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Travis S Emery, Pruthvik A Raghupathi, Satish G Kandlikar
The passage of a single bubble or a stream of bubbles through a liquid-liquid interface is a highly dynamic process that can result in a number of different outcomes. Previous studies focused primarily on a single bubble and single flow regime, and very few investigations have considered bubble streams. In the present work, six different liquid combinations made up of water, ethanol, a perfluorocarbon liquid, PP1, and one of three different viscosity silicone oils are tested with air bubbles from 2-6 mm in diameter rising between 5-55 cm/s...
May 21, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Jesús G Pallarés, José Ramón Lillo-Bevia
To validate the new PowerTap P1® pedals power meter (PP1), thirty-three cyclists performed 12 randomized and counterbalanced graded exercise tests (100-500 W), at 70, 85 and 100 rev·min-1 cadences, in seated and standing positions. A scientific SRM system and a pair of PP1 pedals continuously recorded cadence and power output data. Significantly lower power output values were detected for the PP1 compared to the SRM for all workloads, cadences, and pedalling conditions (2-10 W, p < 0.05), except for the workloads ranged between 150 W to 350 W at 70 rev·min-1 in seated position (p > 0...
June 2018: Journal of Sports Science & Medicine
Brian D Carey, Tatiana Ammosova, Chelsea Pinkham, Xionghao Lin, Weidong Zhou, Lance A Liotta, Sergei Nekhai, Kylene Kehn-Hall
Protein Phosphatase 1 (PP1) is a serine/threonine phosphatase which has been implicated in the regulation of a number of viruses including HIV-1, Ebolavirus and Rift Valley fever virus. Catalytic subunits of PP1 (PP1α, PP1β, or PP1γ) interact with a host of regulatory subunits and target a wide variety of cellular substrates through a combination of short binding motifs, including an RVxF motif present in the majority of PP1 regulatory subunits. Targeting the RVxF interacting site on PP1 with the small molecule, 1E7-03 inhibits HIV-1, Ebolavirus, and Rift Valley fever virus replication...
May 16, 2018: Journal of Virology
Óscar F Gonçalves, Gabriel Rêgo, Tatiana Conde, Jorge Leite, Sandra Carvalho, Olívia Morgan Lapenta, Paulo S Boggio
Previous studies looking at how Mind Wandering (MW) impacts performance in distinct Focused Attention (FA) systems, using the Attention Network Task (ANT), showed that the presence of pure MW thoughts did not impact the overall performance of ANT (alert, orienting and conflict) performance. However, it still remains unclear if the lack of interference of MW in the ANT, reported at the behavioral level, has a neurophysiological correspondence. We hypothesize that a distinct cortical processing may be required to meet attentional demands during MW...
May 15, 2018: Scientific Reports
Isha Nasa, Scott F Rusin, Arminja N Kettenbach, Greg B Moorhead
Protein phosphatase 1 (PP1) is a highly conserved protein phosphatase that performs most of the serine- and threonine-dephosphorylation reactions in eukaryotes and opposes the actions of a diverse set of serine and threonine (Ser-Thr) protein kinases. PP1 gains substrate specificity through binding to a large number (>200) of regulatory proteins that control PP1 localization, activity, and interactions with substrates. PP1 recognizes the well-characterized RVxF binding motif that is present in many of these regulatory proteins, thus generating a multitude of distinct PP1 holoenzymes...
May 15, 2018: Science Signaling
Kun Gao, Yuanyuan Zhang, Qing Shi, Jianong Zhang, Liang Zhang, Huiru Sun, Dongyue Jiao, Xiayin Zhao, Hongru Tao, Youheng Wei, Yuqi Wang, Hexige Saiyin, Shi-Min Zhao, Yao Li, Pingzhao Zhang, Chenji Wang
Cytokinesis is the last step of cell division and is concluded by the abscission of the intercellular bridge that connects two daughter cells. The tight regulation of cytokinesis completion is essential because cytokinesis failure is associated with various human diseases. Here, we report that iASPP, a member of the apoptosis-stimulating proteins of p53 (ASPP) family, is required for proper cell division. iASPP depletion results in abnormal midbody structure and failed cytokinesis. We used protein affinity purification methods to identify the functional partners of iASPP...
May 9, 2018: Cell Death & Disease
Yu Liu, Deyu Zhou, Jiabin Feng, Zhou Liu, Yue Hu, Chang Liu, Xiaohong Kong
Despite the success of combined antiretroviral therapy in recent years, the prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders in people living with HIV-1 is increasing, significantly reducing the health-related quality of their lives. Although neurons cannot be infected by HIV-1, shed viral proteins such as transactivator of transcription (Tat) can cause dendritic damage. However, the detailed molecular mechanism of Tat-induced neuronal impairment remains unknown. In this study, we first showed that recombinant Tat (1-72 aa) induced neurotoxicity in primary cultured mouse neurons...
May 8, 2018: Virologica Sinica
Justin R Welden, Jacob van Doorn, Peter T Nelson, Stefan Stamm
The microtubule-associated protein Tau, generated by the MAPT gene is involved in dozens of neurodegenerative conditions ("tauopathies"), including Alzheimer's disease (AD) and frontotemporal lobar degeneration/frontotemporal dementia (FTLD/FTD). The pre-mRNA of MAPT is well studied and its aberrant pre-mRNA splicing is associated with frontotemporal dementia. Using a PCR screen of RNA from human brain tissues, we found that the MAPT locus generates circular RNAs through a backsplicing mechanism from exon 12 to either exon 10 or 7...
May 2, 2018: Biochimica et Biophysica Acta
Hsin-Yuan Fang, Meng-Yu Hung, Yueh-Min Lin, Sudhir Pandey, Chia-Chien Chang, Kuan-Ho Lin, Chia-Yao Shen, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
Earlier studies have shown that estrogen possess protective function against the development of pathological cardiac hypertrophy. However, the molecular mechanisms of estrogens (E2) protective effect are poorly understood. Additionally, abnormal activation of β-adrenergic signaling have been implicated in the development of pathological cardiac remodeling. However, the role of serine/threonine protein phosphatase 1 (PP1) in pathological cardiac remodeling under the influence of β-adrenergic signaling have been sparsely investigated...
2018: PloS One
Ana B A Wallis, Conrad A Nieduszynski
Background: Understanding DNA replication initiation is essential to understand the mis-regulation of replication seen in cancer and other human disorders. DNA replication initiates from DNA replication origins. In eukaryotes, replication is dependent on cell cycle kinases which function during S phase. Dbf4-dependent kinase (DDK) and cyclin-dependent kinase (CDK) act to phosphorylate the DNA helicase (composed of mini chromosome maintenance proteins: Mcm2-7) and firing factors to activate replication origins...
2018: Wellcome Open Research
Lukas Hafner, Aleksandra Lezaja, Xu Zhang, Laure Lemmens, Maksym Shyian, Benjamin Albert, Cindy Follonier, Jose Manuel Nunes, Massimo Lopes, David Shore, Stefano Mattarocci
The Saccharomyces cerevisiae telomere-binding protein Rif1 plays an evolutionarily conserved role in control of DNA replication timing by promoting PP1-dependent dephosphorylation of replication initiation factors. However, ScRif1 binding outside of telomeres has never been detected, and it has thus been unclear whether Rif1 acts directly on the replication origins that it controls. Here, we show that, in unperturbed yeast cells, Rif1 primarily regulates late-replicating origins within 100 kb of a telomere...
April 24, 2018: Cell Reports
David Y Chiang, Katherina M Alsina, Eleonora Corradini, Martin Fitzpatrick, Li Ni, Satadru K Lahiri, Julia Reynolds, Xiaolu Pan, Larry Scott, Albert J R Heck, Xander H Wehrens
Background -Heart failure (HF) is a complex disease with a rising prevalence despite advances in treatment. Protein phosphatase 1 (PP1) has long been implicated in HF pathogenesis but its exact role is both unclear and controversial. Most previous studies measured only the PP1 catalytic subunit (PP1c) without investigating its diverse set of interactors, which confer localization and substrate specificity to the holoenzyme. In this study we define the PP1 interactome in cardiac tissue and test the hypothesis that this interactome becomes rearranged during HF progression at the level of specific PP1c interactors...
April 18, 2018: Circulation
Kubra Agirman Torenek, Ozkan Miloglu, Osman Murat Bilge
OBJECTIVES: The purpose of this study is to evaluate the compatibility of ultrasonographic data with hand-wrist radiographs taken to determine the extent of pubertal growth and bone age in patients and investigate the usability of ionizing radiation-free ultrasonography instead of conventional radiography. METHODS: In this study, a total of 120 children from 10 to 17 years old (mean age was 168 months ± 27.5 months) were treated with routine radiographs before orthodontic treatment, and ultrasonographic imaging was performed on the wrists the same day...
April 18, 2018: Dento Maxillo Facial Radiology
Pavithra M Dedigama-Arachchige, Nuwan P N Acharige, Mary Kay H Pflum
Phosphorylation is a key post-translational modification in cell signaling, which is regulated by the equilibrium activities of kinases and phosphatases. The biological significance of many phosphorylation events remains poorly characterized due to the scarcity of tools to discover phosphatases substrates. In prior work, we established kinase-catalyzed biotinylation where kinases accept the γ-modified ATP analog, ATP-biotin, to label phosphoproteins. Here, we developed a novel method to study substrates of phosphatases using kinase-catalyzed biotinylation termed K-BIPS (Kinase-catalyzed Biotinylation to Identify Phosphatase Substrates)...
April 6, 2018: Molecular omics
Ana Crespillo-Casado, Zander Claes, Meng S Choy, Wolfgang Peti, Mathieu Bollen, David Ron
The integrated stress response (ISR) is regulated by kinases that phosphorylate the α subunit of translation initiation factor 2 and phosphatases that dephosphorylate it. Genetic and biochemical observations indicate that the eIF2αP -directed holophosphatase, a therapeutic target in diseases of protein misfolding, is comprised of a regulatory subunit, PPP1R15, and a catalytic subunit, protein phosphatase 1 (PP1). In mammals, there are two isoforms of the regulatory subunit, PPP1R15A and PPP1R15B, with overlapping roles in the essential function of eIF2αP dephosphorylation...
May 18, 2018: Journal of Biological Chemistry
Khaled Almansour, Alistair Taverner, Ian M Eggleston, Randall J Mrsny
Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS19 ) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH2 ) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character...
March 31, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Julia Hülsmann, Bojana Kravic, Matthias Weith, Matthias Gstaiger, Ruedi H Aebersold, Ben C Collins, Hemmo Meyer
The ubiquitin-directed AAA-ATPase VCP/p97 facilitates degradation of damaged or misfolded proteins in diverse cellular stress response pathways. Resolving the complexity of its interactions with partner and substrate proteins, and understanding its links to stress signaling is therefore a major challenge. Here, we used affinity-purification SWATH mass spectrometry (AP-SWATH) to identify proteins that specifically interact with the substrate-trapping mutant, p97-E578Q. AP-SWATH identified differential interactions over a large detection range from abundant p97 cofactors to pathway-specific partners and individual ligases such as RNF185 and MUL1 that were trapped in p97-E578Q complexes...
March 29, 2018: Molecular & Cellular Proteomics: MCP
Nicole M L Wong, Wilson W Wong
T cells expressing tumor-specific T cell receptors are promising cancer therapeutic agents, but safety control switches are needed to manage potential side effects arising from overactivity. Here, we present the first dual small molecule-gated ZAP70 signaling switch for the regulation of T cell activity. We show that when an analogue-sensitive ZAP70 allele is fused to the engineered ligand binding domain of the estrogen receptor, ERT2 , its activity can be upregulated to an extent by a metabolite of an FDA-approved tamoxifen, 4-hydroxy-tamoxifen, and downregulated by an ATP analogue, 3-MB-PP1...
April 20, 2018: ACS Synthetic Biology
Sarah Smith-Moore, Stuart J D Neil, Cornel Fraefel, R Michael Linden, Mathieu Bollen, Helen M Rowe, Els Henckaerts
Adeno-associated virus (AAV) is a small human Dependovirus whose low immunogenicity and capacity for long-term persistence have led to its widespread use as vector for gene therapy. Despite great recent successes in AAV-based gene therapy, further improvements in vector technology may be hindered by an inadequate understanding of various aspects of basic AAV biology. AAV is unique in that its replication is largely dependent on a helper virus and cellular factors. In the absence of helper virus coinfection, wild-type AAV establishes latency through mechanisms that are not yet fully understood...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Driele Tavares, Marcelo Gustavo Paulino, Ana Paula Terezan, João Batista Fernandes, Alessandra Giani, Marisa Narciso Fernandes
Cyanobacterial proliferation in river and lakes is the result of eutrophication. The cyanobacterium Radiocystis fernandoi strain R28 produces mostly two MC variants MC-RR and MC-YR and small amounts of other oligopeptides, but does not produce MC-LR. The present study investigated the hepatotoxic potential of the crude extract of the R. fernandoi strain R28 on the Neotropical fish, Piaractus mesopotamicus, at 3, 6, and 24 h after intraperitoneal injection (100 μg MC-LR equivalent per kg-1 body mass) using biochemical and morphological biomarkers of liver damage...
March 21, 2018: Environmental Science and Pollution Research International
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