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Takahito Otani, Miho Matsuda, Akiko Mizokami, Norio Kitagawa, Hiroshi Takeuchi, Eijiro Jimi, Tetsuichiro Inai, Masato Hirata
The uncarboxylated form of osteocalcin (GluOC) regulates glucose and lipid metabolism in mice. We previously showed that low-dose (≤10 ng/ml) GluOC induces the expression of adiponectin and peroxisome proliferator-activated receptor γ (PPARγ) via a cAMP-PKA-ERK-CREB signaling pathway in 3T3-L1 adipocytes. We also noticed that high-dose (≥20 ng/ml) GluOC inhibits the expression of adiponectin and PPARγ in these cells. We have here explored the mechanism underlying these effects of high-dose GluOC...
December 13, 2018: Cell Death & Disease
Iván M Moya, Georg Halder
The Hippo pathway and its downstream effectors, the transcriptional co-activators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), regulate organ growth and cell plasticity during animal development and regeneration. Remarkably, experimental activation of YAP/TAZ in the mouse can promote regeneration in organs with poor or compromised regenerative capacity, such as the adult heart and the liver and intestine of old or diseased mice. However, therapeutic YAP/TAZ activation may cause serious side effects...
December 13, 2018: Nature Reviews. Molecular Cell Biology
Qingqing Qu, Markus F Damian
For literate individuals, does the spoken production of language involve access to orthographic codes? Previous research has rendered mixed results, with a few positive findings contrasting with a range of null findings. In the current experiments, we chose spoken Mandarin as the target language in order to better dissociate sound from spelling. Mandarin speakers named coloured line drawings of common objects with adjective-noun phrases (e.g., /lan2/ /hua1ping2/, "blue vase"). Adjectives and nouns were semantically and phonologically unrelated on all trials, but on critical trials they shared an orthographic radical...
December 12, 2018: Memory & Cognition
Preeti Kumari Chaudhary, Soochong Kim
Platelet activation plays a major role in hemostasis and thrombosis. Various agonists including ADP and thrombin interact with GPCRs which transduce signals from the cell surface to intracellular effectors through various G proteins. Recent studies have elucidated the role of these receptors and their corresponding G proteins in the regulation of events involved in platelet activation. However, these agonists-induced platelet activation in companion animals is poorly understood. This study was designed to characterize the platelet response to various agonists in dog platelets...
December 4, 2018: Journal of Veterinary Science
Eric T Hall, Elizabeth Hoesing, Endre Sinkovics, Esther M Verheyen
Actomyosin contractility can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis. We identified that increased non-muscle myosin II activation and cellular contraction inhibited Wnt target gene transcription in developing Drosophila imaginal discs. Genetic interactions studies were used to show that this effect was due to myosin-induced accumulation of cortical F-actin resulting in clustering and accumulation of E-cadherin to the adherens junctions...
December 12, 2018: Molecular Biology of the Cell
Ashraf S Gorgey, Oksana Witt, Laura O'Brien, Christopher Cardozo, Qun Chen, Edward J Lesnefsky, Zachary A Graham
Mitochondria are responsible for aerobic respiration and large-scale ATP production in almost all cells of the body. Their function is decreased in many neurodegenerative and cardiovascular disease states, in metabolic disorders such as type II diabetes and obesity, and as a normal component of aging. Disuse of skeletal muscle from immobilization or unloading triggers alterations of mitochondrial density and activity. Resultant mitochondrial dysfunction after paralysis, which precedes muscle atrophy, may augment subsequent release of reactive oxygen species leading to protein ubiquitination and degradation...
December 11, 2018: European Journal of Applied Physiology
Guzel Valeeva, Sona Janackova, Azat Nasretdinov, Veronika Rychkova, Roman Makarov, Gregory L Holmes, Roustem Khazipov, Pierre-Pascal Lenck-Santini
Correlated activity in the entorhinal-hippocampal neuronal networks, supported by oscillatory and intermittent population activity patterns is critical for learning and memory. However, when and how correlated activity emerges in these networks during development remains largely unknown. Here, we found that during the first postnatal week in non-anaesthetized head-restrained rats, activity in the superficial layers of the medial entorhinal cortex (MEC) and hippocampus was highly correlated, with intermittent population bursts in the MEC followed by early sharp waves (eSPWs) in the hippocampus...
December 7, 2018: Cerebral Cortex
Na Wang, Peng Xue, Ziyi Li, Yukun Li
Whether insulin receptor substrate 1 (IRS-1) inhibits or promotes the osteogenic proliferation and differentiation in vitro remains controversial. Transcriptional co-activator with PDZ-binding motif (TAZ) plays a vital role in the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), and strongly activates the expression of the osteogenic differentiation markers. In this study, we found that IRS-1 and TAZ followed similar increasing expression patterns at the early stage of osteogenic differentiation...
December 7, 2018: Biology Open
Alexander S Chen, Joanna Wardwell-Ozgo, Nilang N Shah, Deidre Wright, Christina L Appin, Krishanthan Vigneswaran, Daniel J Brat, Harley I Kornblum, Renee D Read
Glioblastoma (GBM) and lower grade gliomas (LGG) are the most common primary malignant brain tumors and are resistant to current therapies. Genomic analyses reveal that signature genetic lesions in GBM and LGG include copy gain and amplification of chromosome 7, amplification, mutation, and overexpression of receptor tyrosine kinases (RTK) such as EGFR, and activating mutations in components of the PI-3 kinase (PI3K) pathway. In Drosophila melanogaster, constitutive co-activation of RTK and PI3K signaling in glial progenitor cells recapitulates key features of human gliomas...
December 10, 2018: Cancer Research
Lydia G Brough, Steven A Kautz, Mark G Bowden, Chris M Gregory, Richard R Neptune
Stroke is the leading cause of long-term disability and individuals post-stroke often experience impaired walking ability. The plantarflexor (PF) muscles are critical to walking through their contributions to the ground reaction forces and body segment energetics. Previous studies have shown muscle activity during walking can be grouped into co-excited muscle sets, or modules. Improper co-activation, or merging of modules, is a common impairment in individuals post-stroke. The purpose of this study was to determine the influence of merged PF modules on walking performance in individuals post stroke by examining balance control, body support and propulsion, and walking symmetry...
November 15, 2018: Journal of Biomechanics
Fei Sun, Constantinos Chronis, Michael Kronenberg, Xiao-Fen Chen, Trent Su, Fides D Lay, Kathrin Plath, Siavash K Kurdistani, Michael F Carey
Metazoan chromosomes are sequentially partitioned into topologically associating domains (TADs) and then into smaller sub-domains. One class of sub-domains, insulated neighborhoods, are proposed to spatially sequester and insulate the enclosed genes through self-association and chromatin looping. However, it has not been determined functionally whether promoter-enhancer interactions and gene regulation are broadly restricted to within these loops. Here, we employed published datasets from murine embryonic stem cells (mESCs) to identify insulated neighborhoods that confine promoter-enhancer interactions and demarcate gene regulatory regions...
November 14, 2018: Molecular Cell
Nao Komatsu, Mikihito Kajiya, Souta Motoike, Manabu Takewaki, Susumu Horikoshi, Tomoyuki Iwata, Kazuhisa Ouhara, Katsuhiro Takeda, Shinji Matsuda, Tsuyoshi Fujita, Hidemi Kurihara
BACKGROUND: Three-dimensional (3D) floating culture clumps of mesenchymal stem cell (MSC)/extracellular matrix (ECM) complexes (C-MSCs) consist of cells and self-produced ECM. Previous studies have demonstrated that C-MSCs can be transplanted into bony lesions without an artificial scaffold to induce bone regeneration. Moreover, osteoinductive medium (OIM)-treated C-MSCs (OIM-C-MSCs) have shown rapid and increased new bone formation in vivo. To apply OIM-C-MSCs for novel bone regenerative cell therapy, their cellular properties at the molecular level must be elucidated...
December 7, 2018: Stem Cell Research & Therapy
Yuwen Wang, Arseni Kostenko, Terrance J Hadlington, Marcel-Philip Luecke, Shenglai Yao, Matthias Driess
While the transformation of carbon monoxide to multicarbon compounds (fuels and organic bulk chemicals) via reductive scission of the enormously strong CO bond is dominated by transition-metals, splitting and deoxygenative reductive coupling of CO under nonmatrix conditions using silicon, the second most abundant nonmetal of the Earth's crust, is extremely scarce and mechanistically not well understood. Herein we report the selective deoxygena-tive homocoupling of carbon monoxide by divalent silicon utilizing the (LSi:)2Xant 1a (Xant = 9,9-dimethyl-xanthene-4,5-diyl; L = PhC(NtBu)2) and (LSi:)2Fc 1b (Fc = 1,1'-ferrocenyl) as four-electron reduction reagents under mild reaction conditions (RT, 1 atm), affording the corresponding disilylketenes, Xant(LSi)2(µ-O)(µ-CCO) 2a and Fc(LSi)2(µ-O)(µ-CCO) 2b, respectively...
December 5, 2018: Journal of the American Chemical Society
Elin Karlsson, Eva Andersson, Jakob Dogan, Stefano Gianni, Per Jemth, Carlo Camilloni
Many intrinsically disordered proteins (IDPs) attain a well-defined structure in a coupled folding and binding reaction with another protein. Such reactions may involve early to late formation of different native structural regions along the reaction pathway. To obtain insights into the transition state for a coupled binding and folding reaction, we performed restrained molecular dynamics simulations using previously determined experimental binding Φb values of the interaction between two IDP domains, the activation domain from the p160 transcriptional co-activator for thyroid hormone and retinoid receptors (ACTR) and the nuclear co-activator binding domain (NCBD) of CREB-binding protein, each forming three well-defined α-helices upon binding...
December 4, 2018: Journal of Biological Chemistry
Simona V Antonova, Matthias Haffke, Eleonora Corradini, Mykolas Mikuciunas, Teck Y Low, Luca Signor, Robert M van Es, Kapil Gupta, Elisabeth Scheer, Harmjan R Vos, László Tora, Albert J R Heck, H T Marc Timmers, Imre Berger
TFIID is a cornerstone of eukaryotic gene regulation. Distinct TFIID complexes with unique subunit compositions exist and several TFIID subunits are shared with other complexes, thereby conveying precise cellular control of subunit allocation and functional assembly of this essential transcription factor. However, the molecular mechanisms that underlie the regulation of TFIID remain poorly understood. Here we use quantitative proteomics to examine TFIID submodules and assembly mechanisms in human cells. Structural and mutational analysis of the cytoplasmic TAF5-TAF6-TAF9 submodule identified novel interactions that are crucial for TFIID integrity and for allocation of TAF9 to TFIID or the Spt-Ada-Gcn5 acetyltransferase (SAGA) co-activator complex...
December 3, 2018: Nature Structural & Molecular Biology
Yvonne Lenz, Jurij Kiefer, Franziska Dietrich, G Björn Stark, Steffen U Eisenhardt
BACKGROUND: Synchronicity of the oral commissure movement of a bilateral smile is a significant goal for reconstruction in facial reanimation and may only be guaranteed with use of the facial nerve as a donor nerve. Yet over the years several studies report some degree of spontaneity in certain patients when using a non-facial donor nerve, which indicates that synchronous initiation of the smile might be achievable with other donor nerves. We designed a prospective cohort study to evaluate whether pre-operative involuntary activation of the masseteric nerve during smile predicts development of a synchronous smile development when using the masseteric nerve for reanimation...
November 22, 2018: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
Peng Zhao, Raghuveer Kavarthapu, Rajakumar Anbazhagan, Mingjuan Liao, Maria L Dufau
The luteinizing hormone receptor (LHR) is essential for sexual development and reproduction in mammals. We have established that Sp1 has a central role in derepression of LHR gene transcription induced by Trichostatin A (TSA) in MCF7 cells. Moreover, the co-activator PC4 which associates directly with Sp1 at the LHR promoter is essential for TSA-mediated LHR transcription. This study explores interactions of PC4 with histone proteins, which presumably triggers chromatin modifications during LHR transcriptional activation...
October 2018: Biochimica et biophysica acta. Gene regulatory mechanisms
Yujing Chi, Yuhong Meng, Junpei Wang, Weili Yang, Zhe Wu, Mei Li, Di Wang, Fangfang Gao, Bin Geng, Lu Tie, Weiping Zhang, Jichun Yang
FAM3B, also known as PANcreatic DERived factor (PANDER), promotes gluconeogenesis and lipogenesis in hepatocytes. However, the underlying mechanism(s) still remains largely unclear. This study determined the mechanism of PANDER-induced FOXO1 activation in hepatocytes. In mouse livers and cultured hepatocytes, PANDER protein is located in both the cytoplasm and nucleus. Nuclear PANDER distribution was increased in the livers of obese mice. In cultured mouse and human hepatocytes, PANDER was co-localized with FOXO1 in the nucleus...
November 28, 2018: Journal of Cellular and Molecular Medicine
Pengju Yang, Hangyu Zhuzhang, Ruirui Wang, Wei Lin, Xinchen Wang
Photosynthetic conversion CO2 into fuel and chemicals is a promising but challenging technology. The bottleneck of this reaction lies in the activation of CO2, owing to the chemical inertness of linear CO2. Herein, we present a defect engineering methodology to construct CO2 activation sites by implanting carbon vacancies (CVs) on the melon polymer (MP) matrix. Positron annihilation spectroscopy confirms the location and density of the CVs in the MP skeleton. In-situ diffuse reflectance infrared fourier transform spectroscopy and density functional theory (DFT) study reveals that the CVs can function as active sites for CO2 activation, while stabilizing COOH* intermediates, thereby boosting the reaction kinetics...
November 28, 2018: Angewandte Chemie
Lynn Yang, Misun Kang, Rui He, Bo Meng, Arvin Pal, Ling Chen, Andrew H Jheon, Sunita P Ho
The novel aspect of this study was to contextualize the co-localization of biomolecular expression in widened and narrowed periodontal ligament (PDL)-space within a mechanically activated periodontal complex. The PDL is unique as it is the only ligament with both innervation and vascularization. Maxillary molars in 6-week-old male C57BL/6 mice (N = 5) were experimentally translated for 2 weeks using an elastic spacer. Contralateral teeth were used as controls. Mechanical testing of the periodontal complex of a mouse in situ and imaging using X-ray micro-computed tomography (micro-XCT) illustrated deformations within blood vessels (BV) of the PDL...
November 28, 2018: Journal of Periodontal Research
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