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https://www.readbyqxmd.com/read/28549952/drug-target-interaction-prediction-using-ensemble-learning-and-dimensionality-reduction
#1
Ali Ezzat, Min Wu, Xiao-Li Li, Chee-Keong Kwoh
Experimental prediction of drug-target interactions is expensive, time-consuming and tedious. Fortunately, computational methods help narrow down the search space for interaction candidates to be further examined via wet-lab techniques. Nowadays, the number of attributes/features for drugs and targets, as well as the amount of their interactions, are increasing, making these computational methods inefficient or occasionally prohibitive. This motivates us to derive a reduced feature set for prediction. In addition, since ensemble learning techniques are widely used to improve the classification performance, it is also worthwhile to design an ensemble learning framework to enhance the performance for drug-target interaction prediction...
May 23, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28549824/the-hsp90-chaperone-network-modulates-candida-virulence-traits
#2
REVIEW
Teresa R O'Meara, Nicole Robbins, Leah E Cowen
Hsp90 is a conserved molecular chaperone that facilitates the folding and function of client proteins. Hsp90 function is dynamically regulated by interactions with co-chaperones and by post-translational modifications. In the fungal pathogen Candida albicans, Hsp90 enables drug resistance and virulence by stabilizing diverse signal transducers. Here, we review studies that have unveiled regulators of Hsp90 function, as well as downstream effectors that govern the key virulence traits of morphogenesis and drug resistance...
May 23, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28548943/intra-tumour-molecular-heterogeneity-of-clear-cell-renal-cell-carcinoma-reveals-the-diversity-of-the-response-to-targeted-therapies-using-patient-derived-xenograft-models
#3
Baoan Hong, Yong Yang, Sheng Guo, Shayiremu Duoerkun, Xiaohu Deng, Dawei Chen, Shijun Yu, Wubin Qian, Qixiang Li, Qing Li, Kan Gong, Ning Zhang
Inter- and intra-tumour molecular heterogeneity is increasingly recognized in clear cell renal cell carcinoma (ccRCC). It may partially explain the diversity of responses to targeted therapies and the various clinical outcomes. In this study, a 56-year-old male ccRCC patient with multiple metastases received radical nephrectomy and resection of the metastatic tumour in chest wall. The surgical specimens were implanted into nude mice to establish patient-derived xenograft (PDX) models with KI2367 model derived from the primary tumour and KI2368 model from the metastastic tumour...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546740/new-developments-in-managing-opioid-addiction-impact-of-a-subdermal-buprenorphine-implant
#4
REVIEW
MariaLisa Itzoe, Michael Guarnieri
Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone)...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28545396/transcriptomic-resources-for-the-medicinal-legume-mucuna-pruriens-de-novo-transcriptome-assembly-annotation-identification-and-validation-of-est-ssr-markers
#5
N Sathyanarayana, Ranjith Kumar Pittala, Pankaj Kumar Tripathi, Ratan Chopra, Heikham Russiachand Singh, Vikas Belamkar, Pardeep Kumar Bhardwaj, Jeff J Doyle, Ashley N Egan
BACKGROUND: The medicinal legume Mucuna pruriens (L.) DC. has attracted attention worldwide as a source of the anti-Parkinson's drug L-Dopa. It is also a popular green manure cover crop that offers many agronomic benefits including high protein content, nitrogen fixation and soil nutrients. The plant currently lacks genomic resources and there is limited knowledge on gene expression, metabolic pathways, and genetics of secondary metabolite production. Here, we present transcriptomic resources for M...
May 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28545374/modulators-of-the-efflux-pump-cdr1p-of-candida-albicans-mechanisms-of-action-and-chemical-features
#6
Viet-Khoa Tran-Nguyen, Rajendra Prasad, Pierre Falson, Ahcène Boumendjel
The multicomponent primary active ATP-binding cassette transporter Cdr1p in the structure of the pathogenic yeast Candida albicans is among the culprits of antifungal agent resistance reported in recent decades. So far, various potential novel inhibitors/ modulators of this protein have been purified, synthesized, and biologically tested, with results showing their ability to effectively reverse CaCdr1p-mediated drug resistance phenomenon. These compounds are of diverse origins, possess non-identical structural features and adopt different mechanisms of action...
May 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28545225/state-of-art-of-cancer-pharmacogenomics-in-latin-american-populations
#7
REVIEW
Andrés López-Cortés, Santiago Guerrero, María Ana Redal, Angel Tito Alvarado, Luis Abel Quiñones
Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28544818/ubiquitination-in-melanoma-pathogenesis-and-treatment
#8
REVIEW
Jinyuan Ma, Weinan Guo, Chunying Li
Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28543438/humanized-mice-a-brief-overview-on-their-diverse-applications-in-biomedical-research
#9
REVIEW
Shigeyoshi Fujiwara
Model animals naturally differ from humans in various respects and results from the former are not directly translatable to the latter. One approach to address this issue is humanized mice that are defined as mice engrafted with functional human cells or tissues. In humanized mice, we can investigate the development and function of human cells or tissues (including their products encoded by human genes) in the in vivo context of a small animal. As such, humanized mouse models have played important roles that cannot be substituted by other animal models in various areas of biomedical research...
May 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28543422/defending-opioid-treatment-agreements-disclosure-not-promises
#10
Joshua B Rager, Peter H Schwartz
In order to receive controlled pain medications for chronic non-oncologic pain, patients often must sign a "narcotic contract" or "opioid treatment agreement" in which they promise not to give pills to others, use illegal drugs, or seek controlled medications from health care providers. In addition, they must agree to use the medication as prescribed and to come to the clinic for drug testing and pill counts. Patients acknowledge that if they violate the opioid treatment agreement (OTA), they may no longer receive controlled medications...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28543168/a-new-tool-to-tackle-the-opioid-epidemic-description-utility-and-results-from-the-maine-diversion-alert-program
#11
Brian J Piper, Clare E Desrosiers, Harriet C Fisher, Kenneth L McCall, Stephanie D Nichols
STUDY OBJECTIVE: The opioid epidemic continues to impact the United States, and new strategies are needed to combat this epidemic. The objective of this study was to analyze 2015 drug arrest data from Maine's Diversion Alert program (diversionalert. org), compare arrest data between the first quarters of 2015 and 2016, and provide an analysis of the sex differences in the arrests as well as information about DA use. STUDY DESIGN: A population-based, descriptive study using data from the Maine Diversion Alert Program...
May 19, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28542880/suicidal-death-of-erythrocytes-in-cancer-and-its-chemotherapy-a-potential-target-in-the-treatment-of-tumor-associated-anemia
#12
REVIEW
Elisabeth Lang, Rosi Bissinger, Syed M Qadri, Florian Lang
In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca(2+) -activity, ceramide, caspases, calpain, p38-kinase, protein-kinase C, Janus-activated kinase 3, casein-kinase 1α, and cyclin-dependent kinase 4...
May 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28542807/genetic-diversity-virulotyping-and-antimicrobial-resistance-susceptibility-of-yersinia-enterocolitica-isolated-from-pigs-and-porcine-products-in-malaysia
#13
Kwai Lin Thong, Lai Kuan Tan, Peck Toung Ooi
BACKGROUND: The objectives of this study were to determine the antimicrobial resistance, virulotypes and genetic diversity of Yersinia enterocolitica isolated from uncooked porcine food and live pigs in Malaysia. RESULTS: Thirty-two non-repeat Y. enterocolitica strains of three bioserotypes (3 variant/O:3, n=27; 1B/O:8, n=3; 1A/O:5, n=2) were analysed. About 90% of strains were multidrug-resistant with MAR index <0.2 and majority of the strains were resistant to nalidixic acid, clindamycin, ampicillin, ticarcillin, tetracycline and amoxicillin...
May 24, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#14
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542523/impact-of-maintenance-immunosuppressive-therapy-on-the-fecal-microbiome-of-renal-transplant-recipients-comparison-between-an-everolimus-and-a-standard-tacrolimus-based-regimen
#15
Gianluigi Zaza, Alessandra Dalla Gassa, Giovanna Felis, Simona Granata, Sandra Torriani, Antonio Lupo
BACKGROUND: The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. METHODS: We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols...
2017: PloS One
https://www.readbyqxmd.com/read/28542223/measuring-changes-in-transmission-of-neglected-tropical-diseases-malaria-and-enteric-pathogens-from-quantitative-antibody-levels
#16
Benjamin F Arnold, Mark J van der Laan, Alan E Hubbard, Cathy Steel, Joseph Kubofcik, Katy L Hamlin, Delynn M Moss, Thomas B Nutman, Jeffrey W Priest, Patrick J Lammie
BACKGROUND: Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays...
May 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28541680/regulatory-mechanisms-and-novel-therapeutic-targeting-strategies-for-protein-tyrosine-phosphatases
#17
Zhi-Hong Yu, Zhong-Yin Zhang
An appropriate level of protein phosphorylation on tyrosine is essential for cells to react to extracellular stimuli and maintain cellular homeostasis. Faulty operation of signal pathways mediated by protein tyrosine phosphorylation causes numerous human diseases, which presents enormous opportunities for therapeutic intervention. While the importance of protein tyrosine kinases in orchestrating the tyrosine phosphorylation networks and in target-based drug discovery has long been recognized, the significance of protein tyrosine phosphatases (PTPs) in cellular signaling and disease biology has historically been underappreciated, due to a large extent to an erroneous assumption that they are largely constitutive and housekeeping enzymes...
May 25, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28541440/estimating-the-number-of-people-who-inject-drugs-a-proposal-to-provide-figures-nationwide-and-its-application-to-france
#18
Eric Janssen
Background: This article provides an original method of estimating the prevalence of injecting drug users (IDU) in France. Method: In order to overcome legal restrictions hampering data linkage, the method relies on a single-source capture-recapture framework and makes use of individual data collected by a standardized survey conducted within treatment centres. Taking the hierarchical structure of data collection into consideration, a multilevel Zelterman regression model was used...
May 25, 2017: Journal of Public Health
https://www.readbyqxmd.com/read/28540552/application-of-ruo2-ni-foam-electrodes-for-remediation-of-ibuprofen-in-soil-matrix-the-effect-of-electrokinetic-parameters
#19
Ching Yuan, Chung-Hsuang Hung, Tzu-Yuan Huang
Pharmaceuticals and personal care products (PPCPs) are an extraordinary and diverse group of chemicals used in veterinary medicine, agriculture, and for human health and cosmetics care. They are considered emerging contaminants and have raised great concern in recent years. Among the PPCPs, ibuprofen (IBP) is one of the most known non-steroidal anti-inflammatory drugs, which has been found at a high concentration in irrigation water in the USA and showed harmful effect for organisms. This study examined IBP degradation performance by an electrokinetic process coupled with 24-96 cm(2) of RuO2/Ni foam (RN) electrodes applied 1-3 V cm(-1) potential gradient for 5-9 days...
May 24, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28539125/do-anti-malarials-in-africa-meet-quality-standards-the-market-penetration-of-non-quality-assured-artemisinin-combination-therapy-in-eight-african-countries
#20
Paul N Newton, Kara Hanson, Catherine Goodman
BACKGROUND: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector...
May 25, 2017: Malaria Journal
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