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https://www.readbyqxmd.com/read/28742026/aire-is-a-critical-spindle-associated-protein-in-embryonic-stem-cells
#1
Bin Gu, Jean-Philippe Lambert, Katie Cockburn, Anne-Claude Gingras, Janet Rossant
Embryonic stem (ES) cells go though embryo-like cell cycles regulated by specialized molecular mechanisms. However, it is not known whether there are ES cell-specific mechanisms regulating mitotic fidelity. Here we showed that Autoimmune Regulator (Aire), a transcription coordinator involved in immune tolerance processes, is a critical spindle-associated protein in mouse ES(mES) cells. BioID analysis showed that AIRE associates with spindle-associated proteins in mES cells. Loss of function analysis revealed that Aire was important for centrosome number regulation and spindle pole integrity specifically in mES cells...
July 25, 2017: ELife
https://www.readbyqxmd.com/read/28741149/the-role-of-peripheral-interleukin-6-in-the-development-of-acute-seizures-following-virus-encephalitis
#2
Matthew F Cusick, Jane E Libbey, Daniel J Doty, Ana Beatriz DePaula-Silva, Robert S Fujinami
Seizure disorders are often associated with infectious etiologies. Infection, via the intracerebral (i.c.) route, of C57BL/6J mice with the Daniels (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) results in approximately 50% of the mice developing acute behavioral seizures. TMEV-DA is the wild-type strain of the virus that replicates within the parenchyma of the brain. A variant of TMEV-DA, TMEV-H101, does not replicate within the parenchyma of the brain. However, infection with TMEV-H101 via the i...
July 24, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28740825/nmdar-hypofunction-and-somatostatin-expressing-gabaergic-interneurons-and-receptors-a-newly-identified-correlation-and-its-effects-in-schizophrenia
#3
REVIEW
Fatemah Alherz, Mohammad Alherz, Hashemiah Almusawi
This review investigates the association between N-methyl-d-Aspartate receptor (NMDAR) hypofunction and somatostatin-expressing GABAergic interneurons (SST +) and how it contributes to the cognitive deficits observed in schizophrenia (SZ). This is based on evidence that NMDAR antagonists caused symptoms resembling SZ in healthy individuals. NMDAR hypofunction in GABAergic interneurons results in the modulation of the cortical network oscillation, particularly in the gamma range (30-80 Hz). These gamma-band oscillation (GBO) abnormalities were found to lead to the cognitive deficits observed in the disorder...
June 2017: Schizophrenia Research. Cognition
https://www.readbyqxmd.com/read/28740544/interleukin-32%C3%AE-inhibits-endothelial-inflammation-vascular-smooth-muscle-cell-activation-and-atherosclerosis-by-upregulating-timp3-and-reck-through-suppressing-microrna-205-biogenesis
#4
Dong Ju Son, Yu Yeon Jung, Young Sik Seo, Heonyong Park, Dong Hun Lee, Sanghyeon Kim, Yoon-Seok Roh, Sang Bae Han, Do Young Yoon, Jin Tae Hong
Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and regulates vascular endothelial cell behavior. Although some IL-32 isoforms have been reported to contribute to vascular inflammation and atherosclerosis, the functional role of IL-32α in vascular inflammation and atherogenesis has not been studied. Methods: IL-32α function was assessed in cells with transient IL-32α overexpression or treated with recombinant human IL-32α by western blotting and mRNA expression analysis. Vascular smooth muscle cell (VSMC) proliferation and migration was examined by BrdU incorporation and wound healing assays, respectively...
2017: Theranostics
https://www.readbyqxmd.com/read/28740463/terminal-differentiation-of-adult-hippocampal-progenitor-cells-is-a-step-functionally-dissociable-from-proliferation-and-is-controlled-by-tis21-id3-and-neurod2
#5
Laura Micheli, Manuela Ceccarelli, Roberta Gioia, Giorgio D'Andrea, Stefano Farioli-Vecchioli, Marco Costanzi, Daniele Saraulli, Vincenzo Cestari, Felice Tirone
Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28739823/interleukin-17a-aggravates-middle-ear-injury-induced-by-streptococcus-pneumoniae-through-p38-mapk-signaling-pathway
#6
Wei Wang, Wenbin Liu, Jiali Liu, Zimeng Wang, Fangmei Fan, Yurong Ma, Chunfang Jin, Yun Xiang, Yifei Huang, Xuemei Zhang, Wenchun Xu, Yibing Yin, Yujuan He
Acute otitis media (AOM) is one of the most common bacterial infection diseases in children aged 2-7 yr worldwide. We previously demonstrated that interleukin (IL)-17A promotes an acute inflammatory response characterized by the influx of neutrophils into the middle ear cavity during Streptococcus pneumoniae (Spn)-induced AOM. Generally, inflammatory response is viewed as an effector that frequently causes local tissue damage. However, little is known about the pathogenic effects of IL-17A in AOM. Here, we investigated the pathogenic effects of IL-17A by using wild-type (WT) and IL-17A knockout (KO) mouse models...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28739822/stress-responsive-hilpda-is-necessary-for-thermoregulation-during-fasting
#7
Matthew J VandeKopple, Jinghai Wu, Lisa A Baer, Naresh C Bal, Santosh K Maurya, Anuradha Kalyanasundaram, Muthu Periasamy, Kristin I Stanford, Amato Giaccia, Nicholas Denko, Ioanna Papandreou
Hypoxia-Inducible Lipid-Droplet Associated protein (HILPDA) has been shown to localize to lipid droplets in nutrient responsive cell types such as hepatocytes and adipocytes. However, its role in the control of whole-body homeostasis is not known. We sought to measure cell-intrinsic and systemic stress responses in a mouse strain harboring whole body Hilpda deficiency. We generated a genetically engineered mouse model of whole body HILPDA deficiency by replacing the coding HILPDA exon with Luciferase. We subjected the knockout animals to environmental stresses and measured whole-animal metabolic and behavioral parameters...
July 24, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28739820/efficient-plastid-transformation-in-arabidopsis
#8
Qiguo Yu, Kerry Ann Lutz, Pal Maliga
Plastid transformation is routine in tobacco, but 100-fold less frequent in Arabidopsis, preventing its use in plastid biology. A recent study revealed that null mutations in ACC2, encoding a plastid-targeted acetyl-CoA-carboxylase, cause hypersensitivity to spectinomycin. We hypothesized that plastid transformation efficiency should increase in the acc2 background, because when ACC2 is absent, fatty acid biosynthesis becomes dependent on translation of the plastid-encoded ACC β-Carboxylase subunit. We bombarded ACC2-defective Arabidopsis leaves with a vector carrying a selectable spectinomycin resistance (aadA) gene and gfp, encoding the green fluorescence protein GFP...
July 24, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28739679/two-populations-of-cytoplasmic-dynein-contribute-to-spindle-positioning-in-c-elegans-embryos
#9
Ruben Schmidt, Lars-Eric Fielmich, Ilya Grigoriev, Eugene A Katrukha, Anna Akhmanova, Sander van den Heuvel
The position of the mitotic spindle is tightly controlled in animal cells as it determines the plane and orientation of cell division. Contacts between cytoplasmic dynein and astral microtubules (MTs) at the cell cortex generate pulling forces that position the spindle. An evolutionarily conserved Gα-GPR-1/2(Pins/LGN)-LIN-5(Mud/NuMA) cortical complex interacts with dynein and is required for pulling force generation, but the dynamics of this process remain unclear. In this study, by fluorescently labeling endogenous proteins in Caenorhabditis elegans embryos, we show that dynein exists in two distinct cortical populations...
July 24, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28739650/lysophosphatidic-acid-receptor-antagonism-protects-against-diabetic-nephropathy-in-a-type-2-diabetic-model
#10
Ming-Zhi Zhang, Xin Wang, Haichun Yang, Agnes B Fogo, Brian J Murphy, Robert Kaltenbach, Peter Cheng, Bradley Zinker, Raymond C Harris
Lysophosphatidic acid (LPA) functions through activation of LPA receptors (LPARs). LPA-LPAR signaling has been implicated in development of fibrosis. However, the role of LPA-LPAR signaling in development of diabetic nephropathy (DN) has not been studied. We examined whether BMS002, a novel dual LPAR1 and LPAR3 antagonist, affects development of DN in endothelial nitric oxide synthase-knockout db/db mice. Treatment of these mice with BMS002 from 8 to 20 weeks of age led to a significant reduction in albuminuria, similar to that observed with renin-angiotensin system inhibition (losartan plus enalapril)...
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28739602/loss-of-prion-protein-is-associated-with-the-development-of-insulin-resistance-and-obesity
#11
Giovanna Brito, Fernada C S Lupinacci, Flávio H Beraldo, Tiago G Santos, Martin Roffé, Marilene H Lopes, Vladmir C C de Lima, Vilma R Martins, Glaucia N M Hajj
Prion protein (PrP(C)) was initially described due to its involvement in transmissible spongiform encephalopathies. It was subsequently demonstrated to be a cell surface molecule involved in many physiological processes, such as vesicle trafficking. Herein, we investigated the roles of PrP(C) in the response to insulin and obesity development.  Two independent PrP(C) knockout (KO) and one PrP(C) overexpressing (TG20) mouse models were fed high-fat diets, and the development of insulin resistance and obesity was monitored...
July 24, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28739572/altenusin-a-non-steroidal-microbial-metabolite-attenuates-non-alcoholic-fatty-liver-disease-by-activating-the-farnesoid-x-receptor
#12
Zhihui Zheng, Zanmei Zhao, Shuqiang Li, Xinhua Lu, Mengxi Jiang, Jie Lin, Yunqi An, Yang Xie, Meishu Xu, Wenbin Shen, Grace Guo, YIxian Huang, Song Li, Xuexia Zhang, Wen Xie
Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The incidence of NAFLD has increased steadily due to its close association with the global epidemic of obesity and type 2 diabetes. However, there is no effective pharmacological therapy approved for NAFLD. Farnesoid X receptor (FXR), a member of the nuclear receptor subfamily, plays important roles in maintaining the homeostasis of bile acids, glucose and lipids. FXR agonists have shown promise for the treatment of NAFLD. Here we report Altenusin (2076A), a natural non-steroidal fungal metabolite, as a novel selective agonist of FXR with an EC50 value of 3...
July 24, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28739528/chronic-hyper-leptinemia-induces-insulin-signaling-disruption-in-adipocytes-implications-of-nos2
#13
Abhishek Gupta, Muheeb Beg, Durgesh Kumar, Kripa Shankar, Salil Varshney, Sujith Rajan, Ankita Srivastava, Kalpana Singh, Satyendra Sonkar, Abbas Ali Mahdi, Madhu Dikshit, Anil Nilkanth Gaikwad
Leptin, following its discovery, has developed a formidable interest in the scientific community to delineate its contribution towards overall metabolic homeostasis. Contradictory reports have been published on leptin administration effects on whole body insulin sensitivity. Following late reports, we surveyed human serum leptin levels along with other metabolic parameters including BMI and HOMA-IR. We found a positive correlation between leptin levels and insulin resistance parameters. Considering the presence of the long form of leptin receptor on adipocytes, we explored the effects of chronic physiological hyper-leptinemic exposure on adipocyte insulin sensitivity...
July 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28739484/protein-kinase-c%C3%AE-%C3%AE-is-dispensable-for-platelet-function-in-thrombosis-and-hemostasis-in-mice
#14
Sarah Beck, Michael Leitges, David Stegner
Platelet activation at sites of vascular injury is crucial for hemostasis, but it may also cause myocardial infarction or ischemic stroke. Upon platelet activation, cytoskeletal reorganization is essential for platelet secretion and thrombus formation. Members of the protein kinase C family, which includes 12 isoforms, are involved in most platelet responses required for thrombus formation. The atypical protein kinase Cι/λ (PKCι/λ) has been implicated as an important mediator of cell polarity, carcinogenesis and immune cell responses...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28739257/lack-of-epithelial-ppar%C3%AE-causes-cystic-adenomatoid-malformations-in-mouse-fetal-lung
#15
Jung-Hwan Kim, Satoshi Yamaori, Tomotaka Tanabe, Mitsuhiro Takagi, Tsutomu Matsubara, Minoru Okamoto, Shioko Kimura, Frank J Gonzalez
Peroxisome proliferator-activated receptor-γ (PPARγ) plays an important role in lipid and glucose metabolism. In this study, the function of PPARγ on lung development was investigated. Lung-specific Pparg conditional knockout mice (Pparg(ΔLuEpC)) were developed using Cre-Lox system. Pparg(ΔLuEpC) mice showed abnormal lung development with enlarged airspaces and followed by increase of apoptotic cells at E14.5 to E18.5. Gene analysis revealed that expression of Pmaip1, a gene related to apoptosis, was significantly increased while expression of Retnla, a gene related to anti-apoptosis, was dramatically decreased in the fetal lung (E14...
July 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28739141/amp-activated-protein-kinase-myocardin-related-transcription-factor-a-signaling-regulates-fibroblast-activation-and-renal-fibrosis
#16
Yuguo Wang, Li Jia, Zhaoyong Hu, Mark L Entman, William E Mitch, Yanlin Wang
Chronic kidney disease is a major cause of death, and renal fibrosis is a common pathway leading to the progression of this disease. Although activated fibroblasts are responsible for the production of the extracellular matrix and the development of renal fibrosis, the molecular mechanisms underlying fibroblast activation are not fully defined. Here we examined the functional role of AMP-activated protein kinase (AMPK) in the activation of fibroblasts and the development of renal fibrosis. AMPKα1 was induced in the kidney during the development of renal fibrosis...
July 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28739140/the-il-4-receptor-%C3%AE-has-a-critical-role-in-bone-marrow-derived-fibroblast-activation-and-renal-fibrosis
#17
Hua Liang, Zhengmao Zhang, Jingyin Yan, Yuguo Wang, Zhaoyong Hu, William E Mitch, Yanlin Wang
Renal fibrosis is a common pathway leading to the progression of chronic kidney disease, and bone marrow-derived fibroblasts contribute significantly to the development of renal fibrosis. However, the signaling mechanisms underlying the activation of these fibroblasts are not completely understood. Here, we examined the role of IL-4 receptor α (IL-4Rα) in the activation of myeloid fibroblasts in two experimental models of renal fibrosis. Compared with wild-type mice, IL-4Rα knockout mice accumulated fewer bone marrow-derived fibroblasts and myofibroblasts in their kidneys...
July 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28738526/the-potential-of-chrysophanol-in-protecting-against-high-fat-induced-cardiac-injury-through-nrf2-regulated-anti-inflammation-anti-oxidant-and-anti-fibrosis-in-nrf2-knockout-mice
#18
Yonggang Lian, Xiangjun Xia, Haiying Zhao, Yunfeng Zhu
Cardiovascular complications induced by high fat are one of the most challenging health problems presently. Oxidative stress, inflammation and fibrosis are major components included in the pathology of diabetic cardiomyopathy. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been reported as an essential therapeutic target in various diseases for its induction of anti-oxidant enzymes, and other protective enzymes. Additionally, a number of Nrf2 activators showed strong anti-inflammatory properties. In the study, we calculated the Nrf2-dependent anti-oxidant, anti-inflammatory and anti-fibrosis effects of chrysophanol in high fat diet-induced diabetic heart injury...
July 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28738256/p53-and-mitf-bcl-2-identified-as-key-pathways-in-the-acquired-resistance-of-nras-mutant-melanoma-to-mek-inhibition
#19
Ahmad Najem, Mohammad Krayem, François Salès, Nader Hussein, Bassam Badran, Caroline Robert, Ahmad Awada, Fabrice Journe, Ghanem E Ghanem
Activating mutations in Neuroblastoma RAS viral oncogene homolog (NRAS) are found in 15-30% of melanomas and are associated with a poor prognosis. Although MAP kinase kinase (MEK) inhibitors used as single agents showed a limited clinical benefit in patients with NRAS-mutant melanoma due to their rather cytostatic effect and high toxicity, their combination with other inhibitors of pathways known to cooperate with MEK inhibition may maximise their antitumour activity. Similarly, in a context where p53 is largely inactivated in melanoma, hyperexpression of Microphthalmia associated transcription factor (MITF) and its downstream anti-apoptotic targets may be the cause of the restraint cytotoxic effects of MEK inhibitors...
July 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28737011/a-distinctive-patchy-osteomalacia-characterises-phospho1-deficient-mice
#20
Alan Boyde, Katherine A Staines, Behzad Javaheri, Jose Luis Millan, Andrew A Pitsillides, Colin Farquharson
The phosphatase PHOSPHO1 is involved in the initiation of biomineralisation. Bones in Phospho1 knockout (KO) mice show histological osteomalacia with frequent bowing of long bones and spontaneous fractures: they contain less mineral, with smaller mineral crystals. However, the consequences of Phospho1 ablation on the microscale structure of bone are not yet fully elucidated. Tibias and femurs obtained from wild-type and Phospho1 null (KO) mice (25-32 weeks old) were embedded in PMMA, cut and polished to produce near longitudinal sections...
August 2017: Journal of Anatomy
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