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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/29457314/latent-source-mining-in-fmri-via-restricted-boltzmann-machine
#2
Xintao Hu, Heng Huang, Bo Peng, Junwei Han, Nian Liu, Jinglei Lv, Lei Guo, Christine Guo, Tianming Liu
Blind source separation (BSS) is commonly used in functional magnetic resonance imaging (fMRI) data analysis. Recently, BSS models based on restricted Boltzmann machine (RBM), one of the building blocks of deep learning models, have been shown to improve brain network identification compared to conventional single matrix factorization models such as independent component analysis (ICA). These models, however, trained RBM on fMRI volumes, and are hence challenged by model complexity and limited training set...
February 18, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29456799/from-ror%C3%AE-t-agonist-to-two-types-of-ror%C3%AE-t-inverse-agonists
#3
Yonghui Wang, Wei Cai, Ting Tang, Qian Liu, Ting Yang, Liuqing Yang, Yingli Ma, Guifeng Zhang, Yafei Huang, Xiaoxia Song, Lisa A Orband-Miller, Qianqian Wu, Ling Zhou, Zhijun Xiang, Jia-Ning Xiang, Stewart Leung, Liming Shao, Xichen Lin, Mercedes Lobera, Feng Ren
Biaryl amides as new RORγt modulators were discovered. The crystal structure of biaryl amide agonist 6 in complex with RORγt ligand binding domain (LBD) was resolved, and both "short" and "long" inverse agonists were obtained by removing from 6 or adding to 6 a proper structural moiety. While "short" inverse agonist ( 8 ) recruits a corepressor peptide and dispels a coactivator peptide, "long" inverse agonist ( 9 ) dispels both. The two types of inverse agonists can be utilized as potential tools to study mechanisms of Th17 transcriptional network inhibition and related disease biology...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29456733/fbxw7-regulates-renal-cell-carcinoma-migration-and-invasion-via-suppression-of-the-epithelial-mesenchymal-transition
#4
Hongchao He, Jun Dai, Zhaoping Xu, Wei He, Xiaojing Wang, Yu Zhu, Haofei Wang
F-box and WD repeat domain containing 7 (Fbxw7) is an F-box protein that belongs to the SKP1-CUL1-F-box protein E3 ligase complex and is responsible for transferring the ubiquitin molecule to the substrate, which results in its recognition and subsequent degradation by proteasomes. Furthermore, it can identify a network of signaling proteins that function in cell growth, diversion and apoptosis. In the present study, Fbxw7 was downregulated in renal cell carcinoma (RCC) tissues compared with the adjacent non-tumor tissues and its expression was significantly associated with the tumor-node-metastasis stage, lymph node metastasis and distant metastasis in patients with RCC...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456523/g-protein-coupled-receptors-as-regulators-of-localized-translation-the-forgotten-pathway
#5
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/29456293/critical-review-of-elementary-flows-in-lca-data
#6
Ashley Edelen, Wesley W Ingwersen, Cristina Rodríguez, Rodrigo A F Alvarenga, Artur Ribeiro de Almeida, Gregor Wernet
Purpose: Elementary flows are essential components of data used for life cycle assessment. A standard list is not used across all sources, as data providers now manage these flows independently. Elementary flows must be consistent across a life cycle inventory for accurate inventory analysis and must correspond with impact methods for impact assessment. With the goal of achieving a global network of LCA databases, a critical review of elementary flow usage and management in LCA data sources was performed...
July 1, 2017: International Journal of Life Cycle Assessment
https://www.readbyqxmd.com/read/29456224/alport-s-syndrome-with-focal-segmental-glomerulosclerosis-lesion-pattern-to-recognize
#7
Afnan A Alsahli, Sara I Alshahwan, Amal O Alotaibi, Khaled O Alsaad, Nourah Aloudah, Mahfooz Farooqui, Abdullah A Al Sayyari
The association between Alport's syndrome (AS) and focal segmental glomerulosclerosis (FSGS) in the same patient is complex and rarely reported. We report a case of a 42-year-old male presenting with proteinuria, microscopic hematuria, elevated serum creatinine and hypertension with unremarkable physical examination apart from obesity. The renal biopsy showed well-established FSGS pattern of injury with mild interstitial fibrosis and tubular atrophy, while the electron microscopic examination demonstrated glomerular basement membranes (GBM) changes compatible with AS...
January 2018: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/29455902/online-social-network-response-to-studies-on-antidepressant-use-in-pregnancy
#8
Simone N Vigod, Ebrahim Bagheri, Fattane Zarrinkalam, Hilary K Brown, Muhammad Mamdani, Joel G Ray
BACKGROUND: About 8% of U.S women are prescribed antidepressant medications around the time of pregnancy. Decisions about medication use in pregnancy can be swayed by the opinion of family, friends and online media, sometimes beyond the advice offered by healthcare providers. Exploration of the online social network response to research on antidepressant use in pregnancy could provide insight about how to optimize decision-making in this complex area. METHODS: For all 17 research articles published on the safety of antidepressant use in pregnancy in 2012, we sought to explore online social network activity regarding antidepressant use in pregnancy, via Twitter, in the 48h after a study was published, compared to the social network activity in the same period 1week prior to each article's publication...
March 2018: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/29455890/passivity-analysis-of-memristor-based-impulsive-inertial-neural-networks-with-time-varying-delays
#9
Peng Wan, Jigui Jian
This paper focuses on delay-dependent passivity analysis for a class of memristive impulsive inertial neural networks with time-varying delays. By choosing proper variable transformation, the memristive inertial neural networks can be rewritten as first-order differential equations. The memristive model presented here is regarded as a switching system rather than employing the theory of differential inclusion and set-value map. Based on matrix inequality and Lyapunov-Krasovskii functional method, several delay-dependent passivity conditions are obtained to ascertain the passivity of the addressed networks...
February 15, 2018: ISA Transactions
https://www.readbyqxmd.com/read/29455865/kin-networks-and-mobility-in-the-transition-to-adulthood
#10
Janel E Benson, Anastassia Bougakova
Family support is critical for launching youth into successful adult lives. Although studies have documented the association between family support and success in the transition to young adulthood, existing work focuses primarily on parental support, giving little attention to extended kin. This narrow definition of family may miss critical exchanges of support, especially among low-income families. Drawing on panel survey data (n=450) and in-depth interviews (n=52) with young women from the Philadelphia Educational Longitudinal Study, this study expands our understanding of family support in the transition to adulthood by examining young adults' kin networks and the types of support and resources embedded within these networks...
2018: Advances in Child Development and Behavior
https://www.readbyqxmd.com/read/29455856/towards-the-development-of-a-modeling-framework-to-track-nitrogen-export-from-lowland-artificial-watersheds-polders
#11
Jiacong Huang, George B Arhonditsis, Junfeng Gao, Dong-Kyun Kim, Feifei Dong
Excess nitrogen (N) export from lowland artificial watersheds (polders) is often assumed to be a major contributor to the cultural eutrophication of downstream aquatic ecosystems. However, the complex transport processes characterizing lowland areas pose significant challenges in accurately quantifying their actual role. In this study, we developed a dynamic model to track N sources and transport pathways in lowland polders. The model is able to accommodate all the unique characteristics of polder dynamics, including artificial drainage, and interactions among surface water, groundwater and soil water...
April 15, 2018: Water Research
https://www.readbyqxmd.com/read/29455662/the-role-of-rictor-downstream-of-receptor-tyrosine-kinase-in-cancers
#12
REVIEW
Ahlem Jebali, Nicolas Dumaz
The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been known for many years but the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway is only starting to emerge. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex 2) kinase activity and as such plays a key role downstream of RTK. Alterations of RICTOR have been identified in a number of cancer cell types and its involvement in tumorigenesis has begun to be unraveled recently...
February 19, 2018: Molecular Cancer
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
#13
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/29455336/utilization-of-organic-nitrogen-by-arbuscular-mycorrhizal-fungi-is-there-a-specific-role-for-protists-and-ammonia-oxidizers
#14
Petra Bukovská, Michael Bonkowski, Tereza Konvalinková, Olena Beskid, Martina Hujslová, David Püschel, Veronika Řezáčová, María Semiramis Gutiérrez-Núñez, Milan Gryndler, Jan Jansa
Arbuscular mycorrhizal (AM) fungi can significantly contribute to plant nitrogen (N) uptake from complex organic sources, most likely in concert with activity of soil saprotrophs and other microbes releasing and transforming the N bound in organic forms. Here, we tested whether AM fungus (Rhizophagus irregularis) extraradical hyphal networks showed any preferences towards certain forms of organic N (chitin of fungal or crustacean origin, DNA, clover biomass, or albumin) administered in spatially discrete patches, and how the presence of AM fungal hyphae affected other microbes...
February 17, 2018: Mycorrhiza
https://www.readbyqxmd.com/read/29455020/bayesian-networks-of-age-estimation-and-classification-based-on-dental-evidence-a-study-on-the-third-molar-mineralization
#15
Emanuele Sironi, Vilma Pinchi, Francesco Pradella, Martina Focardi, Silvia Bozza, Franco Taroni
Not only does the Bayesian approach offer a rational and logical environment for evidence evaluation in a forensic framework, but it also allows scientists to coherently deal with uncertainty related to a collection of multiple items of evidence, due to its flexible nature. Such flexibility might come at the expense of elevated computational complexity, which can be handled by using specific probabilistic graphical tools, namely Bayesian networks. In the current work, such probabilistic tools are used for evaluating dental evidence related to the development of third molars...
February 9, 2018: Journal of Forensic and Legal Medicine
https://www.readbyqxmd.com/read/29454917/marine-derived-xyloketal-derivatives-exhibit-anti-stress-and-anti-ageing-effects-through-hsf-pathway-in-caenorhabditis-elegans
#16
Jie-Bin Zhou, Ying-Lin Zheng, Yi-Xuan Zeng, Jia-Wei Wang, Zhong Pei, Ji-Yan Pang
Ageing is a complex but universal phenomenon that progressively challenges the homeostasis network and finally leads to the dysfunction of organisms and even death. Previous studies demonstrated that xyloketal B and its derivatives, a series of marine novel ketone compounds, possessed unique antioxidative effects on endothelial and neuronal oxidative injuries. In this study, we examined the effects of xyloketal derivatives on extending lifespan and healthspan of Caenorhabditis elegans. The results showed that most selected xyloketals could protect Caenorhabditis elegans against heat stress and extend the lifespan of worms...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29454295/synthetic-and-genetically-encoded-fluorescent-neural-activity-indicators
#17
REVIEW
Claire Deo, Luke D Lavis
The ultimate goal of neuroscience is to relate the complex activity of cells and cell-networks to behavior and cognition. This requires tools and techniques to visualize neuronal activity. Fluorescence microscopy is an ideal tool to measure activity of cells in the brain due to the high sensitivity of the technique and the growing portfolio of optical hardware and fluorescent sensors. Here, we give a chemist's perspective on the recent progress of fluorescent activity indicators that enable the measurement of cellular events in the living brain...
February 14, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29453454/a-microvascularized-tumor-mimetic-platform-for-assessing-anti-cancer-drug-efficacy
#18
Shantanu Pradhan, Ashley M Smith, Charles J Garson, Iman Hassani, Wen J Seeto, Kapil Pant, Robert D Arnold, Balabhaskar Prabhakarpandian, Elizabeth A Lipke
Assessment of anti-cancer drug efficacy in in vitro three-dimensional (3D) bioengineered cancer models provides important contextual and relevant information towards pre-clinical translation of potential drug candidates. However, currently established models fail to sufficiently recapitulate complex tumor heterogeneity. Here we present a chip-based tumor-mimetic platform incorporating a 3D in vitro breast cancer model with a tumor-mimetic microvascular network, replicating the pathophysiological architecture of native vascularized breast tumors...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453421/minimum-energy-control-for-complex-networks
#19
Gustav Lindmark, Claudio Altafini
The aim of this paper is to shed light on the problem of controlling a complex network with minimal control energy. We show first that the control energy depends on the time constant of the modes of the network, and that the closer the eigenvalues are to the imaginary axis of the complex plane, the less energy is required for complete controllability. In the limit case of networks having all purely imaginary eigenvalues (e.g. networks of coupled harmonic oscillators), several constructive algorithms for minimum control energy driver node selection are developed...
February 16, 2018: Scientific Reports
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
#20
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
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