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https://www.readbyqxmd.com/read/28747192/the-european-me-cfs-biomarker-landscape-project-an-initiative-of-the-european-network-euromene
#1
REVIEW
Carmen Scheibenbogen, Helma Freitag, Julià Blanco, Enrica Capelli, Eliana Lacerda, Jerome Authier, Mira Meeus, Jesus Castro Marrero, Zaiga Nora-Krukle, Elisa Oltra, Elin Bolle Strand, Evelina Shikova, Slobodan Sekulic, Modra Murovska
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and severe disease with a considerable social and economic impact. So far, the etiology is not known, and neither a diagnostic marker nor licensed treatments are available yet. The EUROMENE network of European researchers and clinicians aims to promote cooperation and advance research on ME/CFS. To improve diagnosis and facilitate the analysis of clinical trials surrogate markers are urgently needed. As a first step for developing such biomarkers for clinical use a database of active biomarker research in Europe was established called the ME/CFS EUROMENE Biomarker Landscape project and the results are presented in this review...
July 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28746905/a-pm7-dynamic-residue-ligand-interactions-energy-landscape-of-the-bace1-inhibitory-pathway-by-hydroxyethylamine-compounds-part-i-the-flap-closure-process
#2
Carlos Gueto-Tettay, Alejandro Martinez-Consuegra, Joshua Zuchniarz, Luis Roberto Gueto-Tettay, Juan Carlos Drosos-Ramírez
BACE1 is an enzyme of scientific interest because it participates in the progression of Alzheimer's disease. Hydroxyethylamines (HEAs) are a family of compounds which exhibit inhibitory activity toward BACE1 at a nanomolar level, favorable pharmacokinetic properties and oral bioavailability. The first step in the inhibition of BACE1 by HEAs consists of their entrance into the protease active site and the resultant conformational change in the protein, from Apo to closed form. These two conformations differ in the position of an antiparallel loop (called the flap) which covers the entrance to the catalytic site...
July 14, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28746849/death-receptor-5-activation-is-energetically-coupled-to-opening-of-the-transmembrane-domain-dimer
#3
Nagamani Vunnam, Cecily Kristine Campbell-Bezat, Andrew K Lewis, Jonathan N Sachs
The precise mechanism by which binding of tumor necrosis factor ligands to the extracellular domain of their corresponding receptors transmits signals across the plasma membrane has remained elusive. Recent studies have proposed that activation of several tumor necrosis factor receptors, including Death Receptor 5, involves a scissorlike opening of the disulfide-linked transmembrane (TM) dimer. Using time-resolved fluorescence resonance energy transfer, we provide, to our knowledge, the first direct biophysical evidence that Death Receptor 5 TM-dimers open in response to ligand binding...
July 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28745560/genetic-perspective-of-uniparental-mitochondrial-dna-landscape-on-the-punjabi-population-pakistan
#4
Shahzad Bhatti, Sana Abbas, Muhammad Aslamkhan, Marcella Attimonelli, Magali Segundo Trinidad, Hikmet Hakan Aydin, Erica Martinha Silva de Souza, Gerardo Rodriguez Gonzalez
To investigate the uniparental genetic structure of the Punjabi population from mtDNA aspect and to set up an appropriate mtDNA forensic database, we studied maternally unrelated Punjabi (N = 100) subjects from two caste groups (i.e. Arain and Gujar) belonging to territory of Punjab. The complete control region was elucidated by Sanger sequencing and the subsequent 58 different haplotypes were designated into appropriate haplogroups according to the most recently updated mtDNA phylogeny. We found a homogenous dispersal of Eurasian haplogroup uniformity among the Punjab Province and exhibited a strong connotation with the European populations...
July 26, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28745031/a-tale-of-two-tails-the-importance-of-unstructured-termini-in-the-aggregation-pathway-of-%C3%AE-2-microglobulin
#5
Rui J S Loureiro, Diogo Vila-Viçosa, Miguel Machuqueiro, Eugene I Shakhnovich, Patricia F N Faísca
The identification of intermediate states for folding and aggregation is important from a fundamental standpoint and for the design of novel therapeutic strategies targeted at conformational disorders. Protein human β2-microglobulin (HB2m) is classically associated with dialysis related amyloidosis, but the single point mutant D76N was recently identified as the causative agent of a hereditary systemic amyloidosis affecting visceral organs. Here we use D76N as a model system to explore the early stage of the aggregation mechanism of HB2m by means of an integrative approach framed on molecular simulations...
July 26, 2017: Proteins
https://www.readbyqxmd.com/read/28738270/chemical-structure-and-correlation-analysis-of-hiv-1-nnrt-and-nrt-inhibitors-and-database-curated-published-inhibition-constants-with-chemical-structure-in-diverse-datasets
#6
Birgit Viira, Alfonso T García-Sosa, Uko Maran
Human immunodeficiency virus (HIV-1) reverse transcriptase is a major target for designing anti-HIV drugs. Developed inhibitors are divided into non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) and nucleoside analog reverse-transcriptase inhibitors (NRTIs) depending on their mechanism. Given that many inhibitors have been studied and for many of them binding affinity constants have been calculated, it is beneficial to analyze the chemical landscape of these families of inhibitors and correlate these inhibition constants with molecular structure descriptors...
June 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28737470/recent-advances-in-circulating-tumor-cells-and-cell-free-dna-in-metastatic-prostate-cancer-a-review
#7
Sunil Parimi, Jenny J Ko
The treatment landscape of metastatic prostate cancer has changed dramatically over the past five years. As new discoveries are made and further novel therapies become available, there is a heightened urgency to develop biomarkers that can guide prognoses and predict therapy responses. Circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) in the blood have emerged as potential promising tumor avatars. Areas covered: In this review, we describe technological breakthroughs and clinical implementation of the CTCs and ctDNA...
July 24, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28735209/seasonal-performance-of-denitrifying-bioreactors-in-the-northeastern-united-states-field-trials
#8
Bahareh Hassanpour, Shree Giri, William T Pluer, Tammo S Steenhuis, Larry D Geohring
Denitrifying bioreactors are increasingly being used for nitrate removal from agricultural drainage water. Filled with carbon substrates, often woodchips, denitrifying bioreactors provide a favorable anaerobic environment for denitrification. Despite performing well in loess soils in the Midwestern United States, field bioreactors have not yet been evaluated in shallow soils over glacial till that are characteristic for the Northeastern United States. This study, therefore, investigates the performance of bioreactors and provides design criteria for shallow soil with flashy discharges...
July 20, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28729884/genome-wide-landscape-of-position-effects-on-heterogeneous-gene-expression-in-saccharomyces-cerevisiae
#9
Xiao-Le Wu, Bing-Zhi Li, Wen-Zheng Zhang, Kai Song, Hao Qi, Jun-Biao Dai, Ying-Jin Yuan
BACKGROUND: Integration of heterogeneous genes is widely applied in synthetic biology and metabolic engineering. However, knowledge about the effect of integrative position on gene expression remains limited. RESULTS: We established a genome-wide landscape of position effect on gene expression in Saccharomyces cerevisiae. The expression cassette of red fluorescence protein (RFP) gene was constructed and inserted at 1044 loci, which were scattered uniformly in the yeast genome...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28727200/landscape-genetic-analyses-reveal-fine-scale-effects-of-forest-fragmentation-in-an-insular-tropical-bird
#10
Aurélie Khimoun, William Peterman, Cyril Eraud, Bruno Faivre, Nicolas Navarro, Stéphane Garnier
Within the framework of landscape genetics, resistance surface modelling is particularly relevant to explicitly test competing hypotheses about landscape effects on gene flow. To investigate how fragmentation of tropical forest affects population connectivity in a forest-specialist bird species, we optimized resistance surfaces without a priori specification, using least-cost (LCP) or resistance (IBR) distances. We implemented a two-step procedure in order i) to objectively define the landscape thematic resolution (level of detail in classification scheme to describe landscape variables) and spatial extent (area within the landscape boundaries) and then ii) to test the relative role of several landscape features (elevation, roads, land cover) in genetic differentiation in the Plumbeous Warbler (Setophaga plumbea)...
July 20, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28725369/adding-energy-gradients-and-long-distance-dispersal-to-a-neutral-model-improves-predictions-of-madagascan-bird-diversity
#11
Falko T Buschke, Luc Brendonck, Bram Vanschoenwinkel
Macroecological patterns are likely the result of both stochastically neutral mechanisms and deterministic differences between species. In Madagascar, the simplest stochastically neutral hypothesis - the mid-domain effects (MDE) hypothesis - has already been rejected. However, rejecting the MDE hypothesis does not necessarily refute the existence of all other neutral mechanisms. Here, we test whether adding complexity to a basic neutral model improves predictions of biodiversity patterns. The simplest MDE model assumes that: (1) species' ranges are continuous and unfragmented, (2) are randomly located throughout the landscape, and (3) can be stacked independently and indefinitely...
October 2016: Ecology and Evolution
https://www.readbyqxmd.com/read/28724111/agricultural-conservation-planning-framework-3-land-use-and-field-boundary-database-development-and-structure
#12
Mark D Tomer, David E James, Claudette M J Sandoval-Green
Conservation planning information is important for identifying options for watershed water quality improvement and can be developed for use at field, farm, and watershed scales. Translation across scales is a key issue impeding progress at watershed scales because watershed improvement goals must be connected with implementation of farm- and field-level conservation practices to demonstrate success. This is particularly true when examining alternatives for "trap and treat" practices implemented at agricultural-field edges to control (or influence) water flows through fields, landscapes, and riparian corridors within agricultural watersheds...
May 2017: Journal of Environmental Quality
https://www.readbyqxmd.com/read/28720667/mapk-pathway-and-tert-promoter-gene-mutation-pattern-and-its-prognostic-value-in-melanoma-patients%C3%AF-a-retrospective-study-of-2793-cases
#13
Xue Bai, Yan Kong, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Xuan Wang, Lili Mao, Bixia Tang, Siming Li, Bin Lian, Xieqiao Yan, Li Zhou, Jie Dai, Jun Guo, Lu Si
Ethnic differences are conspicuous in melanoma. This study is to obtain a comprehensive view of a genomic landscape and a better understanding of the correlations of gene mutation status with clinicopathological characteristics and disease prognosis in Asian population.<br /><br />Experimental Design: 2793 melanoma patient samples were retrospectively collected and analyzed for mutations in C-KIT, BRAF, NRAS, and PDGFRA coding regions and TERT promoter region by Sanger sequencing. Mutations were correlated to clinicopathological features and overall survival...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28711122/the-establishment-and-management-of-an-observation-unit
#14
REVIEW
Jared Conley, J Stephen Bohan, Christopher W Baugh
The current health care landscape and evidence support the establishment of observation units (OUs) for safe and efficient care for observation patients. Careful attention is required in the design of OU process, location, and layout to enable optimal care and finances. Developing and maintaining protocols to guide patient selection and clinical care are critical. OU management requires a strong, collaborative leadership model, appropriate staffing, and a robust monitoring system for quality, safety, and finances...
August 2017: Emergency Medicine Clinics of North America
https://www.readbyqxmd.com/read/28710314/sarcomatoid-renal-cell-carcinoma-has-a-distinct-molecular-pathogenesis-driver-mutation-profile-and-transcriptional-landscape
#15
Zixing Wang, Tae Beom Kim, Bo Peng, Jose A Karam, Chad J Creighton, Aron Y Joon, Fumi Kawakami, Patricia Trevisan, Eric Jonasch, Chi-Wan Chow, Jaime Rodriguez-Canales, Pheroze Tamboli, Nizar M Tannir, Christopher G Wood, Federico A Monzon, Keith A Baggerly, Marileila Varella-Garcia, Bogdan Czerniak, Ignacio I Wistuba, Gordon B Mills, Kenna Shaw, Ken Chen, Kanishka Sircar
Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity.<br /><br />Experimental Design: We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of non-sarcomatoid RCC (RCC). We evaluated whole exome sequencing, single nucleotide polymorphism, and RNA sequencing data from patients with SRCC (n=65) and RCC (n=598) across different parent RCC subtypes, including clear cell RCC, papillary RCC, and chromophobe RCC subtypes...
July 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28709856/developing-smartphone-apps-for-behavioural-studies-the-alcorisk-app-case-study
#16
Anthony Smith, Kristy de Salas, Ian Lewis, Benjamin Schüz
Advances in mobile technology and significantly increasing utilization of mobile devices such as smartphones and tablets have resulted in a paradigm shift from PC-centric computing to mobile computing. The results of careful analysis conducted of this mobile landscape indicate that there is a growing demand for smart, user-centric, situation-aware mobile software. Invariably, concomitant with this demand is the need for methodologies that can provide support the development of this type of software. In this paper, we propose a semantic framework, called the mobile situation-aware framework, which supports efficient modeling, construction, processing, management, and inference of mobile situation information...
July 11, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#17
REVIEW
Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli
The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF...
July 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28708081/modeling-the-effects-of-urban-design-on-emergency-medical-response-calls-during-extreme-heat-events-in-toronto-canada
#18
Drew A Graham, Jennifer K Vanos, Natasha A Kenny, Robert D Brown
Urban residents are at risk of health-related illness during extreme heat events but the dangers are not equal in all parts of a city. Previous studies have found a relationship between physical characteristics of neighborhoods and the number of emergency medical response (EMR) calls. We used a human energy budget model to test the effects of landscape modifications that are designed to cool the environment on the expected number of EMR calls in two neighborhoods in Toronto, Canada during extreme heat events...
July 14, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28705213/the-therapeutic-landscape-of-hiv-1-via-genome-editing
#19
REVIEW
Alexander Kwarteng, Samuel Terkper Ahuno, Godwin Kwakye-Nuako
Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR-Cas9) are transforming the therapeutic landscape of HIV-1...
July 14, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28704211/how-to-emerge-from-the-conservatism-in-clinical-research-methodology
#20
Nuria Kotecki, Nicolas Penel, Ahmad Awada
PURPOSE OF REVIEW: Despite recent changes in clinical research methodology, many challenges remain in drug development methodology. RECENT FINDINGS: Advances in molecular biology and cancer treatments have changed the clinical research landscape. Thus, we moved from empirical clinical oncology to molecular and immunological therapeutic approaches. Along with this move, adapted dose-limiting toxicities definitions, endpoints, and dose escalation methods have been proposed...
July 12, 2017: Current Opinion in Oncology
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