Effects of defoliation at fruit set on vine physiology and berry composition in cabernet sauvignon grapevines

Grapevine canopy defoliation is a fundamentally important technique for the productivity and quality of grapes. Leaf removal is a pivotal operation on high-density vines which aims to improve air circulation, light exposure, and leaf gas exchange. The effects of leaf removal (LR) on vine physiology and berry composition in Cabernet Sauvignon grapevines were studied during the 2018–2019 growing season in the Bolgheri area, Tuscany, Italy. The basal leaves were removed at fruit set at two severity levels (removal of four basal leaves of each shoot (LR4) and removal of eight basal leaves (LR8)). The two treatments were compared with the not defoliated control (CTRL). The following physiological parameters of vines were measured: leaf gas exchange, leaf water potential, chlorophyll fluorescence and indirect chlorophyll content. The results showed that defoliation increased single leaf photosynthesis. In addition, qualitative grape parameters (phenolic and technological analyses) and daytime and night-time berry temperature were studied. The results showed that leaf removal had an impact on total soluble solids (°Brix), titratable acidity, and pH. The LR8-treated grapes had higher titratable acidity, while those in the LR4 treatment had higher °Brix and extractable anthocyanin and polyphenol content. Berry weight was not significantly influenced by the timing and severity of basal defoliation. Therefore, this research aims to investigate the effects of defoliation at the fruit set on vines performance

Density dependence of the extinction coefficient of a dispersion of spherical metal particles

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An autonomous, in situ light-dark bottle device for determining community respiration and net community production

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography-Methods 16 (2018): 323-338, doi:10.1002/lom3.10247.We describe a new, autonomous, incubation-based instrument that is deployed in situ to determine rates of gross community respiration and net community production in marine and aquatic ecosystems. During deployments at a coastal pier and in the open ocean, the PHORCYS (PHOtosynthesis and Respiration Comparison-Yielding System) captured dissolved oxygen fluxes over hourly timescales that were missed by traditional methods. The instrument uses fluorescence-quenching optodes fitted into separate light and dark chambers; these are opened and closed with piston-like actuators, allowing the instrument to make multiple, independent rate estimates in the course of each deployment. Consistent with other studies in which methods purporting to measure the same metabolic processes have yielded divergent results, respiration rate estimates from the PHORCYS were systematically higher than those calculated for the same waters using a traditional two-point Winkler titration technique. However, PHORCYS estimates of gross respiration agreed generally with separate incubations in bottles fitted with optode sensor spots. An Appendix describes a new method for estimating uncertainties in metabolic rates calculated from continuous dissolved oxygen data. Multiple successful, unattended deployments of the PHORCYS represent a small step toward fully autonomous observations of community metabolism. Yet the persistence of unexplained disagreements among aquatic metabolic rate estimates — such as those we observed between rates calculated with the PHORCYS and two existing, widely-accepted bottle-based methods — suggests that a new community intercalibration effort is warranted to address lingering sources of error in these critical measurements.This research was supported by the U.S. National Science Foundation (awards OCE-1155438 to B.A.S.V.M., J.R.V., and R.G.K., and OCE- 1059884 to B.A.S.V.M.), the Woods Hole Oceanographic Institution through a Cecil and Ida Green Foundation Innovative Technology Award and an Interdisciplinary Science Award, and a U.S. Environmental Protection Agency (EPA) STAR Graduate Fellowship to J.R.C. under Fellowship Assistance Agreement no. FP-91744301-0

Combined isosorbide dinitrate and ibuprofen as a novel therapy for muscular dystrophies : evidence from Phase I studies in healthy volunteers

We designed two Phase I studies that assessed healthy volunteers in order to evaluate the safety and to optimize the dosing of the combination of the drugs isosorbide dinitrate, a nitric oxide donor, and ibuprofen, a nonsteroidal antiinflammatory drug. We designed these studies with the aim of designing a Phase II trial to evaluate the drugs' efficacy in patients affected by Duchenne muscular dystrophy. For the first trial, ISOFEN1, a single-dose, randomized-sequence, open-label, active control, three-treatment cross-over study, was aimed at comparing the pharmacokinetics of ibuprofen 200 mg and isosorbide dinitrate 20 mg when given alone and concomitantly. The pharmacokinetics of ibuprofen given alone versus ibuprofen given concomitantly with isosorbide dinitrate were similar, as documented by the lack of statistically significant differences in the main drug's pharmacokinetic parameters (time to maximal concentration [Tmax], maximal concentration [Cmax], area under the curve [AUC]0-t, and AUC0- 1e). Similarly, we found that the coadministration of ibuprofen did not significantly affect the pharmacokinetics of isosorbide dinitrate. No issues of safety were detected. The second trial, ISOFEN2, was a single-site, dose titration study that was designed to select the maximum tolerated dose for isosorbide dinitrate when coadministered with ibuprofen. Eighteen out of the 19 enrolled subjects tolerated the treatment well, and they completed the study at the highest dose of isosorbide dinitrate applied (80 mg/day). One subject voluntarily decided to reduce the dose of isosorbide dinitrate from 80 mg to 60 mg. The treatment-related adverse events recorded during the study were, for the large majority, episodes of headache that remitted spontaneously in 0.5-1 hour - a known side effect of isosorbide dinitrate. These studies demonstrate that the combination of isosorbide dinitrate and ibuprofen does not lead to pharmacokinetic interactions between the two drugs; they also demonstrate that the combination of isosorbide dinitrate and ibuprofen has optimal tolerability and safety profiles that are similar to those previously reported for isosorbide dinitrate and ibuprofen given alone

The Phyre2 web portal for protein modeling, prediction and analysis

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

Low body weight in females is a risk factor for increased tenofovir exposure and drug-related adverse events

Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone diseases. Factors associated with these drug-related adverse events are poorly characterized. Our objective was to investigate such factors in patients treated long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with basal creatinine clearance >80 mL/min treated with tenofovir for at least 6 months and with at least one assessment of tenofovir plasma trough concentrations were considered. Tenofovir-associated adverse events were defined as the appearance of pathological proteinuria, worsening of renal function or bone demineralization. By multivariate regression analysis, we found that serum creatinine (p\u200a=\u200a0.003) and body weight (p\u200a=\u200a0.002) were the factors independently associated with plasma tenofovir concentrations. In particular, women with body weight50 Kg (160\ub193 vs.71\ub152 ng/mL, p<0.001). High tenofovir plasma trough concentrations and the age of the patients were independently associated with the development of drug-related kidney and bone toxicity. In this retrospective study we have shown that HIV-infected women with low body weight are at risk to be exposed to high tenofovir plasma trough concentrations, ultimately resulting in a significant hazard to develop long-term tenofovir complications

ePlant: Visualizing and Exploring Multiple Levels of Data for Hypothesis Generation in Plant Biology

A big challenge in current systems biology research arises when different types of data must be accessed from separate sources and visualized using separate tools. The high cognitive load required to navigate such a workflow is detrimental to hypothesis generation. Accordingly, there is a need for a robust research platform that incorporates all data and provides integrated search, analysis, and visualization features through a single portal. Here, we present ePlant (http://bar.utoronto.ca/eplant), a visual analytic tool for exploring multiple levels of Arabidopsis thaliana data through a zoomable user interface. ePlant connects to several publicly available web services to download genome, proteome, interactome, transcriptome, and 3D molecular structure data for one or more genes or gene products of interest. Data are displayed with a set of visualization tools that are presented using a conceptual hierarchy from big to small, and many of the tools combine information from more than one data type. We describe the development of ePlant in this article and present several examples illustrating its integrative features for hypothesis generation. We also describe the process of deploying ePlant as an “app” on Araport. Building on readily available web services, the code for ePlant is freely available for any other biological species research

The sub-seasonal to seasonal prediction (S2S) project database

A database containing sub-seasonal to seasonal forecasts from 11 operational centres is available to the research community and will help advance our understanding of the sub-seasonal to seasonal time range. Demands are growing rapidly in the operational prediction and applications communities for forecasts that fill the gap between medium-range weather and long-range or seasonal forecasts. Based on the potential for improved forecast skill at the sub-seasonal to seasonal time range, a sub-seasonal prediction (S2S) research project has been established by the World Weather Research Program/World Climate Research Program. A main deliverable of this project is the establishment of an extensive database, containing sub-seasonal (up to 60 days) forecasts, 3-weeks behind real-time, and reforecasts from 11 operational centers, modelled in part on the THORPEX Interactive Grand Global Ensemble (TIGGE) database for medium range forecasts (up to 15 days). The S2S database, available to the research community since May 2015, represents an important tool to advance our understanding of the sub-seasonal to seasonal time range that has been considered for a long time as a “desert of predictability”. In particular, this database will help identify common successes and shortcomings in the model simulation and prediction of sources of sub-seasonal to seasonal predictability. For instance, a preliminary study suggests that the S2S models underestimate significantly the amplitude of the Madden Julian Oscillation (MJO) teleconnections over the Euro-Atlantic sector. The S2S database represents also an important tool for case studies of extreme events. For instance, a multi-model combination of S2S models displays higher probability of a landfall over Vanuatu islands 2 to 3 weeks before tropical cyclone Pam devastated the islands in March 2015

Structures of Helicobacter pylori Shikimate Kinase Reveal a Selective Inhibitor-Induced-Fit Mechanism

Shikimate kinase (SK), which catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP, is the enzyme in the fifth step of the shikimate pathway for biosynthesis of aromatic amino acids. This pathway is present in bacteria, fungi, and plants but absent in mammals and therefore represents an attractive target pathway for the development of new antimicrobial agents, herbicides, and antiparasitic agents. Here we investigated the detailed structure–activity relationship of SK from Helicobacter pylori (HpSK). Site-directed mutagenesis and isothermal titration calorimetry studies revealed critical conserved residues (D33, F48, R57, R116, and R132) that interact with shikimate and are therefore involved in catalysis. Crystal structures of HpSK·SO4, R57A, and HpSK•shikimate-3-phosphate•ADP show a characteristic three-layer architecture and a conformationally elastic region consisting of F48, R57, R116, and R132, occupied by shikimate. The structure of the inhibitor complex, E114A•162535, was also determined, which revealed a dramatic shift in the elastic LID region and resulted in conformational locking into a distinctive form. These results reveal considerable insight into the active-site chemistry of SKs and a selective inhibitor-induced-fit mechanism