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https://www.readbyqxmd.com/read/28538979/stanniocalcin-1-is-an-ocular-hypotensive-agent-and-a-downstream-effector-molecule-that-is-necessary-for-the-intraocular-pressure-lowering-effects-of-latanoprost
#1
Gavin W Roddy, Kimberly B Viker, Nelson S Winkler, Cindy K Bahler, Bradley H Holman, David Sheikh-Hamad, Uttio Roy Chowdhury, W Daniel Stamer, Michael P Fautsch
Purpose: To identify downstream signaling molecules through which intraocular pressure (IOP) is lowered following treatment with the prostaglandin analog latanoprost. Methods: Total RNA and protein isolated from primary human Schlemm's canal cells (n = 3) treated with latanoprost (free acid; 100 nM) were processed for quantitative PCR and Western blot analysis. IOP was evaluated in stanniocalcin-1 (STC-1-/-) and wild-type mice following treatment with latanoprost or Rho kinase inhibitor Y27632...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28538737/lymphatic-endothelial-s1p-promotes-mitochondrial-function-and-survival-in-naive-t-cells
#2
Alejandra Mendoza, Victoria Fang, Cynthia Chen, Madhavika Serasinghe, Akanksha Verma, James Muller, V Sai Chaluvadi, Michael L Dustin, Timothy Hla, Olivier Elemento, Jerry E Chipuk, Susan R Schwab
Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#3
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538731/a-neural-circuit-architecture-for-angular-integration-in-drosophila
#4
Jonathan Green, Atsuko Adachi, Kunal K Shah, Jonathan D Hirokawa, Pablo S Magani, Gaby Maimon
Many animals keep track of their angular heading over time while navigating through their environment. However, a neural-circuit architecture for computing heading has not been experimentally defined in any species. Here we describe a set of clockwise- and anticlockwise-shifting neurons in the Drosophila central complex whose wiring and physiology provide a means to rotate an angular heading estimate based on the fly's angular velocity. We show that each class of shifting neurons exists in two subtypes, with spatiotemporal activity profiles that suggest different roles for each subtype at the start and end of tethered-walking turns...
May 22, 2017: Nature
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#5
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28538669/the-peroxisome-mitochondria-connection-how-and-why
#6
REVIEW
Marc Fransen, Celien Lismont, Paul Walton
Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have also been recognized as important hubs in redox-, lipid-, inflammatory-, and innate immune-signaling networks. To exert these activities, peroxisomes must interact both functionally and physically with other cell organelles. This review provides a comprehensive look of what is currently known about the interconnectivity between peroxisomes and mitochondria within mammalian cells...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538339/seven-tesla-mri-of-hippocampal-sclerosis-an-in-vivo-feasibility-study-with-histological-correlations
#7
Harald Stefanits, Elisabeth Springer, Ekaterina Pataraia, Christoph Baumgartner, Johannes A Hainfellner, Daniela Prayer, Christian Weisstanner, Thomas Czech, Siegfried Trattnig
INTRODUCTION: Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy in adults. Because approximately half of these patients develop drug resistance, epilepsy surgery designed to remove the epileptogenic zone is an excellent option in selected patients. Histopathological analyses of hippocampal specimens in TLE patients revealed 4 types of Ammon's horn sclerosis, which are correlated with long-term epileptological outcome. The aim of this study was the correlation of noninvasive, high-resolution, morphological magnetic resonance imaging (MRI) at an ultra-high-field (7 T) of the hippocampus in TLE patients with histopathological findings...
May 23, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28538214/profiling-and-bioinformatic-analysis-of-circular-rna-expression-regulated-by-c-myc
#8
Qiheng Gou, Ke Wu, Jian-Kang Zhou, Yuxin Xie, Lunxu Liu, Yong Peng
The c-Myc transcription factor is involved in cell proliferation, cell cycle and apoptosis by activating or repressing transcription of multiple genes. Circular RNAs (circRNAs) are widely expressed non-coding RNAs participating in the regulation of gene expression. Using a high-throughput microarray assay, we showed that Myc regulates the expression of certain circRNAs. A total of 309 up- and 252 down-regulated circRNAs were identified. Among them, randomly selected 8 circRNAs were confirmed by real-time PCR...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28538193/ethyl-pyruvate-protects-pc12-cells-from-oxygen-glucose-deprivation-a-potential-role-in-ischemic-cerebrovascular-disease
#9
Wenbo Li, Jiyu Lou, Liping Wei, Hongying Bai, Yaohui Zhang, Yuqing He
The protective potential of ethyl pyruvate (EP) on neuron has been investigated previously. This study was intended to investigate the effects of EP on the severity of oxygen-glucose deprivation (OGD)-induced injury in neural-like PC12 cells. PC12 cells were exposed to OGD condition with or without EP treatment. Then, cell viability, apoptosis, and the expressions of neurotrophic factors were detected. Further, Sprague-Dawley rats were intravenously administered with 5mg/kg EP for 14 days post-middle cerebral artery occlusion (MCAO)...
May 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28538192/hepatic-anti-inflammatory-effect-of-hexane-extracts-of-dioscorea-batatas-decne-possible-suppression-of-toll-like-receptor-4-mediated-signaling
#10
Hyun Jung Koo, SungRyul Lee, Kwang Jin Chang, Eunsoo Sohn, Eun-Hwa Sohn, Se Chan Kang, Suhkneung Pyo
The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue...
May 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28538177/chemokine-signaling-and-the-regulation-of-bidirectional-leukocyte-migration-in-interstitial-tissues
#11
Davalyn Powell, Sebastien Tauzin, Laurel E Hind, Qing Deng, David J Beebe, Anna Huttenlocher
Motile cells navigate through complex tissue environments that include both attractive and repulsive cues. In response to tissue wounding, neutrophils, primary cells of the innate immune response, exhibit bidirectional migration that is orchestrated by chemokines and their receptors. Although progress has been made in identifying signals that mediate the recruitment phase, the mechanisms that regulate neutrophil reverse migration remain largely unknown. Here, we visualize bidirectional neutrophil migration to sterile wounds in zebrafish larvae and identify specific roles for the chemokine receptors Cxcr1 and Cxcr2 in neutrophil recruitment to sterile injury and infection...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538176/tonic-lat-hdac7-signals-sustain-nur77-and-irf4-expression-to-tune-naive-cd4%C3%A2-t-cells
#12
Darienne R Myers, Tannia Lau, Evan Markegard, Hyung W Lim, Herbert Kasler, Minghua Zhu, Andrea Barczak, John P Huizar, Julie Zikherman, David J Erle, Weiguo Zhang, Eric Verdin, Jeroen P Roose
CD4(+) T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4(+) T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (TH2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538171/proliferation-drives-aging-related-functional-decline-in-a-subpopulation-of-the-hematopoietic-stem-cell-compartment
#13
Kristina Kirschner, Tamir Chandra, Vladimir Kiselev, David Flores-Santa Cruz, Iain C Macaulay, Hyun Jun Park, Juan Li, David G Kent, Rupa Kumar, Dean C Pask, Tina L Hamilton, Martin Hemberg, Wolf Reik, Anthony R Green
Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538164/post-translational-regulation-of-plant-immunity
#14
REVIEW
John Withers, Xinnian Dong
Plants have evolved multi-layered molecular defense strategies to protect against pathogens. Plant immune signaling largely relies on post-translational modifications (PTMs) to induce rapid alterations of signaling pathways to achieve a response that is appropriate to the type of pathogen and infection pressure. In host cells, dynamic PTMs have emerged as powerful regulatory mechanisms that cells use to adjust their immune response. PTM is also a virulence strategy used by pathogens to subvert host immunity through the activities of effector proteins secreted into the host cell...
May 21, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28538016/hypoxia-inducible-factor-activation-in-diabetic-kidney-disease
#15
Patrik Persson, Fredrik Palm
PURPOSE OF REVIEW: Tissue hypoxia is present in kidneys from diabetic patients and constitutes a central pathway to diabetic kidney disease (DKD). This review summarizes regulation of hypoxia inducible factor (HIF) and interventions towards the same for treatment of DKD. RECENT FINDINGS: In the hypoxic diabetic kidney, HIF activity and the effects of HIF signaling seem to be cell-specific. In mesangial cells, elevated glucose levels induce HIF activity by a hypoxia-independent mechanism...
May 19, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28538012/antiphospholipid-syndrome-an-update-for-clinicians-and-scientists
#16
Andrew P Vreede, Paula L Bockenstedt, Jason S Knight
PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is a leading acquired cause of thrombosis and pregnancy loss. Upon diagnosis (which is unlikely to be made until at least one morbid event has occurred), anticoagulant medications are typically prescribed in an attempt to prevent future events. This approach is not uniformly effective and does not prevent associated autoimmune and inflammatory complications. The goal of this review is to update clinicians and scientists on mechanistic and clinically relevant studies from the past 18 months, which have especially focused on inflammatory aspects of APS pathophysiology...
May 22, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28537930/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#17
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537929/orphan-nuclear-receptor-nur77-inhibits-poly-i-c-triggered-acute-liver-inflammation-by-inducing-the-ubiquitin-editing-enzyme-a20
#18
Xiu-Ming Li, Tian-Yu Yang, Xiao-Shun He, Jing-Ru Wang, Wen-Juan Gan, Shen Zhang, Jian-Ming Li, Hua Wu
Inflammation is a key contributor to various types of acute and chronic liver disease. We recently reported that lack of Nur77, an orphan nuclear receptor, contributes to the pathogenesis of inflammatory diseases including inflammatory bowel disease and sepsis. However, whether Nur77 plays a critical role in liver inflammation remains to be fully understood. Employing in vivo acute liver inflammation model in wild-type (Nur77+/+) and Nur77-/- mice, we here found that Nur77 deficiency dramatically increased the production of pro-inflammatory cytokines and accelerated liver injury induced by Poly (I:C)/D-GalN in Nur77-/- mice...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#19
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537922/cooperative-but-distinct-early-co-signaling-events-originate-from-erbb2-and-erbb1-receptors-upon-trastuzumab-treatment-in-breast-cancer-cells
#20
Paola Bagnato, Alessia Castagnino, Katia Cortese, Maria Bono, Silvia Grasso, Grazia Bellese, Tiziana Daniele, Richard Lundmark, Paola Defilippi, Patrizio Castagnola, Carlo Tacchetti
ERBB2 receptor belongs to the ERBB tyrosine kinase receptor family. At variance to the other family members, ERBB2 is a constitutively active orphan receptor. Upon ligand binding and activation, ERBB receptors form homo- or hetero-dimers with the other family members, including ERBB2, promoting an intracellular signaling cascade. ERBB2 is the preferred dimerization partner and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. The specific contribution of ERBB2 in heterodimer signaling is still undefined...
May 8, 2017: Oncotarget
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