1,704 research outputs found
Oligostilbenes from Vitis heyneana
No full textA novel tetrastilbene, heyneanol A, was isolated from stems of Vitis heyneana together with the previously known ampelopsin C, ampelopsin A and (+)-epsilon-viniferin. Its complex polycyclic structure was elucidated by 1D and 2D NMR analyses
WW Domain Proteins in Signaling, Cancer Growth, Neural Diseases, and Metabolic Disorders
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Characterization of water and wildlife strains as a subgroup of Campylobacter jejuni using DNA microarrays.
No full textCampylobacter jejuni is the leading cause of human bacterial gastroenteritis worldwide, but source attribution of the organism is difficult. Previously, DNA microarrays were used to investigate isolate source, which suggested a non-livestock source of infection. In this study we analysed the genome content of 162 clinical, livestock and water and wildlife (WW) associated isolates combined with the previous study. Isolates were grouped by genotypes into nine clusters (C1 to C9). Multilocus sequence typing (MLST) data demonstrated that livestock associated clonal complexes dominated clusters C1-C6. The majority of WW isolates were present in the C9 cluster. Analysis of previously reported genomic variable regions demonstrated that these regions were linked to specific clusters. Two novel variable regions were identified. A six gene multiplex PCR (mPCR) assay, designed to effectively differentiated strains into clusters, was validated with 30 isolates. A further five WW isolates were tested by mPCR and were assigned to the C7-C9 group of clusters. The predictive mPCR test could be used to indicate if a clinical case has come from domesticated or WW sources. Our findings provide further evidence that WW C. jejuni subtypes show niche adaptation and may be important in causing human infection
Search for Higgs boson pairs decaying to WW*WW*, WW*ττ, and ττττ in proton-proton collisions at = 13 TeV
No full textThe results of a search for Higgs boson pair (HH) production in the WW*WW*, WW*ττ, and ττττ decay modes are presented. The search uses 138 fb−1 of proton-proton collision data recorded by the CMS experiment at the LHC at a center-of-mass energy of 13 TeV from 2016 to 2018. Analyzed events contain two, three, or four reconstructed leptons, including electrons, muons, and hadronically decaying tau leptons. No evidence for a signal is found in the data. Upper limits are set on the cross section for nonresonant HH production, as well as resonant production in which a new heavy particle decays to a pair of Higgs bosons. For nonresonant production, the observed (expected) upper limit on the cross section at 95% confidence level (CL) is 21.3 (19.4) times the standard model (SM) prediction. The observed (expected) ratio of the trilinear Higgs boson self-coupling to its value in the SM is constrained to be within the interval −6.9 to 11.1 (−6.9 to 11.7) at 95% CL, and limits are set on a variety of new-physics models using an effective field theory approach. The observed (expected) limits on the cross section for resonant HH production range from 0.18 to 0.90 (0.08 to 1.06) pb at 95% CL for new heavy-particle masses in the range 250–1000 GeV. © The Author(s) 2023.T
Rise and fall of SARS-CoV-2 variants in Rotterdam: Comparison of wastewater and clinical surveillance
No full textMonitoring of SARS-CoV-2 in wastewater (WW) is a promising tool for epidemiological surveillance, correlating not only viral RNA levels with the infection dynamics within the population, but also to viral diversity. However, the complex mixture of viral lineages in WW samples makes tracking of specific variants or lineages circulating in the population a challenging task. We sequenced sewage samples of 9 WW-catchment areas within the city of Rotterdam, used specific signature mutations from individual SARS-CoV-2 lineages to estimate their relative abundances in WW and compared them against those observed in clinical genomic surveillance of infected individuals between September 2020 and December 2021. We showed that especially for dominant lineages, the median of the frequencies of signature mutations coincides with the occurrence of those lineages in Rotterdam's clinical genomic surveillance. This, along with digital droplet RT-PCR targeting signature mutations of specific variants of concern (VOCs), showed that several VOCs emerged, became dominant and were replaced by the next VOC in Rotterdam at different time points during the study. In addition, single nucleotide variant (SNV) analysis provided evidence that spatio-temporal clusters can also be discerned from WW samples. We were able to detect specific SNVs in sewage, including one resulting in the Q183H amino acid change in the Spike gene, that was not captured by clinical genomic surveillance. Our results highlight the potential use of WW samples for genomic surveillance, increasing the set of epidemiological tools to monitor SARS-CoV-2 diversity.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Sanitary Engineerin
Folding mechanisms of individual β-hairpins in a Gō model of Pin1 WW domain by all-atom molecular dynamics simulations
No full textThis paper examines the folding mechanism of an individual ߭hairpin in the presence of other hairpins by using an off-lattice model of a small triple-stranded antiparallel ߭sheet protein, Pin1 WW domain. The turn zipper model and the hydrophobic collapse model originally developed for a single ߭hairpin in literature is confirmed to be useful in describing ߭hairpins in model Pin1 WW domain. We find that the mechanism for folding a specific hairpin is independent of whether it folds first or second, but the formation process are significantly dependent on temperature. More specifically, ߱-߲ hairpin folds via the turn zipper model at a low temperature and the hydrophobic collapse model at a high temperature, while the folding of ߲-߳ hairpin follows the turn zipper model at both temperatures. The change in folding mechanisms is interpreted by the interplay between contact stability (enthalpy) and loop lengths (entropy), the effect of which is temperature dependent.No Full Tex
U24 from Roseolovirus interactions with WW Domains: Canonical vs Non-Canonical
No full textU24 is a C-terminal membrane-anchored protein found in both Human Herpes Virus type 6 and 7 (HHV-6 and HHV-7), with an N-terminal segment that is rich in prolines (PPxY motif in both HHV-6A and 7; PxxP motif in HHV-6A). Previous work has shown that U24 interacts strongly with Nedd4 WW domains, in particular hNedd4L-WW3*. It was also shown that this interaction depends strongly on the nature of the amino acids that are upstream from the PY motif in U24. In this contribution, data was obtained from pull-downs, isothermal titration calorimetry, and NMR to further determine what modulates U24:WW domain interactions. Specifically, three non-canonical WW domains from human Smad ubiquitination regulatory factor (Smurf), namely hSmurf2-WW2, hSmurf2-WW3, and a tandem construct hSmurf2-WW2+3, were studied. Overall, the interactions between U24 and these Smurf WW domains were found to be weaker than those in U24:Nedd4 WW domain pairs, suggesting that U24 function is tightly linked to specific E3 ubiqitin ligases.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Glycan-Cyanovirin-N Interactions and Designed WW Domains: Combining Experimental and Computational Studies
No full textabstract: Cyanovirin-N (CVN) is a cyanobacterial lectin with potent anti-HIV activity, mediated by binding to the N-linked oligosaccharide moiety of the envelope protein gp120. CVN offers a scaffold to develop multivalent carbohydrate-binding proteins with tunable specificities and affinities. I present here biophysical calculations completed on a monomeric-stabilized mutant of cyanovirin-N, P51G-m4-CVN, in which domain A binding activity is abolished by four mutations; with comparisons made to CVNmutDB, in which domain B binding activity is abolished. Using Monte Carlo calculations and docking simulations, mutations in CVNmutDB were considered singularly, and the mutations E41A/G and T57A were found to impact the affinity towards dimannose the greatest. 15N-labeled proteins were titrated with Manα(1-2)Manα, while following chemical shift perturbations in NMR spectra. The mutants, E41A/G and T57A, had a larger Kd than P51G-m4-CVN, matching the trends predicted by the calculations. We also observed that the N42A mutation affects the local fold of the binding pocket, thus removing all binding to dimannose. Characterization of the mutant N53S showed similar binding affinity to P51G-m4-CVN. Using biophysical calculations allows us to study future iterations of models to explore affinities and specificities. In order to further elucidate the role of multivalency, I report here a designed covalent dimer of CVN, Nested cyanovirin-N (Nested CVN), which has four binding sites. Nested CVN was found to have comparable binding affinity to gp120 and antiviral activity to wt CVN. These results demonstrate the ability to create a multivalent, covalent dimer that has comparable results to that of wt CVN.
WW domains are small modules consisting of 32-40 amino acids that recognize proline-rich peptides and are found in many signaling pathways. We use WW domain sequences to explore protein folding by simulations using Zipping and Assembly Method. We identified five crucial contacts that enabled us to predict the folding of WW domain sequences based on those contacts. We then designed a folded WW domain peptide from an unfolded WW domain sequence by introducing native contacts at those critical positions.Dissertation/ThesisDoctoral Dissertation Biochemistry 201
Jewish issue in the Czechoslovak military units in the WW II
No full textBy the birth and during the existence of the Czechoslovak military units abroad during the WW II, the ratio of Jewish volunteers was relatively a high one, as the author presumes. The paper submitted aims to present the problem derived thereof. These should not be simply reduced to the anti-Semite manifestations; here, the major approaches to their resolving are studied, both on the part of the Jewish soldiers as well as on behalf of the military and exile administration
Waterbeweging en menging in het zuidelijke gedeelte van de Noordzee: Eindverslag MLTP-4
No full textOnderzoek is verricht naar verspreidingsmodellen en de gebruikte technieken achter deze modellen. Bij aanvang van de MLTP-periode bestonden er reeds verspreidingsmodellen. Deze modellen vertoonden echter tekortkomingen. De voornaamste daarvan waren: 1)het summiere gebruik van snelheidsgegevens, 2)de sterk vereenvoundige geometrie. Op geen van beide punten is een belangrijke verbetering mogelijk zonder ook het andere punt aan te pakken. De integratie van deze beide elementen in het geheel van de simulatie, diende dus, wat het einddoel van de thematiek betreft, het uitgangspunt te zijn. Wat de waterbeweging betreft ligt het zwaartepunt bij de reststromen, daar de getijbeweging onderwerp van studie was in de thematiek. Verder zijn de getijstromen en vooral de snelheidsgegevens uit modellen die (mede) het getij berekenen van zodanig groot belang voor de verspreidingsprocessen en de modellering daarvan, dat afzonderlijk aandacht wordt besteed aan waterbewegingsmodellen die mede of in hoofdzaak gericht zijn op getijberekening. Tenslotte is er aandacht besteed aan de verspreidingsverschijnselen en de verspreidingsmodellen, welke laatste het einddoel vormen van de thematiek. Als belangrijkste aanbevelingen komen naar voren: 1. Het bevorderen van een versnelling van de bouw van programmatuur voor een verspreidingsmodel op basis van deeltjessimulatie, met inbegrip van de wederzijdse aanpassing van de toeleverende bewegingsmodellen (getijmodellen, stormvloedmodellen) enerzijds en verspreidingsmodel anderzijds. In verband met de "voeding" van het bovenbedoelde model en eventuele andere transportmodellen moet er rekening gehouden worden met: - Voortzetting van het onderzoek naar het reststroomveld en de mogelijkheden van wiskundige modellering daarvan, i.h.b. van de niet-meteo-komponenten. - Voltooiing van het op initiatief van MLTP-4 (zie Texel 1974) gestarte project Numerieke Diepteschematisatie. 2. Vergelijkend onderzoek, vooral uit het oogpunt van rekentijden, kosten en doelmatigheid, van deeltjessimulatie en eindige differentie- of eindige elementenmethoden voor het oplossen van transportproblemen in kombinatie met interakties (met name chemische reakties).MLTP-
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