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Early rescue

Kolter B Grigsby, Gregory N Ruegsegger, Thomas E Childs, Frank W Booth
A gene was sought that could reverse low voluntary running distances in a model of low voluntary wheel-running behavior. In order to confirm the low motivation to wheel-run in our model does not result from defects in reward valuation, we employed sucrose preference and conditioned place preference for voluntary wheel-access. We observed no differences between our model and wild-type rats regarding the aforementioned behavioral testing. Instead, low voluntary runners seemed to require less running to obtain similar rewards for low voluntary running levels compared to wild-type rats...
June 21, 2018: Molecular Neurobiology
Kevin A Bockerstett, Luciana H Osaki, Christine P Petersen, Catherine W Cai, Chun Fung Wong, Thanh-Long M Nguyen, Eric L Ford, Daniel F Hoft, Jason C Mills, James R Goldenring, Richard J DiPaolo
Background & Aims: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin-17A (IL-17A) in causing parietal cell atrophy...
2018: Cellular and Molecular Gastroenterology and Hepatology
Huijuan Liao, Yan Chen, Li Yulong, Shaolong Xue, Mingfeng Liu, Ziyuan Lin, Yanyan Liu, Hsiao Chang Chan, Xiaohu Zhang, Huaqin Sun
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene affect fertility in both sexes. However, the involvement of CFTR in regulating germ cell development remains largely unknown. Here, we used zebrafish model to investigate the role of CFTR in primordial germ cells (PGCs) development. We generated a cftr frameshift mutant zebrafish line using CRISPR/Cas9 technique and investigated the migration of PGCs during early embryo development. Our results showed that loss of Cftr impairs the migration of PGCs from dome stages onwards...
June 21, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Guillaume Hékimian, Tamara Jovanovic, Nicolas Bréchot, Guillaume Lebreton, Pascal Leprince, Jean-Louis Trouillet, Matthieu Schmidt, Ania Nieszkowska, Sébastien Besset, Jean Chastre, Alain Combes, Charles-Edouard Luyt
PURPOSE: To describe patients with refractory cardiogenic shock related to influenza B virus myocarditis rescued by venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO). MATERIAL AND METHODS: Consecutive patients hospitalized in our unit for influenza-associated myocarditis were prospectively included. We also conducted a systematic MEDLINE database literature review through the PubMed search engine, between 1946 and 2017. RESULTS: We report the cases of 4 young patients with fulminant myocarditis requiring VA-ECMO for 6 [5-8] days...
June 9, 2018: Journal of Critical Care
Yuqiang Liu, Cui Chen, Yunlong Liu, Wei Li, Zhihong Wang, Qifeng Sun, Hang Zhou, Xiangjun Chen, Yongchun Yu, Yun Wang, Nashat Abumaria
The TRPM7 chanzyme contributes to several biological and pathological processes in different tissues. However, its role in the CNS under physiological conditions remains unclear. Here, we show that TRPM7 knockdown in hippocampal neurons reduces structural synapse density. The synapse density is rescued by the α-kinase domain in the C terminus but not by the ion channel region of TRPM7 or by increasing extracellular concentrations of Mg2+ or Zn2+ . Early postnatal conditional knockout of TRPM7 in mice impairs learning and memory and reduces synapse density and plasticity...
June 19, 2018: Cell Reports
Elena Guzzolino, Elena Chiavacci, Neha Ahuja, Laura Mariani, Monica Evangelista, Chiara Ippolito, Milena Rizzo, Deborah Garrity, Federico Cremisi, Letizia Pitto
Sphingosine-1-phosphate is a bioactive lipid and a signaling molecule integrated into many physiological systems such as differentiation, proliferation and migration. In mammals S1P acts through binding to a family of five trans-membrane, G-protein coupled receptors (S1PRs) whose complex role has not been completely elucidated. In this study we use zebrafish, in which seven s1prs have been identified, to investigate the role of s1pr1 . In mammals S1PR1 is the most highly expressed S1P receptor in the developing heart and regulates vascular development, but in zebrafish the data concerning its role are contradictory...
2018: Frontiers in Cell and Developmental Biology
Elisabeth Schlögl, Mariya Y Radeva, Franziska Vielmuth, Camilla Schinner, Jens Waschke, Volker Spindler
Pemphigus vulgaris (PV) is a potentially lethal autoimmune disease characterized by blister formation of the skin and mucous membranes and is caused by autoantibodies against desmoglein (Dsg) 1 and Dsg3. Dsg1 and Dsg3 are linked to keratin filaments in desmosomes, adhering junctions abundant in tissues exposed to high levels of mechanical stress. The binding of the autoantibodies leads to internalization of Dsg3 and a collapse of the keratin cytoskeleton-yet, the relevance and interdependence of these changes for loss of cell-cell adhesion and blistering is poorly understood...
2018: Frontiers in Immunology
Qiang Li, Hengli Zhao, Pengyu Pan, Xufang Ru, Shilun Zuo, Jie Qu, Bin Liao, Yujie Chen, Huaizhen Ruan, Hua Feng
Progressive white matter (WM) impairments caused by subarachnoid hemorrhage (SAH) contribute to cognitive deficits and poor clinical prognoses; however, their pathogenetic mechanisms are poorly understood. We investigated the role of nexilin and oligodendrocyte progenitor cell (OPC)-mediated repair in a mouse model of experimental SAH generated via left endovascular perforation. Nexilin expression was enhanced by the elevated migration of OPCs after SAH. Knocking down nexilin by siRNA reduced OPC migration both in vitro and in vivo and abridged WM repair...
2018: Frontiers in Neurology
Alline R Pacheco, Jacob E Lazarus, Brandon Sit, Stefanie Schmieder, Wayne I Lencer, Carlos J Blondel, John G Doench, Brigid M Davis, Matthew K Waldor
Enterohemorrhagic Escherichia coli (EHEC) has two critical virulence factors-a type III secretion system (T3SS) and Shiga toxins (Stxs)-that are required for the pathogen to colonize the intestine and cause diarrheal disease. Here, we carried out a genome-wide CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats with Cas9) loss-of-function screen to identify host loci that facilitate EHEC infection of intestinal epithelial cells. Many of the guide RNAs identified targeted loci known to be associated with sphingolipid biosynthesis, particularly for production of globotriaosylceramide (Gb3), the Stx receptor...
June 19, 2018: MBio
Anthony P Y Liu, Pamela P W Lee, Janette S Y Kwok, Rock Y Y Leung, Alan K S Chiang, Shau-Yin Ha, Daniel K L Cheuk, Godfrey C F Chan
Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2...
June 19, 2018: Pediatric Transplantation
Julia Sellin, Christian Wingen, Dominic Gosejacob, Deniz Senyilmaz, Lea Hänschke, Sven Büttner, Katharina Meyer, Daniele Bano, Pierluigi Nicotera, Aurelio A Teleman, Margret H Bülow
Mutations in peroxin (PEX) genes lead to loss of peroxisomes, resulting in the formation of peroxisomal biogenesis disorders (PBDs) and early lethality. Studying PBDs and their animal models has greatly contributed to our current knowledge about peroxisomal functions. Very-long-chain fatty acid (VLCFA) accumulation has long been suggested as a major disease-mediating factor, although the exact pathological consequences are unclear. Here, we show that a Drosophila Pex19 mutant is lethal due to a deficit in medium-chain fatty acids (MCFAs)...
June 19, 2018: PLoS Biology
Karim A Alkadhi
Long-term potentiation (LTP) is commonly considered as the cellular correlate of learning and memory. In learning and memory impairments, LTP is invariably markedly diminished in the hippocampus, the brain region responsible for memory formation. LTP is measured electrophysiologically in various areas of the hippocampus. Two mechanistically distinct phases of LTP have been identified: early-phase LTP (E-LTP; related to short-term memory) and late-phase LTP (L-LTP; related to long-term memory). These two forms can be severely reduced in a variety of conditions and have been shown to be rescued by treatment with nicotine...
June 18, 2018: Journal of Pharmacology and Experimental Therapeutics
K V Andersen, L Nikolajsen, V Haraldsted, N T Andersen, C F Jepsen, K Soeballe
Background/aims Optimal pain treatment with minimal side-effects is essential for early mobilization and recovery in patients undergoing total knee replacement surgery. Local infiltration analgesia (LIA) with local anaesthetic might be effective and adjuncts such as ketorolac may provide additional effects on opioid requirements and pain. We tested the hypothesis that adding ketorolac significantly improves analgesia after total knee replacement surgery. Methods Sixty patients were enrolled in this prospective double-blinded study and allocated to either group R (placebo) or Group RK (ketorolac 120 mg)...
December 29, 2017: Scandinavian Journal of Pain
Hayley S McLoughlin, Lauren R Moore, Ravi Chopra, Robert Komlo, Megan McKenzie, Kate G Blumenstein, Hien Zhao, Holly B Kordasiewicz, Vikram G Shakkottai, Henry L Paulson
OBJECTIVE: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common dominantly inherited ataxia. Despite advances in understanding this CAG repeat/polyglutamine expansion disease, there are still no therapies to alter its progressive fatal course. Here we investigate whether an antisense oligonucleotide (ASO) targeting the SCA3 disease gene, ATXN3, can prevent molecular, neuropathological, electrophysiological and behavioral features of the disease in a mouse model of SCA3...
June 16, 2018: Annals of Neurology
Alejandra Rosales, Maissa Mhibik, Paul Gissen, Oscar Segarra, Susana Redecillas, Gema Ariceta
BACKGROUND: Arthrogryposis-Renal dysfunction-Cholestasis syndrome (ARC, MIM#208085) is a rare multisystem disease due to mutations in the VPS33B and VIPAR genes, both involved in maintaining apical-basolateral cell polarity. The correlation between mutations and phenotype in the ARC Syndrome is not well described. We report on a 6 year old patient who presented with severe renal Fanconi as first manifestation of ARC related to a combined de novo mutation in the VPS33B gene. CASE PRESENTATION: A 6 year old girl presented during the first year of life with severe renal Fanconi as the first manifestation of ARC-Syndrome...
June 15, 2018: BMC Nephrology
Madushi Wanaguru, David J Barry, Donald J Benton, Nicola J O'Reilly, Kate N Bishop
The murine leukaemia virus (MLV) Gag cleavage product, p12, is essential for both early and late steps in viral replication. The N-terminal domain of p12 binds directly to capsid (CA) and stabilises the mature viral core, whereas defects in the C-terminal domain (CTD) of p12 can be rescued by addition of heterologous chromatin binding sequences (CBSs). We and others hypothesised that p12 tethers the pre-integration complex (PIC) to host chromatin ready for integration. Using confocal microscopy, we have observed for the first time that CA localises to mitotic chromatin in infected cells in a p12-dependent manner...
June 15, 2018: PLoS Pathogens
Manaki Mimura, Toru Kudo, Shan Wu, Donald R McCarty, Masaharu Suzuki
In plants, establishment of the basic body plan during embryogenesis involves complex processes of axis formation, cell fate specification and organ differentiation. While molecular mechanisms of embryogenesis have been well studied in the eudicot Arabidopsis, only a small number of genes regulating embryogenesis has been identified in grass species. Here, we show that a RKD-type RWP-RK transcription factor encoded by Shohai1 (Shai1) is indispensable for embryo and endosperm development in maize. Loss of Shai1 function causes variable morphological defects in the embryo including small scutellum, shoot axis bifurcation and arrest during early organogenesis...
June 14, 2018: Plant Journal: for Cell and Molecular Biology
Woojin Kwon, Seunguk Bang, Hyojung Soh, Won Jun Jeong, Sang Chul Lee, Byung Jo Choi
RATIONALE: Laparoscopic totally extraperitoneal (TEP) inguinal hernia repair is a rapidly evolving, minimally invasive treatment modality for inguinal hernia. Compared with open hernia repair, this method requires a smaller incision, has cosmetic advantages, and facilitates rapid recovery and early return to daily activities because of less postoperative pain. Because general anesthesia is essential for TEP hernia repair, it cannot be performed on patients who have an increased risk of developing complications when placed under general anesthesia...
June 2018: Medicine (Baltimore)
Ute Wessels, El-Sayed M Abdelwhab, Jutta Veits, Donata Hoffmann, Svenja Mamerow, Olga Stech, Jan Hellert, Martin Beer, Thomas C Mettenleiter, Jürgen Stech
Zoonotic highly pathogenic avian influenza viruses (HPAIV) have raised serious public health concerns of a novel pandemic. These strains emerge from low-pathogenic precursors by acquisition of a polybasic hemagglutinin (HA) cleavage site, the prime virulence determinant. However, required co-adaptations of the HA early in HPAIV evolution remained uncertain. To address this question, we generated several HA1/HA2 chimeras and point mutants of an H5N1 clade 2.2.2 HPAIV and an H5N1 low-pathogenic strain. Initial surveys of 3385 HPAIV H5 HA sequences revealed frequencies of 0...
June 13, 2018: Journal of Virology
Janet Lei, Egon J Jacobus, William K Taverner, Kerry D Fisher, Silvio Hemmi, Katy West, Lorna Slater, Fred Lilley, Alice Brown, Brian Champion, Margaret R Duffy, Len W Seymour
BACKGROUND: Oncolytic viruses are currently experiencing accelerated development in several laboratories worldwide, with some forty-seven clinical trials currently recruiting. Many oncolytic viruses combine targeted cytotoxicity to cancer cells with a proinflammatory cell lysis. Due to their additional potential to express immunomodulatory transgenes, they are also often known as oncolytic viral vaccines. However, several types of oncolytic viruses are human-specific and the lack of suitable immune-competent animal models complicates biologically relevant evaluation of their vaccine potential...
June 13, 2018: Journal for Immunotherapy of Cancer
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