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August 27th, 2018

New Kind of Human Brain Cell (Rosehip Neuron) Identified

One of the most intriguing questions about the human brain is also one of the most difficult for neuroscientists to answer: What sets our brains apart from those of other animals? "We really don't understand what makes the human brain special," said Ed Lein, PhD, Investigator at the Allen Institute for Brain Science. "Studying the differences at the level of cells and circuits is a good place to start, and now we have new tools to do just that." In a new study published online on August 27, 2018 in Nature Neuroscience, Dr. Lein and his colleagues reveal one possible answer to that difficult question. The article is titled “Transcriptomic and Morphophysiological Evidence for a Specialized Human Cortical Gabaergic Cell Type.” The research team, co-led by Dr. Lein and Gábor Tamás, PhD, a neuroscientist at the University of Szeged in Szeged, Hungary, has uncovered a new type of human brain cell that has never been seen in mice or other well-studied laboratory animals. Dr. Tamás and University of Szeged doctoral student Eszter Boldog called these new cells "rosehip neurons" – because, to them, the dense bundle each brain cell's axon forms around the cell's center looks just like a rose after it has shed its petals, he said. The newly discovered cells belong to a class of neurons known as inhibitory neurons, which put the brakes on the activity of other neurons in the brain. The study hasn't proven that this special brain cell is unique to humans. But the fact that the special neuron doesn't exist in rodents is intriguing, adding these cells to a very short list of specialized neurons that may exist only in humans or only in primate brains.

Research Reveals FKBP5 Gene Variant Affects Chronic Pain After Traumatic Injury Because It Alters Ability of the Gene to Be Regulated by a MicroRNA

The gene FKBP5 is a critical regulator of the stress response and affects how we respond to environmental stimuli. Previous studies have shown that certain variants of this gene play a role in the development of neuropsychiatric disorders such as posttraumatic stress disorder, depression, suicide risk, and aggressive behavior. But in 2013, University of North Carolina (UNC) School of Medicine researchers were first to show an association between genetic variants in FKBP5 and posttraumatic chronic pain. In particular, the study found that people with a variant or minor/risk allele on chromosome 6 known as rs3800373 are likely to experience more pain after exposure to trauma (such as sexual assault or motor vehicle collision) compared to people who don't have this variant. Now, a new study by the same research group, published in the Journal of Neuroscience, has confirmed this association in a cohort of more than 1,500 people of both European American and African American descent who experienced motor vehicle collision trauma. Sarah Linnstaedt (photo), PhD, Assistant Professor of Anesthesiology and an investigator in the Institute for Trauma Recovery, is the study's lead author. The article is titled “A Functional riboSNitch in the 3′UTR of FKBP5 Alters MicroRNA-320a Binding Efficiency and Mediates Vulnerability to Chronic Posttraumatic Pain.” "In our current study, we showed that the reason this variant affects chronic pain outcomes is because it alters the ability of FKBP5 to be regulated by a microRNA called miR-320a," Dr, Linnstaedt said. MicroRNAs play an important role in the regulation of gene expression, primarily by degrading or repressing the translation of messenger RNA (mRNA). "In individuals with the minor/risk allele, the microRNA does not bind well to FKBP5," she said.

Targeting Key Receptor (TREM-1) May Help Prevent Progression of Liver Damage to Cancer

Problems like obesity and alcoholism appear to chronically trigger in the liver a receptor known to amplify inflammation in response to invaders like bacteria, scientists report. The relentless, increased activity of this receptor (TREM-1) in turn accelerates injury and scarring of the liver, a first step toward cirrhosis and liver cancer, says Dr. Anatolij Horuzsko, reproductive immunologist in the Georgia Cancer Center and Department of Medicine at the Medical College of Georgia at Augusta University. TREM-1 (triggering receptor expressed on myeloid cells-1), is known to help turn up inflammation short-term to help the body deal with external invaders. It has increased activity immediately after an injury as well, when increased inflammation, damage cleanup and collagen production aid healing. But Georgia Cancer Center scientists reported online on August 23, 2018 in the Journal of Clinical Investigation the first evidence that when activated by chronic offending agents, like obesity and hepatitis, TREM-1 instead contributes to a destructive level of inflammation that results in liver damage and possibly cancer. The unhealthy transformation can occur in five to 50 years, depending on factors like the level of insult, and may be largely reversible up to the point of cirrhosis, if the offending agent is stopped, and the liver's natural ability to regenerate takes over. The article is titled “The Innate Immune Receptor TREM-1 Promotes Liver Injury and Fibrosis.” Dr. Horuzsko and his colleagues think TREM-1 could one day be another point of intervention, possibly with a drug that could return TREM-1 activation to normal levels on resident, waste-consuming, watchdog immune cells called Kupffer cells. "Right now, we have treatment for hepatitis C, for example, which is very efficient, if we treat it before too much damage is done.

Connectome Organization in Childhood Acute Lymohoblastic Leukemia (ALL) and Risk of Delayed Neurodevelopment

A new study provides novel insights into the cognitive effects of childhood acute lymphoblastic leukemia (ALL) and of chemotherapeutic treatment in long-term survivors of ALL. The findings from comparative studies of structural and functional connectome organization, showing that connectome disruption is associated with delayed neurodevelopment, were published online on August 1, 2018 in an article in Brain Connectivity, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. You may click on the following link to read the full-text article free on the Brain Connectivity website through September 27, 2018 ( (Editor’s Note: A connectome is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram.” More broadly, a connectome would include the mapping of all neural connections within an organism's nervous system.) In the article entitled "Brain Network Connectivity and Executive Function in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia," Kevin Krull, PhD, St. Jude Children's Research Hospital, Memphis, Tennessee and a team of researchers from St. Jude's and the University of Texas MD Anderson Cancer Center in Houston, Texas, reported poor global connectivity and lower information exchange and network integration in study participants with executive dysfunction - compared to those without - which is one of the most consistently observed deficits observed in this population. The study included 161 long-term survivors of ALL who were 8-21 years of age.

How Cholera Bacterium Survives Aquatic Predators

The cholera-causing bacterium, Vibrio cholerae, is commonly found in aquatic environments, such as oceans, ponds, and rivers. There, the bacterium has evolved formidable skills to ensure its survival, growth, and occasional transmission to humans, especially in endemic areas of the globe. One of the ways the pathogen defends itself against predatory aquatic amoebas involves "hitchhiking" them and hiding inside the amoeba. Once there, the bacterium resists digestion and establishes a replication niche within the host's osmoregulatory organelle. This organelle is essential for the amoeba to balance its internal water pressure with the pressure exerted by the environment. In a new study, the group of Dr. Melanie Blokesch at EPFL (Ecole Polytechnique Fédérale de Lausanne), in collaboration with the BioEM facility headed by Dr. Graham Knott, has deciphered the molecular mechanisms that V. cholerae uses to colonize aquatic amoebas. The study was published online on Aiugust 27, 2018 in Nature Communications. The open-access article is titled “Molecular Insights into Vibrio Cholerae's Intra-Amoebal Host-Pathogen Interactions.” The researchers demonstrated that the pathogen uses specific features that allow it to maintain its intra-amoebal replication niche and to ultimately escape from the succumbed host. Several of these features, including extracellular enzymes and motility, are considered minor virulence factors as they also play a role in human disease. The study suggests that the aquatic milieu provides a training ground for V. cholerae and that adaptation towards amoebal predators might have contributed to V. cholerae's emergence as a major human pathogen.

August 26th

Exosomes Derived from Mesenchymal Stem Cells Alleviate Atopic Dermatitis in Mouse Model

ExoCoBio Inc., based in South Korea, has reported publishing a scientific paper indicating that stem cell-derived exosomes dramatically relieve atopic dermatitis and inhibit a variety of inflammatory targets in Stem Cell Research and Therapy. The open-access article, published online on July 11, 2018, is titled “Exosomes Derived from Human Adipose Tissue-Derived Mesenchymal Stem Cells Alleviate Atopic Dermatitis.” According to the paper, the symptoms of mice having severe atopic dermatitis were significantly improved after administration of stem cell-derived exosomes intravenously or subcutaneously, so that the level of serum immunoglobulin E (IgE), the number of eosinophils in blood, and the number of mast cells in the skin lesion were decreased. It has also been found that the number of inflammatory dendritic epidermal cells (IDECs), which are not found in normal skin but cause an allergic inflammatory response in atopic dermatitis lesions, also significantly decreased to a normal skin level after administration of stem cell-derived exosomes. In addition, the improvement of the symptoms by stem cell-derived exosomes was comparable to that of a steroid drug, prednisolone. While atopic dermatitis is a chronic disease depreciating the quality of life, there is no fundamental treatment to treat it yet. Currently available atopic treatments, such as anti-histamines, steroids, and immunosuppressive drugs, have various side effects such as impaired immune systems, liver & kidney damage during long-term administration, etc. Inhibitory antibodies against various inflammatory cytokines such as IL-4, IL-31, TNF-alpha and IL-23 are under development or on the market to relieve atopic dermatitis symptoms. However, these treatments just relieve atopic dermatitis by blocking the function of one or two specific proteins.

Researchers Discover How Body Regenerates Blood Vessel Lining; Atf3 Gene Seems Key; Findings Could Lead to New Methods to Help Prevent Clots and Repair Damage Linked to Stents

Normal wear and tear damages the blood vessel lining, which is called the endothelial lining. The body, however, has the ability to initiate molecular activity that regenerates and repairs this damage. Now, researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA in California have, for the first time, followed this regeneration in progress and identified the genes and proteins responsible for spurring it. Their findings could eventually lead to novel methods to repair more severe blood vessel damage, including damage that can result from placing stents — metal or plastic mesh tubes that open blocked or narrow blood vessels. The study, led by Dr. Luisa Iruela-Arispe, a UCLA Professor of Molecular, Cell and Developmental Biology and a member of the UCLA Broad Stem Cell Research Center, was published online on August 2, 2018 in Cell Stem Cell. The article is titled “Endothelial Regeneration of Large Vessels Is a Biphasic Process Driven by Local Cells with Distinct Proliferative Capacities.” “The well-being of the endothelial lining is really fundamental for health,” Dr. Iruela-Arispe said. “Understanding how to keep this lining in good shape will help us make progress in treating multiple disease states.” In blood vessels snaking throughout the body — circulating blood to organs and extremities — the endothelial lining acts as a filter and a wall. The composition of the lining, which includes anti-clotting protein on its surface, generally prevents blood from clotting as it moves through the body, and controls what materials — such as inflammatory cells — can enter and exit the blood flow.

UCLA Research Reveals Key Difference in How Stem Cells Act When Stressed Versus When at Rest

Stem Cell Research and Jonsson Comprehensive Cancer Center in California have discovered an important distinction in how blood-forming stem cells are supported by their micro-environments during rest and after injury. The body appears to switch the type of cell that produces a single growth factor during healthy times and during stress or injury — for instance, radiation treatment for cancer. The results could have implications for treating cancer, when people’s blood-forming stem cells may be substantially depleted, and for people undergoing certain types of transplants. The study, led by Dr. John Chute, a member of the center and a Professor of Hematology/Oncology at the David Geffen School of Medicine at UCLA, was published in Cell Stem Cell. The article is titled “Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell Maintenance and Regeneration.” Blood-forming, or hematopoietic, stem cells can differentiate into various types of mature blood elements — white blood cells, red blood cells, and platelets. They live in “vascular niches” in the bone marrow, where different types of surrounding cells support them, partly by secreting compounds called growth factors. The UCLA study focused on a growth factor called pleiotrophin (PTN). Dr. Chute and his team had previously discovered pleiotrophin, but had yet to determine which type of cells secrete it. “In stem cell research, two important questions are, ‘What are the microenvironment cells that regulate stem cells,’ and ‘How do they do it?’” Dr. Chute said. To find out, the team bred mice that lacked pleiotrophin expression in various types of bone marrow cells — including endothelial cells, which line the blood vessels, and stromal cells, which make up connective tissue.

Researchers Identify Link Between Gut Bacteria and Eating for Pleasure, As Opposed to for Hunger

A study of 63 healthy people showed that those with elevated microbiome levels of the metabolite indole (image) -- produced when gut bacteria break down the amino acid tryptophan -- had stronger function and connectivity in specific areas of the brain's reward network. Such activity in the brain indicates that a person is more prone to "hedonic eating," or eating for pleasure rather than for hunger. Those with higher levels of indole also were more likely to have food addiction, as determined by questionnaires they completed. Certain areas of the brain's reward network have long been known to drive eating behaviors. In particular, the nucleus accumbens -- which processes reward stimuli such as food -- and the amygdala -- which helps regulate emotions -- are activated when people are hungry or eating. In this study, people with higher indole levels showed stronger function and connectivity in these two areas. Higher function and connectivity in the brain's reward system could indicate an overactive reward system that promotes and reinforces overeating. Such overactivity of the reward system in obese individuals with food addiction has been reported in previous research. The researchers obtained functional MRI brain imaging from the healthy participants. They collected and analyzed fecal samples in order to determine the presence of particular gut metabolites. The subjects completed questionnaires that measured their propensity for food addiction. The study -- the first in humans to show the association between specific metabolites produced by gut bacteria and overeating behaviors -- suggests that indole, or gut bacteria's ability to produce it, could contribute to such behaviors.

3D Images of Skin Molecule Involved in Temperature Sensation Could Lead to New Treatments for Skin Diseases

Columbia University biomedical researchers have captured close-up views of TRPV3, a skin-cell ion channel protein that plays important roles in sensing temperature, itch, and pain. In humans, defects in this protein can lead to skin diseases such as atopic dermatitis (a type of eczema), vitiligo (uneven skin coloration), skin cancer, and rosacea. All vertebrate DNA, including the woolly mammoth genome, contains the TRPV3 gene. Though the mammoths lived in extremely cold environments, they descended from elephants that lived in the tropics. Researchers think that changes in the TRPV3 genes of mammoths may have helped them withstand lower temperatures. The article was published online on August 20, 2018 in Nature Structural & Molecular Biology, and is titled "Structure and Gating Mechanism of the Transient Receptor Potential Channel TRPV3." Dr. Alexander Sobolevsky's lab at Columbia University Irving Medical Center used a powerful imaging technique called cryo-electron microscopy to take pictures of TRPV3 molecules. Initial 2D images were collected by freezing the molecules in an extremely thin, clear layer of ice and bombarding them with electrons. The researchers then used computational tools to convert the 2D images into detailed molecular 3D models. This is the first time scientists have gotten a glimpse of TRPV3 in atomic detail. The researchers were able to get images of the protein in two states, revealing how the channel opens and closes to let ions flow into skin cells. This exchange of ions prompts the body to react to sensations such as pain, itchiness, and changes in temperature. The group also discovered how a small molecule with anti-cancer properties called 2-APB interacts with and controls the function of this channel.