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https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#1
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28727789/lumpgem-systematic-generation-of-subnetworks-and-elementally-balanced-lumped-reactions-for-the-biosynthesis-of-target-metabolites
#2
Meric Ataman, Vassily Hatzimanikatis
In the post-genomic era, Genome-scale metabolic networks (GEMs) have emerged as invaluable tools to understand metabolic capabilities of organisms. Different parts of these metabolic networks are defined as subsystems/pathways, which are sets of functional roles to implement a specific biological process or structural complex, such as glycolysis and TCA cycle. Subsystem/pathway definition is also employed to delineate the biosynthetic routes that produce biomass building blocks. In databases, such as MetaCyc and SEED, these representations are composed of linear routes from precursors to target biomass building blocks...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28727484/construction-and-analysis-of-circular-rna-molecular-regulatory-networks-in-liver-cancer
#3
Shuangchun Ren, Zhuoyuan Xin, Yinyan Xu, Jianting Xu, Guoqing Wang
Liver cancer is the sixth most prevalent cancer, and the third most frequent cause of cancer-related deaths. Circular RNAs (circRNAs), a kind of special endogenous ncRNAs, have been coming back to the forefront of cancer genomics research. In this study, we employed a systems biology approach to construct and analyze the circRNA molecular regulatory networks in the context of liver cancer. We detected a total of 127 differentially expressed circRNAs and 3,235 differentially expressed mRNAs. We selected the top-5 upregulated circRNAs to construct a circRNA-miRNA-mRNA network...
July 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28727145/transcriptional-control-of-photosynthetic-capacity-conservation-and-divergence-from-arabidopsis-to-rice
#4
REVIEW
Peng Wang, Ross-William Hendron, Steven Kelly
1 I. 1 II. 2 III. 5 IV. 10 12 References 12 SUMMARY: Photosynthesis is one of the most important biological processes on Earth. It provides the consumable energy upon which almost all organisms are dependent, and modulates the composition of the planet's atmosphere. To carry out photosynthesis, plants require a large cohort of genes. These genes encode proteins that capture light energy, store energy in sugars and build the subcellular structures required to facilitate this energy capture. Although the function of many of these genes is known, little is understood about the transcriptional networks that coordinate their expression...
July 20, 2017: New Phytologist
https://www.readbyqxmd.com/read/28726849/o2-controllable-hydrogels-for-studying-cellular-responses-to-hypoxic-gradients-in-three-dimensions-in-vitro-and-in-vivo
#5
Daniel M Lewis, Michael R Blatchley, Kyung Min Park, Sharon Gerecht
Oxygen (O2) acts as a potent upstream regulator of cell function. In both physiological and pathophysiological microenvironments, the O2 concentration is not uniformly distributed but instead follows a gradient that depends on distance from oxygen-carrying blood vessels. Such gradients have a particularly important role in development, tissue regeneration, and tumor growth. In this protocol, we describe how to use our previously reported gelatin-based O2-controllable hydrogels that can provide hypoxic microenvironments in vitro...
August 2017: Nature Protocols
https://www.readbyqxmd.com/read/28726733/interaction-of-mitochondria-with-the-endoplasmic-reticulum-and-plasma-membrane-in-calcium-homeostasis-lipid-trafficking-and-mitochondrial-structure
#6
REVIEW
Jędrzej Szymański, Justyna Janikiewicz, Bernadeta Michalska, Paulina Patalas-Krawczyk, Mariasole Perrone, Wiesław Ziółkowski, Jerzy Duszyński, Paolo Pinton, Agnieszka Dobrzyń, Mariusz R Więckowski
Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles in intact cells with the use of microscopic techniques reveals a new set of different junctions and contact sites between them that contribute to the control and regulation of various cellular processes, such as calcium and lipid exchange or structural reorganization of the mitochondrial network. In recent years, many studies focused their attention on the structure and function of contacts between mitochondria and other organelles...
July 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#7
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28725371/the-role-of-novel-forest-ecosystems-in-the-conservation-of-wood-inhabiting-fungi-in-boreal-broadleaved-forests
#8
Katja Juutilainen, Mikko Mönkkönen, Heikki Kotiranta, Panu Halme
The increasing human impact on the earth's biosphere is inflicting changes at all spatial scales. As well as deterioration and fragmentation of natural biological systems, these changes also led to other, unprecedented effects and emergence of novel habitats. In boreal zone, intensive forest management has negatively impacted a multitude of deadwood-associated species. This is especially alarming given the important role wood-inhabiting fungi have in the natural decay processes. In the boreal zone, natural broad-leaved-dominated, herb-rich forests are threatened habitats which have high wood-inhabiting fungal species richness...
October 2016: Ecology and Evolution
https://www.readbyqxmd.com/read/28724991/benchmarking-selected-computational-gene-network-growing-tools-in-context-of-virus-host-interactions
#9
Biruhalem Taye, Candida Vaz, Vivek Tanavde, Vladimir A Kuznetsov, Frank Eisenhaber, Richard J Sugrue, Sebastian Maurer-Stroh
Several available online tools provide network growing functions where an algorithm utilizing different data sources suggests additional genes/proteins that should connect an input gene set into functionally meaningful networks. Using the well-studied system of influenza host interactions, we compare the network growing function of two free tools GeneMANIA and STRING and the commercial IPA for their performance of recovering known influenza A virus host factors previously identified from siRNA screens. The result showed that given small (~30 genes) or medium (~150 genes) input sets all three network growing tools detect significantly more known host factors than random human genes with STRING overall performing strongest...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724786/emergent-cortical-circuit-dynamics-contain-dense-interwoven-ensembles-of-spike-sequences
#10
Joseph B Dechery, Jason N MacLean
Temporal codes are theoretically powerful encoding schemes, but their precise form in neocortex remains unknown in part because of the large number of possible codes and the difficulty in disambiguating informative spikes from statistical noise. A biologically plausible and computationally powerful temporal coding scheme is the Hebbian assembly phase sequence (APS), which predicts reliable propagation of spikes between functionally related assemblies of neurons. Here, we sought to measure the inherent capacity of neocortical networks to produce reliable sequences of spikes, as would be predicted by an APS code...
July 19, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28724692/enhancing-studies-of-pharmacodynamic-mechanisms-via-measurements-of-metabolic-flux
#11
Natalie A Daurio, Sheng-Ping Wang, Ying Chen, Haihong Zhou, David G McLaren, Thomas P Roddy, Douglas G Johns, Denise Milot, Takhar Kasumov, Mark D Erion, David E Kelley, Stephen F Previs
Drug discovery and development efforts are largely based around a common expectation, namely, direct or indirect action on a cellular process (e.g. statin-mediated enzyme inhibition or insulin-stimulated receptor activation) will have a beneficial impact on physiological homeostasis. To expand on this, one could argue that virtually all pharmacological interventions attempt to influence the flow of traffic in a biochemical network, irrespective of disease or modality. Since stable isotope tracer kinetic methods provide a measure of traffic flow (i...
July 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28724431/biological-embedding-of-childhood-adversity-from-physiological-mechanisms-to-clinical-implications
#12
REVIEW
Anne E Berens, Sarah K G Jensen, Charles A Nelson
BACKGROUND: Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes "biologically embedded" in altered physiology across body systems...
July 20, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28724365/leflunomide-is-equally-efficacious-and-safe-compared-to-low-dose-rituximab-in-refractory-rheumatoid-arthritis-given-in-combination-with-methotrexate-results-from-a-randomized-double-blind-controlled-clinical-trial
#13
Harindu Wijesinghe, Priyadharshini Galappatthy, Rajiva de Silva, Suranjith L Seneviratne, Ushagowry Saravanamuttu, Preethi Udagama, Melanie Hart, Peter Kelleher, Upul Senerath, Rohini Fernandopulle, Lilani P Weerasekera, Lalith S Wijayaratne
BACKGROUND: The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination...
July 19, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28724354/novel-plasmodium-falciparum-metabolic-network-reconstruction-identifies-shifts-associated-with-clinical-antimalarial-resistance
#14
Maureen A Carey, Jason A Papin, Jennifer L Guler
BACKGROUND: Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. RESULTS: Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28723971/termination-factor-rho-from-the-control-of-pervasive-transcription-to-cell-fate-determination-in-bacillus-subtilis
#15
Vladimir Bidnenko, Pierre Nicolas, Aleksandra Grylak-Mielnicka, Olivier Delumeau, Sandrine Auger, Anne Aucouturier, Cyprien Guerin, Repoila Francis, Jacek Bardowski, Stéphane Aymerich, Elena Bidnenko
In eukaryotes, RNA species originating from pervasive transcription are regulators of various cellular processes, from the expression of individual genes to the control of cellular development and oncogenesis. In prokaryotes, the function of pervasive transcription and its output on cell physiology is still unknown. Most bacteria possess termination factor Rho, which represses pervasive, mostly antisense, transcription. Here, we investigate the biological significance of Rho-controlled transcription in the Gram-positive model bacterium Bacillus subtilis...
July 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28723574/proteomic-analysis-of-the-human-tankyrase-protein-interaction-network-reveals-its-role-in-pexophagy
#16
Xu Li, Han Han, Mao-Tian Zhou, Bing Yang, Albert Paul Ta, Nan Li, Junjie Chen, Wenqi Wang
Tankyrase 1 (TNKS) and tankyrase 2 (TNKS2) belong to the poly(ADP-ribose) polymerase family of proteins, which use nicotinamide adenine dinucleotide to modify substrate proteins with ADP-ribose modifications. Emerging evidence has revealed the pathological relevance of TNKS and TNKS2, and identified these two enzymes as potential drug targets. However, the cellular functions and regulatory mechanisms of TNKS/2 are still largely unknown. Through a proteomic analysis, we defined the protein-protein interaction network for human TNKS/2 and revealed more than 100 high-confidence interacting proteins with numerous biological functions in this network...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28722475/ann-qsar-workflow-for-predicting-the-inhibition-of-hiv-1-reverse-transcriptase-by-pyridinone-non-nucleoside-derivatives
#17
Abolfazl Barzegar, Elham Zamani-Gharehchamani, Ali Kadkhodaie-Ilkhchi
AIM: Pyridinone derivatives have high potency against non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant human immunodeficiency virus type-1 strains. Quantitative structure-activity relationship (QSAR) studies on a series of pyridinone derivatives acting as NNRTIs are very important in designing the next generation of NNRTIs. Methodology & results: The QSAR models were developed using linear (single and forward stepwise) and combined nonlinear artificial neural network (ANN) approaches...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28721073/exploration-of-the-molecular-mechanism-of-prostate-cancer-based-on-mrna-and-mirna-expression-profiles
#18
Xing Zhang, YuYan Sun, Peng Wang, Changfu Yang, Shengwei Li
Prostate cancer, the second most common cancer in men, has been rarely explored by integrating mRNA and miRNA expression profiles. In this study, we combined two mRNA expression datasets and six documented miRNAs to uncover the comprehensive molecular mechanism of prostate cancer. Results showed that a total of 30 genes were significantly differentially expressed in 49 tumor samples by comparing with 22 normal samples. Importantly, all samples from the two datasets can be clearly classified into two groups, tumor group and normal group, based on the selected differentially expressed genes (DEGs)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28720887/olfactory-bulb-plasticity-ensures-proper-olfaction-after-severe-impairment-in-postnatal-neurogenesis
#19
D Díaz, R Muñoz-Castañeda, C Ávila-Zarza, J Carretero, J R Alonso, E Weruaga
The olfactory bulb (OB) neurons establish a complex network that ensures the correct processing of the olfactory inputs. Moreover, the OB presents a lifelong addition of new neurons into its existing circuitry. This neurogenesis is considered essential for the OB function. However, its functional impact on physiology and behavior is still unclear. Here, we investigate the mechanisms of OB plasticity that underlie bulbar physiology in relation to severe damage of neurogenesis. The neurogenesis of young mice was altered by ionizing radiation...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720831/minimum-winfree-loop-determines-self-sustained-oscillations-in-excitable-erd%C3%A3-s-r%C3%A3-nyi-random-networks
#20
Yu Qian, Xiaohua Cui, Zhigang Zheng
The investigation of self-sustained oscillations in excitable complex networks is very important in understanding various activities in brain systems, among which the exploration of the key determinants of oscillations is a challenging task. In this paper, by investigating the influence of system parameters on self-sustained oscillations in excitable Erdös-Rényi random networks (EERRNs), the minimum Winfree loop (MWL) is revealed to be the key factor in determining the emergence of collective oscillations...
July 18, 2017: Scientific Reports
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