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https://www.readbyqxmd.com/read/28223698/sex-differences-in-microglial-cx3cr1-signalling-determine-obesity-susceptibility-in-mice
#1
Mauricio D Dorfman, Jordan E Krull, John D Douglass, Rachael Fasnacht, Fernando Lara-Lince, Thomas H Meek, Xiaogang Shi, Vincent Damian, Hong T Nguyen, Miles E Matsen, Gregory J Morton, Joshua P Thaler
Female mice are less susceptible to the negative metabolic consequences of high-fat diet feeding than male mice, for reasons that are incompletely understood. Here we identify sex-specific differences in hypothalamic microglial activation via the CX3CL1-CX3CR1 pathway that mediate the resistance of female mice to diet-induced obesity. Female mice fed a high-fat diet maintain CX3CL1-CX3CR1 levels while male mice show reductions in both ligand and receptor expression. Female Cx3cr1 knockout mice develop 'male-like' hypothalamic microglial accumulation and activation, accompanied by a marked increase in their susceptibility to diet-induced obesity...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28220681/canadian-university-acknowledgment-of-indigenous-lands-treaties-and-peoples
#2
Rima Wilkes, Aaron Duong, Linc Kesler, Howard Ramos
At many Canadian universities it is now common to publicly acknowledge Indigenous lands, treaties, and peoples. Yet, this practice has yet to be considered as a subject of scholarly inquiry. How does this practice vary and why? In this paper we describe the content and practice of acknowledgment, linking this content to treaty relationships (or lack thereof). We show that acknowledgment tends to be one of five general types: of land and title (British Columbia), of specific treaties and political relationships (Prairies), of multiculturalism and heterogeneity (Ontario), of no practice (most of Quebec), and of people, territory, and openness to doing more (Atlantic)...
February 2017: Canadian Review of Sociology, Revue Canadienne de Sociologie
https://www.readbyqxmd.com/read/28208023/transcriptomic-profiling-of-human-hippocampal-progenitor-cells-treated-with-antidepressants-and-its-application-in-drug-repositioning
#3
Timothy R Powell, Tytus Murphy, Sang H Lee, Jack Price, Sandrine Thuret, Gerome Breen
Current pharmacological treatments for major depressive disorder (MDD) are ineffective in a significant proportion of patients, and the identification of new antidepressant compounds has been difficult. 'Connectivity mapping' is a method that can be used to identify drugs that elicit similar downstream effects on mRNA levels when compared to current treatments, and thus may point towards possible repositioning opportunities. We investigated genome-wide transcriptomic changes to human hippocampal progenitor cells treated with therapeutically relevant concentrations of a tricyclic antidepressant (nortriptyline) and a selective serotonin reuptake inhibitor (escitalopram)...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28178176/nlrp12-inflammasome-expression-in-the-rat-brain-in-response-to-lps-during-morphine-tolerance
#4
Sulie L Chang, Wenfei Huang, Xin Mao, Sabroni Sarkar
Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance...
February 6, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28137723/in-vivo-spiking-dynamics-of-intra-and-extratelencephalic-projection-neurons-in-rat-motor-cortex
#5
Akiko Saiki, Yutaka Sakai, Ryoji Fukabori, Shogo Soma, Junichi Yoshida, Masanori Kawabata, Hiromu Yawo, Kazuto Kobayashi, Minoru Kimura, Yoshikazu Isomura
In motor cortex, 2 types of deep layer pyramidal cells send their axons to other areas: intratelencephalic (IT)-type neurons specifically project bilaterally to the cerebral cortex and striatum, whereas neurons of the extratelencephalic (ET)-type, termed conventionally pyramidal tract-type, project ipsilaterally to the thalamus and other areas. Although they have totally different synaptic and membrane potential properties in vitro, little is known about the differences between them in ongoing spiking dynamics in vivo...
January 30, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28134781/implications-for-diverse-functions-of-the-linc-complexes-based-on-the-structure
#6
REVIEW
Miki Hieda
The linker of nucleoskeleton and cytoskeleton (LINC) complex is composed of the outer and inner nuclear membrane protein families Klarsicht, Anc-1, and Syne homology (KASH), and Sad1 and UNC-84 (SUN) homology domain proteins. Increasing evidence has pointed to diverse functions of the LINC complex, such as in nuclear migration, nuclear integrity, chromosome movement and pairing during meiosis, and mechanotransduction to the genome. In metazoan cells, the nuclear envelope possesses the nuclear lamina, which is a thin meshwork of intermediate filaments known as A-type and B-type lamins and lamin binding proteins...
January 26, 2017: Cells
https://www.readbyqxmd.com/read/28125396/current-insights-into-lmna-cardiomyopathies-existing-models-and-missing-lincs
#7
Daniel Brayson, Catherine M Shanahan
The nuclear lamina is a critical structural domain for the maintenance of genomic stability and whole-cell mechanics. Mutations in the LMNA gene, which encodes nuclear A-type lamins lead to the disruption of these key cellular functions, resulting in a number of devastating diseases known as laminopathies. Cardiomyopathy is a common laminopathy and is highly penetrant with poor prognosis. To date, cell mechanical instability and dysregulation of gene expression have been proposed as the main mechanisms driving cardiac dysfunction, and indeed discoveries in these areas have provided some promising leads in terms of therapeutics...
January 2, 2017: Nucleus
https://www.readbyqxmd.com/read/28109290/characterizing-breast-conditions-at-an-open-access-breast-clinic-in-south-africa-a-model-that-is-more-than-cancer-care-for-a-resource-limited-setting
#8
Sarah Rayne, Naomi Lince-Deroche, Cheryl Hendrickson, Kate Shearer, Faith Moyo, Pam Michelow, Grace Rubin, Carol Benn, Cynthia Firnhaber
BACKGROUND: While most breast-related research focuses on cancer, presentation of symptomatic persons in non-screened environments requires understanding the spectrum of breast diseases so as to plan services in resource-constrained settings. This study presents the variety of breast disease managed at a government, open-access breast clinic in South Africa. METHODS: We performed a retrospective file review using a systematic random sample of patients 18 years and above presenting for breast care over a 14-month period...
January 21, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28102353/cofilin-regulates-nuclear-architecture-through-a-myosin-ii-dependent-mechanotransduction-module
#9
O'Neil Wiggan, Bryce Schroder, Diego Krapf, James R Bamburg, Jennifer G DeLuca
Structural features of the nucleus including shape, size and deformability impact its function affecting normal cellular processes such as cell differentiation and pathological conditions such as tumor cell migration. Despite the fact that abnormal nuclear morphology has long been a defining characteristic for diseases such as cancer relatively little is known about the mechanisms that control normal nuclear architecture. Mounting evidence suggests close coupling between F-actin cytoskeletal organization and nuclear morphology however, mechanisms regulating this coupling are lacking...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101692/the-assembly-and-function-of-perinuclear-actin-cap-in-migrating-cells
#10
Miloslava Maninova, Josef Caslavsky, Tomas Vomastek
Stress fibers are actin bundles encompassing actin filaments, actin-crosslinking, and actin-associated proteins that represent the major contractile system in the cell. Different types of stress fibers assemble in adherent cells, and they are central to diverse cellular processes including establishment of the cell shape, morphogenesis, cell polarization, and migration. Stress fibers display specific cellular organization and localization, with ventral fibers present at the basal side, and dorsal fibers and transverse actin arcs rising at the cell front from the ventral to the dorsal side and toward the nucleus...
January 18, 2017: Protoplasma
https://www.readbyqxmd.com/read/28091529/long-non-coding-rna-linc-ram-enhances-myogenic-differentiation-by-interacting-with-myod
#11
Xiaohua Yu, Yong Zhang, Tingting Li, Zhao Ma, Haixue Jia, Qian Chen, Yixia Zhao, Lili Zhai, Ran Zhong, Changyin Li, Xiaoting Zou, Jiao Meng, Antony K Chen, Pier Lorenzo Puri, Meihong Chen, Dahai Zhu
Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes. Here we report on functional identification and characterization of a novel long intergenic non-coding RNA with MyoD-regulated and skeletal muscle-restricted expression that promotes the activation of the myogenic program, and is therefore termed Linc-RAM (Linc-RNA Activator of Myogenesis). Linc-RAM is transcribed from an intergenic region of myogenic cells and its expression is upregulated during myogenesis. Notably, in vivo functional studies show that Linc-RAM knockout mice display impaired muscle regeneration due to the differentiation defect of satellite cells...
January 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28077629/sun2-silencing-impairs-cd4-t-cell-proliferation-and-alters-sensitivity-to-hiv-1-infection-independently-of-cyclophilin-a
#12
Daniel A Donahue, Françoise Porrot, Norbert Couespel, Olivier Schwartz
: Linker of nucleoskeleton and cytoskeleton (LINC) complexes connect the nucleus to the cytoskeleton in eukaryotic cells. We previously reported that overexpression of SUN2, an inner nuclear membrane protein and LINC complex component, inhibits HIV infection between reverse transcription and nuclear import in a capsid-specific manner. We also reported that SUN2 silencing does not modulate HIV infection in several cell lines. Silencing of SUN2 was recently reported to decrease HIV infection of CD4 T cells, an effect suggested to result from modulation of CypA-dependent steps of HIV infection...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28071740/elucidating-the-modes-of-action-for-bioactive-compounds-in-a-cell-specific-manner-by-large-scale-chemically-induced-transcriptomics
#13
Michio Iwata, Ryusuke Sawada, Hiroaki Iwata, Masaaki Kotera, Yoshihiro Yamanishi
The identification of the modes of action of bioactive compounds is a major challenge in chemical systems biology of diseases. Genome-wide expression profiling of transcriptional responses to compound treatment for human cell lines is a promising unbiased approach for the mode-of-action analysis. Here we developed a novel approach to elucidate the modes of action of bioactive compounds in a cell-specific manner using large-scale chemically-induced transcriptome data acquired from the Library of Integrated Network-based Cellular Signatures (LINCS), and analyzed 16,268 compounds and 68 human cell lines...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069634/a-review-of-connectivity-map-and-computational-approaches-in-pharmacogenomics
#14
Aliyu Musa, Laleh Soltan Ghoraie, Shu-Dong Zhang, Galina Galzko, Olli Yli-Harja, Matthias Dehmer, Benjamin Haibe-Kains, Frank Emmert-Streib
Large-scale perturbation databases, such as Connectivity Map (CMap) or Library of Integrated Network-based Cellular Signatures (LINCS), provide enormous opportunities for computational pharmacogenomics and drug design. A reason for this is that in contrast to classical pharmacology focusing at one target at a time, the transcriptomics profiles provided by CMap and LINCS open the door for systems biology approaches on the pathway and network level. In this article, we provide a review of recent developments in computational pharmacogenomics with respect to CMap and LINCS and related applications...
January 9, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28060557/control-of-nuclear-organization-by-f-actin-binding-proteins
#15
Karin Pfisterer, Asier Jayo, Maddy Parsons
The regulation of nuclear shape and deformability is a key factor in controlling diverse events from embryonic development to cancer cell metastasis, but the mechanisms governing this process are still unclear. Our recent study demonstrated an unexpected role for the F-actin bundling protein fascin in controlling nuclear plasticity through a direct interaction with Nesprin-2. Nesprin-2 is a component of the LINC complex that is known to couple the F-actin cytoskeleton to the nuclear envelope. We demonstrated that fascin, which is predominantly associated with peripheral F-actin rich filopodia, binds directly to Nesprin-2 at the nuclear envelope in a range of cell types...
January 6, 2017: Nucleus
https://www.readbyqxmd.com/read/28057128/-expression-and-function-of-long-intergenic-non-protein-coding-rna-regulator-of-reprogramming-in-high-grade-ovarian-serous-cancer
#16
H H Jiang, Y H Lou, X Y Wang, Y Han, Z M Cui
Objective: To investigate the expression of long intergenic non-protein coding RNA-regulator of reprogramming (Linc-ROR) in high-grade ovarian serous cancer, and explore the relationship between Linc-ROR expression and biological function of high-grade ovarian serous cancer. Methods: A total of 34 high-grade ovarian serous cancer tissue samples and 19 normal fallopian tube tissue samples were collected between June 2014 and February 2016. Real-time reverse transcription (RT)-PCR was used to detect the Linc-ROR mRNA expression in different samples...
December 25, 2016: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/28053048/identifying-new-antiepileptic-drugs-through-genomics-based-drug-repurposing
#17
Nasir Mirza, Greame J Sills, Munir Pirmohamed, Anthony G Marson
Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of the antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28049722/the-linc-complex-contributes-to-heterochromatin-organisation-and-transcriptional-gene-silencing-in-plants
#18
Axel Poulet, Céline Duc, Maxime Voisin, Sophie Desset, Sylvie Tutois, Emmanuel Vanrobays, Matthias Benoit, David E Evans, Aline V Probst, Christophe Tatout
The LInker of Nucleoskeleton and Cytoskeleton (LINC) complex is an evolutionary well-conserved protein bridge connecting the cytoplasmic and nuclear compartments across the nuclear membrane. While recent data support its function in nuclear morphology and meiosis, its implication in chromatin organisation has not been studied in plants. Here 3D imaging methods have been used to investigate nuclear morphology and chromatin organisation in interphase nuclei of the model plant Arabidopsis thaliana, in which heterochromatin cluster in conspicuous chromatin domains called chromocentres...
January 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28035049/opposing-roles-for-distinct-linc-complexes-in-regulation-of-the-small-gtpase-rhoa
#19
Ketan Thakar, Christopher K May, Anna Rogers, Christopher W Carroll
Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27999969/functions-of-long-intergenic-non-coding-linc-rnas-in-plants
#20
Masashi Yamada
Whole transcriptome analyses in many organisms have revealed that most transcribed RNAs do not encode proteins. These non-coding RNAs likely contribute to the regulation of gene expression during the development of multicellular organisms. In eukaryotes, the roles of small RNAs, one class of non-coding RNAs, in transcriptional and post-transcriptional regulation have been well characterized. However, the functions of a second class of non-coding RNAs, long intergenic noncoding (linc) RNAs, are relatively unknown, especially in plants...
January 2017: Journal of Plant Research
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