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https://www.readbyqxmd.com/read/28547390/mono-substitution-effects-on-antimicrobial-activity-of-stapled-heptapeptides
#1
Huy X Luong, Do-Hee Kim, Ngoan T Mai, Bong-Jin Lee, Young-Woo Kim
We previously reported a de novo design of antimicrobial heptapeptide helices using Verdine's all-hydrocarbon peptide stapling system. One of the important structure-activity relationships we found from these previous studies was that extending of the hydrophobic face by replacing of alanine with leucine in positon 5 increases antimicrobial activity. In this study, to further improve the activity profile of this peptide series, we investigated the substitution effects of position 5 on conformational and proteolytic stability as well as antimicrobial and hemolytic activity...
May 25, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28538176/tonic-lat-hdac7-signals-sustain-nur77-and-irf4-expression-to-tune-naive-cd4%C3%A2-t-cells
#2
Darienne R Myers, Tannia Lau, Evan Markegard, Hyung W Lim, Herbert Kasler, Minghua Zhu, Andrea Barczak, John P Huizar, Julie Zikherman, David J Erle, Weiguo Zhang, Eric Verdin, Jeroen P Roose
CD4(+) T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4(+) T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (TH2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28448128/total-chemical-synthesis-and-folding-of-all-l-and-all-d-variants-of-oncogenic-kras-g12v
#3
Adam M Levinson, John H McGee, Andrew G Roberts, Gardner S Creech, Ting Wang, Michael T Peterson, Ronald C Hendrickson, Gregory L Verdine, Samuel J Danishefsky
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered "undruggable" due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-l- and all-d-amino acid biotinylated variants of oncogenic mutant KRas(G12V)...
May 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28447069/long-term-calorie-restriction-in-humans-is-not-associated-with-indices-of-delayed-immunologic-aging-a-descriptive-study
#4
A Janet Tomiyama, Jeffrey M Milush, Jue Lin, James M Flynn, Pankaj Kapahi, Eric Verdin, Elizabeth Sinclair, Simon Melov, Elissa S Epel
BACKGROUND: Delayed immunologic aging is purported to be a major mechanism through which calorie restriction (CR) exerts its anti-aging effects in non-human species. However, in non-obese humans, the effect of CR on the immune system has been understudied relative to its effects on the cardiometabolic system. OBJECTIVE: To examine whether CR is associated with delayed immunologic aging in non-obese humans. METHODS: We tested whether long-term CR practitioners (average 10.03 years of CR) evidenced decreased expression of T cell immunosenescence markers and longer immune cell telomeres compared to gender-, race/ethnicity-, age-, and education-matched "healthy" Body Mass Index (BMI) and "overweight"/"obese" BMI groups...
March 31, 2017: Nutrition and Healthy Aging
https://www.readbyqxmd.com/read/28408723/nucleic-acid-detection-with-crispr-cas13a-c2c2
#5
Jonathan S Gootenberg, Omar O Abudayyeh, Jeong Wook Lee, Patrick Essletzbichler, Aaron J Dy, Julia Joung, Vanessa Verdine, Nina Donghia, Nichole M Daringer, Catherine A Freije, Cameron Myhrvold, Roby P Bhattacharyya, Jonathan Livny, Aviv Regev, Eugene V Koonin, Deborah T Hung, Pardis C Sabeti, James J Collins, Feng Zhang
Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting clustered regularly interspaced short palindromic repeats (CRISPR) effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous ribonuclease activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity...
April 28, 2017: Science
https://www.readbyqxmd.com/read/28376236/inland-waters-and-their-role-in-the-carbon-cycle-of-alaska
#6
Sarah M Stackpoole, David E Butman, David W Clow, Kristine L Verdin, Benjamin V Gaglioti, Hélène Genet, Robert G Striegl
The magnitude of Alaska (AK) inland waters carbon (C) fluxes is likely to change in the future due to amplified climate warming impacts on the hydrology and biogeochemical processes in high latitude regions. Although current estimates of major aquatic C fluxes represent an essential baseline against which future change can be compared, a comprehensive assessment for AK has not yet been completed. To address this gap, we combined available datasets and applied consistent methodologies to estimate river lateral C export to the coast, river and lake carbon dioxide (CO2 ) and methane (CH4 ) emissions, and C burial in lakes for the six major hydrologic regions in the state...
April 4, 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28195575/a-land-data-assimilation-system-for-sub-saharan-africa-food-and-water-security-applications
#7
Amy McNally, Kristi Arsenault, Sujay Kumar, Shraddhanand Shukla, Pete Peterson, Shugong Wang, Chris Funk, Christa D Peters-Lidard, James P Verdin
Seasonal agricultural drought monitoring systems, which rely on satellite remote sensing and land surface models (LSMs), are important for disaster risk reduction and famine early warning. These systems require the best available weather inputs, as well as a long-term historical record to contextualize current observations. This article introduces the Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (FLDAS), a custom instance of the NASA Land Information System (LIS) framework. The FLDAS is routinely used to produce multi-model and multi-forcing estimates of hydro-climate states and fluxes over semi-arid, food insecure regions of Africa...
February 14, 2017: Scientific Data
https://www.readbyqxmd.com/read/28181251/iv-results-links-between-spatial-assembly-later-spatial-skills-and-concurrent-and-later-mathematical-skills
#8
Brian N Verdine, Roberta Michnick Golinkoff, Kathy Hirsh-Pasek, Nora S Newcombe
No abstract text is available yet for this article.
March 2017: Monographs of the Society for Research in Child Development
https://www.readbyqxmd.com/read/28181250/causal-inference-and-the-spatial-math-link-in-early-childhood
#9
Drew H Bailey
Verdine et al. (2017) present compelling evidence for a causal effect of spatial skills on children's mathematics achievement in early childhood. In additional analyses of the correlation matrix reported by Verdine et al., I present evidence that the spatial-math link is not merely an epiphenomenon of general cognitive demands of both tasks. However, the question of whether the link is due to a causal effect of spatial skills on mathematics skills, a causal effect of mathematics skills on spatial skills, or common factors influencing both during this developmental period is a more difficult one to answer...
March 2017: Monographs of the Society for Research in Child Development
https://www.readbyqxmd.com/read/28181249/v-results-individual-difference-factors-in-spatial-and-mathematical-skills
#10
Brian N Verdine, Roberta Michnick Golinkoff, Kathy Hirsh-Pasek, Nora S Newcombe
No abstract text is available yet for this article.
March 2017: Monographs of the Society for Research in Child Development
https://www.readbyqxmd.com/read/28181248/i-spatial-skills-their-development-and-their-links-to-mathematics
#11
Brian N Verdine, Roberta Michnick Golinkoff, Kathy Hirsh-Pasek, Nora S Newcombe
Understanding the development of spatial skills is important for promoting school readiness and improving overall success in STEM (science, technology, engineering, and mathematics) fields (e.g., Wai, Lubinski, Benbow, & Steiger, 2010). Children use their spatial skills to understand the world, including visualizing how objects fit together, and can practice them via spatial assembly activities (e.g., puzzles or blocks). These skills are incorporated into measures of overall intelligence and have been linked to success in subjects like mathematics (Mix & Cheng, 2012) and science (Pallrand & Seeber, 1984; Pribyl & Bodner, 1987)...
March 2017: Monographs of the Society for Research in Child Development
https://www.readbyqxmd.com/read/28181247/vi-discussion-and-implications-how-early-spatial-skills-predict-later-spatial-and-mathematical-skills
#12
Brian N Verdine, Roberta Michnick Golinkoff, Kathy Hirsh-Pasek, Nora S Newcombe
No abstract text is available yet for this article.
March 2017: Monographs of the Society for Research in Child Development
https://www.readbyqxmd.com/read/28181246/ii-methods-for-longitudinal-study-of-preschool-spatial-and-mathematical-skills
#13
Brian N Verdine, Roberta Michnick Golinkoff, Kathy Hirsh-Pasek, Nora S Newcombe
No abstract text is available yet for this article.
March 2017: Monographs of the Society for Research in Child Development
https://www.readbyqxmd.com/read/28181245/iii-results-considering-the-2-d-and-3-d-trials-of-the-tosa-separately-and-together
#14
Brian N Verdine, Roberta Michnick Golinkoff, Kathy Hirsh-Pasek, Nora S Newcombe
No abstract text is available yet for this article.
March 2017: Monographs of the Society for Research in Child Development
https://www.readbyqxmd.com/read/28130451/structural-basis-for-the-lesion-scanning-mechanism-of-the-muty-dna-glycosylase
#15
Lan Wang, Srinivas Chakravarthy, Gregory L Verdine
The highly mutagenic A:8-oxoguanine (oxoG) base pair is generated mainly by misreplication of the C:oxoG base pair, the oxidation product of the C:G base pair. The A:oxoG base pair is particularly insidious because neither base in it carries faithful information to direct the repair of the other. The bacterial MutY (MUTYH in humans) adenine DNA glycosylase is able to initiate the repair of A:oxoG by selectively cleaving the A base from the A:oxoG base pair. The difference between faithful repair and wreaking mutagenic havoc on the genome lies in the accurate discrimination between two structurally similar base pairs: A:oxoG and A:T...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28076787/impdh2-is-an-intracellular-target-of-the-cyclophilin-a-and-sanglifehrin-a-complex
#16
Khian Hong Pua, Dylan T Stiles, Mathew E Sowa, Gregory L Verdine
Natural products have demonstrated utility in the clinic and can also act as probes to understand complex cellular pathways. Sanglifehrin A (SFA) is a mixed polyketide and non-ribosomal peptide synthase natural product with sub-nano-molar affinity for its receptor cyclophilin A (PPIA). It has been shown to behave in vitro as an immune suppressant. Here, we identify inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) as an intracellular target of the PPIA-SFA binary complex. The formation of this ternary complex does not inhibit the enzymatic activity of IMPDH2...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28061412/nature-of-fly-ash-amendments-differently-influences-oxidative-stress-alleviation-in-four-forest-tree-species-and-metal-trace-element-phytostabilization-in-aged-contaminated-soil-a-long-term-field-experiment
#17
Sonia Labidi, Stéphane Firmin, Anthony Verdin, Géraldine Bidar, Frédéric Laruelle, Francis Douay, Pirouz Shirali, Joël Fontaine, Anissa Lounès-Hadj Sahraoui
Aided phytostabilization using coal fly ashes (CFAs) is an interesting technique to clean-up polluted soils and valorizing industrial wastes. In this context, our work aims to study the effect of two CFAs: silico-aluminous (CFA1) and sulfo-calcic (CFA2) ones, 10 years after their addition, on the phytostabilization of a highly Cd (cadmium), Pb (lead) and Zn (zinc) contaminated agricultural soil, with four forest tree species: Robinia pseudoacacia, Alnus glutinosa, Acer pseudoplatanus and Salix alba. To assess the effect of CFAs on trees, leaf fatty acid composition, malondialdehyde (MDA), oxidized and reduced glutathione contents ratio (GSSG: GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), Peroxidase (PO) and Superoxide dismutase (SOD) activities were examined...
April 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27978436/the-mtor-complex-controls-hiv-latency
#18
Emilie Besnard, Shweta Hakre, Martin Kampmann, Hyung W Lim, Nina N Hosmane, Alyssa Martin, Michael C Bassik, Erik Verschueren, Emilie Battivelli, Jonathan Chan, J Peter Svensson, Andrea Gramatica, Ryan J Conrad, Melanie Ott, Warner C Greene, Nevan J Krogan, Robert F Siliciano, Jonathan S Weissman, Eric Verdin
A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells...
December 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27914859/fine-and-ultrafine-atmospheric-particulate-matter-at-a-multi-influenced-urban-site-physicochemical-characterization-mutagenicity-and-cytotoxicity
#19
Yann Landkocz, Frédéric Ledoux, Véronique André, Fabrice Cazier, Paul Genevray, Dorothée Dewaele, Perrine J Martin, Capucine Lepers, Anthony Verdin, Lucie Courcot, Saâd Boushina, François Sichel, Maurizio Gualtieri, Pirouz Shirali, Dominique Courcot, Sylvain Billet
Particulate Matter (PM) air pollution is one of the major concerns for environment and health. Understanding the heterogeneity and complexity of fine and ultrafine PM is a fundamental issue notably for the assessment of PM toxicological effects. The aim of this study was to evaluate mutagenicity and cytotoxicity of a multi-influenced urban site PM, with or without the ultrafine fraction. For this purpose, PM2.5-0.3 (PM with aerodynamic diameter ranging from 0.3 to 2.5 μm) and PM2.5 were collected in Dunkerque, a French coastal industrial city and were extensively characterized for their physico-chemical properties, including inorganic and organic species...
February 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27843757/comparison-between-manual-and-automated-methods-for-ki-67-immunoexpression-quantification-in-ameloblastomas
#20
COMPARATIVE STUDY
Rogelio González-González, Nelly Molina-Frechero, Ramón G Carreón-Burciaga, Sandra López-Verdín, Carlos Robles-Bonilla, Vanesa Pereira-Prado, Ronell Bologna-Molina
Ameloblastoma is a common and unpredictable odontogenic tumor with high relapse rates. Several studies assessing the proliferative capacity of these neoplasms have been published, mainly using the protein Ki-67. Cell counts must be completed to determine the cell proliferation rate. Multiple methods have been developed for this purpose. The most widely used method is the labeling index, which has undergone changes over time to better facilitate cell counting. Here, we compared manual cell counting methods with automated cell counting (ImmunoRatio) to determine the relative effectiveness of these methods...
2016: Analytical Cellular Pathology (Amsterdam)
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