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Ines Marek, Robert Becker, Fabian B Fahlbusch, Carlos Menendez-Castro, Wolfgang Rascher, Christoph Daniel, Gudrun Volkert, Andrea Hartner
BACKGROUND/AIMS: Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin (Itga8-/-) healing of glomerulonephritis is delayed. As Itga8 is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that Itga8 facilitates phagocytosis of apoptotic cells and matrix components by MC...
March 10, 2018: Cellular Physiology and Biochemistry
Ni Zhu, Bing Yi, Zhifu Guo, Guanxin Zhang, Shengdong Huang, Yongwen Qin, Xianxian Zhao, Jianxin Sun
BACKGROUND/AIMS: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI), a key component in regulating myofilament function in the heart. METHODS: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes...
March 10, 2018: Cellular Physiology and Biochemistry
Yanping Chen, Yingjun Chi, Qingchang Meng, Xiaolin Wang, Deyue Yu
In plants, various proteins are regulated by the ubiquitin-mediated system in response to different environmental stresses, such as drought, cold and heat. The Skp1-Cullin-F-box (SCF) complex, one of the multisubunit E3 ligases, has been shown to be involved in abiotic response pathways. In this study, Glycine max SKP1-like 1 (GmSK1), which had the typical characteristics of an SKP1 protein, with an alpha/beta structure, targeted to the cytoplasm and nucleus, was isolated from soybean [Glycine max (L.)]. GmSK1 was constitutively expressed in all the tested tissues, especially in the roots...
March 7, 2018: Plant Physiology and Biochemistry: PPB
Naif O Al-Harbi, Ahmed Nadeem, Sheikh F Ahmad, Moureq R Alotaibi, Abdullah F AlAsmari, Wael A Alanazi, Mohammad M Al-Harbi, Ahmad M El-Sherbeeny, Khalid E Ibrahim
Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues...
March 12, 2018: International Immunopharmacology
Lucie Angel, Badiâa Bouazzaoui, Michel Isingrini, Séverine Fay, Laurence Taconnat, Sandrine Vanneste, Moïse Ledoux, Valérie Gissot, Caroline Hommet, Fréderic Andersson, Laurent Barantin, Jean-Philippe Cottier, Jérémy Pasco, Thomas Desmidt, Frédéric Patat, Vincent Camus, Jean-Pierre Remenieras
Aging is characterized by a cognitive decline of fluid abilities and is also associated with electrophysiological changes. The vascular hypothesis proposes that brain is sensitive to vascular dysfunction which may accelerate age-related brain modifications and thus explain age-related neurocognitive decline. To test this hypothesis, cognitive performance was measured in 39 healthy participants from 20 to 80 years, using tests assessing inhibition, fluid intelligence, attention and crystallized abilities. Brain functioning associated with attentional abilities was assessed by measuring the P3b ERP component elicited through an auditory oddball paradigm...
March 12, 2018: Brain and Cognition
Qiang Wang, Feiyang Liu, Shuang Qi, Ziping Qi, Xiao-E Yan, Beilei Wang, Aoli Wang, Wei Wang, Cheng Chen, Xiaochuan Liu, Zongru Jiang, Zhenquan Hu, Li Wang, Wenchao Wang, Tao Ren, Shanchun Zhang, Cai-Hong Yun, Qingsong Liu, Jing Liu
Through exploration of the non-highly conserved allosteric hydrophobic pocket generated by DFG-out shifting in the inactive conformation, we discovered a highly selective type II PDGFRα kinase inhibitor 15i (CHMFL-PDGFRα-159), which exhibited strong potency against purified PDGFRα (IC50 : 132 nM) but not structurally similar PDGFRβ, ABL, c-KIT and VEGFR2 kinases. In addition, it displayed a high selectivity profile (S score (10) = 0.02) at the concentration of 1 μM among 468 kinases/mutants in the KINOMEscan profiling...
March 12, 2018: European Journal of Medicinal Chemistry
Emily Wonder, Lorena Simón-Gracia, Pablo Scodeller, Ramsey N Majzoub, Venkata Ramana Kotamraju, Kai K Ewert, Tambet Teesalu, Cyrus R Safinya
Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells...
March 2, 2018: Biomaterials
Yasmine Baktash, Anisha Madhav, Kelly E Coller, Glenn Randall
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms...
March 14, 2018: Cell Host & Microbe
Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram F Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm
The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic. Here, we demonstrate that L.m. infection of macrophages in vivo exclusively evokes LC3-associated phagocytosis (LAP), but not canonical autophagy, and that targeting of L.m. by LAP is required for anti-listerial immunity. The pathway leading to LAP induction in response to L.m. infection emanates from the β2 integrin Mac-1 (CR3, integrin αM β2 ), a receptor recognizing diverse microbial ligands...
March 14, 2018: Cell Host & Microbe
Baruch B Hertzog, Yael Kaufman, Debabrata Biswas, Miriam Ravins, Poornima Ambalavanan, Reuven Wiener, Veronique Angeli, Swaine L Chen, Emanuel Hanski
Bacteria use quorum sensing (QS) to regulate gene expression. We identified a group A Streptococcus (GAS) strain possessing the QS system sil, which produces functional bacteriocins, through a sequential signaling pathway integrating host and bacterial signals. Host cells infected by GAS release asparagine (ASN), which is sensed by the bacteria to alter its gene expression and rate of proliferation. We show that upon ASN sensing, GAS upregulates expression of the QS autoinducer peptide SilCR. Initial SilCR expression activates the autoinduction cycle for further SilCR production...
March 14, 2018: Cell Host & Microbe
Guo-Ying Sun, Hui-Hui Yang, Xin-Xin Guan, Wen-Jing Zhong, Yong-Ping Liu, Ming-Yuan Du, Xiao-Qin Luo, Yong Zhou, Cha-Xiang Guan
Vasoactive intestinal peptide (VIP) is one of the most abundant neuropeptides in the lungs with various biological characters. We have reported that VIP inhibited the expressions of TREM-1 and IL-17A, which are involved in the initiation and amplification of inflammation in acute lung injury (ALI). However, the overall effect of VIP on ALI remains unknown. The aim of this study is to investigate the therapeutic effect of VIP mediated by lentivirus (Lenti-VIP) on lipopolysaccharide (LPS)-induced murine ALI. We found that the expression of intrapulmonary VIP peaked at day7 after the intratracheal injection of Lenti-VIP...
March 12, 2018: Molecular Immunology
Li Chen, Nathchar Naowarojna, Heng Song, Shu Wang, Jianyun Wang, Zixin Deng, Changming Zhao, Pinghua Liu
Ovothiol is a histidine thiol derivative. The biosynthesis of ovothiol involves an extremely efficient trans-sulfuration strategy. The non-heme iron enzyme OvoA catalyzed oxidative coupling be-tween cysteine and histidine is one of the key steps. Besides catalyzing the oxidative coupling between cysteine and histidine, OvoA also catalyzes the oxi-dation of cysteine to cysteine sulfinic acid (cysteine dioxygenase activity). Thus far, very little mecha-nistic information is available for OvoA-catalysis. In this report, we measured the kinetic isotope effect (KIE) in OvoA-catalysis using the isotopically sensitive branching method...
March 15, 2018: Journal of the American Chemical Society
Suhyung Cho, Donghui Choe, Eunju Lee, Sun Chang Kim, Bernhard Ø Palsson, Byung-Kwan Cho
Along with functional advances in the use of CRISPR/Cas9 for genome editing, endonuclease-deficient Cas9 (dCas9) has provided a versatile molecular tool for exploring gene functions. In principle, differences in cell phenotypes that result from the RNA-guided modulation of transcription levels by dCas9 are critical for inferring with gene function; however, the effect of intracellular dCas9 expression on bacterial morphology has not been systematically elucidated. Here, we observed unexpected morphological changes in Escherichia coli mediated by dCas9, which were then characterized using RNA sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq)...
March 15, 2018: ACS Synthetic Biology
Nigel Scrutton, Uzma Choudry, Derren Heyes, Samantha Hardman, Michiyo Sakuma, Igor Sazanovich, Joyce Woodhouse, Eugenio De La Mora, Martin Pederson, Michael Wulff, Martin Weik, Giorgio Schiro
Phytochromes are bilin-containing photoreceptors that are typically sensitive to the red / far-red region of the visible spectrum. Recently phytochromes from certain eukaryotic algae have become attractive targets for optogenetic applications because of their unique ability to respond to multiple wavelengths of light. Here, we have used a combination of time-resolved spectroscopy and structural approaches across picosecond to second timescales to map photochemical mechanisms and structural change in this atypical group of phytochromes...
March 15, 2018: Chembiochem: a European Journal of Chemical Biology
Bin Li, Yaqing Liu, Changjin Wan, Zhiyuan Liu, Ming Wang, Dianpeng Qi, Jiancan Yu, Pingqiang Cai, Meng Xiao, Yi Zeng, Xiaodong Chen
Memristive synapses based on resistive switching are promising electronic devices that emulate the synaptic plasticity in neural systems. Short-term plasticity (STP), reflecting a temporal strengthening of the synaptic connection, allows artificial synapses to perform critical computational functions, such as fast response and information filtering. To mediate this fundamental property in memristive electronic devices, the regulation of the dynamic resistive change is necessary for an artificial synapse. Here, it is demonstrated that the orientation of mesopores in the dielectric silica layer can be used to modulate the STP of an artificial memristive synapse...
March 15, 2018: Advanced Materials
Armando Andres Roca Suarez, Nicolaas Van Renne, Thomas F Baumert, Joachim Lupberger
Signal transducer and activator of transcription 3 (STAT3) is a key regulator of numerous physiological functions, including the immune response. As pathogens elicit an acute phase response with concerted activation of STAT3, they are confronted with two evolutionary options: either curtail it or employ it. This has important consequences for the host, since abnormal STAT3 function is associated with cancer development and other diseases. This review provides a comprehensive outline of how human viruses cope with STAT3-mediated inflammation and how this affects the host...
March 2018: PLoS Pathogens
Luca Palazzese, Marta Czernik, Domenico Iuso, Paola Toschi, Pasqualino Loi
Recently we have demonstrated the possibility to replace histones with protamine, through the heterologous expression of human protamine 1 (hPrm1) gene in sheep fibroblasts. Here we have optimized protaminization of somatic nucleus by adjusting the best concentration and exposure time to trichostatin A (TSA) in serum-starved fibroblasts (nuclear quiescence), before expressing Prm1 gene. To stop cell proliferation, we starved cells in 0.5% FBS in MEM ("starved"-ST group), whereas in the Control group (CTR) the cells were cultured in 10% FBS in MEM...
2018: PloS One
Dilyana Filipova, Margit Henry, Tamara Rotshteyn, Anna Brunn, Mariana Carstov, Martina Deckert, Jürgen Hescheler, Agapios Sachinidis, Gabriele Pfitzer, Symeon Papadopoulos
In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels-the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)-underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14...
2018: PloS One
Stella Arelaki, Athanasios Arampatzioglou, Konstantinos Kambas, Efthimios Sivridis, Alexandra Giatromanolaki, Konstantinos Ritis
Inflammation is a hallmark of colorectal cancer (CRC). Neutrophils are well-known mediators in tumor biology but their role in solid tumors, including CRC, was redefined by neutrophil extracellular traps (NETs). Given that it was recently demonstrated that platelet-derived polyP primes neutrophils to release NETs, we examined surgical specimens from CRC to investigate the presence of polyP, as a possible NET inducer. Biopsies with adenomas, hyperplastic polyps, inflammatory bowel disease and healthy colon tissues were used as controls...
2018: PloS One
Aurore Quinault, Corinne Leloup, Geoffrey Denwood, Coralie Spiegelhalter, Marianne Rodriguez, Philippe Lefebvre, Nadia Messaddeq, Quan Zhang, Catherine Dacquet, Luc Pénicaud, Stephan C Collins
The rhythmic nature of insulin secretion over the 24h cycle in pancreatic islets has been mostly investigated using transcriptomics studies showing that modulation of insulin secretion over this cycle is achieved via distal stages of insulin secretion. We set out to measure β-cell exocytosis using in depth cell physiology techniques at several time points. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J islets in culture for 24h exhibit higher insulin secretion during the corresponding dark phase than in the light phase (Zeitgeber Time ZT20 and ZT8, respectively, in vivo)...
2018: PloS One
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