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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458125/pluripotent-stem-cells-for-uncovering-the-role-of-mitochondria-in-human-brain-function-and-dysfunction
#2
REVIEW
Annika Zink, Josef Priller, Alessandro Prigione
Mitochondrial dysfunctions are a known pathogenetic mechanism of a number of neurological and psychiatric disorders. At the same time, mutations in genes encoding for components of the mitochondrial respiratory chain cause mitochondrial diseases, which commonly exhibit neurological symptoms. Mitochondria are therefore critical for the functionality of the human nervous system. The importance of mitochondria stems from their key roles in cellular metabolism, calcium handling, redox and protein homeostasis, and overall cellular homeostasis through their dynamic network...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458096/identification-of-macrophage-related-candidate-genes-in-lupus-nephritis-using-bioinformatics-analysis
#3
Bingyan Shu, Yi Fang, Weichun He, Junwei Yang, Chunsun Dai
Lupus nephritis (LN) is a chronic autoimmune disorder. Here we try to identify the candidate genes in macrophages related to LN. We performed a systematic search in the Gene Expression Omnibus (GEO) database for microarray in human mononuclear cells and mouse macrophages of LN. The results of clustering and venn analysis of different GEO datasets showed that 8 genes were up-regulated and 2 genes down-regulated in samples from both human and mouse LN. The data from gene network and GO analysis revealed that CD38 and CCL2 were localized in the core of the network...
February 16, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29457794/recon3d-enables-a-three-dimensional-view-of-gene-variation-in-human-metabolism
#4
Elizabeth Brunk, Swagatika Sahoo, Daniel C Zielinski, Ali Altunkaya, Andreas Dräger, Nathan Mih, Francesco Gatto, Avlant Nilsson, German Andres Preciat Gonzalez, Maike Kathrin Aurich, Andreas Prlić, Anand Sastry, Anna D Danielsdottir, Almut Heinken, Alberto Noronha, Peter W Rose, Stephen K Burley, Ronan M T Fleming, Jens Nielsen, Ines Thiele, Bernhard O Palsson
Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures...
February 19, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29456889/a-bibliometric-analysis-in-gene-research-of-myocardial-infarction-from-2001-to-2015
#5
Huaqiang Zhou, Wulin Tan, Zeting Qiu, Yiyan Song, Shaowei Gao
Objectives: We aimed to evaluate the global scientific output of gene research of myocardial infarction and explore their hotspots and frontiers from 2001 to 2015, using bibliometric methods. Methods: Articles about the gene research of myocardial infarction between 2001 and 2015 were retrieved from the Web of Science Core Collection (WoSCC). We used the bibliometric method and Citespace V to analyze publication years, journals, countries, institutions, research areas, authors, research hotspots, and trends...
2018: PeerJ
https://www.readbyqxmd.com/read/29456585/neuroinflammation-and-neurohormesis-in-the-pathogenesis-of-alzheimer-s-disease-and-alzheimer-linked-pathologies-modulation-by-nutritional-mushrooms
#6
REVIEW
Angela Trovato Salinaro, Manuela Pennisi, Rosanna Di Paola, Maria Scuto, Rosalia Crupi, Maria Teresa Cambria, Maria Laura Ontario, Mario Tomasello, Maurizio Uva, Luigi Maiolino, Edward J Calabrese, Salvatore Cuzzocrea, Vittorio Calabrese
Human life develops and expands not only in time and space, but also in the retrograde permanent recollection and interweaving of memories. Therefore, individual human identity depends fully on a proper access to the autobiographical memory. Such access is hindered or lost under pathological conditions such as Alzheimer's disease, including recently associated oxidant pathologies, such as ocular neural degeneration occurring in glaucoma or neurosensorial degeneration occurring in Menière's disease. Oxidative stress and altered antioxidant systems have been suggested to play a role in the aetiology of major neurodegenerative disorders, and altered expression of genes sensing oxidative stress, as well as decreased cellular stress response mechanisms could synergistically contribute to the course of these oxidant disorders...
2018: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/29456523/g-protein-coupled-receptors-as-regulators-of-localized-translation-the-forgotten-pathway
#7
REVIEW
Aurélie Tréfier, Lucie P Pellissier, Astrid Musnier, Eric Reiter, Florian Guillou, Pascale Crépieux
G protein-coupled receptors (GPCRs) exert their physiological function by transducing a complex signaling network that coordinates gene expression and dictates the phenotype of highly differentiated cells. Much is known about the gene networks they transcriptionally regulate upon ligand exposure in a process that takes hours before a new protein is synthesized. However, far less is known about GPCR impact on the translational machinery and subsequent mRNA translation, although this gene regulation level alters the cell phenotype in a strikingly different timescale...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29456143/neocortical-association-cell-types-in-the-forebrain-of-birds-and-alligators
#8
Steven D Briscoe, Caroline B Albertin, Joanna J Rowell, Clifton W Ragsdale
The avian dorsal telencephalon has two vast territories, the nidopallium and the mesopallium, both of which have been shown to contribute substantially to higher cognitive functions. From their connections, these territories have been proposed as equivalent to mammalian neocortical layers 2 and 3, various neocortical association areas, or the amygdala, but whether these are analogies or homologies by descent is unknown. We investigated the molecular profiles of the mesopallium and the nidopallium with RNA-seq...
February 14, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29455671/oncogenic-fusion-proteins-adopt-the-insulin-like-growth-factor-signaling-pathway
#9
REVIEW
Haim Werner, Shilhav Meisel-Sharon, Ilan Bruchim
The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455584/hepes-activates-a-mit-tfe-dependent-lysosomal-autophagic-gene-network-in-cultured-cells-a-call-for-caution
#10
Marc J Tol, Martijn J C van der Lienden, Tanit L Gabriel, Jacob J Hagen, Saskia Scheij, Tineke Veenendaal, Judith Klumperman, Wilma E Donker-Koopman, Arthur J Verhoeven, Hermen Overkleeft, Johannes M Aerts, Carmen A Argmann, Marco van Eijk
In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated...
February 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29455385/transcriptome-analysis-of-wild-type-and-afss-deletion-mutant-strains-identifies-synergistic-transcriptional-regulator-of-afss-for-a-high-antibiotic-producing-strain-of-streptomyces-coelicolor-a3-2
#11
Min Woo Kim, Bo-Rahm Lee, SungYong You, Eun-Jung Kim, Ji-Nu Kim, Eunjung Song, Yung-Hun Yang, Daehee Hwang, Byung-Gee Kim
Most secondary metabolism in Actinobacteria is controlled by multi-layered, gene-regulatory networks. These regulatory mechanisms are not easily identified due to their complexity. As a result, when a strong transcriptional regulator (TR) governs activation of biosynthetic pathways of target antibiotics such as actinorhodin (ACT), additional enhancement of the biosynthesis is difficult in combination with other TRs. To find out any "synergistic transcriptional regulators (sTRs)" that show an additive effect on the major, often strong, transcriptional regulator (mTR), here, we performed a clustering analysis using the transcriptome datasets of an mTR deletion mutant and wild-type strain...
February 17, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29454635/sleep-behavior-and-eeg-oscillations-in-aged-dp-16-1yey-mice-a-down-syndrome-model
#12
J Levenga, D J Peterson, P Cain, C A Hoeffer
Down syndrome (DS) results from the triplication of genes located on human chromosome 21 (Hsa21). Though many cognitive and behavioral impairments are associated with DS, sleep disturbances remain poorly understood despite being a reported phenotype in approximately 60% of individuals diagnosed with DS. In this study, sleep and electroencephalography (EEG) oscillations were recorded from aged (12-14 mos.) Dp(16)1Yey/+ mice (Dp16), a mouse model of DS. We observed disrupted sleep demonstrated by increased activity during the dark phase and increased time awake at the expense of NREM sleep compared to wild-type mice...
February 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29454183/the-fine-balance-between-mutualism-and-antagonism-in-the-epichlo%C3%A3-festucae-grass-symbiotic-interaction
#13
REVIEW
Barry Scott, Kimberly Green, Daniel Berry
Epichloë endophytes form mutualistic symbiotic associations with aerial tissues of temperate grasses. Intercalary growth of hyphae within the leaves enables fungal growth to be synchronized with host leaf growth, leading to formation of a highly structured and tightly regulated symbiotic network. Mutations in fungal genes that disrupt cell-cell fusion and other key signalling pathways lead to an antagonistic interaction characterized by unregulated growth of endophytic hyphae and detrimental effects on host growth...
February 14, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29454117/the-differentially-expressed-genes-of-human-sporadic-cerebral-cavernous-malformations
#14
Xiangjiang Lin, Guolu Meng, Xing Liu, Tengfei Yu, Chuanfeng Bai, Xiaobin Fei, Shengze Deng, Jizong Zhao, Shulin Ren, Junting Zhang, Zhen Wu, Shuo Wang, Jianguo Zhang, Liwei Zhang
OBJECTIVES: To understand the development of Sporadic cerebral cavernous malformations (SCCM) comprehensively, we analyzed gene expression profiles in SCCMs by the gene microarray. METHODS: The total number of the specimens collected in our study was 14, 7 of which were SCCMs, and the others were controls that were obtained from normal brain vessels. The total RNA was extracted and hybridized with Oligonucleotide array containing 21522 genes. The analysis of Gene Ontology (GO) items and molecular pathways was performed based on the GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases...
February 14, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29454060/aop-db-a-database-resource-for-the-exploration-of-adverse-outcome-pathways-through-integrated-association-networks
#15
Maureen E Pittman, Stephen W Edwards, Cataia Ives, Holly M Mortensen
The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability to, automatically and on a large scale, integrate AOP knowledge with publically available sources of biological high-throughput data and its derived associations. To support the discovery and development of putative (existing) and potential AOPs, we introduce the AOP-DB, an exploratory database resource that aggregates association relationships between genes and their related chemicals, diseases, pathways, species orthology information, ontologies, and gene interactions...
February 14, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29453676/properties-of-bacterial-communities-attached-to-artificial-substrates-in-a-hypereutrophic-urban-river
#16
Xianlei Cai, Ling Yao, Qiyue Sheng, Luyao Jiang, Randy A Dahlgren, Ting Wang
Bacterial communities of biofilms growing on artificial substrates were examined at two time periods (7 and 14 days) and two locations (lentic and lotic areas) in a hypereutrophic urban river of eastern China. Previous studies in this river network indicated that variations of microbial communities were the major factor affecting the distribution of antibiotic resistant genes highlighting the importance of understanding controls of microbial communities. Bacterial communities associated with biofilms were determined using epifluorescence microscopy and high-throughput sequencing...
February 16, 2018: AMB Express
https://www.readbyqxmd.com/read/29453388/identifying-noncoding-risk-variants-using-disease-relevant-gene-regulatory-networks
#17
Long Gao, Yasin Uzun, Peng Gao, Bing He, Xiaoke Ma, Jiahui Wang, Shizhong Han, Kai Tan
Identifying noncoding risk variants remains a challenging task. Because noncoding variants exert their effects in the context of a gene regulatory network (GRN), we hypothesize that explicit use of disease-relevant GRNs can significantly improve the inference accuracy of noncoding risk variants. We describe Annotation of Regulatory Variants using Integrated Networks (ARVIN), a general computational framework for predicting causal noncoding variants. It employs a set of novel regulatory network-based features, combined with sequence-based features to infer noncoding risk variants...
February 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29453387/structural-determinants-of-the-sine-b2-element-embedded-in-the-long-non-coding-rna-activator-of-translation-as-uchl1
#18
Peter Podbevšek, Francesca Fasolo, Carlotta Bon, Laura Cimatti, Sabine Reißer, Piero Carninci, Giovanni Bussi, Silvia Zucchelli, Janez Plavec, Stefano Gustincich
Pervasive transcription of mammalian genomes leads to a previously underestimated level of complexity in gene regulatory networks. Recently, we have identified a new functional class of natural and synthetic antisense long non-coding RNAs (lncRNA) that increases translation of partially overlapping sense mRNAs. These molecules were named SINEUPs, as they require an embedded inverted SINE B2 element for their UP-regulation of translation. Mouse AS Uchl1 is the representative member of natural SINEUPs. It was originally discovered for its role in increasing translation of Uchl1 mRNA, a gene associated with neurodegenerative diseases...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453355/co-expression-network-analysis-and-cis-regulatory-element-enrichment-determine-putative-functions-and-regulatory-mechanisms-of-grapevine-atl-e3-ubiquitin-ligases
#19
Darren C J Wong, Pietro Ariani, Simone Castellarin, Annalisa Polverari, Elodie Vandelle
Arabidopsis thaliana Toxicos en Levadura (ATL) proteins are a subclass of the RING-H2 zinc finger binding E3 ubiquitin ligases. The grapevine (Vitis vinifera) ATL family was recently characterized, revealing 96 members that are likely to be involved in several physiological processes through protein ubiquitination. However, the final targets and biological functions of most ATL E3 ligases are still unknown. We analyzed the co-expression networks among grapevine ATL genes across a set of transcriptomic data related to defense and abiotic stress, combined with a condition-independent dataset...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453178/seasonal-dynamics-of-tetracycline-resistance-gene-transport-in-the-sumas-river-agricultural-watershed-of-british-columbia-canada
#20
Patricia L Keen, Charles W Knapp, Kenneth J Hall, David W Graham
Environmental transport of contaminants that can influence the development of antibiotic resistance in bacteria is an important concern in the management of ecological and human health risks. Agricultural regions are locales where practices linked to food crop and livestock production can introduce contaminants that could alter the selective pressures for the development of antibiotic resistance in microbiota. This is important in regions where the use of animal manure or municipal biosolids as waste and/or fertilizer could influence selection for antibiotic resistance in pathogenic bacterial species...
February 13, 2018: Science of the Total Environment
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