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https://www.readbyqxmd.com/read/28430139/the-metalloproteinase-adam28-promotes-metabolic-dysfunction-in-mice
#1
Lakshini Herat, Caroline Rudnicka, Yasunori Okada, Satsuki Mochizuki, Markus Schlaich, Vance Matthews
Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28425622/targeted-disruption-of-nf1-in-osteocyte-increases-fgf23-and-osteoid-with-osteomalacia-like-bone-phenotype
#2
Nobuhiro Kamiya, Ryosuke Yamaguchi, Olumide Aruwajoye, Audrey Kim, Gen Kuroyanagi, Matthew Phipps, Naga Suresh Adapala, Jian Q Feng, Harry K W Kim
Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype...
April 20, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28423616/suppression-of-microrna-16-protects-against-acute-myocardial-infarction-by-reversing-beta2-adrenergic-receptor-down-regulation-in-rats
#3
Jiaqi Liu, Fei Sun, Yuying Wang, Wanqi Yang, Hongwen Xiao, Yue Zhang, Renzhong Lu, Haixia Zhu, Yuting Zhuang, Zhenwei Pan, Zhiguo Wang, Zhimin Du, Yanjie Lu
microRNA-16 (miR-16) has been shown to be up-regulated in ischemic heart. Beta2-adrenoreceptor (β2-AR) exerts cardioprotective property in ischemic injury. This study aims to determine the effect of miR-16 in cardiac injury in rats and the possible involvement of β2-AR in this process. Acute myocardial infarction (AMI) model in rats was induced by ligation of left coronary artery. Neonatal rat ventricular cells (NRVCs) were cultured in vitro tests. The cardiomyocyte model of oxidative injury was mimicked by hydrogen peroxide...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421534/immune-alterations-in-cd8-t-cells-are-associated-with-neuronal-c-c-and-c-x-c-chemokine-receptor-regulation-through-adenosine-a2a-receptor-signaling-in-a-btbr-t-itpr3-tf-j-autistic-mouse-model
#4
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Raish Mohammad, Sabry M Attia
Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T(+) Itpr3(tf)/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421533/changes-in-the-prefrontal-glutamatergic-and-parvalbumin-systems-of-mice-exposed-to-unpredictable-chronic-stress
#5
Ryan Shepard, Laurence Coutellier
The prefrontal cortex (PFC) is highly sensitive to the effects of stress, a known risk factor of mood disorders including anxiety and depression. Abnormalities in PFC functioning have been well described in humans displaying stress-induced depressive symptoms, and hypoactivity of the PFC is now recognized to be a key feature of the depressed brain. However, little is known about the causes and mechanisms leading to this altered prefrontal functional activity in the context of stress-related mood disorders. We previously showed that unpredictable chronic mild stress (UCMS) in mice increases prefrontal expression of parvalbumin (PV), an activity-dependent calcium-binding albumin protein expressed in a specific subtype of GABAergic neurons, highlighting a potential mechanism through which chronic stress leads to hypofunction of the PFC...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421528/postnatal-lps-challenge-impacts-escape-learning-and-expression-of-plasticity-factors-mmp9-and-timp1-in-rats-effects-of-repeated-training
#6
Alexander Trofimov, Tatyana Strekalova, Niall Mortimer, Olga Zubareva, Alexander Schwarz, Evgeniy Svirin, Aleksei Umriukhin, Andrei Svistunov, Klaus-Peter Lesch, Victor Klimenko
Bacterial intoxication associated with inflammatory conditions during development can impair brain functions, in particular evolutionarily novel forms of memory, such as explicit learning. Little is known about the dangers of early-life inflammation on more basic forms of learning, for example, the acquisition of motor escape abilities, which are generally better preserved under pathological conditions. To address this limitation in knowledge, an inflammatory response was elicited in Wistar pups by lipopolysaccharide (LPS) injections (25 μg/kg) on postnatal days P15, P18 and P21...
April 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28420331/arsenic-treatment-increase-aurora-a-overexpression-through-e2f1-activation-in-bladder-cells
#7
Yu-Ting Kao, Chin-Han Wu, Shan-Ying Wu, Sheng-Hui Lan, Hsiao-Sheng Liu, Ya-Shih Tseng
BACKGROUND: Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation...
April 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28418093/hypoxia-inducible-factor-1-alpha-does-not-regulate-osteoclastogenesis-but-enhances-bone-resorption-activity-via-prolyl-4-hydroxylase-2
#8
Philippa A Hulley, Tammie Bishop, Aude Vernet, Jurgen E Schneider, James R Edwards, Nick A Athanasou, Helen J Knowles
Osteogenic-angiogenic coupling is promoted by the Hypoxia-Inducible Factor 1-alpha (HIF-1α) transcription factor, provoking interest in HIF activation as a therapeutic strategy to improve osteoblast mineralisation and treat pathological osteolysis. However, HIF also enhances the bone resorbing activity of mature osteoclasts. It is therefore essential to determine the full effect(s) of HIF on both the formation and bone-resorbing function of osteoclasts in order to understand how they might respond to such a strategy...
April 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28412386/characterization-of-rodent-constitutively-active-estrogen-receptor-%C3%AE-variants-and-their-constitutive-transactivation-mechanisms
#9
Hirotaka Ishii, Yujiro Hattori, Arisa Munetomo, Hiroshi Watanabe, Yasuo Sakuma, Hitoshi Ozawa
Estrogen receptor α (ERα) mRNAs exhibit remarkable heterogeneity owing to complicated alternative splicing. Some encode C-terminally-truncated ERα proteins, which display ligand-independent transactivation or dominant-negative activity. We previously characterized C-terminally-truncated ERα mRNA variants with cryptic sequences in humans and mice, and demonstrated that helices in the ligand-binding domains (LBDs) of ERα variants contribute to ligand-independent transcriptional activity. However, existence of non-conventional coding exons and generation of constitutively active ERα variants have remained to be examined in rats...
April 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28412353/crystal-structure-of-rna-polymerase-ii-from-komagataella-pastoris
#10
Haruhiko Ehara, Takashi Umehara, Shun-Ichi Sekine, Shigeyuki Yokoyama
RNA polymerase II (Pol II) is a 12-subunit protein complex that conducts the transcription of mRNA and some small RNAs. In this work, the crystal structure of Pol II from the methylotropic yeast Komagataella pastoris (Pichia pastoris) was determined. While the structure is highly homologous to that of Pol II from the budding yeast Saccharomyces cerevisiae, the stalk and clamp modules of the K. pastoris Pol II displayed large inward rotations, closing the central cleft to a greater extent than in the known S...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28408319/deriving-and-testing-of-dysplastic-murine-hepatocytes-a-new-platform-in-liver-cancer-research
#11
Sharon Pok, Harpreet Vohra, Charbel Wehbe, Vanessa A Barn, Evi Arfianti, Yock-Young Dan, Geoffrey C Farrell, Narci C Teoh
Dysplastic hepatocytes(DH) represent altered hepatocytes with potential for malignant transformation. To date, most research on pathways to hepatocarcinogenesis has focused on use of "hepatoma" cell-lines derived from hepatocellular carcinoma(HCC). We describe a novel technique for deriving/culturing DH and demonstrate their utility for functional studies in vitro, compared to primary hepatocytes(PH) and HCC. PH and DH were prepared by portal vein collagenase perfusion from C57BL/6J mice. DH were subsequently subjected to FACS...
April 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28406397/evolutionary-changes-in-transcription-factor-coding-sequence-quantitatively-alter-sensory-organ-development-and-function
#12
Simon Weinberger, Matthew P Topping, Jiekun Yan, Annelies Claeys, Natalie De Geest, Duru Ozbay, Talah Hassan, Xiaoli He, Joerg T Albert, Bassem A Hassan, Ariane Ramaekers
'Toolkit' genes are highly conserved developmental regulators. While changes in their regulatory elements contribute to morphological evolution, the role of coding sequence (CDS) evolution remains unresolved. We used CDS-specific knock-ins of the proneural transcription factor Atonal homologs (ATHs) to address this question. Drosophila Atonal CDS was endogenously replaced with that of distant ATHs at key phylogenetic positions, non-ATH proneural genes, and the closest CDS to ancestral proneural genes. ATHs and the ancestral-like gene rescued sensory organ fate in atonal mutants, in contrast to non-ATHs...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28405880/steap4-expression-in-human-islets-is-associated-with-differences-in-body-mass-index-sex-hba1c-and-inflammation
#13
Hannah M Gordon, Neil Majithia, Patrick E MacDonald, Jocelyn E Manning Fox, Poonam R Sharma, Frances L Byrne, Kyle L Hoehn, Carmella Evans-Molina, Linda Langman, Kenneth L Brayman, Craig S Nunemaker
OBJECTIVE: STEAP4 (six-transmembrane epithelial antigen of the prostate 4) is a metalloreductase that has been shown previously to protect cells from inflammatory damage. Genetic variants in STEAP4 have been associated with numerous metabolic disorders related to obesity, including putative defects in the acute insulin response to glucose in type 2 diabetes. PURPOSE: We examined whether obesity and/or type 2 diabetes altered STEAP4 expression in human pancreatic islets...
April 12, 2017: Endocrine
https://www.readbyqxmd.com/read/28404930/microrna-regulation-of-progesterone-receptor-in-breast-cancer
#14
Avital Gilam, Ayelet Shai, Itamar Ashkenazi, Liat Appel Sarid, Assi Drobot, Amitai Bickel, Noam Shomron
Hormone receptor status is of significant value when deciding on anti-estrogenic adjuvant therapy for breast cancer tumors. However, while estrogen receptor (ER) regulation was intensively studied, the regulation of progesterone receptor (PR) levels has not been extensively investigated. MicroRNAs (miRNAs, miRs) are post-transcriptional negative regulators of gene expression involved in diverse cellular processes. The aim of this study was to identify miRNAs that regulate PR in breast cancer.We mapped potential miRNA binding sites for miR-181a, miR-23a and miR-26b on PR mRNA and demonstrated a direct regulation of PR by these three miRNAs by in-vitro Luciferase binding assays...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404918/human-a-l-fucosidase-1-attenuates-the-invasive-properties-of-thyroid-cancer
#15
Giancarlo Vecchio, Alessia Parascandolo, Chiara Allocca, Clara Ugolini, Fulvio Basolo, Marco Moracci, Andrea Strazzulli, Beatrice Cobucci-Ponzano, Mikko O Laukkanen, Maria Domenica Castellone, Nobuo Tsuchida
Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#16
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
April 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28402856/chd8-mutation-leads-to-autistic-like-behaviors-and-impaired-striatal-circuits
#17
Randall J Platt, Yang Zhou, Ian M Slaymaker, Ashwin S Shetty, Niels R Weisbach, Jin-Ah Kim, Jitendra Sharma, Mitul Desai, Sabina Sood, Hannah R Kempton, Gerald R Crabtree, Guoping Feng, Feng Zhang
Autism spectrum disorder (ASD) is a heterogeneous disease, but genetically defined models can provide an entry point to studying the molecular underpinnings of this disorder. We generated germline mutant mice with loss-of-function mutations in Chd8, a de novo mutation strongly associated with ASD, and demonstrate that these mice display hallmark ASD behaviors, macrocephaly, and craniofacial abnormalities similar to patient phenotypes. Chd8(+/-) mice display a broad, brain-region-specific dysregulation of major regulatory and cellular processes, most notably histone and chromatin modification, mRNA and protein processing, Wnt signaling, and cell-cycle regulation...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28399943/bipolar-disorder-patients-display-reduced-serum-complement-levels-and-elevated-peripheral-blood-complement-expression-levels
#18
Uğur Akcan, Sercan Karabulut, Cem İsmail Küçükali, Sibel Çakır, Erdem Tüzün
OBJECTIVE: Bipolar disorder (BD) patients have recently been shown to exhibit increased proinflammatory cytokine levels indicating the role of inflammation in this disease. As inflammatory responses often include complement level alterations and complement production is influenced by cytokines, we aimed to find out whether complement system is activated in BD in a time-dependent manner and complement factors are involved in BD pathogenesis. METHODS: Serum C4, factor B, sC5b-9 and neuron-specific enolase levels were measured by enzyme-linked immunosorbent assay, whereas peripheral blood mononuclear cell messenger RNA (mRNA) expression levels of C1q, C4, factor B and CD55 were measured by real-time polymerase chain reaction in chronic BD patients (n=22), first episode BD patients (n=24) and healthy controls (n=19)...
April 12, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/28399858/ku80-correlates-with-neoadjuvant-chemotherapy-resistance-in-human-lung-adenocarcinoma-but-reduces-cisplatin-pemetrexed-induced-apoptosis-in-a549-cells
#19
Bin Shang, Yang Jia, Gang Chen, Zhou Wang
BACKGROUND: Ku80 is a DNA repair protein which involves in cell apoptosis and chemoresistance. However, it is unclear whether Ku80 correlates with the efficiency of neoadjuvant chemotherapy in human lung adenocarcinoma, and modulates cisplatin/pemetrexed-induced lung cancer cell apoptosis in vitro. METHODS: We recruited 110 patients with stage IIIA lung adenocarcinoma, who received 2 cycles of neoadjuvant chemotherapy, and their lungs were reevaluated by CT scan...
April 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28398634/ski-regulates-smads-and-taz-signaling-to-suppress-lung-cancer-progression
#20
Mian Xie, Xiaojun Wu, Jinjun Zhang, Jiexia Zhang, Xiangxiang Li
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, displays both pro-oncogenic and anti-oncogenic activities in human cancer. The mechanisms underlying these conflicting observations have not been fully understood. Herein, we investigated the mechanism underlying the tumor suppressor activity of Ski. To investigate the effect of Ski re-activation on TGF-β and Hippo/TAZ pathway, we measured its effect on the endogenous Smad target genes (PAI-1 and P15(INK4B) ) and TAZ target gene CTGF. The results revealed that Ski exerted its inhibitory activity in TGF-β1/Smad signaling pathway...
April 11, 2017: Molecular Carcinogenesis
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