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https://www.readbyqxmd.com/read/28213174/evidence-of-the-presence-of-a-calmodulin-sensitive-plasma-membrane-ca-2-atpase-in-trypanosoma-equiperdum
#1
María Carolina Pérez-Gordones, José Rubén Ramírez-Iglesias, Vincenza Cervino, Graciela L Uzcanga, Gustavo Benaim, Marta Mendoza
Trypanosoma equiperdum belongs to the subgenus Trypanozoon, which has a significant socio-economic impact by limiting animal protein productivity worldwide. Proteins involved in the intracellular Ca(2+) regulation are prospective chemotherapeutic targets since several drugs used in experimental treatment against trypanosomatids exert their action through the disruption of the parasite intracellular Ca(2+) homeostasis. Therefore, the plasma membrane Ca(2+)-ATPase (PMCA) is considered as a potential drug target...
February 14, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28212175/advances-in-epilepsy-gene-discovery-and-implications-for-epilepsy-diagnosis-and-treatment
#2
Joseph D Symonds, Sameer M Zuberi, Michael R Johnson
PURPOSE OF REVIEW: Epilepsy genetics is shifting from the academic pursuit of gene discovery to a clinical discipline based on molecular diagnosis and stratified medicine. We consider the latest developments in epilepsy genetics and review how gene discovery in epilepsy is influencing the clinical classification of epilepsy and informing new therapeutic approaches and drug discovery. RECENT FINDINGS: Recent studies highlighting the importance of mutation in GABA receptors, NMDA receptors, potassium channels, G-protein coupled receptors, mammalian target of rapamycin pathway and chromatin remodeling are discussed...
February 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28209180/are-products-with-an-orphan-designation-for-oncology-indications-different-from-products-for-other-rare-indications-a-retrospective-analysis-of-european-orphan-designations-granted-between-2002-2012
#3
Kim Pauwels, Isabelle Huys, Minne Casteels, Kristina Larsson, Caroline Voltz, Karri Penttila, Thomas Morel, Steven Simoens
BACKGROUND: Orphan designated medicinal products benefit from regulatory and economic incentives for orphan drug development. Approximately 40% of orphan designations target rare neoplastic disorders, referring to rare cancers. In order to provide more insights in drugs for rare neoplastic disorders that are under development and to better understand the role of orphan designation in the development of oncology drugs, this study investigates the characteristics of the product, the indication and the applicants as well as the stage of development of products with an orphan designation for rare neoplastic disorders and compares them with products with an orphan designation for other rare indications...
February 16, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28207809/kazakhstan-can-achieve-ambitious-hiv-targets-despite-expected-donor-withdrawal-by-combining-improved-art-procurement-mechanisms-with-allocative-and-implementation-efficiencies
#4
Andrew J Shattock, Clemens Benedikt, Aliya Bokazhanova, Predrag Đurić, Irina Petrenko, Lolita Ganina, Sherrie L Kelly, Robyn M Stuart, Cliff C Kerr, Tatiana Vinichenko, Shufang Zhang, Christoph Hamelmann, Manoela Manova, Emiko Masaki, David P Wilson, Richard T Gray
BACKGROUND: Despite a non-decreasing HIV epidemic, international donors are soon expected to withdraw funding from Kazakhstan. Here we analyze how allocative, implementation, and technical efficiencies could strengthen the national HIV response under assumptions of future budget levels. METHODOLOGY: We used the Optima model to project future scenarios of the HIV epidemic in Kazakhstan that varied in future antiretroviral treatment unit costs and management expenditure-two areas identified for potential cost-reductions...
2017: PloS One
https://www.readbyqxmd.com/read/28205533/a-data-driven-approach-for-evaluating-multi-modal-therapy-in-traumatic-brain-injury
#5
Jenny Haefeli, Adam R Ferguson, Deborah Bingham, Adrienne Orr, Seok Joon Won, Tina I Lam, Jian Shi, Sarah Hawley, Jialing Liu, Raymond A Swanson, Stephen M Massa
Combination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28204826/pathway-deviation-based-biomarker-and-multi-effect-target-identification-in-asbestos-related-squamous-cell-carcinoma-of-the-lung
#6
Jiang Du, Lin Zhang
Asbestos-related lung carcinoma is one of the most devastating occupational cancers, and effective techniques for early diagnosis are still lacking. In the present study, a systematic approach was applied to detect a potential biomarker for asbestos-related lung cancer (ARLC); in particular asbestos-related squamous cell carcinoma (ARLC-SCC). Microarray data (GSE23822) were retrieved from the Gene Expression Omnibus database, including 26 ARLC-SCCs and 30 non-asbestos-related squamous cell lung carcinomas (NARLC-SCCs)...
February 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28201871/a-targeted-contrast-agent-specific-to-an-oncoprotein-in-tumor-microenvironment-with-the-potential-for-detection-and-risk-stratification-of-prostate-cancer-with-mri
#7
Zheng Han, Yajuan Li, Sarah Roelle, Zhuxian Zhou, Yuchi Liu, Rob Sabatelle, Aidan DeSanto, Xin Yu, Hui Zhu, Cristina Magi-Galluzzi, Zheng-Rong Lu
Accurate detection and risk stratification are paramount to the clinical management of prostate cancer. Current diagnostic methods, including prostate specific antigen (PSA) screening, are unable to differentiate high-risk tumors from low-risk tumors, resulting in overdiagnosis and overtreatment of numerous patients. A peptide targeted contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein in tumor microenvironment, EDB-FN, was synthesized for non-invasive detection and characterization of aggressive prostate cancer...
February 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28194977/a-spectral-counting-approach-to-measure-selectivity-of-high-resolution-lc-ms-methods-for-environmental-analysis
#8
Justin B Renaud, Lyne Sabourin, Edward Topp, Mark W Sumarah
Advances in high resolution mass spectrometers have allowed for the development of non-targeted screening methods, where datasets can be archived and retrospectively mined as new environmental contaminants are identified. We have developed a spectral counting approach to calculate the selectivities of LC-MS acquisition modes taking mass accuracy, sample matrix and the analyte properties into account. The selectivities of high resolution MS (HRMS) alone or in combination with all-ion-fragmentation (AIF), data-independent-acquisition (DIA) and data-dependent-acquisition (DDA) modes, performed on a Q-Exactive Orbitrap were compared by retrospectively screening surface water samples for 95 pharmaceuticals...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28194146/modulation-of-replicative-lifespan-in-cryptococcus-neoformans-implications-for-virulence
#9
Tejas Bouklas, Neena Jain, Bettina C Fries
The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28191709/ultrasensitive-fluorogenic-reagents-for-neuraminidase-titration
#10
Zhizeng Gao, Masahiro Niikura, Stephen G Withers
Influenza viral neuraminidase plays a crucial role during infections. It is a major target for the development of anti-influenza drugs and is also attracting increasing attention as a vaccine target as evidence accumulates that neuraminidase-neutralizing antibodies contribute to protection. However, no method currently exists to accurately and efficiently measure concentrations of active neuraminidase in virus samples or other crude mixtures, which hampers development on both fronts. In this report, we describe the development of a selective and sensitive active-site titration reagent for neuraminidase that can quantify viral neuraminidases down to sub-nanomolar levels in crude samples, with no background from non-viral neuraminidases...
February 13, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28188804/metabolite-profiling-of-infection-associated-metabolic-markers-of-onchocerciasis
#11
Sasisekhar Bennuru, Sara Lustigman, David Abraham, Thomas B Nutman
The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the "end game". Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LC-MS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and -uninfected individuals (n=20)...
February 7, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28188791/structure-and-sequence-based-functional-annotation-of-zika-virus-ns2b-protein-computational-insights
#12
Daniel Aguilera-Pesantes, Miguel A Méndez
While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity...
February 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28183242/decoding-corticotropin-releasing-factor-receptor-type-1-crystal-structures
#13
Andrew S Doré, Andrea Bortolato, Kaspar Hollenstein, Robert K Y Cheng, Randy J Read, Fiona H Marshall
The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28179884/cellular-signaling-pathways-in-insulin-resistance-systems-biology-analyses-of-microarray-dataset-reveals-new-drug-target-gene-signatures-of-type-2-diabetes-mellitus
#14
Syed Aun Muhammad, Waseem Raza, Thanh Nguyen, Baogang Bai, Xiaogang Wu, Jake Chen
Purpose: Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder affecting large set of population of the world. To widen the scope of understanding of genetic causes of this disease, we performed interactive and toxicogenomic based systems biology study to find potential T2DM related genes after cDNA differential analysis. Methods: From the list of 50-differential expressed genes (p < 0.05), we found 9-T2DM related genes using extensive data mapping. In our constructed gene-network, T2DM-related differentially expressed seeder genes (9-genes) are found to interact with functionally related gene signatures (31-genes)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28179308/renieramycin-m-attenuates-cancer-stem-cell-like-phenotypes-in-h460-lung-cancer-cells
#15
Natchanun Sirimangkalakitti, Supakarn Chamni, Khanit Suwanborirux, Pithi Chanvorachote
BACKGROUND/AIM: Cancer stem cells (CSCs) are a subpopulation of cancer cells that possess self-renewal and differentiation capacities. CSCs contribute to drug-resistance, cancer recurrence and metastasis, thus development of CSC-targeted therapeutic strategies has recently received significant attention in cancer research. In this study, the potential efficacy of renieramycin M (RM) isolated from the sponge Xestospongia species, was examined against lung CSCs. MATERIALS AND METHODS: Colony and spheroid formation assays, as well as western blotting analysis of lung CSC protein markers were employed to determine the CSC-like phenotypes of H460 lung cancer cells after treatment with RM at non-toxic concentrations...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28179039/cannabis-use-and-adherence-to-antipsychotic-medication-a-systematic-review-and-meta-analysis
#16
E Foglia, T Schoeler, E Klamerus, K Morgan, S Bhattacharyya
BACKGROUND: Substance use may increase the risk of non-adherence to antipsychotics, resulting in negative outcomes in patients with psychosis. METHOD: We aimed to quantitatively summarize evidence regarding the effect of cannabis use, the most commonly used illicit drug amongst those with psychosis, on adherence to antipsychotic medication. Studies were identified through a systematic database search. Adopting random-effects models, pooled odds ratios (OR) for risk of non-adherence to antipsychotic medications were calculated comparing: cannabis-users at baseline v...
February 9, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28178331/large-scale-bioactivity-analysis-of-the-small-molecule-assayed-proteome
#17
Tyler William H Backman, Daniel S Evans, Thomas Girke
This study presents an analysis of the small molecule bioactivity profiles across large quantities of diverse protein families represented in PubChem BioAssay. We compared the bioactivity profiles of FDA approved drugs to non-FDA approved compounds, and report several distinct patterns characteristic of the approved drugs. We found that a large fraction of the previously reported higher target promiscuity among FDA approved compounds, compared to non-FDA approved bioactives, was frequently due to cross-reactivity within rather than across protein families...
2017: PloS One
https://www.readbyqxmd.com/read/28175958/metabolic-and-co-metabolic-transformation-of-diclofenac-by-enterobacter-hormaechei-d15-isolated-from-activated-sludge
#18
Salima Aissaoui, Houria Ouled-Haddar, Mohamed Sifour, Kamel Harrouche, Haitham Sghaier
The presence of non-steroidal anti-inflammatory drugs, such as diclofenac (DCF), in the environment, is an emerging problem due to their harmful effects on non-target organisms, even at low concentrations. We studied the biodegradation of DCF by the strain D15 of Enterobacter hormaechei. The strain was isolated from an activated sludge, and identified as E. hormaechei based on its physiological characteristics and its 16 S RNA sequence. Using HPTLC and GC-MS methods, we demonstrated that this strain metabolized DCF at an elimination rate of 52...
March 2017: Current Microbiology
https://www.readbyqxmd.com/read/28167918/quantifying-effects-of-pharmacological-blockers-of-cardiac-autonomous-control-using-variability-parameters
#19
Renata Miyabara, Karsten Berg, Jan F Kraemer, Ovidiu C Baltatu, Niels Wessel, Luciana A Campos
Objective: The aim of this study was to identify the most sensitive heart rate and blood pressure variability (HRV and BPV) parameters from a given set of well-known methods for the quantification of cardiovascular autonomic function after several autonomic blockades. Methods: Cardiovascular sympathetic and parasympathetic functions were studied in freely moving rats following peripheral muscarinic (methylatropine), β1-adrenergic (metoprolol), muscarinic + β1-adrenergic, α1-adrenergic (prazosin), and ganglionic (hexamethonium) blockades...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28163917/mitochondrial-mutations-and-metabolic-adaptation-in-pancreatic-cancer
#20
Rae-Anne Hardie, Ellen van Dam, Mark Cowley, Ting-Li Han, Seher Balaban, Marina Pajic, Mark Pinese, Mary Iconomou, Robert F Shearer, Jessie McKenna, David Miller, Nicola Waddell, John V Pearson, Sean M Grimmond, Leonid Sazanov, Andrew V Biankin, Silas Villas-Boas, Andrew J Hoy, Nigel Turner, Darren N Saunders
BACKGROUND: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited...
2017: Cancer & Metabolism
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