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41.
42.
Martin Tiphaine C. Visconti Alessia Spector Tim D. Falchi Mario 《Applied microbiology and biotechnology》2018,102(20):8629-8646
Owing to the increased cost-effectiveness of high-throughput technologies, the number of studies focusing on the human microbiome and its connections to human health and disease has recently surged. However, best practices in microbiology and clinical research have yet to be clearly established. Here, we present an overview of the challenges and opportunities involved in conducting a metagenomic study, with a particular focus on data processing and analytical methods.
相似文献43.
Schumacher J Otte AC Becker T Sun Y Wienker TF Wirth B Franke P Abou Jamra R Propping P Deckert J Nöthen MM Cichon S 《Human genetics》2003,114(1):115-117
A duplication of chromosome 15q24-q26 (DUP25) has been reported to be associated with anxiety disorders. We tested for the presence of DUP25 in a sample of 50 patients with panic disorder and 50 controls using a quantitative real-time PCR approach. Contrary to the original finding, our results were compatible with the absence of DUP25, and no significant difference could be detected between patients and controls (P=1.0). Thus, our study does not support the hypothesis of an involvement of DUP25 in panic disorder. 相似文献
44.
Stefan Balabanov Thomas Wilhelm Simone Venz Gunhild Keller Christian Scharf Heike Pospisil Melanie Braig Christine Barett Carsten Bokemeyer Reinhard Walther Tim H. Brümmendorf Andreas Schuppert 《PloS one》2013,8(1)
In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs. 相似文献
45.
Jane E. Greig Philipp A. du Cros Clair Mills Wilfred Ugwoeruchukwu Andrew Etsetowaghan Adetola Grillo Adetoro Tayo-Adetoro Kunle Omiyale Tim Spelman Daniel P. O’Brien 《PloS one》2013,8(8)
Objectives
In Lagos, Nigeria, Médecins Sans Frontières (MSF) and the Ministry of Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based clinic. We performed a cross-sectional study to compare factors associated with raised viral load between patients with (“experienced”) and without (“naïve”) prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also examined factors influencing ARV adherence in experienced patients prior to clinic entry.Methods
We included adult patients receiving ART from MSF who answered a questionnaire about previous antiretroviral use. Multivariate logistic regression was used to estimate odds ratios (OR) for raised viral load (≥1000 copies/mL).Results
1246 (96%) patients answered: 1075 (86%) reported no, and 171 (14%) some, prior ARV exposure. ARV-naïve patients were more immunosuppressed at baseline: 65% vs 37% (p<0.001) had CD4<200; 17% vs 9% (p = 0.013) were WHO stage 4. Proportionately more experienced than naïve patients had raised viral loads (20% vs 9%, p<0.001) on ART in the MSF/MoH clinic. Raised viral load was associated with prior ARV experience (adjusted OR = 3.74, 95%CI 2.09–6.70, p<0.001) and complete interruption of current ART (adjusted OR = 3.71, 95%CI 2.06–6.68, p<0.001). Higher CD4 at time of VL and a higher self-rated score of recent adherence were associated with lower OR of a raised viral load. Among experienced patients who missed pills before joining MSF/MoH, most common reasons were because ARVS were not affordable (58%) or available (33%), with raised viral load associated with being unsure how to take them (OR = 3.16, 95%CI 1.10–9.12, p = 0.033).Conclusions
Patients previously exposed to ARVs had increased OR of raised viral load. The cost and availability of ARVs were common reasons for missing ARVs before joining the MSF/MoH clinic, and inadequate patient knowledge was associated with raised viral load. 相似文献46.
Christina R?hr Martin Kerick Axel Fischer Alexander Kühn Karl Kashofer Bernd Timmermann Andriani Daskalaki Thomas Meinel Dmitriy Drichel Stefan T. B?rno Anja Nowka Sylvia Krobitsch Alice C. McHardy Christina Kratsch Tim Becker Andrea Wunderlich Christian Barmeyer Christian Viertler Kurt Zatloukal Christoph Wierling Hans Lehrach Michal R. Schweiger 《PloS one》2013,8(7)
MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. 相似文献
47.
Native bird species show latitudinal gradients in body size across species (Bergmann's rule), but whether or not such gradients are recapitulated in the alien distributions of bird species are unknown. Here, we test for the existence of Bergmann's rule in alien bird species worldwide, and investigate the causes of the observed patterns. Published databases were used to obtain the worldwide distributions of established alien bird populations, the locations of alien bird introductions, and bird body masses. Randomisation tests and linear models were used to assess latitudinal patterns in the body masses of introduced and established alien bird populations. Established alien bird species exhibit Bergmann's rule, but this is largely explained by where alien bird species have been introduced: latitudinal variation in the body masses of established alien bird species simply reflects latitudinal variation in the body masses of introduced species. There is some evidence that body mass is implicated in whether or not established species’ alien ranges spread towards or contract away from the Equator following establishment. However, most alien bird ranges are encompassed by the latitudinal band(s) to which the species was introduced. Bergmann's rule in alien birds is therefore a consequence of where humans have introduced different species, rather than of natural processes operating after population introduction. 相似文献
48.
Ecosystems - Native biodiversity often depends on remnant vegetation for survival in agricultural landscapes. However, the size and shape of remnant patches can affect their conservation values... 相似文献
49.
Jeffrey A. Pfefferkorn Meihua Tu Kevin J. Filipski Angel Guzman-Perez Jianwei Bian Gary E. Aspnes Matthew F. Sammons Wei Song Jian-Cheng Li Christopher S. Jones Leena Patel Tim Rasmusson Dongxiang Zeng Kapil Karki Michael Hamilton Richard Hank Karen Atkinson John Litchfield Robert Aiello Levenia Baker Alan Robertson 《Bioorganic & medicinal chemistry letters》2012,22(23):7100-7105
Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy. 相似文献