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https://www.readbyqxmd.com/read/28542506/impact-evaluation-of-different-cash-based-intervention-modalities-on-child-and-maternal-nutritional-status-in-sindh-province-pakistan-at-6-mo-and-at-1-y-a-cluster-randomised-controlled-trial
#1
Bridget Fenn, Tim Colbourn, Carmel Dolan, Silke Pietzsch, Murtaza Sangrasi, Jeremy Shoham
BACKGROUND: Cash-based interventions (CBIs), offer an interesting opportunity to prevent increases in wasting in humanitarian aid settings. However, questions remain as to the impact of CBIs on nutritional status and, therefore, how to incorporate them into emergency programmes to maximise their success in terms of improved nutritional outcomes. This study evaluated the effects of three different CBI modalities on nutritional outcomes in children under 5 y of age at 6 mo and at 1 y. METHODS AND FINDINGS: We conducted a four-arm parallel longitudinal cluster randomised controlled trial in 114 villages in Dadu District, Pakistan...
May 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28539447/a-map-of-the-arenavirus-nucleoprotein-host-protein-interactome-reveals-that-jun%C3%A3-n-virus-selectively-impairs-the-antiviral-activity-of-pkr
#2
Benjamin R King, Dylan Hershkowitz, Philip L Eisenhauer, Marion E Weir, Christopher M Ziegler, Joanne Russo, Emily A Bruce, Bryan A Ballif, Jason Botten
Arenaviruses are enveloped negative-strand RNA viruses that cause significant human disease. Encoding only four proteins to accomplish the viral life cycle, each arenavirus protein likely plays unappreciated accessory roles during infection. Here, we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoprotein (NP) of the Old World arenavirus lymphocytic choriomeningitis (LCMV) and the New World arenavirus Junín Candid #1 (JUNV). Bioinformatic analysis of the identified protein partners of NP revealed that host translation appears to be a key biological process engaged during infection...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28537876/activation-of-perk-branch-of-er-stress-mediates-homocysteine-induced-bkca%C3%A2-channel-dysfunction-in-coronary-artery-via-foxo3a-dependent-regulation-of-atrogin-1
#3
Wen-Tao Sun, Xiang-Chong Wang, Shiu-Kwong Mak, Guo-Wei He, Xiao-Cheng Liu, Malcolm John Underwood, Qin Yang
The molecular mechanism of endoplasmic reticulum (ER) stress in vascular pathophysiology remains inadequately understood. We studied the role of ER stress in homocysteine-induced impairment of coronary dilator function, with uncovering the molecular basis of the effect of ER stress on smooth muscle large-conductance Ca2+-activated K+ (BKCa) channels. The vasodilatory function of BKCa channels was studied in a myograph using endothelium-denuded porcine small coronary arteries. Primary cultured porcine coronary artery smooth muscle cells were used for mRNA and protein measurements and current recording of BKCa channels...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28527816/adar1-is-targeted-by-mir-143-to-regulate-il-1%C3%AE-induced-endothelial-activation-through-the-nf%C3%AE%C2%BAb-pathway
#4
Yuanzhuo Chen, Hu Peng, Shuqin Zhou, Yugang Zhuang
Excessive endothelial activation by inflammatory mediators is a critical contributing factor of sepsis pathophysiology. ADAR1 (adenosine deaminase acting on RNA), an enzyme that binds and edits double-stranded RNAs, exhibits immune regulatory properties. Whether ADAR1 is involved in the pathophysiology of sepsis is unclear. In the present study, we used human umbilical endothelial cells (HUVECs) as an in vitro model system to investigate the roles of ADAR1 in interleukin (IL)-1β-induced endothelial activation...
May 17, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28527062/the-prokineticin-system-an-interface-between-neural-inflammation-and-pain
#5
Silvia Franchi, Paola Sacerdote, Alberto Panerai
Prokineticins (PK) 1 and 2 belong to a new family of chemokines capable to interact with two different G coupled receptors: Prokineticin receptor (PKR)1 and 2. Both prokineticins and their receptors are widely distributed in different tissues and regulate several biological functions. In particular, a role of the PK system in inflammation and nociception has been established. PKRs are expressed in regions of the nervous system associated with pain and in primary sensitive neurons they colocalize with transient potential receptor vanilloid-TRPV1 providing an anatomical interaction in nociceptor sensitization...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28522733/activation-of-perk-elicits-memory-impairment-through-inactivation-of-creb-and-downregulation-of-psd95-following-traumatic-brain-injury
#6
Tanusree Sen, Rajaneesh Gupta, Helen Kaiser, Nilkantha Sen
The PKR-like ER kinase (PERK) a transmembrane protein resides in the endoplasmic reticulum (ER) and activation of PERK serve as a key sensor of ER-stress which has been implicated in Traumatic Brain Injury (TBI). The loss of memory is one of the most common symptoms following TBI; however, the precise role of PERK activation in memory impairment after TBI has not been well elucidated. Here we have shown that blocking the activation of PERK using GSK2656157 prevents the loss of dendritic spines and rescues memory deficits following TBI...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28511573/inhibition-of-pkr-ameliorates-lipopolysaccharide-induced-acute-lung-injury-by-suppressing-nf-%C3%AE%C2%BAb-pathway-in-mice
#7
Yinjiao Li, Jinglei Xiao, Yongchang Tan, Jun Wang, Yan Zhang, Xiaoming Deng, Yan Luo
Acute lung injury (ALI) is characterized by dramatic lung inflammation and alveolar epithelial cell death. Although protein kinase R (PKR) (double-stranded RNA-activated serine/threonine kinase) has been implicated in inflammatory response to bacterial cell wall components, whether it plays roles in lipopolysaccharide (LPS)-induced ALI remains unclear. This study was aimed to reveal whether and how PKR was involved in LPS-induced ALI pathology and the potential effects of its specific inhibitor, C16 (C13H8N4OS)...
May 17, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28507276/dicer-protein-levels-elevated-by-mild-hyperthermia-promote-a-pro-survival-phenotype
#8
Anand S Devasthanam, Thomas B Tomasi
Cellular exposure to mild stress (39.5°C-41.5°C) induces thermotolerance, rendering cells resistant to a subsequent heat shock (>42°C) insult. We found that mild hyperthermia at 39.5°C leads to elevations in dicer, a protein well-known for its role in microRNA processing and for its role in cellular stress responses. However, whether elevated dicer protein levels play a role in sustaining a thermotolerant phenotype has, to our knowledge, not been reported. Here we demonstrate that elevated dicer protein is linked to a thermotolerant phenotype in the cervical carcinoma cell line HeLa and in murine embryonic fibroblasts (MEF), and demonstrate that dicer plays a role in mediating PKR and eIF2α phosphorylation...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498443/silencing-of-both-atf4-and-perk-inhibits-cell-cycle-progression-and-promotes-the-apoptosis-of-differentiating-chondrocytes
#9
Zhimeng Wu, Meiling Li, Wei Zheng, Qin Hu, Zhi Cheng, Fengjin Guo
In the current study, we demonstrate that the silencing of protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK) and activating transcription factor 6 (ATF4) (using small interfering RNA expression constructs) inhibits the chondrocyte cell cycle and proliferation in vitro and ex vivo. The silencing of PERK alone using siRNA against PERK (siPERK) led to arrest in the G1 phase, it decreased the number of cells in the S phase, and delayed progressoin to the G2‑M phase. Co-transfection with siRNA against ATF (siATF4) led to a more profound inhibitory effect on cell cycle progression...
May 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28484023/coronavirus-nonstructural-protein-15-mediates-evasion-of-dsrna-sensors-and-limits-apoptosis-in-macrophages
#10
Xufang Deng, Matthew Hackbart, Robert C Mettelman, Amornrat O'Brien, Anna M Mielech, Guanghui Yi, C Cheng Kao, Susan C Baker
Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28445962/psma-homing-dsrna-chimeric-protein-vector-kills-prostate-cancer-cells-and-activates-anti-tumor-bystander-responses
#11
Yael Langut, Nufar Edinger, Efrat Flashner-Abramson, Naomi Melamed-Book, Mario Lebendiker, Yael Levi-Kalisman, Shoshana Klein, Alexander Levitzki
The treatment of metastatic androgen-resistant prostate cancer remains a challenge. We describe a protein vector that selectively delivers synthetic dsRNA, polyinosinic/polycytidylic acid (polyIC), to prostate tumors by targeting prostate specific membrane antigen (PSMA), which is overexpressed on the surface of prostate cancer cells.The chimeric protein is built from the double stranded RNA (dsRNA) binding domain of PKR tethered to a single chain anti-PSMA antibody. When complexed with polyIC, the chimera demonstrates selective and efficient killing of prostate cancer cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442604/hepatitis-c-virus-indirectly-disrupts-dna-damage-induced-p53-responses-by-activating-protein-kinase-r
#12
Jonathan K Mitchell, Bentley R Midkiff, Benjamin Israelow, Matthew J Evans, Robert E Lanford, Christopher M Walker, Stanley M Lemon, David R McGivern
Many DNA tumor viruses promote cellular transformation by inactivating the critically important tumor suppressor protein p53. In contrast, it is not known whether p53 function is disrupted by hepatitis C virus (HCV), a unique, oncogenic RNA virus that is the leading infectious cause of liver cancer in many regions of the world. Here we show that HCV-permissive, liver-derived HepG2 cells engineered to constitutively express microRNA-122 (HepG2/miR-122 cells) have normal p53-mediated responses to DNA damage and that HCV replication in these cells potently suppresses p53 responses to etoposide, an inducer of DNA damage, or nutlin-3, an inhibitor of p53 degradation pathways...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28440222/dual-leucine-zipper-kinase-dependent-perk-activation-contributes-to-neuronal-degeneration-following-insult
#13
Martin Larhammar, Sarah Huntwork-Rodriguez, Zhiyu Jiang, Hilda Solanoy, Arundhati Sengupta Ghosh, Bei Wang, Joshua S Kaminker, Kevin Huang, Jeffrey Eastham-Anderson, Michael Siu, Zora Modrusan, Madeline M Farley, Marc Tessier-Lavigne, Joseph W Lewcock, Trent A Watkins
The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress Response (ISR) is implicated in neurodegenerative disease, although the regulators and consequences of PERK activation following neuronal injury are poorly understood. Here we show that PERK signaling is a component of the mouse MAP kinase neuronal stress response controlled by the Dual Leucine Zipper Kinase (DLK) and contributes to DLK-mediated neurodegeneration. We find that DLK-activating insults ranging from nerve injury to neurotrophin deprivation result in both c-Jun N-terminal Kinase (JNK) signaling and the PERK- and ISR-dependent upregulation of the Activating Transcription Factor 4 (ATF4)...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28432927/type-2-bvdv-n-pro-suppresses-ifn-1-pathway-signaling-in-bovine-cells-and-augments-brsv-replication
#14
Abdulrahman A Alkheraif, Christina L Topliff, Jay Reddy, Chandirasegaran Massilamany, Ruben O Donis, Gregor Meyers, Kent M Eskridge, Clayton L Kelling
Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional N(pro) mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28426973/non-linear-enhancement-of-mrna-delivery-efficiencies-by-influenza-a-derived-ns1-protein-engendering-host-gene-inhibition-property
#15
Kyle K L Phua, Yi Liu, Shun Hui Sim
Nucleic acid induced immunogenicity remains a significant impediment in biomedical therapeutics because the innate immune system is a complex network overlaid with functional redundancies. Herein we report that non-structural protein 1 (NS1), an immune evasion protein derived from influenza A virus, when co-delivered in mRNA format is a potent mRNA transfection enhancer without toxicity. Transfection enhancement is mediated by NS1's effector domain through inhibition of IRF3 and PKR, activators of early anti-viral responses as well as CPSF30, a non immunostimulating protein...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28410401/ripk3-interacts-with-mavs-to-regulate-type-i-ifn-mediated-immunity-to-influenza-a-virus-infection
#16
Jeffrey Downey, Erwan Pernet, François Coulombe, Benoit Allard, Isabelle Meunier, Joanna Jaworska, Salman Qureshi, Donald C Vinh, James G Martin, Philippe Joubert, Maziar Divangahi
The type I interferon pathway plays a critical role in both host defense and tolerance against viral infection and thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be involved in anti-viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus (IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/- mice are highly susceptible to IAV infection, exhibiting elevated pulmonary viral load and heightened morbidity and mortality...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28389754/roles-of-grp78-in-female-mammalian-reproduction
#17
Cheng Zhang
The glucose-regulated protein (GRP78) also referred to as immunoglobulin heavy chain binding protein (Bip) is one of the best characterized endoplasmic reticulum (ER) chaperone proteins, which belongs to the heat-shock protein (HSP) family. GRP78 as a central regulator of ER stress (ERS) plays many important roles in cell survival and apoptosis through controlling the activation of transmembrane ERS sensors: PKR-like ER-associated kinase (PERK), inositol requiring kinase 1 (IRE1), and activating transcription factor 6 (ATF6)...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28389244/colostrum-oxytocin-modulates-cellular-stress-response-inflammation-and-autophagy-markers-in-newborn-rat-gut-villi
#18
Benjamin Y Klein, Hadassah Tamir, Robert J Ludwig, Sara B Glickstein, Martha G Welch
Little is known about the role of oxytocin (OT) in colostrum during early gut colonization. We previously showed that transient OT receptor (OTR) expression on newborn rat enterocytes coincides with the milk-suckling period, and that OT activates endoplasmic reticulum stress sensors in cultured enterocytes. Here, we explored whether colostrum-OT attenuates stress in newborn villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase)...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28374749/pkr-activation-and-eif2%C3%AE-phosphorylation-mediate-human-globin-mrna-splicing-at-spliceosome-assembly
#19
Lena Ilan, Farhat Osman, Lise Sarah Namer, Einav Eliahu, Smadar Cohen-Chalamish, Yitzhak Ben-Asouli, Yona Banai, Raymond Kaempfer
Short elements in mammalian mRNA can control gene expression by activating the RNA-dependent protein kinase PKR that attenuates translation by phosphorylating cytoplasmic eukaryotic initiation factor 2α (eIF2α). We demonstrate a novel, positive role for PKR activation and eIF2α phosphorylation in human globin mRNA splicing. PKR localizes in splicing complexes and associates with splicing factor SC35. Splicing and early-stage spliceosome assembly on β-globin pre-mRNA depend strictly on activation of PKR by a codon-containing RNA fragment within exon 1 and on phosphorylation of nuclear eIF2α on Serine 51...
April 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28371616/salvianolic-acid-a-protects-retinal-pigment-epithelium-from-ox-ldl-induced-inflammation-in-an-age-related-macular-degeneration-model
#20
Ke Mao, Wanting Shu, Qinghua Qiu, Qing Gu, Xingwei Wu
BACKGROUND: Salvianolic acid A (Sal A), an active monomer of Salvia miltiorrhiza, is a phenolic carboxylic acid derivative. The present study was performed to investigate the underlying mechanism of the anti-inflammation effect of Sal A, especially focusing on mTOR-KEAP1-Nrf2 and P2X7R-PKR-NLRP3 signaling pathways. METHODS: SD mice were divided into four groups: PBS, oxidized-low density lipoprotein (ox-LDL, 3 mg/kg), and ox-LDL (3 mg/kg) + Sal A (5 mg/kg) and + Sal A (10 mg/ml) groups...
February 2017: Discovery Medicine
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