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https://www.readbyqxmd.com/read/28934717/expression-of-c-ebp%C3%AE-in-myeloid-progenitors-during-sepsis-promotes-immunosuppression
#1
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs...
September 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28934391/homozygous-kidins220-loss-of-function-variants-in-fetuses-with-cerebral-ventriculomegaly-and-limb-contractures
#2
I-L Mero, H H Mørk, Y Sheng, A Blomhoff, G L Opheim, Aa Erichsen, M D Vigeland, K K Selmer
Heterozygous mutations in KIDINS220 were recently suggested a cause of spastic paraplegia, intellectual disability, nystagmus and obesity. All patients carried terminal nonsense de novo mutations that seemed to escape nonsense-mediated mRNA decay. The mechanism for pathogenicity is yet unexplained, as it seems that heterozygous loss-of-function variants of KIDINS220 are generally well tolerated. We present a consanguineous couple who experienced four pregnancy terminations due to repeated findings in the fetuses comprising enlarged cerebral ventricles and limb contractures...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934386/expression-of-the-neuropathy-associated-mtmr2-gene-rescues-mtm1-associated-myopathy
#3
Matthieu A Raess, Belinda S Cowling, Dimitri L Bertazzi, Christine Kretz, Bruno Rinaldi, Jean-Marie Xuereb, Pascal Kessler, Norma B Romero, Bernard Payrastre, Sylvie Friant, Jocelyn Laporte
Myotubularins (MTMs) are active or dead phosphoinositides phosphatases defining a large protein family conserved through evolution and implicated in different neuromuscular diseases. Loss-of-function mutations in MTM1 cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the MTM1-related protein MTMR2 cause a recessive Charcot-Marie-Tooth peripheral neuropathy. Here we aimed to determine the functional specificity and redundancy of MTM1 and MTMR2, and to assess their abilities to compensate for a potential therapeutic strategy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934385/hearing-loss-without-overt-metabolic-acidosis-in-atp6v1b1-deficient-mrl-mice-a-new-genetic-model-for-non-syndromic-deafness-with-enlarged-vestibular-aqueducts
#4
Cong Tian, Leona H Gagnon, Chantal Longo-Guess, Ron Korstanje, Susan M Sheehan, Kevin K Ohlemiller, Angela D Schrader, Jaclynn M Lett, Kenneth R Johnson
Mutations of the human ATP6V1B1 gene cause distal renal tubular acidosis (dRTA; OMIM #267300) often associated with sensorineural hearing impairment; however, mice with a knockout mutation of Atp6v1b1 were reported to exhibit a compensated acidosis and normal hearing. We discovered a new spontaneous mutation (vortex, symbol vtx) of Atp6v1b1 in an MRL/MpJ (MRL) colony of mice. In contrast to the reported phenotype of the knockout mouse, which was developed on a primarily C57BL/6 (B6) strain background, MRL-Atp6v1b1vtx/vtx mutant mice exhibit profound hearing impairment, which is associated with enlarged endolymphatic compartments of the inner ear...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934221/stage-specific-requirement-of-platelet-derived-growth-factor-receptor-%C3%AE-in-embryonic-development
#5
Chen Qian, Carol Wing Yan Wong, Zhongluan Wu, Qiuming He, Huimin Xia, Paul Kwong Hang Tam, Kenneth Kak Yuen Wong, Vincent Chi Hang Lui
BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures...
2017: PloS One
https://www.readbyqxmd.com/read/28933666/regulation-of-proliferation-in-developing-human-tooth-germs-by-msx-muscle-segment-homeodomain-proteins-and-cyclin-dependent-kinase-inhibitor-p19-ink4d
#6
Darko Kero, Katarina Vukojevic, Petra Stazic, Danijela Sundov, Snjezana Mardesic Brakus, Mirna Saraga-Babic
Before the secretion of hard dental tissues, tooth germs undergo several distinctive stages of development (dental lamina, bud, cap and bell). Every stage is characterized by specific proliferation patterns, which is regulated by various morphogens, growth factors and homeodomain proteins. The role of MSX homeodomain proteins in odontogenesis is rather complex. Expression domains of genes encoding for murine Msx1/2 during development are observed in tissues containing highly proliferative progenitor cells. Arrest of tooth development in Msx knockout mice can be attributed to impaired proliferation of progenitor cells...
September 21, 2017: Organogenesis
https://www.readbyqxmd.com/read/28933662/deficiency-of-serotonin-in-raphe-neurons-and-altered-behavioral-responses-in-tryptophan-hydroxylase-2-knockout-medaka-oryzias-latipes
#7
Satoshi Ansai, Hiroshi Hosokawa, Shingo Maegawa, Kiyoshi Naruse, Youhei Washio, Kenji Sato, Masato Kinoshita
Serotonin (5-hydroxytryptamine [5-HT]) is a bioactive monoamine that acts as a neurotransmitter in the central and peripheral nervous system of animals. Teleost fish species have serotonergic neurons in the raphe nuclei of the brainstem; however, the role of 5-HT in the raphe neurons in teleost fish remains largely unknown. Here, we established a medaka (Oryzias latipes) strain with targeted disruption of tryptophan hydroxylase 2 (tph2) gene that is involved in the 5-HT synthesis in the raphe nuclei. Immunohistochemistry and mass spectrometry analysis revealed that the homozygous mutants (tph2(Δ13/Δ13)) lacked the ability to synthesize 5-HT in the raphe neurons...
September 21, 2017: Zebrafish
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#8
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933358/substrate-deprivation-therapy-to-reduce-glycosaminoglycan-synthesis-improves-aspects-of-neurological-and-skeletal-pathology-in-mps-i-mice
#9
Ainslie L K Derrick-Roberts, Matilda R Jackson, Carmen E Pyragius, Sharon Byers
Mucopolysaccharidosis type I (MPS I) is the most common form of the MPS group of genetic diseases. MPS I results from a deficiency in the lysosomal enzyme α-l-iduronidase, leading to accumulation of undegraded heparan and dermatan sulphate glycosaminoglycan (GAG) chains in patient cells. MPS children suffer from multiple organ failure and die in their teens to early twenties. In particular, MPS I children also suffer from profound mental retardation and skeletal disease that restricts growth and movement. Neither brain nor skeletal disease is adequately treated by current therapy approaches...
February 23, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28933279/zinc-transporter-protein-tzn-1-may-also-play-a-role-in-conidiation-pathway-of-neurospora-crassa-an-insight-using-proteogenomic-approachusing-proteogenomic-approach
#10
Divya Rupa Venkata Pandala, Jogeswar Gadi, Kiranmayi Patnala
Zinc transporter (tzn-1) of Neurospora crassa plays a crucial role in conidiation pathway, as its removal results in aconidiation which was reported in our earlier studies. Present study depicts the role of tzn-1 in conidiation process, by comparing knockout (KO) mutants zinc transporter KO (Δtzn-1) and aconidiating gene KO (Δacon-3) with wild oak ridge (OR) 74 'A' strain by 'Proteo-genomic' approach. Firstly, nine commonly overexpressed protein spots from the two sets (Δtzn-1 to wild and Δacon-3 to wild) were analyzed by combining 2-Dimensional gel electrophoresis (2DE) with Matrix Associated Laser Desorption/Ionization mass spectrometry -Peptide Mass Fingerprint (MALDI-PMF)...
September 19, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28933219/suppression-of-trim32-enhances-motor-function-repair-after-traumatic-brain-injury-associated-with-antiapoptosis
#11
Zi-Bin Zhang, Liu-Lin Xiong, Bin-Tuan Lu, Hui-Xiang Zhang, Piao Zhang, Ting-Hua Wang
To investigate the role of Trim32 in traumatic brain injury (TBI), adult male Sprague Dawley (SD) rats and mice were randomly divided into sham (n = 6) and TBI groups ( n = 24), respectively. Then, mice were assigned into Trim32 knockout mice (Trim32-KO [+/-]) and wild-type (WT) littermates. The TBI model used was the Feeney free-falling model, and neurological function was evaluated after TBI using a neurological severity score (NSS). Reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry were used to investigate the expression of Trim32 in the damaged cortex...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28933027/learning-directed-acyclic-graphs-from-large-scale-genomics-data
#12
Fabio Nikolay, Marius Pesavento, George Kritikos, Nassos Typas
In this paper, we consider the problem of learning the genetic interaction map, i.e., the topology of a directed acyclic graph (DAG) of genetic interactions from noisy double-knockout (DK) data. Based on a set of well-established biological interaction models, we detect and classify the interactions between genes. We propose a novel linear integer optimization program called the Genetic-Interactions-Detector (GENIE) to identify the complex biological dependencies among genes and to compute the DAG topology that matches the DK measurements best...
September 20, 2017: EURASIP Journal on Bioinformatics & Systems Biology
https://www.readbyqxmd.com/read/28932356/interleukin-19-is-cardioprotective-in-dominant-negative-cyclic-adenosine-monophosphate-response-element-binding-protein-mediated-heart-failure-in-a-sex-specific-manner
#13
Danielle R Bruns, Alexander R Ghincea, Christian V Ghincea, Yasu-Taka Azuma, Peter A Watson, Michael V Autieri, Lori A Walker
AIM: To investigate the role of interleukin-19 (IL-19) in a murine model of female-dominant heart failure (HF). METHODS: Expression of one copy of a phosphorylation-deficient cyclic adenosine monophosphate response-element binding protein (dnCREB) causes HF, with accelerated morbidity and mortality in female mice compared to males. We assessed expression of IL-19, its receptor isoforms IL-20R α/β, and downstream IL-19 signaling in this model of female-dominant HF...
August 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28932185/hyperactivity-of-hypothalamic-pituitary-adrenal-axis-due-to-dysfunction-of-the-hypothalamic-glucocorticoid-receptor-in-sigma-1-receptor-knockout-mice
#14
Tingting Di, Suyun Zhang, Juan Hong, Tingting Zhang, Ling Chen
Sigma-1 receptor knockout (σ1R-KO) mice exhibit a depressive-like phenotype. Because σ1R is highly expressed in the neuronal cells of hypothalamic paraventricular nuclei (PVN), this study investigated the influence of σ1R deficiency on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Here, we show that the levels of basal serum corticosterone (CORT), adrenocorticotropic hormone (ACTH) and corticotrophin releasing factor (CRF) as well as the level of CRF mRNA in PVN did not significantly differ between adult male σ1R-KO mice and wild-type (WT) mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28931923/mllt10-knockout-mouse-model-reveals-critical-role-of-af10-dependent-h3k79-methylation-in-midfacial-development
#15
Honami Ogoh, Kazutsune Yamagata, Tomomi Nakao, Lisa L Sandell, Ayaka Yamamoto, Aiko Yamashita, Naomi Tanga, Mai Suzuki, Takaya Abe, Issay Kitabayashi, Toshio Watanabe, Daisuke Sakai
Epigenetic regulation is required to ensure the precise spatial and temporal pattern of gene expression that is necessary for embryonic development. Although the roles of some epigenetic modifications in embryonic development have been investigated in depth, the role of methylation at lysine 79 (H3K79me) is poorly understood. Dot1L, a unique methyltransferase for H3K79, forms complexes with distinct sets of co-factors. To further understand the role of H3K79me in embryogenesis, we generated a mouse knockout of Mllt10, the gene encoding Af10, one Dot1L complex co-factor...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931858/loss-of-p73-in-ependymal-cells-during-the-perinatal-period-leads-to-aqueductal-stenosis
#16
Masashi Fujitani, Ryohei Sato, Toshihide Yamashita
The p53 family member p73 plays a critical role in brain development. p73 knockout mice exhibit a number of deficits in the nervous system, such as neuronal death, hydrocephalus, hippocampal dysgenesis, and pheromonal defects. Among these phenotypes, the mechanisms of hydrocephalus remain unknown. In this study, we generated a p73 knock-in (KI) mutant mouse and a conditional p73 knockout mouse. The homozygous KI mutants showed aqueductal stenosis. p73 was expressed in the ependymal cell layer and several brain areas...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931752/l-dopa-sensitizes-vasomotor-tone-by-modulating-the-vascular-alpha1-adrenergic-receptor
#17
Daiki Masukawa, Motokazu Koga, Anna Sezaki, Yuka Nakao, Yuji Kamikubo, Tatsuo Hashimoto, Yuki Okuyama-Oki, Aderemi Caleb Aladeokin, Fumio Nakamura, Utako Yokoyama, Hiromichi Wakui, Hiroshi Ichinose, Takashi Sakurai, Satoshi Umemura, Koichi Tamura, Yoshihiro Ishikawa, Yoshio Goshima
Blood pressure is regulated by extrinsic factors including noradrenaline, the sympathetic neurotransmitter that controls cardiovascular functions through adrenergic receptors. However, the fine-tuning system of noradrenaline signaling is relatively unknown. We here show that l-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of catecholamines, sensitizes the vascular adrenergic receptor alpha1 (ADRA1) through activation of L-DOPA receptor GPR143. In WT mice, intravenous infusion of the ADRA1 agonist phenylephrine induced a transient elevation of blood pressure...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931751/essential-role-of-kir5-1-channels-in-renal-salt-handling-and-blood-pressure-control
#18
Oleg Palygin, Vladislav Levchenko, Daria V Ilatovskaya, Tengis S Pavlov, Oleh M Pochynyuk, Howard J Jacob, Aron M Geurts, Matthew R Hodges, Alexander Staruschenko
Supplementing diets with high potassium helps reduce hypertension in humans. Inwardly rectifying K+ channels Kir4.1 (Kcnj10) and Kir5.1 (Kcnj16) are highly expressed in the basolateral membrane of distal renal tubules and contribute to Na+ reabsorption and K+ secretion through the direct control of transepithelial voltage. To define the importance of Kir5.1 in blood pressure control under conditions of salt-induced hypertension, we generated a Kcnj16 knockout in Dahl salt-sensitive (SS) rats (SSKcnj16-/-). SSKcnj16-/- rats exhibited hypokalemia and reduced blood pressure, and when fed a high-salt diet (4% NaCl), experienced 100% mortality within a few days triggered by salt wasting and severe hypokalemia...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931573/chd7-collaborates-with-sox2-to-regulate-activation-of-oligodendrocyte-precursor-cells-after-spinal-cord-injury
#19
Toru Doi, Toru Ogata, Junji Yamauchi, Yasuhiro Sawada, Sakae Tanaka, Motoshi Nagao
Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury, to generate myelinating OLs; however, the underlying mechanisms remain poorly understood. Here we show that Chd7 regulates OPC activation after spinal cord injury (SCI). Chd7 is expressed in OPCs in the adult spinal cord and its expression is upregulated with a concomitant increase in Sox2 expression following SCI. OPC-specific ablation of Chd7 in the injured mice leads to reduced OPC proliferation, the loss of OPC identity, and impaired OPC differentiation...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28931551/endoplasmic-reticulum-membrane-protein-complex-subunit-10-emc10-is-a-bone-marrow-derived-angiogenic-growth-factor-promoting-tissue-repair-after-myocardial-infarction
#20
Marc R Reboll, Mortimer Korf-Klingebiel, Stefanie Klede, Felix Polten, Eva Brinkmann, Ines Reimann, Hans-Joachim Schönfeld, Maria Bobadilla, Jan Faix, George Kensah, Ina Gruh, Michael Klintschar, Matthias Gaestel, Hans W Niessen, Andreas Pich, Johann Bauersachs, Joseph A Gogos, Yong Wang, Kai C Wollert
Background -Clinical trials of bone marrow cell (BMC)-based therapies after acute myocardial infarction (MI) have produced mostly neutral results. Treatment with specific BMC-derived secreted proteins may provide an alternative biologic approach to improving tissue repair and heart function after MI. We recently performed a bioinformatic secretome analysis in BMCs from patients with acute MI and discovered a poorly characterized secreted protein, endoplasmic reticulum membrane protein complex subunit 10 (EMC10), showing activity in an angiogenic screen...
September 20, 2017: Circulation
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