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Simple, Inexpensive Blood Test Detects Alzheimer’s Years Before Symptoms Occur

There is currently no cure for Alzheimer’s disease. It is often argued that progress in drug research has been hampered by the fact that the disease can only be diagnosed when it is too late for an effective intervention. Alzheimer’s disease is thought to begin long before patients show typical symptoms like memory loss. Scientists have now developed a blood test for Alzheimer’s disease and found that it can detect early indicators of the disease long before the first symptoms appear in patients. The blood test would thus offer an opportunity to identify those at risk and may thereby open the door to new avenues in drug discovery. The research was published online on April 6, 2018 in EMBO Molecular Medicine. The open-access article is titled “Amyloid Blood Biomarker Detects Alzheimer's Disease.” One of the hallmarks of Alzheimer's disease is the accumulation of amyloid-β plaques in the patient’s brain. The blood test, developed by Dr. Klaus Gerwert and his team at Ruhr University Bochum, Germany, works by measuring the relative amounts of a pathological and a healthy form of amyloid-β in the blood. The pathological form is a misfolded version of this molecule and known to initiate the formation of toxic plaques in the brain. Toxic amyloid-β molecules start accumulating in the patients’ body 15-20 years before disease onset. In the present study, Dr. Gerwert and colleagues from Germany and Sweden addressed whether the blood test would be able to pick up indications of pathological amyloid-β in very early phases of the disease. The researchers first focused on patients in the early, so-called “prodromal” stages of the disease from the Swedish BioFINDER cohort conducted by Dr. Oskar Hanson.

Germ Cells in the Teleost Fish Medaka Have an Inherent Feminizing Effect

The gender of living organisms is determined either by genetic factors and/or by environmental factors. Interestingly, however, a team of researchers led by Nagoya University scientists previously found that the occurrence of more germ cells - biological cells capable of uniting with one from the opposite sex to form a new individual - in female medaka (teleost fish) gonads is essential for female differentiation of gonads. When germ cells are removed in medaka, XX (female) fish show female-to-male sex reversal, while XY (male) fish with excessive germ cells, which is usually associated with egg production, exhibit male-to-female sex reversal. "This finding implies that, in addition to the most well- known role of germ cells developing into eggs or sperm and produce the next generation, germ cells have a unique and surprising potential to change their surrounding environment," says Dr. Toshiya Nishimura, first author of the current study. "However, the molecular basis of, and the stage of gametogenesis critical for, feminization remain unknown." This question set the researchers to delve more deeply into the topic. In their latest study, they generated three different medaka mutants to demonstrate that the feminizing effect of germ cells is not a result of the progression of gametogenesis or a sexual fate decision of germ cells. They found that the different stages of germ cells in XX mutants have an ability to feminize the gonads, resulting in the formation of gonads with ovarian structures. In addition to normal ovarian development, the increased number of gonocytes (fetal and neonatal germ cells) is sufficient for male-to-female sex reversal in XY medaka.

Somatic Genomic Editing Will Enable Precision Tumor Modeling and “Greatly Accelerate the Pre-Clinical Testing of Novel Targeted Therapies” for Cancer

Researchers from the Seve Ballesteros Foundation-CNIO Brain Tumor Group at the Spanish National Cancer Research Centre (CNIO) have developed an extremely powerful and versatile mouse model that will improve cancer research and accelerate pre-clinical testing of novel targeted therapies. Their work was published online on April 13, 2018 in Nature Communications. The open-access article is titled “Somatic Genome Editing with the RCAS-TVA-CRISPR-Cas9 System For Precision Tumor Modeling.” “A current high priority in cancer research is to functionally validate candidate genetic alterations that are relevant for cancer progression and treatment response. In order to do so, it is essential to develop flexible models that can speed up the identification of cancer driver genes among the large number of passenger alterations,” state the authors. In order to achieve this, researchers led by Dr. Massimo Squatrito combined two technologies - the genome editing tool CRISPR-Cas9 and the gene delivery system RCAS/TVA - to generate a mouse model that brings the possibility of mimicking the genetic complexity of cancer. Dr. Barbara Oldrini and Dr. Álvaro Curiel-García, co-lead authors in the study, used this novel model to recapitulate some of the genetic alterations found in gliomas. In particular, they studied a gene fusion encoding a family of kinases called NTRK and a common mutation of the BRAF gene, both identified not only in glioma, but also in other tumor types. "What we have shown using this new model is that we now have the ability to generate specific complex genetic alterations and to study how they contribute to glioma pathogenesis,” explains Dr. Squatrito.

Antibacterial Treatment for Translocated Gut Bacterium May Have Relevance for Systemic Lupus & Autoimmune Liver Disease, Yale Study Suggests

Bacteria found in the small intestines of mice and humans can travel to other organs and trigger an autoimmune response, according to a new Yale study. The researchers also found that the autoimmune reaction can be suppressed with an antibiotic or vaccine designed to target the bacteria, they said. The findings, published in the March 9, 2018 issue of Science, suggest promising new approaches for treating chronic autoimmune conditions, including systemic lupus and autoimmune liver disease, the researchers said. The article is titled “Translocation of a gut pathobiont drives autoimmunity in mice and humans.” Gut bacteria have been linked to a range of diseases, including autoimmune conditions characterized by immune system attack of healthy tissue. To shed light on this link, a Yale research team focused on Enterococcus gallinarum, a bacterium they discovered is able to spontaneously “translocate” outside of the gut to lymph nodes, the liver, and spleen. In models of genetically susceptible mice, the researchers observed that in tissues outside the gut, E. gallinarum initiated the production of auto-antibodies and inflammation — hallmarks of the autoimmune response. They confirmed the same mechanism of inflammation in cultured liver cells of healthy people, and the presence of this bacterium in livers of patients with autoimmune disease. Through further experiments, the research team found that they could suppress autoimmunity in mice with an antibiotic or a vaccine aimed at E. gallinarum. With either approach, the researchers were able to suppress growth of the bacterium in the tissues and blunt its effects on the immune system. “When we blocked the pathway leading to inflammation, we could reverse the effect of this bug on autoimmunity,” said senior author Martin Kriegel, MD.

Double-Drug Strategy Blocks Escape Route for Most Lung Cancers—"Finding Has Possibility of Dramatically Altering How We Treat Lung Cancer”

A one-two combo punch using two currently available drugs could be an effective treatment for the majority of lung cancers, a study by scientists with the University of Texas (UT) Southwestern’s Simmons Cancer Center shows. Researchers found that a combination of drugs – one targeting epidermal growth factor receptor (EGFR) and one targeting tumor necrosis factor (TNF) – effectively blocks the cancer from using TNF as an escape route. Using a mouse model, the researchers showed that when TNF is also blocked, the cancer becomes sensitive to EGFR treatment. “There has been a tremendous effort over the past several years to block EGFR as a treatment for lung cancer, but this therapy only works in a small subset of patients. The cancer fights back with a bypass pathway,” said senior author Dr. Amyn Habib (photo) with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern and a staff physician at the Dallas Veterans Affairs Medical Center. “Blocking both of these proteins could be a treatment that is beneficial for the majority of lung cancer patients,” said Dr. Habib, Associate Professor of Neurology and Neurotherapeutics with UT Southwestern’s Peter O’Donnell Jr. Brain Institute. Lung cancer is the most common cause of cancer deaths in the U.S. for both men and women, according to the National Cancer Institute and, in 2017, lung cancer caused 26 percent of all cancer deaths. Non-small cell lung cancer (NSCLC), the type of lung cancer for which the EGFR/TNF inhibitor combination would be effective, comprises approximately 85 percent of all lung cancers. The latest findings build on previous work by Dr. Habib’s lab showing that the same combination of drugs was successful in a mouse model of glioblastoma, a deadly type of brain cancer.

World First--Drug to Treat Skin Lesions in Tuberous Sclerosis Complex Approved

Scientists at Osaka University in Japan have developed a new drug treating skin lesions in tuberous sclerosis complex (TSC), a rare intractable disease, a world first. Following the physician-led clinical studies I and II by Osaka University, and Phase III clinical trials by a pharmaceutical company, the drug was approved within 6 months of the drug application by the SAKIGAKE Designation System, an early approval system led by the Japanese government, on March 23, 2018 and was then commercialized. This drug is the first drug designated by the SAKIGAKE system. The details of physician-led clinical studies I and II were published in JAMA Dermatology on January 1, 2017. The open-access article is titled: “Efficacy and Safety of Topical Sirolimus Therapy for Facial Angiofibromas in the Tuberous Sclerosis Complex A Randomized Clinical Trial.” TSC is an inherited autosomal dominant disease caused by mutations in TSC1 (hamartin) and TSC2 (tuberin) genes. Mutations in the TSC1 and TSC2 tumor suppressor genes cause hyperactivation of the mTORC1 (mammalian target of rapamycin complex 1), developing neoplastic lesions called hamartomas in numerous organs, such as the brain, skin, kidneys, and lungs. The symptoms of TSC include epilepsy, learning disabilities, developmental delays, and autism spectrum disorder in addition to hamartoma. Of the various symptoms, skin problems, such as facial angiofibromas, develop in more than 90 percent of patients with TSC. Hemorrhage, secondary bacterial infection, pain, and functional disorder associated with lesions inflict suffering on patients, severely compromising their quality of life for cosmetic reasons.

Link Between Eating Red Meat & Distal Colon Cancer Seen inn UK Women

A new study suggests that a diet free from red meat significantly reduces the risk of a type of colon cancer in women living in the United Kingdom. University of Leeds researchers were part of an international team that assessed whether red meat, poultry, fish, or vegetarian diets are associated with risk of colon and rectal cancer. When comparing the effects of these diets to cancer development in specific subsites of the colon, they found that those regularly eating red meat compared to a red meat-free diet had higher rates of distal colon cancer -- cancer found on the descending section of the colon, where feces are stored. Lead author Dr. Diego Rada Fernandez de Jauregui is part of the Nutritional Epidemiology Group (NEG) at Leeds, and the University of the Basque Country in Spain. He said: "The impact of different types of red meat and dietary patterns on cancer locations is one of the biggest challenges in the study of diet and colorectal cancer. Our research is one of the few studies looking at this relationship and while further analysis in a larger study is needed, it could provide valuable information for those with family history of colorectal cancer and those working on prevention." More than 2.2 million new cases of colorectal cancer, also known as bowel cancer, are expected worldwide by 2030. It is the third most commonly diagnosed cancer in UK women. Previous studies have suggested that eating lots of red and processed meat increases the risk of colorectal cancer and it is estimated that around 1 in 5 bowel cancers in the UK are linked to eating these meats. However, there is limited available information about specific dietary patterns and the site of cancer occurrence in the bowel.

Cat-Like “Hearing” Achieved with Device Tens of Trillions Times Smaller Than Human Eardrum

Case Western Reserve University researchers have achieved cat-like “hearing” with a device 10,000,000,000,000 times smaller than human eardrum. The researchers are developing atomically thin "drumheads" able to receive and transmit signals across a radio frequency range far greater than what we can hear with the human ear. But the drumhead is tens of trillions times smaller in volume and 100,000 times thinner than the human eardrum. The advances will likely contribute to making the next generation of ultralow-power communications and sensory devices smaller and with greater detection and tuning ranges. "Sensing and communication are key to a connected world," said Philip Feng, PhD, an Associate Professor of Electrical Engineering and Computer Science and corresponding author on a paper about the work published in the March 30, 2018 issue of Science Advances. The article is titled “Electrically Tunable Single- and Few-Layer Mos2 Nanoelectromechanical Systems With Broad Dynamic Range.” "In recent decades, we have been connected with highly miniaturized devices and systems, and we have been pursuing ever-shrinking sizes for those devices." The challenge with miniaturization: Also achieving a broader dynamic range of detection, for small signals, such as sound, vibration, and radio waves. "In the end, we need transducers that can handle signals without losing or compromising information at both the 'signal ceiling' (the highest level of an undistorted signal) and the 'noise floor' (the lowest detectable level)," Dr. Feng said. While this work was not geared toward specific devices currently on the market, researchers said, it was focused on measurements, limits, and scaling which would be important for essentially all transducers. Those transducers may be developed over the next decade, but for now, Dr.

Researchers Find New “Organ” Missed by Gold Standard Methods for Visualizing Anatomy & Disease; Newfound Network Is Source of Lymph; Stunning “Finding Has Potential to Drive Dramatic Advances In Medicine”

Researchers have identified a previously unknown feature of human anatomy with implications for the function of all organs, most tissues, and the mechanisms of most major diseases. Published online on March 27, 2018 in Scientific Reports, a new study co-led by an New York University (NYU) School of Medicine pathologist reveals that layers of the body long thought to be dense, connective tissues—below the skin’s surface, lining the digestive tract, lungs, and urinary systems, and surrounding arteries, veins, and the fascia between muscles—are instead interconnected, fluid-filled compartments. This series of spaces, supported by a meshwork of strong (collagen) and flexible (elastin) connective tissue proteins, may act like shock absorbers that keep tissues from tearing as organs, muscles, and vessels squeeze, pump, and pulse as part of daily function. Tbe open-access article is titled “Structure and Distribution of an Unrecognized Interstitium in Human Tissues.” Importantly, the finding that this layer is a highway of moving fluid may explain why cancer that invades it becomes much more likely to spread. Draining into the lymphatic system, the newfound network is the source of lymph, the fluid vital to the functioning of immune cells that generate inflammation. Furthermore, the cells that reside in the space, and collagen bundles they line, change with age, and may contribute to the wrinkling of skin, the stiffening of limbs, and the progression of fibrotic, sclerotic, and inflammatory diseases.The field has long known that more than half the fluid in the body resides within cells, and about a seventh inside the heart, blood vessels, lymph nodes, and lymph vessels. The remaining fluid is “interstitial,” and the current study is the first to define the interstitium as an organ in its own right, and as one of the largest of the body, say the authors.

"Butterflies of the Soul"--New Study Sheds Light on Developmental Origins of Interneurons

Modern neuroscience, for all its complexity, can trace its roots directly to a series of pen-and-paper sketches rendered by Nobel laureate Santiago Ramón y Cajal in the late 19th and early 20th centuries. His observations and drawings exposed the previously hidden composition of the brain, revealing neuronal cell bodies and delicate projections that connect individual neurons together into intricate networks. As he explored the nervous systems of various organisms under his microscope, a natural question arose: What makes a human brain different from the brain of any other species? At least part of the answer, Ramón y Cajal hypothesized, lay in a specific class of neuron--one found in a dazzling variety of shapes and patterns of connectivity, and present in higher proportions in the human brain than in the brains of other species. He dubbed them the "butterflies of the soul." Known as interneurons, these cells play critical roles in transmitting information between sensory and motor neurons, and, when defective, have been linked to diseases such as schizophrenia, autism, and intellectual disability. Despite more than a century of study, however, it remains unclear why interneurons are so diverse and what specific functions the different subtypes carry out. Now, in a study published in the March 22, 2018 issue of Nature, researchers from Harvard Medical School (HMS), the New York Genome Center, New York University, and the Broad Institute of MIT and Harvard have detailed for the first time how interneurons emerge and diversify in the brain.

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