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https://www.readbyqxmd.com/read/28107009/nmr-and-computation-reveal-a-pressure-sensitive-folded-conformation-of-trp-cage
#1
Soichiro Kitazawa, Martin J Fossat, Scott A McCallum, Angel E Garcia, Catherine Ann Royer
Beyond defining the structure and stability of folded states of proteins, primary amino acid sequences determine all of the features of their conformational landscapes. Characterizing how sequence modulates the population of protein excited states or folding pathways requires atomic level detailed structural and energetic information. Such insight is essential for improving protein design strategies, as well as for interpreting protein evolution. Here, high pressure NMR and molecular dynamics simulations were combined to probe the conformational landscape of a small model protein, the tryptophan cage variant, Tc5b...
January 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28103937/the-influence-of-marketing-on-the-sports-betting-attitudes-and-consumption-behaviours-of-young-men-implications-for-harm-reduction-and-prevention-strategies
#2
Emily G Deans, Samantha L Thomas, Jeffrey Derevensky, Mike Daube
BACKGROUND: Gambling can cause significant health and social harms for individuals, their families, and communities. While many studies have explored the individual factors that may lead to and minimise harmful gambling, there is still limited knowledge about the broader range of factors that may contribute to gambling harm. There are significant regulations to prevent the marketing of some forms of gambling but comparatively limited regulations relating to the marketing of newer forms of online gambling such as sports betting...
January 19, 2017: Harm Reduction Journal
https://www.readbyqxmd.com/read/28101268/traditional-versus-online-biology-courses-connecting-course-design-and-student-learning-in-an-online-setting
#3
Rachel Biel, Cynthia J Brame
Online courses are a large and growing part of the undergraduate education landscape, but many biology instructors are skeptical about the effectiveness of online instruction. We reviewed studies comparing the effectiveness of online and face-to-face (F2F) undergraduate biology courses. Five studies compared student performance in multiple course sections at community colleges, while eight were smaller scale and compared student performance in particular biology courses at a variety of types of institutions...
December 2016: Journal of Microbiology & Biology Education: JMBE
https://www.readbyqxmd.com/read/28098411/an-efficient-basket-trial-design
#4
Kristen M Cunanan, Alexia Iasonos, Ronglai Shen, Colin B Begg, Mithat Gönen
The landscape for early phase cancer clinical trials is changing dramatically because of the advent of targeted therapy. Increasingly, new drugs are designed to work against a target such as the presence of a specific tumor mutation. Because typically only a small proportion of cancer patients will possess the mutational target, but the mutation is present in many different cancers, a new class of basket trials is emerging, whereby the drug is tested simultaneously in different baskets, that is, subgroups of different tumor types...
January 18, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28098236/wind-wave-behavior-in-fetch-and-depth-limited-estuaries
#5
Arash Karimpour, Qin Chen, Robert R Twilley
Wetland dominated estuaries serve as one of the most productive natural ecosystems through their ecological, economic and cultural services, such as nursery grounds for fisheries, nutrient sequestration, and ecotourism. The ongoing deterioration of wetland ecosystems in many shallow estuaries raises concerns about the contributing erosive processes and their roles in restraining coastal restoration efforts. Given the combination of wetlands and shallow bays as landscape components that determine the function of estuaries, successful restoration strategies require knowledge of wind wave behavior in fetch and depth limited water as a critical design feature...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098136/exome-and-genome-sequencing-of-nasopharynx-cancer-identifies-nf-%C3%AE%C2%BAb-pathway-activating-mutations
#6
Yvonne Y Li, Grace T Y Chung, Vivian W Y Lui, Ka-Fai To, Brigette B Y Ma, Chit Chow, John K S Woo, Kevin Y Yip, Jeongsun Seo, Edwin P Hui, Michael K F Mak, Maria Rusan, Nicole G Chau, Yvonne Y Y Or, Marcus H N Law, Peggy P Y Law, Zoey W Y Liu, Hoi-Lam Ngan, Pok-Man Hau, Krista R Verhoeft, Peony H Y Poon, Seong-Keun Yoo, Jong-Yeon Shin, Sau-Dan Lee, Samantha W M Lun, Lin Jia, Anthony W H Chan, Jason Y K Chan, Paul B S Lai, Choi-Yi Fung, Suet-Ting Hung, Lin Wang, Ann Margaret V Chang, Simion I Chiosea, Matthew L Hedberg, Sai-Wah Tsao, Andrew C van Hasselt, Anthony T C Chan, Jennifer R Grandis, Peter S Hammerman, Kwok-Wai Lo
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28095712/current-views-on-the-potential-for-development-of-a-hiv-vaccine
#7
Kristen W Cohen, Nicole Frahm
Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses...
January 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28094063/a-change-in-landscape-lessons-learned-from-abandonment-of-ancient-wari-agricultural-terraces-in-southern-peru
#8
Ana C Londoño, Patrick Ryan Williams, Megan L Hart
Ancient agricultural terrace practices have survived for millennia, sustaining populations through extreme climatic shifts and political regime changes. In arid regions with abrupt relief such as Southern Peru, agricultural terracing is undergoing a resurgence, as has seen revitalization of once abandoned terrace and hydraulic systems. Wari terraces at Cerro Baul provide clues to past cultural practices. They also document sustainable farming practices by using resilient land management techniques which can help combat desertification and degradation of arable lands...
January 13, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28089111/the-molecular-landscape-of-colitis-associated-carcinogenesis
#9
Deborah Saraggi, Matteo Fassan, Claudia Mescoli, Marco Scarpa, Nicola Valeri, Andrea Michielan, Renata D'Incá, Massimo Rugge
In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IFN-γ), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-κB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters...
December 21, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28079698/pediatric-hand-surgery-in-global-health-the-role-for-international-outreach
#10
Karen Y Chung, Amanda Hanemaayer, Dan Poenaru
PURPOSE: There is emerging interest in hand surgery and global health. This was emphasized at the 2015 presidential address at the American Society for Surgery of Hand. Children are prioritized because of their increased risk for trauma and higher potential for better outcomes. This study aims to identify how hand surgical volunteer programs can benefit the pediatric hand surgical landscape in global health. There has been no literature review to date. METHODS: This institutional review board-approved review systematically searched PubMed, Embase, Medline, African Journal Online, and the Journal of Hand Surgery...
February 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28076825/polar-aromatic-periphery-increases-agonist-potency-of-spirocyclic-free-fatty-acid-receptor-gpr40-agonists-inspired-by-ly2881835
#11
Mikhail Krasavin, Alexey Lukin, Daria Bagnyukova, Nikolay Zhurilo, Aleksei Golovanov, Sergey Zozulya, Ihor Zahanich, Daniel Moore, Irina G Tikhonova
A series of spirocyclic compounds inspired by Eli Lilly's phase 1 antidiabetic FFA1 receptor agonist LY2881835 was designed to include polar aromatic periphery groups and explore a possibility of building additional contacts with the target near the agonist binding site. The frontrunner compound in the series (9i) was shown to be a potent (EC50 = 260 nM) FFA1 agonist with excellent aqueous (PBS) solubility and good Caco-2 permeability. The observed structure-activity relationships were rationalized by a docking study...
January 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28074402/riparian-rehabilitation-planning-in-an-urban-rural-gradient-integrating-social-needs-and-ecological-conditions
#12
Bárbara Guida-Johnson, Gustavo A Zuleta
In the present context of global change and search for sustainability, we detected a gap between restoration and society: local communities are usually only considered as threats or disturbances when planning for restoration. To bridge this gap, we propose a landscape design framework for planning riparian rehabilitation in an urban-rural gradient. A spatial multi-criteria analysis was used to assess the priority of riversides by considering two rehabilitation objectives simultaneously-socio-environmental and ecological-and two sets of criteria were designed according to these objectives...
January 10, 2017: Ambio
https://www.readbyqxmd.com/read/28073919/trub1-is-the-predominant-pseudouridine-synthase-acting-on-mammalian-mrna-via-a-predictable-and-conserved-code
#13
Modi Safra, Ronit Nir, Daneyal Farouq, Schraga Schwartz
Following synthesis, RNA can be modified with over 100 chemically distinct modifications, which can potentially regulate RNA expression post-transcriptionally. Pseudouridine (Ψ) was recently established to be widespread and dynamically regulated on yeast mRNA, but less is known about Ψ presence, regulation and biogenesis in mammalian mRNA. Here, we sought to characterize the Ψ landscape on mammalian mRNA, to identify the main Ψ-synthases (PUSs) catalyzing Ψ formation, and to understand the factors governing their specificity towards selected targets...
January 10, 2017: Genome Research
https://www.readbyqxmd.com/read/28067020/spatial-detection-of-outlier-loci-with-moran-eigenvector-maps-mem
#14
Helene H Wagner, Mariana Chávez-Pesqueira, Brenna R Forester
The spatial signature of micro-evolutionary processes structuring genetic variation may play an important role in the detection of loci under selection. However, the spatial location of samples hasn't yet been used to quantify this. Here, we present a new two-step method of spatial outlier detection at the individual and deme levels using the power spectrum of Moran eigenvector maps (MEM). The MEM power spectrum quantifies how the variation in a variable, such as the frequency of an allele at a SNP locus, is distributed across a range of spatial scales defined by MEM spatial eigenvectors...
January 9, 2017: Molecular Ecology Resources
https://www.readbyqxmd.com/read/28062299/bio-nano-interface-the-impact-of-biological-environment-on-nanomaterials-and-their-delivery-properties
#15
REVIEW
Kaimin Cai, Andrew Z Wang, Lichen Yin, Jianjun Cheng
The past several decades have witnessed the rapid development of nanomedicine (NM) which integrates the advancement of various interdisciplinary areas of science, engineering, and medicine. While a few clinical successes of NM greatly change the landscape of disease diagnosis and treatment, there are several areas of NM remaining to be explored. One such area is the complicated interactions between the NM and biological environment post administration, and how such interaction affects the biological performance of NM...
January 3, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28059276/one-dimensional-searches-for-finding-new-lens-design-solutions-efficiently
#16
Zhe Hou, Irina Livshits, Florian Bociort
A special structure is present in the lens design landscape that makes it different from a general global optimization problem: many local minimums are closely related to minimums of simpler problems and can therefore be found by decomposing the search for them in simple steps. We show here that in the design landscape of a wide-angle pinhole lens and in closely related optimization landscapes, all good local minimums found by other methods can be obtained easily with a succession of one-dimensional searches starting from simpler systems...
December 20, 2016: Applied Optics
https://www.readbyqxmd.com/read/28054091/constrained-evolution-of-a-bispecific-enzyme-lessons-for-biocatalyst-design
#17
E Sugrue, C Scott, C J Jackson
One of the central goals of protein design and engineering is to be able to accurately predict the effects of a mutation on stability and activity. However, the genetic context into which mutations are introduced can lead to complex interactions between the mutation and other amino acids and unpredictable, non-additive, effects. This phenomenon is known as intramolecular epistasis and has been shown to restrict evolutionary paths through laboratory directed evolution experiments and ancestral protein reconstruction, but has rarely been studied at a quantitative level in naturally evolving enzymes...
January 5, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28052511/sound-settlement-noise-surpasses-land-cover-in-explaining-breeding-habitat-selection-of-secondary-cavity-nesting-birds
#18
Nathan J Kleist, Robert P Guralnick, Alexander Cruz, Clinton D Francis
Birds breeding in heterogeneous landscapes select nest sites by cueing in on a variety of factors from landscape features and social information to the presence of natural enemies. We focus on determining the relative impact of anthropogenic noise on nest site occupancy, compared to amount of forest cover, which is known to strongly influence the selection process. We examine chronic, industrial noise from natural gas wells directly measured at the nest box as well as site-averaged noise, using a well-established field experimental system in northwestern New Mexico...
January 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28051113/a-comprehensive-custom-panel-design-for-routine-hereditary-cancer-testing-preserving-control-improving-diagnostics-and-revealing-a-complex-variation-landscape
#19
Elisabeth Castellanos, Bernat Gel, Inma Rosas, Eva Tornero, Sheila Santín, Raquel Pluvinet, Juan Velasco, Lauro Sumoy, Jesús Del Valle, Manuel Perucho, Ignacio Blanco, Matilde Navarro, Joan Brunet, Marta Pineda, Lidia Feliubadaló, Gabi Capellá, Conxi Lázaro, Eduard Serra
We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28046073/spatio-temporal-variation-in-landscape-composition-may-speed-resistance-evolution-of-pests-to-bt-crops
#20
Anthony R Ives, Cate Paull, Andrew Hulthen, Sharon Downes, David A Andow, Ralph Haygood, Myron P Zalucki, Nancy A Schellhorn
Transgenic crops that express insecticide genes from Bacillus thuringiensis (Bt) are used worldwide against moth and beetle pests. Because these engineered plants can kill over 95% of susceptible larvae, they can rapidly select for resistance. Here, we use a model for a pyramid two-toxin Bt crop to explore the consequences of spatio-temporal variation in the area of Bt crop and non-Bt refuge habitat. We show that variability over time in the proportion of suitable non-Bt breeding habitat, Q, or in the total area of Bt and suitable non-Bt habitat, K, can increase the overall rate of resistance evolution by causing short-term surges of intense selection...
2017: PloS One
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