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https://www.readbyqxmd.com/read/29148236/emerging-roles-of-er-stress-in-the-aetiology-and-pathogenesis-of-alzheimer-s-disease
#1
REVIEW
Yannis Gerakis, Claudio Hetz
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synaptic dysfunction and accumulation of abnormal aggregates formed by amyloid-β peptides or phophorylated Tau proteins. Accumulating evidence suggests that alterations in the buffering capacity of the proteostasis network is a salient feature of AD. The endoplasmic reticulum (ER) is the main compartment involved in protein folding and secretion and is drastically affected in AD neurons. ER stress triggers the activation of the Unfolded Protein Response (UPR), a signal transduction pathway that enforces adaptive programs to recover homeostasis or trigger apoptosis of irreversibly damaged cells...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#2
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147782/common-functional-variants-of-the-glutamatergic-system-in-autism-spectrum-disorder-with-high-and-low-intellectual-abilities
#3
Andreas G Chiocchetti, Afsheen Yousaf, Hannah S Bour, Denise Haslinger, Regina Waltes, Eftichia Duketis, Tomas Jarczok, Michael Sachse, Monica Biscaldi, Franziska Degenhardt, Stefan Herms, Sven Cichon, Jörg Ackermann, Ina Koch, Sabine M Klauck, Christine M Freitag
The genetic architecture underlying Autism spectrum disorder (ASD) has been suggested to differ between individuals with lower (IQ ≤ 70; LIQ) and higher intellectual abilities (IQ > 70; HIQ). Among the identified pathomechanisms, the glutamatergic signalling pathway is of specific interest in ASD. We investigated 187 common functional variants of this neurotransmitter system for association with ASD and with symptom severity in two independent samples, a German (German-ALL: N = 583 families) and the Autism Genome Project cohort (AGP-ALL: N = 2001 families), split into HIQ, and LIQ subgroups...
November 16, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29146913/autophagy-acts-through-traf3-and-relb-to-regulate-gene-expression-via-antagonism-of-smad-proteins
#4
Alice C Newman, Alain J Kemp, Yvette Drabsch, Christian Behrends, Simon Wilkinson
Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146573/prostanoid-ep4-agonist-l-902-688-activates-ppar%C3%AE-and-attenuates-pulmonary-arterial-hypertension
#5
Hsin-Hsien Li, Hsao-Hsun Hsu, Gwo-Jyh Chang, I-Chen Chen, Wan-Jing Ho, Pei-Chen Hsu, Wei-Jan Chen, Jong-Hwei Su Pang, Chung-Chi Huang, Ying-Ju Lai
Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cyclic adenosine monophosphate (cAMP) synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH) but this signaling may occur through nuclear peroxisome proliferator-activated receptor-gamma (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activate signal transduction...
November 16, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29146556/shedding-light-on-the-role-of-camp-in-mammalian-sperm-physiology
#6
REVIEW
Melanie Balbach, Vera Beckert, Jan N Hansen, Dagmar Wachten
Mammalian fertilization relies on sperm finding the egg and penetrating the egg vestments. All steps in a sperm's lifetime crucially rely on changes in the second messenger cAMP (cyclic adenosine monophosphate). In recent years, it has become clear that signal transduction in the sperm is not a continuum, but rather organized in subcellular domains, e.g. the sperm head and the sperm flagellum, with the latter being further separated into the midpiece, principal piece,and endpiece. To understand the underlying signaling pathways controlling sperm function in more detail, experimental approaches are needed that allow to study sperm signaling with spatial and temporal precision...
November 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29146454/beyond-immunity-the-imd-pathway-as-a-coordinator-of-host-defense-organismal-physiology-and-behavior
#7
Zongzhao Zhai, Xiaoshan Huang, Yulong Yin
The humoral arm of host defense in Drosophila relies on two evolutionarily conserved NFκB signaling cascades, the Toll and the immune deficiency (Imd) pathways. The Imd signaling pathway senses and neutralizes Gram-negative bacteria. Its activity is tightly adjusted, allowing the host to simultaneously prevent infection by pathogenic bacteria and tolerate beneficial gut microbiota. Over-activation of Imd signaling is detrimental at least in part by causing gut dysbiosis that further exacerbates intestinal pathologies...
November 13, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29145629/the-reactome-pathway-knowledgebase
#8
Antonio Fabregat, Steven Jupe, Lisa Matthews, Konstantinos Sidiropoulos, Marc Gillespie, Phani Garapati, Robin Haw, Bijay Jassal, Florian Korninger, Bruce May, Marija Milacic, Corina Duenas Roca, Karen Rothfels, Cristoffer Sevilla, Veronica Shamovsky, Solomon Shorser, Thawfeek Varusai, Guilherme Viteri, Joel Weiser, Guanming Wu, Lincoln Stein, Henning Hermjakob, Peter D'Eustachio
The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism, and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression profiles or somatic mutation catalogues from tumor cells...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29142596/role-and-underlying-mechanisms-of-the-interstitial-protein-periostin-in-the-diagnosis-and-treatment-of-malignant-tumors
#9
Dong Ye, Zhi Sen Shen, Shi Jie Qiu, Qun Li, Guo Li Wang
Invasion and metastasis are the major characteristics of malignant tumors and are complex processes involving multiple genes. Gene regulation is a precise, large and complex biological control system, and its underlying mechanisms remain to be elucidated. Mesenchymal-specific genes are expressed primarily by mesenchymal cells, and the expression products of these genes are molecules with various structures and functions, including secreted proteins and extracellular matrix proteins. The periostin gene has been newly identified as a mesenchymal-specific gene and an extracellular-matrix secreted protein...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142103/an-intracellular-activation-of-smoothened-independent-of-hedgehog-stimulation-in-drosophila
#10
Kai Jiang, Yajuan Liu, Jie Zhang, Jianhang Jia
Smoothened (Smo), a GPCR family protein, plays a critical role in the reception and transduction of Hedgehog (Hh) signal. Smo is phosphorylated and activated on the cell surface, however, it is unknown whether Smo can be intracellularly activated. Here, we demonstrate that inactivation of the ESCRT-III causes dramatic accumulation of Smo, and subsequent activation of Hh signaling. In contrast, inactivation of ESCRTs 0-II induces mild Smo accumulation. We provide evidence that Kurtz (Krz), the Drosophila β-arrestin2, acts in parallel with the ESCRTs 0-II pathway to sort Smo to the multivesicular bodies and lysosome-mediated degradation...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29141644/lipopolysaccharide-pretreatment-increases-protease-activated-receptor-2-expression-and-monocyte-chemoattractant-protein-1-secretion-in-vascular-endothelial-cells
#11
Hung-Hsing Chao, Po-Yuan Chen, Wen-Rui Hao, Wei-Ping Chiang, Tzu-Hurng Cheng, Shih-Hurng Loh, Yuk-Man Leung, Ju-Chi Liu, Jin-Jer Chen, Li-Chin Sung
BACKGROUND: This study investigated whether lipopolysaccharide (LPS) increase protease-activated receptor-2 (PAR-2) expression and enhance the association between PAR-2 expression and chemokine production in human vascular endothelial cells (ECs). METHODS: The morphology of ECs was observed through microphotography in cultured human umbilical vein ECs (EA. hy926 cells) treated with various LPS concentrations (0, 0.25, 0.5, 1, and 2 μg/mL) for 24 h, and cell viability was assessed using the MTT assay...
November 15, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29141550/autophagy-as-a-potential-therapeutic-target-in-breast-cancer-treatment
#12
Natalia Lisiak, Ewa Toton, Maria Rybczynska
One of the crucial reasons of breast cancer therapy failure is an impairment of mechanisms responsible for metabolism and cellular homeostasis, which makes it difficult to foresee the response to the treatment. Targeted therapy in breast cancer is dictated by the expression of specific molecules such as growth factor or hormone receptors. Many types of breast cancer exhibit different abnormalities in the apoptotic pathway, which confer the resistance to many forms of chemotherapy. Because of the fundamental importance of autophagy in the development and progression of cancer and its ability to affect treatment response, there has been an immense research on molecular regulation and signal transduction mechanisms that control this process...
November 14, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29140975/natural-variation-of-a-sensor-kinase-controlling-a-conserved-stress-response-pathway-in-escherichia-coli
#13
Manuela Roggiani, Srujana S Yadavalli, Mark Goulian
Previous studies have shown that exponentially growing Escherichia coli can detect mild acidity (~pH 5.5) and, in response, synthesize enzymes that protect against severe acid shock. This adaptation is controlled by the EvgS/EvgA phosphorelay, a signal transduction system present in virtually every E. coli isolate whose genome has been sequenced. Here we show that, despite this high level of conservation, the EvgS/EvgA system displays a surprising natural variation in pH-sensing capacity, with some strains entirely non-responsive to low pH stimulus...
November 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29140271/molecular-targeted-therapies-for-epidermal-growth-factor-receptor-and-its-resistance-mechanisms
#14
REVIEW
Toshimitsu Yamaoka, Motoi Ohba, Tohru Ohmori
Cancer therapies targeting epidermal growth factor receptor (EGFR), such as small-molecule kinase inhibitors and monoclonal antibodies, have been developed as standard therapies for several cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, and squamous cell carcinoma of the head and neck. Although these therapies can significantly prolong progression-free survival, curative effects are not often achieved because of intrinsic and/or acquired resistance. The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations, activation of alternative pathways, phenotypic transformation, and resistance to apoptotic cell death...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29138823/mechanical-strain-promotes-osteogenic-differentiation-of-bone-mesenchymal-stem-cells-from-ovariectomized-rats-via-the-phosphoinositide-3%C3%A2-kinase-akt-signaling-pathway
#15
Ningjuan Ouyang, Peng Zhang, Runqing Fu, Guofang Shen, Lingyong Jiang, Bing Fang
Osteoporosis has become an overwhelming public health problem worldwide. As an elementary physiological factor to regulate bone formation and regeneration, mechanical strain may be used as a non‑invasive intervention in osteoporosis prevention and treatment. However, little is known regarding the underlying mechanism. The aim of the current study was to investigate the effect of continuous mechanical strain (CMS) on osteogenic differentiation of bone mesenchymal stem cells (BMSCs) from ovariectomized rats (OVX BMSCs)...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138820/matrine-suppresses-cardiac-fibrosis-by-inhibiting-the-tgf%C3%A2-%C3%AE-smad-pathway-in-experimental-diabetic-cardiomyopathy
#16
Yong Zhang, Lei Cui, Gongchang Guan, Junkui Wang, Chuan Qiu, Tielin Yang, Yan Guo, Zhongwei Liu
Cardiac fibrosis is one of the pathological characteristics of diabetic cardiomyopathy (DbCM). Matrine treatment has proven to be effective in cases of organ fibrosis and cardiovascular diseases. In the present study, the anti-fibrosis-associated cardioprotective effects of matrine on DbCM were investigated. Rats with experimental DbCM were administered matrine orally. Cardiac functions were evaluated using invasive hemodynamic examinations. Cardiac compliance was assessed in isolated hearts. Using Sirius Red and fluorescence staining, the collagen in diabetic hearts was visualized...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138433/transcriptomic-analysis-of-the-regulation-of-stalk-development-in-flowering-chinese-cabbage-brassica-campestris-by-rna-sequencing
#17
Xinmin Huang, Yuling Lei, Hongling Guan, Yanwei Hao, Houcheng Liu, Guangwen Sun, Riyuan Chen, Shiwei Song
Flowering Chinese cabbage is a stalk vegetable whose quality and yield are directly related to stalk development. However, no comprehensive investigations on stalk development have been performed. To address this issue, the present study used RNA sequencing to investigate transcriptional regulation at three key stages (seedling, bolting, and flowering) of stalk development in flowering Chinese cabbage. Anatomical analysis revealed that cell division was the main mode of stalk thickening and elongation at all key stages...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137952/neural-egfl-like-1-regulates-cartilage-maturation-through-runt-related-transcription-factor-3-mediated-indian-hedgehog-signaling
#18
Chenshuang Li, Zhong Zheng, Jie Jiang, Wenlu Jiang, Kevin Lee, Emily A Berthiaume, Eric C Chen, Cymbeline T Culiat, Yan-Heng Zhou, Xinli Zhang, Kang Ting, Chia Soo
The pro-chondrogenic function of runt-related transcription factor 2 (Runx2) was previously considered to be dependent on direct binding with the promoter of Indian hedgehog (Ihh)-the major regulator of chondrocyte differentiation, proliferation, and maturation. Our previous studies identified neural EGFL like 1 (Nell-1) as a Runx2-responsive growth factor for chondrogenic differentiation and maturation. In this study, we further revealed that the pro-chondrogenic activities of Nell-1 also rely on Ihh signaling, by showing: [1] Nell-1 significantly elevated Ihh signal transduction, [2] Nell-1 deficiency markedly reduced Ihh activation in chondrocytes, and [3] Nell-1-stimulated chondrogenesis was significantly reduced by the specific hedgehog inhibitor, cyclopamine...
November 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29137913/neutrophil-cd16b-crosslinking-induces-lipid-raft-mediated-activation-of-shp-2-and-affects-cytokine-expression-and-retarded-neutrophil-apoptosis
#19
H Yang, H Jiang, Y Song, D J Chen, X J Shen, J H Chen
Two different types of FcRs for IgG are constitutively expressed on the surface of human neutrophils, namely, FcγRIIA (CD32a) and FcγRIIIB (CD16b). Unlike FcγRIIA, FcγRIIIb is GPI anchored to the cell membrane and its signal transduction is still ambiguous. To further understand the signal transduction of CD16b, we compared neutrophil cytokine expression and apoptosis by the cross-linking of CD32a and CD16b respectively. We found that both CD32a and CD16b crosslinking can activate neutrophils, but did not exactly share cytokine expression profiles...
November 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29137840/resolvin-d1-attenuates-imiquimod-induced-mice-psoriasiform-dermatitis-through-mapks-and-nf-%C3%AE%C2%BAb-pathways
#20
Juntao Xu, Xiaoru Duan, Feng Hu, Devesh Poorun, Xinxin Liu, Xin Wang, Song Zhang, Lu Gan, Mengwen He, Ke Zhu, Zhangyin Ming, Hongxiang Chen
BACKGROUND: Resolvin D1 (RvD1), a pro-resolution lipid mediator derived from docosahexaenoic acid (DHA), has been described to promote several kinds of inflammatory resolution. However, the effects and anti-inflammatory mechanisms of RvD1 on psoriasis have not been previously reported. OBJECTIVE: The present study aimed to determine the protective effects and the underlying mechanisms of RvD1 on imiquimod (IMQ)-induced psoriasiform dermatitis. METHODS: Mice were topically treated with IMQ to develop psoriasiform dermatitis on their shaved back, pretreated intraperitoneally (i...
November 11, 2017: Journal of Dermatological Science
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