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https://www.readbyqxmd.com/read/28230307/cdkl5-deficiency-entails-sleep-apneas-in-mice
#1
Viviana Lo Martire, Sara Alvente, Stefano Bastianini, Chiara Berteotti, Alessandro Silvani, Alice Valli, Rocchina Viggiano, Elisabetta Ciani, Giovanna Zoccoli
A recently discovered neurodevelopmental disorder caused by the mutation of the cyclin-dependent kinase-like 5 gene (CDKL5) entails complex autistic-like behaviours similar to Rett syndrome, but its impact upon physiological functions remains largely unexplored. Sleep-disordered breathing is common and potentially life-threatening in patients with Rett syndrome; however, evidence is limited in children with CDKL5 disorder, and is lacking altogether in adults. The aim of this study was to test whether the breathing pattern during sleep differs between adult Cdkl5 knockout (Cdkl5-KO) and wild-type (WT) mice...
February 23, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28230289/mice-lacking-bcas1-a-novel-myelin-associated-protein-display-hypomyelination-schizophrenia-like-abnormal-behaviors-and-upregulation-of-inflammatory-genes-in-the-brain
#2
Tetsuya Ishimoto, Kensuke Ninomiya, Ran Inoue, Masato Koike, Yasuo Uchiyama, Hisashi Mori
The abnormal expression and function of myelin-related proteins contribute to nervous system dysfunction associated with neuropsychiatric disorders; however, the underlying mechanism of this remains unclear. We found here that breast carcinoma amplified sequence 1 (BCAS1), a basic protein abundant in the brain, was expressed specifically in oligodendrocytes and Schwann cells, and that its expression level was decreased by demyelination. This suggests that BCAS1 is a novel myelin-associated protein. BCAS1 knockout mice displayed schizophrenia-like behavioral abnormalities and a tendency toward reduced anxiety-like behaviors...
February 23, 2017: Glia
https://www.readbyqxmd.com/read/28230162/n-acetylated-proline-glycine-proline-accelerates-cutaneous-wound-healing-and-neovascularization-by-human-endothelial-progenitor-cells
#3
Yang Woo Kwon, Soon Chul Heo, Tae Wook Lee, Gyu Tae Park, Jung Won Yoon, Il Ho Jang, Seung-Chul Kim, Hyun-Chang Ko, Youngjae Ryu, Hyeona Kang, Chang Man Ha, Sang Chul Lee, Jae Ho Kim
Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230092/rtfc-4931414p19rik-regulates-in-vitro-thyroid-differentiation-and-in-vivo-thyroid-function
#4
Yang Yu, Chang Liu, Junxia Zhang, Mimi Zhang, Wei Wen, Xianhui Ruan, Dapeng Li, Shuang Zhang, Ming Gao, Lingyi Chen
Thyroid is a one of the most important endocrine organs. Understanding the molecular mechanism underlying thyroid development and function, as well as thyroid diseases, is beneficial for the clinical treatment of thyroid diseases and tumors. Through genetic linkage analysis and exome sequencing, we previously identified an uncharacterized gene C14orf93 (RTFC, mouse homolog: 4931414P19Rik) as a novel susceptibility gene for familial non-medullary thyroid carcinoma, and demonstrated its function in promoting thyroid tumor...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228748/chromogranin-a-regulation-of-obesity-and-peripheral-insulin-sensitivity
#5
REVIEW
Gautam K Bandyopadhyay, Sushil K Mahata
Chromogranin A (CgA) is a prohormone and granulogenic factor in endocrine and neuroendocrine tissues, as well as in neurons, and has a regulated secretory pathway. The intracellular functions of CgA include the initiation and regulation of dense-core granule biogenesis and sequestration of hormones in neuroendocrine cells. This protein is co-stored and co-released with secreted hormones. The extracellular functions of CgA include the generation of bioactive peptides, such as pancreastatin (PST), vasostatin, WE14, catestatin (CST), and serpinin...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28228591/the-swi-snf-chromatin-regulator-brg1-modulates-the-transcriptional-regulatory-activity-of-the-ebv-dna-polymerase-processivity-factor-bmrf1
#6
Mei-Tzu Su, Ya-Ting Wang, Yen-Ju Chen, Su-Fang Lin, Ching-Hwa Tsai, Mei-Ru Chen
During lytic phase of Epstein-Barr virus (EBV), binding of the transactivator Zta to the origin of lytic replication (oriLyt) and the BHLF1 transcript, forming a stable RNA-DNA hybrid, are required to initiate viral DNA replication. EBV-encoded viral DNA replication proteins form complexes to amplify viral DNA. BMRF1, the viral DNA polymerase accessory factor, is essential for lytic DNA replication and also known as a transcriptional regulator of the expression of BHLF1 and BALF2 (ssDNA-binding protein). In order to determine systematically how BMRF1 regulates viral transcription, a BMRF1 knockout bacmid was generated to analyze viral gene expression using a viral DNA microarray...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228507/alcohol-dehydrogenase-5-is-a-source-of-formate-for-de-novo-purine-biosynthesis-in-hepg2-cells
#7
Sajin Bae, James Chon, Martha S Field, Patrick J Stover
Background: Formate provides one-carbon units for de novo purine and thymidylate (dTMP) synthesis and is produced via both folate-dependent and folate-independent pathways. Folate-independent pathways are mediated by cytosolic alcohol dehydrogenase 5 (ADH5) and mitochondrial aldehyde dehydrogenase 2 (ALDH2), which generate formate by oxidizing formaldehyde. Formate is a potential biomarker of B-vitamin-dependent one-carbon metabolism.Objective: This study investigated the contributions of ADH5 and ALDH2 to formate production and folate-dependent de novo purine and dTMP synthesis in HepG2 cells...
February 22, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28228267/nrf2-improves-leptin-and-insulin-resistance-provoked-by-hypothalamic-oxidative-stress
#8
Yoko Yagishita, Akira Uruno, Toshiaki Fukutomi, Ritsumi Saito, Daisuke Saigusa, Jingbo Pi, Akiyoshi Fukamizu, Fumihiro Sugiyama, Satoru Takahashi, Masayuki Yamamoto
The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout (KO) of selenocysteine-tRNA (Trsp) using rat-insulin-promoter-driven-Cre (RIP-Cre). These Trsp-KO (Trsp(RIP)KO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic β cells, leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals are suppressed, and numbers of proopiomelanocortin-positive neurons in the hypothalamus are decreased...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228252/complete-disruption-of-the-kainate-receptor-gene-family-results-in-corticostriatal-dysfunction-in-mice
#9
Jian Xu, John J Marshall, Herman B Fernandes, Toshihiro Nomura, Bryan A Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T Swanson, Anis Contractor
Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226770/a-multiscale-model-based-analysis-of-the-multi-tissue-interplay-underlying-blood-glucose-regulation-in-type-i-diabetes
#10
Federico Wadehn, Stephan Schaller, Thomas Eissing, Markus Krauss, Lars Kupfer, Federico Wadehn, Stephan Schaller, Thomas Eissing, Markus Krauss, Lars Kupfer, Federico Wadehn, Markus Krauss, Lars Kupfer, Stephan Schaller, Thomas Eissing
A multiscale model for blood glucose regulation in diabetes type I patients is constructed by integrating detailed metabolic network models for fat, liver and muscle cells into a whole body physiologically-based pharmacokinetic/pharmacodynamic (pBPK/PD) model. The blood glucose regulation PBPK/PD model simulates the distribution and metabolization of glucose, insulin and glucagon on an organ and whole body level. The genome-scale metabolic networks in contrast describe intracellular reactions. The developed multiscale model is fitted to insulin, glucagon and glucose measurements of a 48h clinical trial featuring 6 subjects and is subsequently used to simulate (in silico) the influence of geneknockouts and drug-induced enzyme inhibitions on whole body blood glucose levels...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225907/characterisation-of-iunh-gene-knockout-strain-from-mycobacterium-tuberculosis
#11
Anne Drumond Villela, Valnês da Silva Rodrigues, Antônio Frederico Michel Pinto, Priscila Lamb Wink, Zilpa Adriana Sánchez-Quitian, Guilherme Oliveira Petersen, Maria Martha Campos, Luiz Augusto Basso, Diógenes Santiago Santos
BACKGROUND: Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis. The better understanding of important metabolic pathways from M. tuberculosis can contribute to the development of novel therapeutic and prophylactic strategies to combat TB. Nucleoside hydrolase (MtIAGU-NH), encoded by iunH gene (Rv3393), is an enzyme from purine salvage pathway in M. tuberculosis. MtIAGU-NH accepts inosine, adenosine, guanosine, and uridine as substrates, which may point to a pivotal metabolic role...
March 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28225891/soy-milk-versus-simvastatin-for-preventing-atherosclerosis-and-left-ventricle-remodeling-in-ldl-receptor-knockout-mice
#12
L Santos, A P Davel, T I R Almeida, M R Almeida, E A Soares, G J M Fernandes, S F Magalhães, V G Barauna, J A D Garcia
Functional food intake has been highlighted as a strategy for the prevention of cardiovascular diseases by reducing risk factors. In this study, we compared the effects of oral treatment with soy milk and simvastatin on dyslipidemia, left ventricle remodeling and atherosclerotic lesion of LDL receptor knockout mice (LDLr-/-) fed a hyperlipidic diet. Forty 3-month old male LDLr-/- mice were distributed into four groups: control group (C), in which animals received standard diet; HL group, in which animals were fed a hyperlipidic diet; HL+SM or HL+S groups, in which animals were submitted to a hyperlipidic diet plus soy milk or simvastatin, respectively...
February 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28225087/ampk-deficiency-in-chondrocytes-accelerated-the-progression-of-instability-induced-and-ageing-associated-osteoarthritis-in-adult-mice
#13
Sheng Zhou, Wanli Lu, Liang Chen, Qiting Ge, Dongyang Chen, Zhihong Xu, Dongquan Shi, Jin Dai, Jianxin Li, Huangxian Ju, Yi Cao, Jinzhong Qin, Shuai Chen, Huajian Teng, Qing Jiang
Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225067/generation-of-gross-chromosomal-rearrangements-by-a-single-engineered-dna-double-strand-break
#14
Zhijun Qiu, Zhenhua Zhang, Anna Roschke, Tamas Varga, Peter D Aplan
Gross chromosomal rearrangements (GCRs), including translocations, inversions amplifications, and deletions, can be causal events leading to malignant transformation. GCRs are thought to be triggered by DNA double strand breaks (DSBs), which in turn can be spontaneous or induced by external agents (eg. cytotoxic chemotherapy, ionizing radiation). It has been shown that induction of DNA DSBs at two defined loci can produce stable balanced chromosomal translocations, however, a single engineered DNA DSB could not...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225019/trpv1-deletion-impaired-fracture-healing-and-inhibited-osteoclast-and-osteoblast-differentiation
#15
Lin-Hai He, Meng Liu, Yang He, E Xiao, Lu Zhao, Ting Zhang, Hua-Qian Yang, Yi Zhang
Fracture healing, in which osteoclasts and osteoblasts play important roles, has drawn much clinical attention. Osteoclast deficiency or decreased osteoblast activity will impair fracture healing. TRPV1 is a member of the Ca(2+) permeable cation channel subfamily, and pharmacological inhibition of TRPV1 prevents ovariectomy-induced bone loss, which makes TRPV1 a potential target for osteoporosis. However, whether long term TRPV1 inhibition or TRPV1 deletion will affect the fracture healing process is unclear...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224202/germline-specific-dgcr8-knockout-in-zebrafish-using-a-back-approach
#16
Yun Liu, Zeyao Zhu, Idy H T Ho, Yujian Shi, Yuxin Xie, Jianzhen Li, Yong Zhang, Matthew T V Chan, Christopher H K Cheng
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#17
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223821/asparaginyl-endopeptidase-improves-the-resistance-of-microtubule-targeting-drugs-in-gastric-cancer-through-iqgap1-modulating-the-egfr-jnk-erk-signaling-pathway
#18
Yuehong Cui, Qian Li, Hong Li, Yan Wang, Hongshan Wang, Weidong Chen, Shangmin Zhang, Jian Cao, Tianshu Liu
PURPOSE: In recent years, understanding of the role of asparaginyl endopeptidase (AEP) in tumorigenesis has steadily increased. In this study, we investigated whether AEP expression correlates with sensitivity to chemotherapeutic drugs in gastric cancer and explored the mechanism. PATIENTS AND METHODS: AEP expression in the serum of patients' peripheral blood was measured by enzyme-linked immunosorbent assay. Patient survival time was evaluated using univariate and multivariate analyses...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223698/sex-differences-in-microglial-cx3cr1-signalling-determine-obesity-susceptibility-in-mice
#19
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/28223477/znf307-zinc-finger-protein-307-acts-as-a-negative-regulator-of-pressure-overload-induced-cardiac-hypertrophy
#20
Chang-Jiang Yu, Chen Liang, Yu-Xia Li, Qing-Qing Hu, Wei-Wan Zheng, Na Niu, Xu Yang, Zi-Rui Wang, Xiao-Di Yu, Bao-Long Zhang, Bin-Lin Song, Zhi-Ren Zhang
Pathological cardiac hypertrophy is a key risk factor for heart failure. We found that the protein expression levels of the ZNF307 (zinc finger protein 307) were significantly increased in heart samples from both human patients with dilated cardiomyopathy and mice subjected to aortic banding. Therefore, we aimed to elucidate the role of ZNF307 in the development of cardiac hypertrophy and to explore the signal transduction events that mediate the effect of ZNF307 on cardiac hypertrophy, using cardiac-specific ZNF307 transgenic (ZNF307-TG) mice and ZNF307 global knockout (ZNF307-KO) mice...
February 21, 2017: Hypertension
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