling. Results of the sequencing are discussed by a team of oncologists, genetics specialists, pathologists, bioinformatics specialists and genetic counsellors, among others, at a precision medicine tumour board. This group discusses all results and assesses the feasibility of pursuing treatment options based on the genomic findings. Genetic sequencing involves looking at all of the DNA and RNA expressed within a tumor. Scientists comb through this enormous amount of data to identify anomalies that may prove to be targets for existing approved or experimental therapies. In addition, the program sequences patients’ normal genome. This means it’s able to identify hereditary genetic variations, or those inherited from a mother or father and potentially passed down to children. Researchers found these hereditary variations in 11 percent of patients, none of which had been previously identified through family history. “That was a major surprise — that 11 percent of patients had a genetic change that increases cancer risk is much higher than we would expect. This has significant impact not only on the patients, but also on their families, who may carry a genetic susceptibility to cancer,” Cobain says. MI-ONCOSEQ requires a fresh biopsy, whereas many commercial sequencing tools can use frozen tissue samples. This ensures the U-M researchers can perform a more comprehensive analysis. Commercial tests analyse only about 350 genes while MI-ONCOSEQ’s more thorough analysis of both DNA and RNA covers at least 1,700 genes. This means many anomalies were identified that would not have been found on panel-based tests. Because MI-ONCOSEQ is run as a research study, patients do not pay for sequencing. Cobain cites an example of a patient with cholangiocarcinoma, a cancer of the bile duct. Sequencing revealed a novel gene fusion that would not have been identified through panel-based tests. The patient was able to enroll on a clinical trial targeting the gene fusion and had an excellent response to that therapy. “This would not have been found by a commercial assay,” Cobain says. “Sequencing is beginning to have a real impact on treatment recommendations. It’s important to consider this testing early in the patient’s clinical course in order to improve our ability to act on the results and impact the patient’s course.”
Michigan University labblog.uofmhealth.org/rounds/genetic-sequencing-can-influence-treatment-for-advanced-cancer
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Five simple medical tests together provide a broader and more accurate assessment of heart-disease risk than currently used methods, cardiologists at UT Southwestern Medical Center found. Combined, results from the five tests – an EKG, a limited CT scan, and three blood tests – better predict who will develop heart disease compared with standard strategies that focus on blood pressure, cholesterol, diabetes, and smoking history, researchers reported. “This set of tests is really powerful in identifying unexpected risk among individuals with few traditional risk factors. These are people who would not be aware that they are at risk for heart disease and might not be targeted for preventive therapies,” said Dr. James de Lemos, Professor of Internal Medicine. The five tests, and the information they provide:
A 12-lead EKG provides information about hypertrophy, or thickening of the heart muscle.
A coronary calcium scan, a low-radiation imaging test, identifies calcified plaque buildup in the arteries of the heart.
A blood test for C-reactive protein indicates inflammation.
A blood test for the hormone NT-proBNP indicates stress on the heart.
A blood test for high-sensitivity troponin T indicates damage to heart muscle. Troponin testing is regularly used by hospitals to diagnose heart attacks, but high-sensitivity troponin fine-tunes that measure, pointing to small amounts of damage that can be detected in individuals without any symptoms or warning signs.
Four of the five tests are currently readily available and the fifth – high-sensitivity troponin T – will be available soon. Researchers used data from two large population studies, including the Dallas Heart Study, that each followed a large group of healthy individuals for more than a decade. Their study was partly funded by NASA to develop strategies for predicting heart disease in astronauts. The new study focused on a broader spectrum of cardiovascular disease events rather than only those related to cholesterol plaque buildup, as traditional risk assessment does.
UT Southwestern Medical Center www.utsouthwestern.edu/newsroom/news-releases/year-2017/mar/risk-assessment-khera.html
Most of us would be lost without Google maps or similar route-guidance technologies. And when those mapping tools include additional data about traffic or weather, we can navigate even more effectively. For scientists who navigate the mammalian genome to better understand genetic causes of disease, combining various types of data sets makes finding their way easier, too.
A team at the Salk Institute has developed a computational algorithm that integrates two different data types to make locating key regions within the genome more precise and accurate than other tools. The method could help researchers conduct vastly more targeted searches for disease-causing genetic variants in the human genome, such as ones that promote cancer or cause metabolic disorders.
“Most of the variation between individuals is in noncoding regions of the genome,” says senior author Joseph Ecker, a Howard Hughes Medical Institute investigator and director of Salk’s Genomic Analysis Laboratory. “These regions don’t code for proteins, but they still contain genetic variants that cause disease. We just haven’t had very effective tools to locate these areas in a variety of tissues and cell types—until now.”
Only about two percent of our DNA is made up of genes, which code for proteins that keep us healthy and functional. For many years, the other 98 percent was thought to be extraneous “junk.” But, as science has developed ever more sophisticated tools to probe the genome, it has become clear that much of that so-called junk has vital regulatory roles. For example, sections of DNA called “enhancers” dictate where and when the gene information is read out.
Increasingly, mutations or disruption in enhancers have been tied to major causes of human disease, but enhancers have been hard to locate within the genome. Clues about them can be found in certain types of experimental data, such as in the binding of proteins that regulate gene activity, chemical modifications of proteins (called histones) that DNA wraps around, or in the presence of chemical compounds called methyl groups in DNA that turn genes on or off (an epigenetic factor called DNA methylation). Typically, computational methods for finding enhancers have relied on histone modification data. But Ecker’s new system, called REPTILE (for “regulatory-element prediction based on tissue-specific local epigenomic signatures”), combines histone modification and methylation data to predict which regions of the genome contain enhancers. In the team’s experiments, REPTILE proved more accurate at finding enhancers than algorithms that rely on histone modification alone.
“The novelty of this method is that it uses DNA methylation to really narrow down the candidate regulatory sequences suggested by histone modification data,” says Yupeng He, a Salk graduate student and first author of the paper. “We were then able to test REPTILE’S predictions in the lab and validate them with experimental data, which gave us a high degree of confidence in the algorithm’s ability to find enhancers.”
Salk Institute
www.salk.edu/news-release/finding-way-around-dna/
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Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or ‘Oudtshoorn skin’, in Afrikaners.
KWE causes a redness of the palms and soles with consecutive cycles of peeling of large sections of thick skin, often exacerbated during winter months. Oudtshoorn is a town in the Western Cape province of South Africa where the disorder was present in large families.
Afrikaners are Afrikaans-language speakers descended from predominantly Dutch, German and French settlers, who arrived in South Africa in the 17th and 18th centuries. Afrikaners have a high risk for several genetic disorders, the best known being familial hypercholesterolaemia (inherited high cholesterol leading to heart attacks early in life) and porphyria (sensitivity of the skin to ultra-violet exposure and adverse reactions to specific drugs).
These disorders are common because of founder mutations brought to South Africa by small groups of immigrants who settled in the Cape of Good Hope and whose descendants are now spread throughout the country. KWE is one of these less well-known founder genetic disorders.
KWE was first described as a unique and discrete skin disorder in 1977 by Wits dermatologist, Professor George Findlay. He noticed that it occurred in families and had a dominant mode of inheritance – i.e., on average, if a parent has the condition about half the children inherit it in every generation.
In addition to identifying the genetic mutation for scientific purposes, this research now enables dermatologists to make a definitive diagnosis of KWE in patients. It further enables researchers to understand similar skin disorders and is a starting point for developing possible treatments.
Chemistry researchers develop a simple diagnostic test that can identify the level of cocaine in a person’s urine or oral fluid. The new test offers a low cost, quick method that could be used for testing at the roadside, in the workplace or in prisons
Current commercially available portable testing kits can give false positive results and cannot tell how much cocaine a person has ingested
For the first time, the researchers have been able to prove that it is possible to confidently detect levels of cocaine and their metabolites using a compact ‘mass spectrometer’ (a chemical-based analytical technique). The test uses chromatography to separate cocaine from other compounds and can not only detect the presence of cocaine but also give quantitative data about the amount of cocaine a person has ingested.
The test was found to offer a level of sensitivity below the cut-off level normally used for oral fluid drug testing, meaning that it can detect even low levels of cocaine in a person’s urine or oral fluid. The technique potentially offers an effective solution for scenarios where a rapid test is required. This could include roadside testing by police of motorists, and also drug testing in the workplace and in prisons.
While there are a number of portable tests for cocaine commercially available, these are mainly based on antibody reagents, which cannot offer quantitative data and – since the cocaine antibody can bind to something that is not cocaine – can give false positive results.
The research paper’s lead author, Mahado Ismail of the University of Surrey, explained, “Surface mass spectrometry is used in a wide range of disciplines to obtain chemical information from the surface of a sample. However until now it has not been possible to translate this method to low cost, portable testing.
“This new method, which extracts analytes from a surface and separates them using chromatography, has been shown to provide a sensitive, accurate result. Our next step will be to test the efficacy of the system for monitoring other drugs of abuse, while we are also looking for follow-on funding to further develop the test.”
University of Surrey
http://tinyurl.com/z65q5du
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What can’t graphene do? You can scratch “detect cancer” off of that list.
By interfacing brain cells onto graphene, researchers at the University of Illinois at Chicago have shown they can differentiate a single hyperactive cancerous cell from a normal cell, pointing the way to developing a simple, non-invasive tool for early cancer diagnosis.
“This graphene system is able to detect the level of activity of an interfaced cell,” says Vikas Berry, associate professor and head of chemical engineering at UIC, who led the research along with Ankit Mehta, assistant professor of clinical neurosurgery in the UIC College of Medicine.
“Graphene is the thinnest known material and is very sensitive to whatever happens on its surface,” Berry said. The nanomaterial is composed of a single layer of carbon atoms linked in a hexagonal chicken-wire pattern, and all the atoms share a cloud of electrons moving freely about the surface.
“The cell’s interface with graphene rearranges the charge distribution in graphene, which modifies the energy of atomic vibration as detected by Raman spectroscopy,” Berry said, referring to a powerful workhorse technique that is routinely used to study graphene.
The atomic vibration energy in graphene’s crystal lattice differs depending on whether it’s in contact with a cancer cell or a normal cell, Berry said, because the cancer cell’s hyperactivity leads to a higher negative charge on its surface and the release of more protons.
“The electric field around the cell pushes away electrons in graphene’s electron cloud,” he said, which changes the vibration energy of the carbon atoms. The change in vibration energy can be pinpointed by Raman mapping with a resolution of 300 nanometers, he said, allowing characterization of the activity of a single cell.
The study looked at cultured human brain cells, comparing normal astrocytes to their cancerous counterpart, the highly malignant brain tumour glioblastoma multiforme. The technique is now being studied in a mouse model of cancer, with results that are “very promising,” Berry said. Experiments with patient biopsies would be further down the road.
“Once a patient has brain tumour surgery, we could use this technique to see if the tumour relapses,” Berry said. “For this, we would need a cell sample we could interface with graphene and look to see if cancer cells are still present.”
The same technique may also work to differentiate between other types of cells or the activity of cells.
University of Illinois at Chicago
news.uic.edu/first-use-of-graphene-to-detect-cancer-cells
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