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https://www.readbyqxmd.com/read/28340511/quantitative-mapping-reveals-age-and-sex-differences-in-vasopressin-but-not-oxytocin-immunoreactivity-in-the-rat-social-behavior-neural-network
#1
Brett T DiBenedictis, Elizabeth R Nussbaum, Harry K Cheung, Alexa H Veenema
The neuropeptides vasopressin (AVP) and oxytocin (OT) have been implicated in the regulation of numerous social behaviors in adult and juvenile animals. AVP and OT signaling predominantly occur within a circuit of interconnected brain regions known collectively as the "social behavior neural network" (SBNN). Importantly, AVP and OT signaling within the SBNN has been shown to differentially regulate diverse social behaviors, depending on the age and/or sex of the animal. We hypothesized that variation in the display of these behaviors is due in part to age and sex differences in AVP and OT synthesis within the SBNN...
March 24, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28340352/human-epistatic-interaction-controls-il7r-splicing-and-increases-multiple-sclerosis-risk
#2
Gaddiel Galarza-Muñoz, Farren B S Briggs, Irina Evsyukova, Geraldine Schott-Lerner, Edward M Kennedy, Tinashe Nyanhete, Liuyang Wang, Laura Bergamaschi, Steven G Widen, Georgia D Tomaras, Dennis C Ko, Shelton S Bradrick, Lisa F Barcellos, Simon G Gregory, Mariano A Garcia-Blanco
Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha chain gene (sIL7R) produced by alternative splicing of IL7R exon 6. Here, we identified the RNA helicase DDX39B as a potent activator of this exon and consequently a repressor of sIL7R, and we found strong genetic association of DDX39B with MS risk. Indeed, we showed that a genetic variant in the 5' UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340336/a-dna-based-t-cell-receptor-reveals-a-role-for-receptor-clustering-in-ligand-discrimination
#3
Marcus J Taylor, Kabir Husain, Zev J Gartner, Satyajit Mayor, Ronald D Vale
A T cell mounts an immune response by measuring the binding strength of its T cell receptor (TCR) for peptide-loaded MHCs (pMHC) on an antigen-presenting cell. How T cells convert the lifetime of the extracellular TCR-pMHC interaction into an intracellular signal remains unknown. Here, we developed a synthetic signaling system in which the extracellular domains of the TCR and pMHC were replaced with short hybridizing strands of DNA. Remarkably, T cells can discriminate between DNA ligands differing by a single base pair...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340277/immunomodulatory-and-neuroprotective-effect-of-cryopreserved-allogeneic-mesenchymal-stem-cells-on-spinal-cord-injury-in-rats
#4
I R Rosado, P H Carvalho, E G L Alves, T M Tagushi, J L Carvalho, J F Silva, M S L Lavor, K M Oliveira, R Serakides, A M Goes, E G Melo
This study aimed to evaluate the immunomodulatory and neuroprotective effects of allogeneic and cryopreserved mesenchymal stem cells (MSCs) on spinal cord injury. A total of 120 rats were distributed into the following groups: negative control (NC) - without injury, positive control (PC) - with injury without treatment, and group treated with MSC (GMSC) - with injury and treated. Motor function was evaluated by the BBB test at 24, 48, and 72 h and at 8 and 21 postoperative days. Spinal cords were evaluated by histopathology and immunohistochemistry to determine the expression of CD68, NeuN, and GFAP...
March 22, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28339739/unabated-occupational-risk-in-a-patient-with-rheumatoid-pulmonary-fibrosis
#5
V K Holden, S J Kligerman, T G Hastings, S E Hines
Background: This case highlights the importance of considering hypersensitivity pneumonitis (HP) in the differential diagnosis of interstitial lung disease (ILD) and of obtaining an occupational history so that remediable risk factors may be identified and managed. Aims: To report a case of a chicken sexer with severe rheumatoid arthritis (RA) who developed progressively worsening dyspnoea and restrictive lung disease associated with pulmonary fibrosis. Methods: Clinical investigation included physical examination, occupational history, pulmonary function tests (PFTs), chest imaging and bronchoalveolar lavage (BAL), as well as serological tests including standard IgE bird feather mixture and local IgG precipitin preparation to chicken excrement...
February 23, 2017: Occupational Medicine
https://www.readbyqxmd.com/read/28339567/role-of-biomechanical-forces-in-hyperfiltration-mediated-glomerular-injury-in-congenital-anomalies-of-the-kidney-and-urinary-tract
#6
Tarak Srivastava, Ganesh Thiagarajan, Uri S Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T McCarthy, Virginia J Savin, Mukut Sharma
Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear...
January 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339471/expression-quantitative-trait-loci-for-pax8-contributes-to-the-prognosis-of-hepatocellular-carcinoma
#7
Shijie Ma, Jianshui Yang, Ci Song, Zijun Ge, Jing Zhou, Guoxin Zhang, Zhibin Hu
Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC). By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs) within a newly identified long non-coding RNA (lncRNA) AC016683.6 as expression quantitative trait loci (eQTLs) for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28339459/functional-classification-of-dna-variants-by-hybrid-minigenes-identification-of-30-spliceogenic-variants-of-brca2-exons-17-and-18
#8
Eugenia Fraile-Bethencourt, Beatriz Díez-Gómez, Valeria Velásquez-Zapata, Alberto Acedo, David J Sanz, Eladio A Velasco
Mutation screening of the breast cancer genes BRCA1 and BRCA2 identifies a large fraction of variants of uncertain clinical significance (VUS) whose functional and clinical interpretations pose a challenge for genomic medicine. Likewise, an increasing amount of evidence indicates that genetic variants can have deleterious effects on pre-mRNA splicing. Our goal was to investigate the impact on splicing of a set of reported variants of BRCA2 exons 17 and 18 to assess their role in hereditary breast cancer and to identify critical regulatory elements that may constitute hotspots for spliceogenic variants...
March 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#9
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28335481/genetic-variants-contributing-to-colistin-cytotoxicity-identification-of-tgif1-and-hoxd10-using-a-population-genomics-approach
#10
Michael T Eadon, Ronald J Hause, Amy L Stark, Ying-Hua Cheng, Heather E Wheeler, Kimberly S Burgess, Eric A Benson, Patrick N Cunningham, Robert L Bacallao, Pierre C Dagher, Todd C Skaar, M Eileen Dolan
Colistin sulfate (polymixin E) is an antibiotic prescribed with increasing frequency for severe Gram-negative bacterial infections. As nephrotoxicity is a common side effect, the discovery of pharmacogenomic markers associated with toxicity would benefit the utility of this drug. Our objective was to identify genetic markers of colistin cytotoxicity that were also associated with expression of key proteins using an unbiased, whole genome approach and further evaluate the functional significance in renal cell lines...
March 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335009/open-chromatin-profiling-of-human-postmortem-brain-infers-functional-roles-for-non-coding-schizophrenia-loci
#11
John F Fullard, Claudia Giambartolomei, Mads E Hauberg, Ke Xu, Georgios Voloudakis, Zhiping Shao, Christopher Bare, Joel T Dudley, Manuel Mattheisen, Nikolaos K Robakis, Vahram Haroutunian, Panos Roussos
Open chromatin provides access to DNA binding proteins for the correct spatiotemporal regulation of gene expression. Mapping chromatin accessibility has been widely used to identify the location of cis regulatory elements (CREs) including promoters and enhancers. CREs show tissue- and cell-type specificity and disease-associated variants are often enriched for CREs in the tissues and cells that pertain to a given disease. To better understand the role of CREs in neuropsychiatric disorders we applied the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq) to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain by fluorescence-activated nuclear sorting (FANS)...
March 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334933/disrupted-in-schizophrenia-1is-essential-for-normal-hypothalamic-pituitary-interrenal-hpi-axis-function
#12
Helen Eachus, Charlotte Bright, Vincent T Cunliffe, Marysia Placzek, Jonathan D Wood, Penelope J Watt
Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334900/cdk12-regulates-alternative-last-exon-mrna-splicing-and-promotes-breast-cancer-cell-invasion
#13
Jerry F Tien, Alborz Mazloomian, S-W Grace Cheng, Christopher S Hughes, Christalle C T Chow, Leanna T Canapi, Arusha Oloumi, Genny Trigo-Gonzalez, Ali Bashashati, James Xu, Vicky C-D Chang, Sohrab P Shah, Samuel Aparicio, Gregg B Morin
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334751/atp13a2-park9-regulates-endo-lysosomal-cargo-sorting-and-proteostasis-through-a-novel-pi-3-5-p2-mediated-scaffolding-function
#14
S Demirsoy, S Martin, S Motamedi, S van Veen, T Holemans, C Van den Haute, A Jordanova, V Baekelandt, P Vangheluwe, P Agostinis
ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334045/plasma-soluble-l-selectin-in-medicated-patients-with-schizophrenia-and-healthy-controls
#15
Satyajit Mohite, Fang Yang, Pooja A Amin, Giovana Zunta-Soares, Gabriela D Colpo, Laura Stertz, Ajaykumar N Sharma, Gabriel R Fries, Consuelo Walss-Bass, Jair C Soares, Olaoluwa O Okusaga
Immune dysfunction has been implicated in the pathophysiology of schizophrenia. Leukocyte migration to the site of inflammation is a fundamental step of immune response which involves P-, E-, and L-selectins. Elevated selectin levels have been reported in un-medicated first-episode patients with schizophrenia but not in medicated patients with multi-episode schizophrenia. We measured fasting plasma soluble P-, E-, and L-selectin in 39 medicated patients with multi-episode schizophrenia and 19 healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28334000/temperature-and-food-quantity-effects-on-the-harpacticoid-copepod-nitocra-spinipes-combining-in-vivo-bioassays-with-population-modeling
#16
Josef Koch, Thuy T Bui, Elin Lundström Belleza, Markus Brinkmann, Henner Hollert, Magnus Breitholtz
The harpacticoid copepod Nitocra spinipes has become a popular model species for toxicity testing over the past few decades. However, the combined influence of temperature and food shortage, two climate change-related stressors, has never been assessed in this species. Consequently, effects of three temperatures (15, 20 and 25°C) and six food regimes (between 0 and 5 × 105 algal cells/mL) on the life cycle of N. spinipes were examined in this study. Similarly to other copepod species, development times and brood sizes decreased with rising temperatures...
2017: PloS One
https://www.readbyqxmd.com/read/28333899/-stem-progenitor-cells-in-diseases-of-the-respiratory-tract
#17
EDITORIAL
Tadeusz Płusa
Stem cells (SCs - stem cells) are characterized by plasticity and the ability to differentiate into other cell types. They are obtained from bone marrow, peripheral blood and cord blood. Mesenchymal stem cells (MSCs) shows a broad immunomodulating, increases the number of regulatory T cells (Treg), modifies the activity of T cells, dendritic cells and NK (natural killer). Direct impact on reducing the release of proinflammatory cytokines and increased release of proinflammatory cytokines. Within the respiratory tract has a number of resident stem and progenitor cells referred to as L-MSCs (lung mesenchymal stem cells) whose presence was confirmed by markers as defined in the trachea, epithelial cells and alveolar...
March 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28333374/odontoclastogenesis-of-mouse-papilla-derived-mdpc-23-cells-induced-by-lps
#18
C Li, W T Qi, H W Jiang
AIM: To investigate the role of LPS in the odontoclast differentiation of MDPC-23 cells. It was hypothesized that MDPC 23 odontoblast-like cells may function as odontoclasts under the influence of LPS. METHODOLOGY: MDPC-23 cells were cultured in the presence of 0.1 or 1 μg/mL LPS for 6 days. Cell viability was determined using the CCK8 assay. TRAP staining, dentine resorption assay and ROS detection by confocal laser scanning microscope were used to test the odontoclast-like function of the induced cells...
March 23, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28333195/genome-wide-genetic-analyses-highlight-mitogen-activated-protein-kinase-mapk-signaling-in-the-pathogenesis-of-endometriosis
#19
Outi Uimari, Nilufer Rahmioglu, Dale R Nyholt, Katy Vincent, Stacey A Missmer, Christian Becker, Andrew P Morris, Grant W Montgomery, Krina T Zondervan
STUDY QUESTION: Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER: GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways...
February 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28333147/solute-carrier-family-12-member-5-promotes-tumor-invasion-metastasis-of-bladder-urothelial-carcinoma-by-enhancing-nf-%C3%AE%C2%BAb-mmp-7-signaling-pathway
#20
J Y Liu, Y B Dai, X Li, K Cao, D Xie, Z T Tong, Z Long, H Xiao, M K Chen, Y L Ye, B Liu, J Tan, J Tang, Z Z Xu, Y Gan, Y H Zhou, F Deng, L Y He
Solute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers. However, the clinical significance and biological role of SLC12A5 in human bladder urothelial carcinoma (BUC) remains unclear. In this study, the expression of SLC12A5 was examined in clinical specimens of primary BUC and in BUC cell lines using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC)...
March 23, 2017: Cell Death & Disease
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