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https://www.readbyqxmd.com/read/28916199/erk-and-rock-functionally-interact-in-a-signaling-network-that-is-compensationally-upregulated-in-spinal-muscular-atrophy
#1
Niko Hensel, Svetlana Baskal, Lisa Marie Walter, Hella Brinkmann, Manuela Gernert, Peter Claus
Spinal Muscular Atrophy (SMA) is a motoneuron disease caused by low levels of functional survival of motoneuron protein (SMN). Molecular disease mechanisms downstream of functional SMN loss are still largely unknown. Previous studies suggested an involvement of Rho kinase (ROCK) as well as the extracellular signal-regulated kinases (ERK) pathways in the pathomechanism. Both pathways are bi-directionally linked and inhibit each other. Thus, we hypothesize that both pathways regulate SMA pathophysiology in vivo in a combined manner rather than acting separately...
September 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28911859/recent-development-of-signaling-pathways-inhibitors-of-melanogenesis
#2
REVIEW
Thanigaimalai Pillaiyar, Manoj Manickam, Sang-Hun Jung
Human skin, eye and hair color rely on the production of melanin, depending on its quantity, quality, and distribution, Melanin plays a monumental role in protecting the skin against the harmful effect of ultraviolet radiation and oxidative stress from various environmental pollutants. However, an excessive production of melanin causes serious dermatological problems such as freckles, solar lentigo (age spots), melasma, as well as cancer. Hence, the regulation of melanin production is important for controlling the hyper-pigmentation...
September 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28887034/a-novel-gene-cilia-flagella-associated-protein-44-encoding-an-enzyme-cleaving-ftsz-and-tubulin-contributes-to-the-regulation-of-secretory-pathway
#3
Akiko S Tanaka, Masahiko Tanaka
We identified a novel gene, encoding the central region of the cilia and flagella-associated protein 44 (Cfap44), that regulates trafficking of cellular components and morphology via the cleavage of cellular proteins (particularly β-tubulin). Although Cfap44 is registered in GenBank, the functions of both the central part and full-length protein are unknown except for a polymorphism associated with proprotein convertase 9 activity, the third gene of familiar hyper-cholesterolemia. In mice and humans, both unspliced and spliced RNAs were transcribed, and the spliced form was predominantly transcribed in the brain and embryonic tissues...
September 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28859967/a-jak2-selective-inhibitor-potently-reverses-the-immune-suppression-by-modulating-the-tumor-microenvironment-for-cancer-immunotherapy
#4
Wei He, Yi Zhu, Ruoyu Mu, Jinzhi Xu, Xiaoyi Zhang, Chunming Wang, Qiu Li, Zhen Huang, Junfeng Zhang, Yi Pan, Jianlin Han, Lei Dong
Small molecule therapeutics can be potent tools for cancer immunotherapy. They may be devised to target the tumor associated macrophages (TAMs) and regulatory T cells (Treg), which are major immunosuppressive cells in the tumor microenvironment. The infiltration and functionalization of these cells, which essentially promote tumor development, are mediated by the hyper-activation of the Jak-STAT3 signaling pathway. Here, we demonstrated that compound 9#, a novel inhibitor of Jak2, could suppress Jak2-STAT3 signaling in macrophages (peritoneal macrophages and THP-1 cells) and direct the macrophages towards the pro-inflammatory (M1-like) phenotype...
August 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28818497/drp1-regulates-mitochondrial-morphology-and-cell-proliferation-in-cutaneous-squamous-cell-carcinoma
#5
Shinya Kitamura, Teruki Yanagi, Keisuke Imafuku, Hiroo Hata, Riichiro Abe, Hiroshi Shimizu
BACKGROUND: Dynamin-related protein 1 (Drp1) mediates mitochondrial fission. Recently, several studies have shown that Drp1 plays an important role in some cancers. However, little is known about Drp1 in cutaneous squamous cell carcinoma (SCC). OBJECTIVE: To investigate the role of Drp1 in the tumorigenesis of cutaneous SCCs. METHODS AND RESULTS: We investigated cell proliferation, cell cycle, mitochondrial morphology, and MAPK signaling pathway using cutaneous SCC A431 and DJM1 cells that were transfected with shRNA vectors targeting Drp1...
August 5, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28777000/quantitative-proteomics-reveals-temporal-proteomic-changes-in-signaling-pathways-during-bv2-mouse-microglial-cell-activation
#6
Jongmin Woo, Dohyun Han, Joseph Injae Wang, Joonho Park, Hyunsoo Kim, Youngsoo Kim
The development of systematic proteomic quantification techniques in systems biology research has enabled one to perform an in-depth analysis of cellular systems. We have developed a systematic proteomic approach that encompasses the spectrum from global to targeted analysis on a single platform. We have applied this technique to an activated microglia cell system to examine changes in the intracellular and extracellular proteomes. Microglia become activated when their homeostatic microenvironment is disrupted...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28762854/lethal-concentration-of-perfluoroisobutylene-induces-acute-lung-injury-in-mice-mediated-via-cytokine-storm-oxidative-stress-and-apoptosis
#7
Yingjie Zhang, Lei Fan, Ronggang Xi, Zhonghua Mao, Dan Shi, Ding Ding, Zhiran Zhang, Xiaobo Wang
Perfluoroisobutylene (PFIB) is a highly toxic gas that targets the lungs. Low-level inhalation of the gas can lead to acute lung injury (ALI), pulmonary edema and even death. No specific anti-PFIB drugs are currently available and the pathogenesis of PFIB-induced ALI is not fully understood. Early direct oxidative injury and a secondary hyper-inflammatory response are recognized as the primary mechanisms of PFIB-induced ALI. In the present study, our data demonstrate for the first time that a cytokine storm is associated with PFIB-induced ALI...
August 1, 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/28728506/microsatellite-instability-and-promoter-hypermethylation-of-dna-repair-genes-in-hematologic-malignancies-a-forthcoming-direction-toward-diagnostics
#8
Priyanjali Bhattacharya, Trupti N Patel
OBJECTIVE: The objective of our review is to highlight the significance of microsatellite hypervariation in diagnostics of hematologic malignancies. METHODS: For the past few decades, extensive experiments in cancer research have explored all the possible pathways and a number of deleterious mutations that either make the tumor suppressor genes (TSGs) dysfunctional or cause the proto-oncogenes to behave abnormally by changing the cellular phenotype hence rendering disease...
July 20, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28679532/the-non-homologous-end-joining-factor-nej1-inhibits-resection-mediated-by-dna2-sgs1-nuclease-helicase-at-dna-double-strand-breaks
#9
Kyle S Sorenson, Brandi L Mahaney, Susan P Lees-Miller, Jennifer A Cobb
Double strand breaks (DSBs) represent highly deleterious DNA damage and need to be accurately repaired. Homology-directed repair and non-homologous end joining (NHEJ) are the two major DSB repair pathways that are highly conserved from yeast to mammals. The choice between these pathways is largely based on 5' to 3' DNA resection, and NHEJ proceeds only if resection has not been initiated. In yeast, yKu70/80 rapidly localizes to the break, protecting DNA ends from nuclease accessibility, and recruits additional NHEJ factors, including Nej1 and Lif1...
September 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28672003/endogenous-small-interfering-rnas-associated-with-maize-embryonic-callus-formation
#10
Fei Ge, Xing Huang, Hongmei Hu, Yanling Zhang, Zhaoling Li, Chaoying Zou, Huanwei Peng, Lujiang Li, Shibin Gao, Guangtang Pan, Yaou Shen
The induction efficiency of maize embryonic callus is highly dependent on the genotype, and only a few lines possess a high capacity for callus formation. Although certain genes and pathways have been reported to contribute to the regulation of callus induction, to the best of our knowledge, the functions of the small interfering RNAs (siRNAs) involved in this process remain unknown. In this study, we identified 861 differentially expressed siRNAs and 576 target genes in the callus induction process. These target genes were classified into 3 clusters, and their functions involve controlling metalloexopeptidase activity, catalase activity, transcription regulation, and O-methyltransferase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28655714/epidermal-growth-factor-receptor-restoration-rescues-the-fatty-liver-regeneration-in-mice
#11
Teresa A Zimmers, Xiaoling Jin, Zongxiu Zhang, Yanlin Jiang, Leonidas G Koniaris
BACKGROUND: Hepatic steatosis is a common histological finding in obese patients. Even mild steatosis is associated with delayed hepatic regeneration and poor outcomes following liver resection or transplantation. We sought to identify and target molecular pathways that mediate this dysfunction. MATERIAL AND METHODS: Lean mice and mice made obese through feeding of a high fat, hyper-caloric diet underwent 70% or 80% hepatectomy. RESULTS: After 70% resection, obese mice demonstrated 100% survival but experienced increased liver injury, reduced energy stores, reduced mitoses, increased necroapoptosis and delayed recovery of liver mass...
June 27, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28648366/-oxidative-stress-in-perinatal-asphyxia-and-hypoxic-ischaemic-encephalopathy
#12
Antonio Nuñez, Isabel Benavente, Dorotea Blanco, Héctor Boix, Fernando Cabañas, Mercedes Chaffanel, Belén Fernández-Colomer, José Ramón Fernández-Lorenzo, Begoña Loureiro, María Teresa Moral, Antonio Pavón, Inés Tofé, Eva Valverde, Máximo Vento
Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways...
June 22, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/28582473/connectivity-in-ictal-single-photon-emission-computed-tomography-perfusion-a-cortico-cortical-evoked-potential-study
#13
Simon Tousseyn, Balu Krishnan, Zhong I Wang, Sattawut Wongwiangjunt, Chetan S Nayak, John C Mosher, Guiyun Wu, Wim Van Paesschen, Richard M Leahy, Jorge A Gonzalez-Martinez, Juan Bulacio, Imad M Najm, Andreas V Alexopoulos, Dileep R Nair
Subtraction ictal and interictal single photon emission computed tomography can demonstrate complex ictal perfusion patterns. Regions with ictal hyperperfusion are suggested to reflect seizure onset and propagation pathways. The significance of ictal hypoperfusion is not well understood. The aim of this study was to verify whether ictal perfusion changes, both hyper- and hypoperfusion, correspond to electrically connected brain networks. A total of 36 subtraction ictal and interictal perfusion studies were analysed in 31 consecutive medically refractory focal epilepsy patients, evaluated by stereo-electroencephalography that demonstrated a single focal onset...
July 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28554479/rice-pcg-gene-osemf2b-controls-seed-dormancy-and-seedling-growth-by-regulating-the-expression-of-osvp1
#14
Min Chen, Shiyong Xie, Yidan Ouyang, Jialing Yao
The induction and release of seed dormancy are a precisely regulated process that influences seed germination. ABA promotes seed dormancy but suppresses seed germination and seedling growth. However, how chromatin and epigenetic mechanisms regulate the expression of ABA related genes during these processes remains unclear. Polycomb gene OsEMF2b was required for regulation of seed dormancy and seedling growth by dynamically activating and repressing ABA signal response genes. Downregulation of OsEMF2b led to vivipary and decreased expression level of OsVP1, which was involved in ABA signal pathway in seed dormancy...
July 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28535128/low-and-high-let-ionizing-radiation-induces-delayed-homologous-recombination-that-persists-for-two-weeks-before-resolving
#15
Christopher P Allen, Hirokazu Hirakawa, Nakako Izumi Nakajima, Sophia Moore, Jingyi Nie, Neelam Sharma, Mayumi Sugiura, Yuko Hoki, Ryoko Araki, Masumi Abe, Ryuichi Okayasu, Akira Fujimori, Jac A Nickoloff
Genome instability is a hallmark of cancer cells and dysregulation or defects in DNA repair pathways cause genome instability and are linked to inherited cancer predisposition syndromes. Ionizing radiation can cause immediate effects such as mutation or cell death, observed within hours or a few days after irradiation. Ionizing radiation also induces delayed effects many cell generations after irradiation. Delayed effects include hypermutation, hyper-homologous recombination, chromosome instability and reduced clonogenic survival (delayed death)...
July 2017: Radiation Research
https://www.readbyqxmd.com/read/28508477/the-novel-intracellular-protein-creg-inhibits-hepatic-steatosis-obesity-and-insulin-resistance
#16
Quan-Yu Zhang, Ling-Ping Zhao, Xiao-Xiang Tian, Cheng-Hui Yan, Yang Li, Yan-Xia Liu, Pi-Xiao Wang, Xiao-Jing Zhang, Ya-Ling Han
Cellular repressor of E1A-stimulated genes (CREG), a novel cellular glycoprotein, has been identified as a suppressor of various cardiovascular diseases because of its capacity to reduce hyperplasia, maintain vascular homeostasis, and promote endothelial restoration. However, the effects and mechanism of CREG in metabolic disorder and hepatic steatosis remain unknown. Here, we report that hepatocyte-specific CREG deletion dramatically exacerbates high-fat diet and leptin deficiency-induced (ob/ob) adverse effects such as obesity, hepatic steatosis, and metabolic disorders, whereas a beneficial effect is conferred by CREG overexpression...
May 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28502844/a-novel-approach-to-map-induced-activation-of-neuronal-networks-using-chemogenetics-and-functional-neuroimaging-in-rats-a-proof-of-concept-study-on-the-mesocorticolimbic-system
#17
Theresia J M Roelofs, Jeroen P H Verharen, Geralda A F van Tilborg, Linde Boekhoudt, Annette van der Toorn, Johannes W de Jong, Mieneke C M Luijendijk, Willem M Otte, Roger A H Adan, Rick M Dijkhuizen
Linking neural circuit activation at whole-brain level to neuronal activity at cellular level remains one of the major challenges in neuroscience research. We set up a novel functional neuroimaging approach to map global effects of locally induced activation of specific midbrain projection neurons using chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology) combined with pharmacological magnetic resonance imaging (phMRI) in the rat mesocorticolimbic system. Chemogenetic activation of DREADD-targeted mesolimbic or mesocortical pathways, i...
May 11, 2017: NeuroImage
https://www.readbyqxmd.com/read/28429652/atypical-regulators-of-wnt-%C3%AE-catenin-signaling-as-potential-therapeutic-targets-in-hepatocellular-carcinoma
#18
REVIEW
Jianxiang Chen, Muthukumar Rajasekaran, Kam M Hui
Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma...
June 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28425930/the-peculiar-glycolytic-pathway-in-hyperthermophylic-archaea-understanding-its-whims-by-experimentation-in-silico
#19
Yanfei Zhang, Theresa Kouril, Jacky L Snoep, Bettina Siebers, Matteo Barberis, Hans V Westerhoff
Mathematical models are key to systems biology where they typically describe the topology and dynamics of biological networks, listing biochemical entities and their relationships with one another. Some (hyper)thermophilic Archaea contain an enzyme, called non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN), which catalyzes the direct oxidation of glyceraldehyde-3-phosphate to 3-phosphoglycerate omitting adenosine 5'-triphosphate (ATP) formation by substrate-level-phosphorylation via phosphoglycerate kinase...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28379062/inhibition-of-microrna-21-by-an-antagomir-ameliorates-allergic-inflammation-in-a-mouse-model-of-asthma
#20
Hwa Young Lee, Hea Yon Lee, Joon Young Choi, Jung Hur, In Kyoung Kim, Young Kyoon Kim, Ji Young Kang, Sook Young Lee
AIM OF THE STUDY: MicroRNA-21 (miR-21) is up-regulated during allergic airway inflammation, reflecting a Th2 immune response. We investigated the effects of an miR-21 antagomir and its mechanism of action in a mouse model of acute bronchial asthma. MATERIALS AND METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered by intranasal inhalation from the day of sensitization. Changes in cell counts, Th2 cytokine levels in bronchoalveolar (BAL) fluid, and airway hyper-responsiveness (AHR) were examined...
April 2017: Experimental Lung Research
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