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https://www.readbyqxmd.com/read/28098782/auranofin-inhibits-the-enzyme-activity-of-pasteurella-multocida-toxin-pmt-in-human-cells-and-protects-cells-from-intoxication
#1
Stefan Carle, Thorsten Brink, Joachim H C Orth, Klaus Aktories, Holger Barth
The AB-type protein toxin from Pasteurella multocida (PMT) contains a functionally important disulfide bond within its catalytic domain, which must be cleaved in the host cell cytosol to render the catalytic domain of PMT into its active conformation. Here, we found that the reductive potential of the cytosol of target cells, and more specifically, the activity of the thioredoxin reductase (TrxR) is crucial for this process. This was demonstrated by the strong inhibitory effect of the pharmacological TrxR inhibitor auranofin, which inhibited the intoxication of target cells with PMT, as determined by analyzing the PMT-catalyzed deamidation of GTP-binding proteins (G-proteins) in the cytosol of cells...
January 13, 2017: Toxins
https://www.readbyqxmd.com/read/28096686/peptide-consensus-sequence-determination-for-the-enhancement-of-the-antimicrobial-activity-and-selectivity-of-antimicrobial-peptides
#2
Ammar Almaaytah, Ya'u Ajingi, Ahmad Abualhaijaa, Shadi Tarazi, Nizar Alshar'i, Qosay Al-Balas
The rise of multidrug-resistant bacteria is causing a serious threat to the world's human population. Recent reports have identified bacterial strains displaying pan drug resistance against antibiotics and generating fears among medical health specialists that humanity is on the dawn of entering a post-antibiotics era. Global research is currently focused on expanding the lifetime of current antibiotics and the development of new antimicrobial agents to tackle the problem of antimicrobial resistance. In the present study, we designed a novel consensus peptide named "Pepcon" through peptide consensus sequence determination among members of a highly homologous group of scorpion antimicrobial peptides...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28096354/loss-of-get-pathway-orthologs-in-arabidopsis-thaliana-causes-root-hair-growth-defects-and-affects-snare-abundance
#3
Shuping Xing, Dietmar Gerald Mehlhorn, Niklas Wallmeroth, Lisa Yasmin Asseck, Ritwika Kar, Alessa Voss, Philipp Denninger, Vanessa Aphaia Fiona Schmidt, Markus Schwarzländer, York-Dieter Stierhof, Guido Grossmann, Christopher Grefen
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096301/phosphoinositol-3-phosphate-acts-as-a-timer-for-reactive-oxygen-species-production-in-the-phagosome
#4
Zhi Min Song, Leïla Bouchab, Elodie Hudik, Romain Le Bars, Oliver Nüsse, Sophie Dupré-Crochet
Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40(phox) by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40(phox) and p67(phox) at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28094444/the-current-state-of-nad-dependent-histone-deacetylases-sirtuins-as-novel-therapeutic-targets
#5
REVIEW
Matthias Schiedel, Dina Robaa, Tobias Rumpf, Wolfgang Sippl, Manfred Jung
Sirtuins are NAD(+) -dependent protein deacylases that cleave off acetyl, as well as other acyl groups, from the ε-amino group of lysines in histones and other substrate proteins. Seven sirtuin isotypes (Sirt1-7) have been identified in mammalian cells. As sirtuins are involved in the regulation of various physiological processes such as cell survival, cell cycle progression, apoptosis, DNA repair, cell metabolism, and caloric restriction, a dysregulation of their enzymatic activity has been associated with the pathogenesis of neoplastic, metabolic, infectious, and neurodegenerative diseases...
January 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28093838/fusaric-acid-contributes-to-virulence-of-fusarium-oxysporum-on-plant-and-mammalian-hosts
#6
Cristina López-Díaz, Vahid Rahjoo, Michael Sulyok, Veronica Ghionna, Adela Martín-Vicente, Javier Capilla, Antonio Di Pietro, Manuel S López-Berges
Fusaric acid (FA) is among the oldest identified secondary metabolites produced by Fusarium species, known for a long time to display strong phytotoxicity and moderate toxicity to animal cells; however, the cellular targets of FA as well as its function in fungal pathogenicity remain unknown. Here, we investigated the role of FA in Fusarium oxysporum, a soil-borne cross-kingdom pathogen that causes vascular wilt on more than a hundred plant species and opportunistic infections in humans. Targeted deletion of fub1, encoding a predicted orthologue of the polyketide synthase involved in FA biosynthesis in F...
January 17, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28092500/a-model-of-a-synthetic-biological-communication-interface-between-mammalian-cells-and-mechatronic-systems
#7
Keith C Heyde, Warren C Ruder
The creation of communication interfaces between abiotic and biotic systems represents a significant research challenge. In this work, we design and model a system linking the biochemical signaling pathways of mammalian cells to the actions of a mobile robotic prosthesis. We envision this system as a robotic platform carrying an optically monitored bioreactor that harbors mammalian cells. The cellular, optical signal is captured by an onboard fluorescent microscope and converted into an electronic signal. We first present a design for the overall cell-robot system, with a specific focus on the design of the synthetic gene networks needed for the system...
December 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28092361/designed-cell-consortia-as-fragrance-programmable-analog-to-digital-converters
#8
Marius Müller, Simon Ausländer, Andrea Spinnler, David Ausländer, Julian Sikorski, Marc Folcher, Martin Fussenegger
Synthetic biology advances the rational engineering of mammalian cells to achieve cell-based therapy goals. Synthetic gene networks have nearly reached the complexity of digital electronic circuits and enable single cells to perform programmable arithmetic calculations or to provide dynamic remote control of transgenes through electromagnetic waves. We designed a synthetic multilayered gaseous-fragrance-programmable analog-to-digital converter (ADC) allowing for remote control of digital gene expression with 2-bit AND-, OR- and NOR-gate logic in synchronized cell consortia...
January 16, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28089267/probes-for-monitoring-regulated-exocytosis
#9
REVIEW
Wen-Hong Li
Regulated secretion is a fundamental cellular process that serves diverse functions in neurobiology, endocrinology, immunology, and numerous other aspects of animal physiology. In response to environmental or biological cues, cells release contents of secretory granules into an extracellular medium to communicate with or impact neighboring or distant cells through paracrine or endocrine signaling. To investigate mechanisms governing stimulus-secretion coupling, to better understand how cells maintain or regulate their secretory activity, and to characterize secretion defects in human diseases, probes for tracking various exocytotic events at the cellular or sub-cellular level have been developed over the years...
January 9, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28088900/synaptic-plasticity-dementia-and-alzheimer-disease
#10
Pietro Giusti, Stephen D Skaper, Laura Facci, Morena Zusso
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment...
January 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28086803/compendium-of-tcdd-mediated-transcriptomic-response-datasets-in-mammalian-model-systems
#11
Stephenie D Prokopec, Kathleen E Houlahan, Ren X Sun, John D Watson, Cindy Q Yao, Jamie Lee, Christine P'ng, Renee Pang, Alexander H Wu, Lauren C Chong, Ashley B Smith, Nicholas J Harding, Ivy D Moffat, Jere Lindén, Sanna Lensu, Allan B Okey, Raimo Pohjanvirta, Paul C Boutros
BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28078826/the-impact-of-ph-inhomogeneities-on-cho-cell-physiology-and-fed-batch-process-performance-two-compartment-scale-down-modelling-and-intracellular-ph-excursion
#12
Matthias Brunner, Philipp Braun, Philipp Doppler, Christoph Posch, Dirk Behrens, Christoph Herwig, Jens Fricke
Due to high mixing times and base addition from top of the vessel, pH inhomogeneities are most likely to occur during large-scale mammalian processes. The goal of this study was to set-up a scale-down model of a 10-12 m(3) stirred tank bioreactor and to investigate the effect of pH perturbations on CHO cell physiology and process performance. Short-term changes in extracellular pH were hypothesized to affect intracellular pH and thus cell physiology. Therefore, batch fermentations, including pH shifts to 9...
January 12, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28077706/connexin-mediated-signaling-in-nonsensory-cells-is-crucial-for-the-development-of-sensory-inner-hair-cells-in-the-mouse-cochlea
#13
Stuart L Johnson, Federico Ceriani, Oliver Houston, Roman Polishchuk, Elena Polishchuk, Giulia Crispino, Veronica Zorzi, Fabio Mammano, Walter Marcotti
: Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and connexin 30 (Cx30) have been linked to syndromic and nonsyndromic hearing loss in mice and humans. The release of ATP from connexin hemichannels in cochlear nonsensory cells has been proposed to be the main trigger for action potential activity in immature sensory inner hair cells (IHCs), which is crucial for the refinement of the developing auditory circuitry. Using connexin knock-out mice, we show that IHCs fire spontaneous action potentials even in the absence of ATP-dependent intercellular Ca(2+) signaling in the nonsensory cells...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077358/biological-signaling-by-carbon-monoxide-and-carbon-monoxide-releasing-molecules-co-rms
#14
Roberto Motterlini, Roberta Foresti
Carbon monoxide (CO) is continuously produced in mammalian cells during degradation of heme. It is a stable gaseous molecule that reacts selectively with transition metals in a specific redox state and these characteristics restrict the interaction of CO with defined biological targets that transduce its signaling activity. Because of the high affinity of CO for ferrous heme, these targets can be grouped into heme-containing proteins, representing a large variety of sensors and enzymes with a series of diverse function in the cell and the organism...
January 11, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28077334/the-neuroprotective-compound-p7c3-a20-promotes-neurogenesis-and-improves-cognitive-function-after-ischemic-stroke
#15
Zachary B Loris, Andrew A Pieper, W Dalton Dietrich
Ischemic stroke is a devastating condition with few therapeutic interventions available. The neuroprotective compound P7C3-A20 inhibits mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute injury. P7C3 compounds enhance flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The effectiveness of P7C3-A20 treatment on chronic histopathological and behavioral outcomes and neurogenesis after ischemic stroke has not previously been established...
January 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28074902/a-reduced-mechanical-model-for-camp-modulated-gating-in-hcn-channels
#16
Stephanie Weißgraeber, Andrea Saponaro, Gerhard Thiel, Kay Hamacher
We developed an in silico mechanical model to analyze the process of cAMP-induced conformational modulations in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which conduct cations across the membrane of mammalian heart and brain cells. The structural analysis reveals a quaternary twist in the cytosolic parts of the four subunits in the channel tetramer. This motion augments the intrinsic dynamics of the very same protein structure. The pronounced differences between the cAMP bound and unbound form include a mutual interaction between the C-linker of the cyclic nucleotide binding domain (CNBD) and the linker between the S4 and S5 transmembrane domain of the channel...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073824/a-drosophila-toolkit-for-defining-gene-function-in-spermatogenesis
#17
Nicole A Siddall, Gary R Hime
Expression profiling and genomic sequencing methods enable the accumulation of vast quantities of data that relate to expression of genes during the maturation of male germ cells from primordial germ cells to spermatozoa, and potential mutations that underlie male infertility. However, determination of gene function in specific aspects of spermatogenesis or linking abnormal gene function with infertility remain rate limiting, as even in an era of CRISPR analysis of gene function in mammalian models, this still requires considerable resources and time...
January 10, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28069833/clasp2-ensures-mitotic-fidelity-and-prevents-differentiation-of-epidermal-keratinocytes
#18
Marta N Shahbazi, Daniel Peña-Jimenez, Francesca Antonucci, Matthias Drosten, Mirna Perez-Moreno
Epidermal homeostasis is tightly controlled by a balancing act of self-renewal or terminal differentiation of proliferating basal keratinocytes. An increase in DNA content as a consequence of a mitotic block is a recognized mechanism underlying keratinocyte differentiation, but the molecular mechanisms involved in this process are not yet fully understood. Using cultured primary keratinocytes, here we report that the expression of the mammalian Microtubule and Kinetochore-associated protein Clasp2 is intimately associated to the basal proliferative makeup of keratinocytes, and its deficiency leads to premature differentiation...
January 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28069585/expression-of-hmgb2-indicates-worse-survival-of-patients-and-is-required-for-the-maintenance-of-warburg-effect-in-pancreatic-cancer
#19
Xin Cai, Hongjian Ding, Yanxia Liu, Gaofeng Pan, Qingguo Li, Zhen Yang, Weiyan Liu
High mobility group proteins (HMGs) are the second most abundant chromatin proteins and exert global genomic functions in the establishment of active or inactive chromatin domains. Through interaction with nucleosomes, transcription factors, nucleosome-remodeling machines and histones, the HMGs family proteins contribute to the fine tuning of transcription in response to rapid environmental changes. Mammalian high mobility group Bs (HMGBs) are characterized by two tandem HMG box domains followed by a long acidic tail...
January 9, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28068331/modelling-systemic-iron-regulation-during-dietary-iron-overload-and-acute-inflammation-role-of-hepcidin-independent-mechanisms
#20
Mihaela Enculescu, Christoph Metzendorf, Richard Sparla, Maximilian Hahnel, Johannes Bode, Martina U Muckenthaler, Stefan Legewie
Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tighly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms...
January 9, 2017: PLoS Computational Biology
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