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https://www.readbyqxmd.com/read/28731029/nrp2-is-sufficient-to-instruct-circuit-formation-of-mitral-cells-to-mediate-odour-induced-attractive-social-responses
#1
Kasumi Inokuchi, Fumiaki Imamura, Haruki Takeuchi, Ryang Kim, Hiroyuki Okuno, Hirofumi Nishizumi, Haruhiko Bito, Takefumi Kikusui, Hitoshi Sakano
Odour information induces various innate responses that are critical to the survival of the individual and for the species. An axon guidance molecule, Neuropilin 2 (Nrp2), is known to mediate targeting of olfactory sensory neurons (primary neurons), to the posteroventral main olfactory bulb (PV MOB) in mice. Here we report that Nrp2-positive (Nrp2(+)) mitral cells (MCs, second-order neurons) play crucial roles in transmitting attractive social signals from the PV MOB to the anterior part of medial amygdala (MeA)...
July 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28727895/how-to-become-a-killer-or-is-it-all-accidental-virulence-strategies-in-oral-streptococci
#2
Izabela Sitkiewicz
Streptococci are a diverse group of gram positive microorganisms sharing common virulence traits and similar strategies to escape the oral niche and establish an infection in other parts of the host organism. Invasive infection with oral streptococci is "a perfect storm" that requires the concerted action of multiple biotic and abiotic factors. Our understanding of streptococcal pathogenicity and infectivity should probably be less mechanistic and driven not only by the identification of novel virulence factors...
July 20, 2017: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/28727200/landscape-genetic-analyses-reveal-fine-scale-effects-of-forest-fragmentation-in-an-insular-tropical-bird
#3
Aurélie Khimoun, William Peterman, Cyril Eraud, Bruno Faivre, Nicolas Navarro, Stéphane Garnier
Within the framework of landscape genetics, resistance surface modelling is particularly relevant to explicitly test competing hypotheses about landscape effects on gene flow. To investigate how fragmentation of tropical forest affects population connectivity in a forest-specialist bird species, we optimized resistance surfaces without a priori specification, using least-cost (LCP) or resistance (IBR) distances. We implemented a two-step procedure in order i) to objectively define the landscape thematic resolution (level of detail in classification scheme to describe landscape variables) and spatial extent (area within the landscape boundaries) and then ii) to test the relative role of several landscape features (elevation, roads, land cover) in genetic differentiation in the Plumbeous Warbler (Setophaga plumbea)...
July 20, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28726577/will-optogenetics-be-used-to-treat-chronic-pain-patients
#4
Hélène Beaudry, Ihab Daou, Alfredo Ribeiro-da-Silva, Philippe Séguéla
Chronic pain affects a third of the population and current treatments produce limited relief and severe side effects. An alternative strategy to decrease pain would be to directly modulate somatosensory pathways using optogenetics. Optogenetics involves the use of genetically encoded and optically active proteins, namely opsins, to control neuronal circuits. In preclinical animal models, optical silencing of peripheral nociceptors has been shown to alleviate both inflammatory and neuropathic pain. An opsin-based gene therapy to treat chronic pain patients is not ready yet, but encouraging advances have been made in optical and viral technology...
July 20, 2017: Pain Management
https://www.readbyqxmd.com/read/28723766/lady-with-wings-a-case-report-of-giant-neurofibromatosis-type-i
#5
Suraj Maharjan, Xiucun Li, Jianli Cui, Yang Liu, Laijin Lu
RATIONALE: Neurofibromatosis type I (NF-I) accounts for approximately 90% of neurofibromatosis. NF-I is an autosomal dominant genetic disease which results from the gene mutation of NF-I situated in chromosome 17q11.2. PATIENT CONCERNS: A 32-year-old lady presented with a giant wing like structure on her back which started growing from her childhood. DIAGNOSIS: A diagnosis of NF-I was confirmed as she presented with multiple cutaneous nodules, multiple café-au-lait macules of different sizes, scoliosis deformity, and positive family history of neurofibroma...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28716885/cytokines-and-long-noncoding-rnas
#6
Susan Carpenter, Katherine A Fitzgerald
Cytokines and long noncoding RNAs (lncRNAs) are intertwined in the regulatory circuit controlling immunity. lncRNA expression levels are altered following cytokine stimulation in a cell-type-specific fashion. lncRNAs, in turn, regulate the inducible expression of cytokines following immune activation. These studies position lncRNAs as important regulators of gene expression within the complex pathways of the immune system. Our understanding of the functions of lncRNAs is just beginning. Current methodologies for functionally understanding how these transcripts mediate their effects are unable to keep up with the speed of genomic outputs cataloging thousands of these novel genes...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716058/srf-modulates-seizure-occurrence-activity-induced-gene-transcription-and-hippocampal-circuit-reorganization-in-the-mouse-pilocarpine-epilepsy-model
#7
Pascal Lösing, Cristina Elena Niturad, Merle Harrer, Christopher Meyer Zu Reckendorf, Theresa Schatz, Daniela Sinske, Holger Lerche, Snezana Maljevic, Bernd Knöll
A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance...
July 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28711343/innexin-expression-in-electrically-coupled-motor-circuits
#8
REVIEW
Adriane Otopalik, Brian Lane, David J Schulz, Eve Marder
The many roles of innexins, the molecules that form gap junctions in invertebrates, have been explored in numerous species. Here, we present a summary of innexin expression and function in two small, central pattern generating circuits found in crustaceans: the stomatogastric ganglion and the cardiac ganglion. The two ganglia express multiple innexin genes, exhibit varying combinations of symmetrical and rectifying gap junctions, as well as gap junctions within and across different cell types. Past studies have revealed correlations in ion channel and innexin expression in coupled neurons, as well as intriguing functional relationships between ion channel conductances and electrical coupling...
July 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28709113/reprogramming-cellular-functions-with-engineered-membrane-proteins
#9
REVIEW
Caroline Arber, Melvin Young, Patrick Barth
Taking inspiration from Nature, synthetic biology utilizes and modifies biological components to expand the range of biological functions for engineering new practical devices and therapeutics. While early breakthroughs mainly concerned the design of gene circuits, recent efforts have focused on engineering signaling pathways to reprogram cellular functions. Since signal transduction across cell membranes initiates and controls intracellular signaling, membrane receptors have been targeted by diverse protein engineering approaches despite limited mechanistic understanding of their function...
July 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28708138/blocking-endothelin-1-receptor-%C3%AE-catenin-circuit-sensitizes-to-chemotherapy-in-colorectal-cancer
#10
Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Rosanna Sestito, Valentina Caprara, Valeriana Di Castro, Ruggero De Maria, Anna Bagnato
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28705801/the-mir-15-family-reinforces-the-transition-from-proliferation-to-differentiation-in-pre-b-cells
#11
Silke E Lindner, Michael Lohmüller, Bianka Kotkamp, Fabian Schuler, Zeynep Knust, Andreas Villunger, Sebastian Herzog
Precursor B lymphocytes expand upon expression of a pre-B cell receptor (pre-BCR), but then transit into a resting state in which immunoglobulin light chain gene recombination is initiated. This bi-phasic sequence is orchestrated by the IL-7 receptor (IL-7R) and pre-BCR signaling, respectively, but little is known about microRNAs fine-tuning these events. Here, we show that pre-B cells lacking miR-15 family functions exhibit prolonged proliferation due to aberrant expression of the target genes cyclin E1 and D3...
July 13, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28702647/an-enhanced-htert-promoter-driven-crispr-cas9-system-selectively-inhibits-the-progression-of-bladder-cancer-cells
#12
Xinbo Huang, Chengle Zhuang, Changshui Zhuang, Tiefu Xiong, Yawen Li, Yaoting Gui
The current therapies for treating tumors are lacking in efficacy and specificity. Synthetic biology principles may bring some new possible methods for curing cancer. Here we present a synthetic logic circuit based on the CRISPR/Cas9 system. The CRISPR/Cas9 technology has been applied in many biological fields, including cancer research. In this study, the expression of Cas9 nuclease was controlled indirectly by an enhanced hTERT promoter using the GAL4/upstream activating sequence (UAS) binding system. Cas9 was driven by 5XUAS, single guide RNA (sgRNA) was used to target mutant or wild-type HRAS, and the fusion gene GAL4-P65 was driven by the enhanced hTERT promoter...
July 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28701772/genetic-targeting-and-anatomical-registration-of-neuronal-populations-in-the-zebrafish-brain-with-a-new-set-of-bac-transgenic-tools
#13
Dominique Förster, Irene Arnold-Ammer, Eva Laurell, Alison J Barker, António M Fernandes, Karin Finger-Baier, Alessandro Filosa, Thomas O Helmbrecht, Yvonne Kölsch, Enrico Kühn, Estuardo Robles, Krasimir Slanchev, Tod R Thiele, Herwig Baier, Fumi Kubo
Genetic access to small, reproducible sets of neurons is key to an understanding of the functional wiring of the brain. Here we report the generation of a new Gal4- and Cre-driver resource for zebrafish neurobiology. Candidate genes, including cell type-specific transcription factors, neurotransmitter-synthesizing enzymes and neuropeptides, were selected according to their expression patterns in small and unique subsets of neurons from diverse brain regions. BAC recombineering, followed by Tol2 transgenesis, was used to generate driver lines that label neuronal populations in patterns that, to a large but variable extent, recapitulate the endogenous gene expression...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700913/impact-of-zygosity-on-bimodal-phenotype-distributions
#14
Thomas Holst-Hansen, Elena Abad, Aura Muntasell, Miguel López-Botet, Mogens H Jensen, Ala Trusina, Jordi Garcia-Ojalvo
Allele number, or zygosity, is a clear determinant of gene expression in diploid cells. However, the relationship between the number of copies of a gene and its expression can be hard to anticipate, especially when the gene in question is embedded in a regulatory circuit that contains feedback. Here, we study this question making use of the natural genetic variability of human populations, which allows us to compare the expression profiles of a receptor protein in natural killer cells among donors infected with human cytomegalovirus with one or two copies of the allele...
July 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28700657/increased-transgene-expression-level-of-rabies-virus-vector-for-transsynaptic-tracing
#15
Shinya Ohara, Yasuhiro Sota, Sho Sato, Ken-Ichiro Tsutsui, Toshio Iijima
Viral vectors that can infect neurons transsynaptically and can strongly express foreign genes are useful for investigating the organization of neural circuits. We previously developed a propagation-competent rabies virus (RV) vector based on a highly attenuated HEP-Flury strain (rHEP5.0-CVSG), which selectively infects neurons and propagates between synaptically connected neurons in a retrograde direction. Its relatively low level of transgene expression, however, makes immunostaining necessary to visualize the morphological features of infected neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28700081/spinal-nociceptive-circuit-analysis-with-recombinant-adeno-associated-viruses-the-impact-of-serotypes-and-promoters
#16
Karen Haenraets, Edmund Foster, Helge Johannssen, Vinnie Kandra, Noemie Frezel, Timothy Steffen, Valeria Jaramillo, Jean-Charles Paterna, Hanns Ulrich Zeilhofer, Hendrik Wildner
Recombinant adeno-associated virus (rAAV) vector-mediated gene transfer into genetically defined neuron subtypes has become a powerful tool to study the neuroanatomy of neuronal circuits in the brain and to unravel their functions. More recently this methodology has also become popular for the analysis of spinal cord circuits. To date a variety of naturally occurring AAV serotypes and genetically modified capsid variants are available but transduction efficiency in spinal neurons, target selectivity and the ability for retrograde tracing are only incompletely characterized...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28699024/transcriptome-sequencing-reveals-astrocytes-as-a-therapeutic-target-in-heat-stroke
#17
Bing Niu, Tao Zhang, Huaiqiang Hu, Bingzhen Cao
Heat-stroke is a serious form of hyperthermia with high mortality, and can induce severe central nervous system disorders. The neurovascular unit (NVU), which consists of vascular cells, glial cells, and neurons, controls blood-brain barrier (BBB) permeability and cerebral blood flow, and maintains the proper functioning of neuronal circuits. However, the detailed function of each BBB component in heat-stroke remains unknown. In order to interpret alterations caused by heat stress, we performed transcriptome comparison of neuron and astrocyte primary cultures after heat treatment...
July 11, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28698206/expression-of-pim-kinases-in-reed-sternberg-cells-fosters-immune-privilege-and-tumor-cell-survival-in-hodgkin-lymphoma
#18
Maciej Szydłowski, Monika Prochorec-Sobieszek, Anna Szumera-Cieckiewicz, Edyta Derezinska, Grazyna Hoser, Danuta Wasilewska, Olga Szymanska-Giemza, Ewa Jabłonska, Emilia Białopiotrowicz, Tomasz Sewastianik, Anna Polak, Wojciech Czardybon, Michał Gałezowski, Renata Windak, Jan Maciej Zaucha, Krzysztof Warzocha, Krzysztof Brzózka, Przemysław Juszczynski
Reed-Sternberg (RS) cells of classical Hodgkin lymphoma (cHL) express multiple immunoregulatory proteins that shape the cHL microenvironment and allow tumor cells to evade immune surveillance. Expression of certain immunoregulatory proteins is modulated by pro-survival transcription factors, such as NFκB and STATs. Since these factors also induce expression of the oncogenic PIM1/2/3 serine/threonine kinases, and since PIMs modulate transcriptional activity of NFκB and STATs, we hypothesized that these kinases support RS cell survival and foster their immune privilege...
July 11, 2017: Blood
https://www.readbyqxmd.com/read/28696429/glud1-linked-to-schizophrenia-controls-the-burst-firing-of-dopamine-neurons
#19
N Benamer, F Marti, R Lujan, R Hepp, T G Aubier, A A M Dupin, G Frébourg, S Pons, U Maskos, P Faure, Y A Hay, B Lambolez, L Tricoire
Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#20
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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