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Jayne Wilkins, Kyle S Brown, Simen Oestmo, Telmo Pereira, Kathryn L Ranhorn, Benjamin J Schoville, Curtis W Marean
There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change...
2017: PloS One
Melody Chiu, Lucien McBeth, Puneet Sindhwani, Terry D Hinds
The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively...
2017: PPAR Research
D Patel, G Gorelik, B Richardson
OBJECTIVE: Lupus develops when genetically predisposed people encounter certain drugs or environmental agents causing oxidative stress such as infections and sun exposure, and then typically follows a chronic relapsing course with flares triggered by the exogenous stressors. Current evidence indicates that these environmental agents can trigger lupus flares by inhibiting the replication of DNA methylation patterns during mitosis in CD4(+) T cells, altering the expression of genes suppressed by this mechanism that convert normal "helper" cells into auto reactive cells which promote lupus flares...
December 2016: Lupus (Los Angeles)
Chong Xu, Xiaoxue Wang, Chenjian Gu, Hai Zhang, Ruijie Zhang, Xiaoqing Dong, Chunxiao Liu, Xiaoyu Hu, Xiang Ji, Shile Huang, Long Chen
Celastrol, a plant-derived triterpene, has neuroprotective benefit in the models of neurodegenerative disorders that are characterized by overproduction of reactive oxygen species (ROS). Recently, we have reported that cadmium (Cd) activates c-Jun N-terminal kinase (JNK) pathway leading to neuronal cell death by inducing ROS inactivation of protein phosphatase 5 (PP5), and celastrol prevents Cd-activated JNK pathway against neuronal apoptosis. Therefore, we hypothesized that celastrol could hinder Cd induction of ROS-dependent PP5-JNK signaling pathway from apoptosis in neuronal cells...
April 2017: Journal of Neurochemistry
Baocheng Hu, Xiang Wang, Shuofeng Hu, Xiaomin Ying, Ping Wang, Xiangming Zhang, Jian Wang, Hongyan Wang, Ya Wang
miR-21, as an oncogene that overexpresses in most human tumors, is involved in radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance occurs through promoting repair of DNA double strand breaks, which includes facilitating both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ occurs through targeting GSK3B (a novel target of miR-21), which affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity...
February 24, 2017: Journal of Biological Chemistry
Kun Han, Zhihua Gan, Shuchen Lin, Haiyan Hu, Zan Shen, Daliu Min
Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults. However, the involvement of serine/threonine phosphatase type 5 (PP5) in osteosarcoma remains unclear. The aim of this study was to evaluate the functional role of PP5 in osteosarcoma cells. Firstly, we found that PP5 is widely expressed in several human osteosarcoma cell lines. Then we used lentivirus-delivered siRNA to silence PP5 expression in Saos-2 and U2OS cell lines. Knockdown of endogenous PP5 expression by shRNA-expressing lentivirus significantly decreased the viability and proliferation of the osteosarcoma cells...
2017: Acta Biochimica Polonica
Aaron Armstrong
Reported here are the results of a taphonomic analysis of the small mammals (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (≤20 kg adult body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1) and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This study provides a comprehensive taphonomic analysis of MSA small mammals with a focus on discerning the role of humans in their accumulation and the implications for human behavioral adaptations...
December 2016: Journal of Human Evolution
Michael J Twiner, Gregory J Doucette, Yucheng Pang, Chao Fang, Craig J Forsyth, Christopher O Miles
Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays...
November 4, 2016: Marine Drugs
Sophia M LeMaire, Viswanathan Raghuram, Cameron R Grady, Christina M Pickering, Chung-Lin Chou, Ezigbobiara N Umejiego, Mark A Knepper
Phosphorylation of the aquaporin-2 (AQP2) water channel at four COOH-terminal serines plays a central role in the regulation of water permeability of the renal collecting duct. The level of phosphorylation at these sites is determined by a balance between phosphorylation by protein kinases and dephosphorylation by phosphatases. The phosphatases that dephosphorylate AQP2 have not been identified. Here, we use large-scale data integration techniques to identify serine-threonine phosphatases likely to interact with AQP2 in renal collecting duct principal cells...
January 1, 2017: American Journal of Physiology. Renal Physiology
Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Lance A Stechschulte, Chunxi Ge, Terry D Hinds, Edwin R Sanchez, Renny T Franceschi, Beata Lecka-Czernik
Peroxisome proliferator-activated receptor γ (PPARγ) and runt-related transcription factor 2 (RUNX2) are key regulators of mesenchymal stem cell (MSC) differentiation toward adipocytes and osteoblasts, respectively. Post-translational modifications of these factors determine their activities. Dephosphorylation of PPARγ at Ser-112 is required for its adipocytic activity, whereas phosphorylation of RUNX2 at serine 319 (Ser-319) promotes its osteoblastic activity. Here we show that protein phosphatase 5 (PP5) reciprocally regulates each receptor by targeting each serine...
November 18, 2016: Journal of Biological Chemistry
Mark Swingle, Claude-Henry Volmar, S Adrian Saldanha, Peter Chase, Christina Eberhart, Edward A Salter, Brandon D'Arcy, Chad E Schroeder, Jennifer E Golden, Andrzej Wierzbicki, Peter Hodder, Richard E Honkanen
Although there has been substantial success in the development of specific inhibitors for protein kinases, little progress has been made in the identification of specific inhibitors for their protein phosphatase counterparts. Inhibitors of PP1 and PP5 are desired as probes for research and to test their potential for drug development. We developed and miniaturized (1536-well plate format) nearly identical homogeneous, fluorescence intensity (FLINT) enzymatic assays to detect inhibitors of PP1 or PP5. The assays were used in an ultra-high-throughput screening (uHTS) campaign, testing >315,000 small-molecule compounds...
January 2017: SLAS Discovery
Fuminori Yamaguchi, Mitsumasa Tsuchiya, Seiko Shimamoto, Tomohito Fujimoto, Hiroshi Tokumitsu, Masaaki Tokuda, Ryoji Kobayashi
Oxidative stress is the consequence of an imbalance between the production of harmful reactive oxygen species and the cellular antioxidant system for neutralization, and it activates multiple intracellular signaling pathways, including apoptosis signal-regulating kinase 1 (ASK1). Protein phosphatase 5 (PP5) is a serine/threonine phosphatase involved in oxidative stress responses. Previously, we reported that S100 proteins activate PP5 in a calcium-dependent manner. S100 proteins belong to a family of small EF-hand calcium-binding proteins involved in many processes such as cell proliferation, differentiation, apoptosis, and inflammation...
2016: Tohoku Journal of Experimental Medicine
Yasunori Sugiyama, Sho Yamashita, Yuuki Uezato, Yukako Senga, Syouichi Katayama, Naoki Goshima, Yasushi Shigeri, Noriyuki Sueyoshi, Isamu Kameshita
To analyze a variety of protein phosphatases, we developed phosphorylated TandeMBP (P-TandeMBP), in which two different mouse myelin basic protein isoforms were fused in tandem, as a protein phosphatase substrate. P-TandeMBP was prepared efficiently in four steps: (1) phosphorylation of TandeMBP by a protein kinase mixture (Ca(2+)/calmodulin-dependent protein kinase Iδ, casein kinase 1δ, and extracellular signal-regulated kinase 2); (2) precipitation of both P-TandeMBP and protein kinases to remove ATP, Pi, and ADP; (3) acid extraction of P-TandeMBP with HCl to remove protein kinases; and (4) neutralization of the solution that contains P-TandeMBP with Tris...
November 15, 2016: Analytical Biochemistry
L Chachi, M Abbasian, A Gavrila, A Alzahrani, O Tliba, P Bradding, A J Wardlaw, C Brightling, Y Amrani
BACKGROUND: The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics. METHODS: Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR...
January 2017: Allergy
Jasmeen Oberoi, Diana M Dunn, Mark R Woodford, Laura Mariotti, Jacqualyn Schulman, Dimitra Bourboulia, Mehdi Mollapour, Cara K Vaughan
The serine/threonine phosphatase protein phosphatase 5 (PP5) regulates hormone- and stress-induced cellular signaling by association with the molecular chaperone heat shock protein 90 (Hsp90). PP5-mediated dephosphorylation of the cochaperone Cdc37 is essential for activation of Hsp90-dependent kinases. However, the details of this mechanism remain unknown. We determined the crystal structure of a Cdc37 phosphomimetic peptide bound to the catalytic domain of PP5. The structure reveals PP5 utilization of conserved elements of phosphoprotein phosphatase (PPP) structure to bind substrate and provides a template for many PPP-substrate interactions...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Alessandro Guarracino, Luca Lacitignola, Edoardo Auriemma, Valentina De Monte, Salvatore Grasso, Antonio Crovace, Francesco Staffieri
This randomized controlled trial study aimed to identify the optimal positive pressure (PP) level that can clear atelectasis while avoiding pulmonary hyperinflation during the breath-hold technique in dogs undergoing thoracic computed tomography (CT). Sixty dogs affected by mammary tumors undergoing thoracic CT for the screening of pulmonary metastases were randomly assigned to six groups with different levels of PP during the breath-hold technique: 0 (control), 5 (PP5), 8 (PP8), 10 (PP10), 12 (PP12), and 15 (PP15) cmH2 O...
September 2016: Veterinary Radiology & Ultrasound
Reem M Hashem, Kamel Ma Hassanin, Laila A Rashed, Mohamed O Mahmoud, Mohamed G Hassan
Apoptosis signal-regulating kinase 1 (ASK1), a redox-sensor mitogen-activated protein kinase kinase kinase (MAPKKK) that activates p38 MAPK pathways in oxidative stress-induced hepatotoxicity in D-galactosamine/lipopolysaccharide (D-GalN/LPS) model, is a key central pathway in which specific targeting of ASK1 deactivation is of a great therapeutic potential. We tested the effect of silibinin and vitamin E in curative and prophylactic manner of treatment on the negative modulators of ASK1, thioredoxin1 (Trx1), thioredoxin reductase1 (TrxR1), and the protein phosphatase (PP5), whereas they have previously proven to have hepatoprotective effect...
June 2016: Experimental Biology and Medicine
Xiaojiao Zheng, Lianxiao Zhang, Bohong Jin, Fubin Zhang, Duoyi Zhang, Lining Cui
Ovarian cancer is the most common cause of gynecological cancer-related mortality. Serine/threonine protein phosphatase 5 (PP5, PPP5C) has been recognized to be involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, including cell growth, differentiation, proliferation, motility and apoptosis. In this study, to evaluate the functional role of PP5 in ovarian cancer cells, lentivirus-mediated RNA interference (RNAi) was applied to silence PPP5C in the human ovarian cancer cell line CAOV-3...
January 2016: Oncology Letters
Marat R Talipov, Ramesh Jasti, Rajendra Rathore
π-Conjugated organic oligomers/polymers hold great promise as long-range charge-transfer materials for modern photovoltaic applications. However, a set of criteria for the rational design of functional materials is not yet available, in part because of a lack of understanding of charge distribution in extended π-conjugated systems of different topologies, and concomitant effects on redox and optical properties. Herein we demonstrate the role of cyclic versus linear topology in controlling the redox/optical properties and hole distribution in poly-p-phenylenes (PPs) with the aid of experiment, computation, and our recently developed multistate parabolic model (MPM)...
December 2, 2015: Journal of the American Chemical Society
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