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https://www.readbyqxmd.com/read/28918262/circuit-changes-in-motor-cortex-during-motor-skill-learning
#1
Andrew E Papale, Bryan M Hooks
Motor cortex is important for motor skill learning, particularly the dexterous skills necessary for our favorite sports and careers. We are especially interested in understanding how plasticity in motor cortex contributes to skill learning. Although human studies have been helpful in understanding the importance of motor cortex in learning skilled tasks, animal models are necessary for achieving a detailed understanding of the circuitry underlying these behaviors and the changes that occur during training. We review data from these models to try to identify sites of plasticity in motor cortex, focusing on rodents as a model system...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28918017/efficacy-and-safety-profile-of-tricyclo-dna-antisense-oligonucleotides-in-duchenne-muscular-dystrophy-mouse-model
#2
Karima Relizani, Graziella Griffith, Lucía Echevarría, Faouzi Zarrouki, Patricia Facchinetti, Cyrille Vaillend, Christian Leumann, Luis Garcia, Aurélie Goyenvalle
Antisense oligonucleotides (AONs) hold promise for therapeutic splice-switching correction in many genetic diseases. However, despite advances in AON chemistry and design, systemic use of AONs is limited due to poor tissue uptake and sufficient therapeutic efficacy is still difficult to achieve. A novel class of AONs made of tricyclo-DNA (tcDNA) is considered very promising for the treatment of Duchenne muscular dystrophy (DMD), a neuromuscular disease typically caused by frameshifting deletions or nonsense mutations in the gene-encoding dystrophin and characterized by progressive muscle weakness, cardiomyopathy, and respiratory failure in addition to cognitive impairment...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916644/subset-and-tissue-defined-stat5-thresholds-control-homeostasis-and-function-of-innate-lymphoid-cells
#3
Alejandro V Villarino, Giuseppe Sciumè, Fred P Davis, Shigeru Iwata, Beatrice Zitti, Gertraud W Robinson, Lothar Hennighausen, Yuka Kanno, John J O'Shea
Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor (TF) STAT5 is critical for accumulation of all known ILC subsets in mice and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15...
September 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28916626/contextual-fear-conditioning-in-zebrafish
#4
Justin W Kenney, Ian C Scott, Sheena A Josselyn, Paul W Frankland
Zebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in the ability to precisely manipulate the zebrafish genome, much less is known about many aspects of learning and memory in adult fish. Here, we describe the development of a contextual fear conditioning paradigm using an electric shock as the aversive stimulus. We find that contextual fear conditioning is modulated by shock intensity, prevented by an established amnestic agent (MK-801), lasts at least 14 d, and exhibits extinction...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916543/cryopyrin-associated-periodic-syndromes-in-italian-patients-evaluation-of-the-rate-of-somatic-nlrp3-mosaicism-and-phenotypic-characterization
#5
Denise Lasigliè, Anna Mensa-Vilaro, Denise Ferrera, Roberta Caorsi, Federica Penco, Giuseppe Santamaria, Marco Di Duca, Giulia Amico, Kenji Nakagawa, Francesca Antonini, Alberto Tommasini, Rita Consolini, Antonella Insalaco, Marco Cattalini, Laura Obici, Romina Gallizzi, Francesca Santarelli, Genny Del Zotto, Mariasavina Severino, Anna Rubartelli, Roberto Ravazzolo, Alberto Martini, Isabella Ceccherini, Ryuta Nishikomori, Marco Gattorno, Juan I Arostegui, Silvia Borghini
OBJECTIVE: To evaluate the rate of somatic NLRP3 mosaicism in an Italian cohort of mutation-negative patients with cryopyrin-associated periodic syndrome (CAPS). METHODS: The study enrolled 14 patients with a clinical phenotype consistent with CAPS in whom Sanger sequencing of the NLRP3 gene yielded negative results. Patients' DNA were subjected to amplicon-based NLRP3 deep sequencing. RESULTS: Low-level somatic NLRP3 mosaicism has been detected in 4 patients, 3 affected with chronic infantile neurological cutaneous and articular syndrome and 1 with Muckle-Wells syndrome...
September 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28916386/molecular-mechanisms-of-the-r61t-mutation-in-apolipoprotein-e4-a-dynamic-rescue
#6
Benfeard Williams, Marino Convertino, Jhuma Das, Nikolay V Dokholyan
The apolipoprotein E4 (ApoE4) gene is the strongest genetic risk factor for Alzheimer's disease (AD). With respect to the other common isoforms of this protein (ApoE2 and ApoE3), ApoE4 is characterized by lower stability that underlies the formation of a stable interaction between the protein's N- and C-terminal domains. AD-related cellular dysfunctions have been linked to this ApoE4 misfolded state. In this regard, it has been reported that the mutation R61T is able to rescue the deleterious cellular effects of ApoE4 by preventing the formation of the misfolded intermediate state...
September 12, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28916377/clinical-and-molecular-characterization-of-two-chinese-patients-with-type-2-congenital-generalized-lipodystrophy
#7
Ruimin Chen, Xin Yuan, Jian Wang, Ying Zhang
BACKGROUND: Type 2 congenital generalized lipodystrophy (CGL2, OMIM 269700) is a rare autosomal recessive disease, characterized by the generalized absence of adipose tissue at birth or in early infancy. Pathogenic variants in BSCL2 gene have been reported to be responsible for CGL2. The aim of this study is to analyze the clinical and genetic characteristics of two Chinese patients with CGL2, and with particular focus on the BSCL2 gene sequence variants. METHODS: Medical history, clinical manifestations, physical examination, laboratory data, and ultrasonography findings were analyzed for the two patients with CGL2...
September 12, 2017: Gene
https://www.readbyqxmd.com/read/28916270/understanding-taurine-cns-activity-using-alternative-zebrafish-models
#8
REVIEW
Nathana J Mezzomo, Barbara D Fontana, Allan V Kalueff, Leonardo J G Barcellos, Denis B Rosemberg
Taurine is a highly abundant "amino acid" in the brain. Despite the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action...
September 12, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28915264/inhibition-of-infection-spread-by-co-transmitted-defective-interfering-particles
#9
Ashley Baltes, Fulya Akpinar, Bahar Inankur, John Yin
Although virus release from host cells and tissues propels the spread of many infectious diseases, most virus particles are not infectious; many are defective, lacking essential genetic information needed for replication. When defective and viable particles enter the same cell, the defective particles can multiply while interfering with viable particle production. Defective interfering particles (DIPs) occur in nature, but their role in disease pathogenesis and spread is not known. Here, we engineered an RNA virus and its DIPs to express different fluorescent reporters, and we observed how DIPs impact viral gene expression and infection spread...
2017: PloS One
https://www.readbyqxmd.com/read/28915148/adult-fmr1-knockout-mice-present-with-deficiencies-in-hippocampal-interleukin-6-and-tumor-necrosis-factor-%C3%AE-expression
#10
Samantha L Hodges, Suzanne O Nolan, Joseph H Taube, Joaquin N Lugo
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a single genetic mutation in the FMR1 gene. Mutations in the FMR1 gene are the largest monogenic cause of autism spectrum disorder (ASD), and thus both disorders share many of the same cognitive and behavioral impairments. There is increasing evidence suggesting that dysregulated immune responses play a role in the pathophysiology of ASD; however, the association between FXS and altered immunity requires further investigation. This study examined whether Fmr1 knockout (KO) and wild-type mice on a FVB/NJ background strain had altered cytokine expression at baseline levels in the hippocampus...
September 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28914311/comparing-caenorhabditis-elegans-gentle-and-harsh-touch-response-behavior-using-a-multiplexed-hydraulic-microfluidic-device
#11
Patrick D McClanahan, Joyce H Xu, Christopher Fang-Yen
The roundworm Caenorhabditis elegans is an important model system for understanding the genetics and physiology of touch. Classical assays for C. elegans touch, which involve manually touching the animal with a probe and observing its response, are limited by their low throughput and qualitative nature. We developed a microfluidic device in which several dozen animals are subject to spatially localized mechanical stimuli with variable amplitude. The device contains 64 sinusoidal channels through which worms crawl, and hydraulic valves that deliver touch stimuli to the worms...
September 15, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28913805/real-time-pcr-for-the-detection-of-precise-transgene-copy-number-in-wheat
#12
Angelica Giancaspro, Agata Gadaleta, Antonio Blanco
Despite the unceasing advances in genetic transformation techniques, the success of common delivery methods still lies on the behavior of the integrated transgenes in the host genome. Stability and expression of the introduced genes are influenced by several factors such as chromosomal location, transgene copy number and interaction with the host genotype. Such factors are traditionally characterized by Southern blot analysis, which can be time-consuming, laborious, and often unable to detect the exact copy number of rearranged transgenes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28912643/decreased-glial-gaba-and-tonic-inhibition-in-cerebellum-of-mouse-model-for-attention-deficit-hyperactivity-disorder-adhd
#13
Yoo Sung Kim, Junsung Woo, C Justin Lee, Bo-Eun Yoon
About 5~12% of school-aged children suffer from the Attention-Deficit/Hyperactivity Disorder (ADHD). However, the core mechanism of ADHD remains unclear. G protein-coupled receptor kinase-interacting protein-1 (GIT1) has recently been reported to be associated with ADHD in human and the genetic deletion of GIT1 result in ADHD-like behaviors in mice. Mice lacking GIT1 shows a shift in neuronal excitation/inhibition (E/I) balance. However, the pricise mechanism for E/I imbalance and the role of neuron-glia interaction in GIT1 knockout (KO) mice have not been studied...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28912243/thirst-associated-preoptic-neurons-encode-an-aversive-motivational-drive
#14
William E Allen, Laura A DeNardo, Michael Z Chen, Cindy D Liu, Kyle M Loh, Lief E Fenno, Charu Ramakrishnan, Karl Deisseroth, Liqun Luo
Water deprivation produces a drive to seek and consume water. How neural activity creates this motivation remains poorly understood. We used activity-dependent genetic labeling to characterize neurons activated by water deprivation in the hypothalamic median preoptic nucleus (MnPO). Single-cell transcriptional profiling revealed that dehydration-activated MnPO neurons consist of a single excitatory cell type. After optogenetic activation of these neurons, mice drank water and performed an operant lever-pressing task for water reward with rates that scaled with stimulation frequency...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28911965/physiological-roles-of-cns-muscarinic-receptors-gained-from-knockout-mice
#15
REVIEW
Morgane Thomsen, Gunnar Sørensen, Ditte Dencker
Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28911169/obesity-induced-infertility-in-male-mice-is-associated-with-disruption-of-crisp4-expression-and-sperm-fertilization-capacity
#16
Beatriz C Borges, David Garcia-Galiano, Sanseray da Silveira Cruz-Machado, Xingfa Han, Galina B Gavrilina, Thomas L Saunders, Richard J Auchus, Saher S Hammoud, Gary D Smith, Carol F Elias
Approximately 15% of human couples of reproductive age have impaired fertility, and the male component accounts for about half of these cases. The etiology is usually unknown, but high correlation with the increase in obesity rates is documented. In this study, we show that diet-induced and genetically obese mice display copulatory behavior comparable to controls, but the number of females impregnated by obese males is remarkably low. Screening for changes in gene expression in the male reproductive tract showed decreased Crisp4 expression in testis and epididymis of obese mice...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28910928/-a-twin-study-of-genetic-and-environmental-influences-on-relationship-between-attention-deficit-and-anxiety-depression-in-children-and-adolescents
#17
S S Wang, T J Chen, C Y Ji
Objective: To understand the genetic and environmental influences on the relationship between attention deficit and anxiety/depression in children and adolescents. Methods: A total of 1 062 same-sex twins aged 6-18 years were included in this study. A parent-rated child behavior checklist (CBCL) was used in the assessment. Software Mx was used to fit the univariate model of structural equation. The relationship between attention deficit and anxiety/depression was analyzed through bivariate genetic modeling...
September 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28910617/whole-cell-recording-of-neuronal-membrane-potential-during-behavior
#18
REVIEW
Carl C H Petersen
Neuronal membrane potential is of fundamental importance for the mechanistic understanding of brain function. This review discusses progress in whole-cell patch-clamp recordings for low-noise measurement of neuronal membrane potential in awake behaving animals. Whole-cell recordings can be combined with two-photon microscopy to target fluorescently labeled neurons, revealing cell-type-specific membrane potential dynamics of retrogradely or genetically labeled neurons. Dual whole-cell recordings reveal behavioral modulation of membrane potential synchrony and properties of synaptic transmission in vivo...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28910603/apolipoprotein-a-iv-constrains-hpa-and-behavioral-stress-responsivity-in-a-strain-dependent-manner
#19
Amy E B Packard, Jintao Zhang, Brent Myers, Chih-Wei Ko, Fei Wang, Patrick Tso, Yvonne M Ulrich-Lai
There is a critical gap in our knowledge of the mechanisms that govern interactions between daily life experiences (e.g., stress) and metabolic diseases, despite evidence that stress can have profound effects on cardiometabolic health. Apolipoprotein A-IV (apoA-IV) is a protein found in chylomicrons (lipoprotein particles that transport lipids throughout the body) where it participates in lipid handling and the regulation of peripheral metabolism. Moreover, apoA-IV is expressed in brain regions that regulate energy balance including the arcuate nucleus...
September 1, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28910524/cover-image-volume-175c-number-3-september-2017
#20
(no author information available yet)
The cover image, by Gene S. Fisch, is based on the Introduction Introduction to Behavioral Phenotypes In Medical Genetics, DOI: 10.1002/ajmg.c.31573.
September 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
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