169,939 research outputs found
Semisynthetic derivatives of concanamycin A and C, as inhibitors of V- and P-type ATPases: Structure-activity investigations and developments of photoaffinity probes
No full textV-type ATPases are inhibited by the plecomacrolides bafilomycin and concanamycin, which exert their inhibitory potential at nanomolar concentrations. In addition, some P-type ATPases are inhibited at micromolar concentrations. We initiated intensive structure-activity investigations with semisynthetic concanamycin derivatives to approach the following two questions: (i) What is the pharmacophor, the structural key element, of the plecomacrolides that leads to their inhibitory potential against V- and P-type ATPases? (ii) Where is the binding site within these two different types of ATPases? In a first step, we examined where chemical modifications (O-acylations, substitutions, eliminations) could be placed without seriously affecting the inhibitory potential of the macrolides. In a second step, we used the knowledge of these structure-activity investigations to introduce traceable elements (fluorescent or radioactive) or nitrene-generating azido or carbene-generating diazirine-groups able to bind the inhibitors to their target covalently. These studies led finally to the synthesis of two photoaffinity probes that were used in labeling experiments with the purified plasma membrane V-type ATPase of Manduca sexta (described in a following paper, Huss, M., Gassel, M., Ingenhorst, G., Drose, S., Zeeck, A., Altendorf, K., Wieczorek, H., manuscript submitted)
Synthesis of a doubly labelled concanamycin derivative for ATPase binding studies
No full textThe synthesis of a doubly labelled concanamycin derivative for binding studies with V- and P-type ATPases is described. The starting point was 21-deoxyconcanolide A (6), which was generated from concanamycin A (1) in three steps and which exhibited the full ATPase inhibitor activity, with the advantage of a stability better than that of 1. Through use of a suitable protecting group for 6, the carbene-generating diazirine residue and I-125 were introduced regio- and stereo- selectively. The inhibitory efficacy of the resulting 23-iodo(I-125)-9-O-[p-(trifluoroethyldiazirinyl)benzoyl]-21,23- dideoxyconcanolide A (11b) turned out to be high enough for labelling studies. Photoaffinity labelling experiments clearly showed that 11b is a suitable derivative with which to determine the binding site of concanamycin-like compounds in different ATPases
Phenotype and SNP marker data for an intermediate wheatgrass (Thinopyrum intermedium) nested association mapping (NAM) population evaluated in St. Paul, MN and Salina, KS in 2017 and 2018
No full textPlease see the readme file for more information.An intermediate wheatgrass (Thinopyrum intermedium) Nested Association Mapping (NAM) population was evaluated at the University of Minnesota Agricultural Experiment Station in St. Paul, MN and The Land Institute in Salina, KS for two years (2017 and 2018). The population (n = 1,168 with both phenotype and genotype data) consisted of ten families where each progeny shares one common parent and was planted in a RCBD design with two blocks surrounded by a border plant. The phenotypic dataset includes 33 traits ranging from morphological, maturity, yield components and domestication traits, and a note column which indicates whether the plants were later identified as selfs and/or other observations. The genotype data was derived from genotyping by sequencing and includes over 8,000 SNP markers. The consensus genetic map was created in JoinMap and used for linkage mapping both within and combined across populations.Malone Family Foundation; Perennial Agriculture Project; The Land InstituteAltendorf, Kayla R; DeHaan, Lee R; Anderson, James A; Larson, Steven R. (2021). Phenotype and SNP marker data for an intermediate wheatgrass (Thinopyrum intermedium) nested association mapping (NAM) population evaluated in St. Paul, MN and Salina, KS in 2017 and 2018. Retrieved from the University Digital Conservancy, https://doi.org/10.13020/cnpv-kf72
A highly enantioselective receptor for N-protected glutamate and anomalous solvent-dependent binding properties
No full textJost M, Greie JC, Stemmer N, Wilking SD, Altendorf K, Sewald N. The first total synthesis of efrapeptin C. Angewandte Chemie International Edition. 2002;41(22):4267-4269
CadC-mediated activation of the cadBA promoter in Escherichia coli
No full textThe transcriptional activator CadC in Escherichia coli, a member of the ToxR-like proteins, activates transcription of the cadBA operon encoding the lysine decarboxylase CadA and the lysine-cadaverine antiporter CadB. cadBA is induced under conditions of acidic external pH and exogenous lysine; anoxic conditions raise the expression level up to 10 times. To characterize the binding mechanism of CadC, procedures for the purification of this membrane-integrated protein and its reconstitution into proteoliposomes were established. The binding sites of CadC upstream of the cadBA promoter region were determined by in vitro DNaseI protection analysis. Two regions were protected during DNaseI digestion, one from - 144 to - 112 bp, designated Cad1, and another one from - 89 to - 59 bp, designated Cad2. Binding of purified CadC to Cad1 and Cad2 was further characterized by DNA-binding assays, indicating that CadC was able to bind to both DNA fragments. Genetic analysis with promoter-lacZ fusions confirmed that both sites, Cad1 and Cad2, are essential for activation of cadBA transcription. Moreover, these experiments revealed that binding of H-NS upstream of the CadC-binding sites is necessary for repression of cadBA expression at neutral pH and under aerobic conditions. Based on these results, a model for transcriptional regulation of the cadBA operon is proposed, according to which H-NS is involved in the formation of a repression complex under non-inducing conditions. This complex is dissolved by binding of CadC to Cad1 under inducing conditions. Upon binding of CadC to Cad2 cadBA expression is activated. Copyright (C) 2005 S. Karger AG, Basel
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
ATP Synthesis Catalyzed by the ATP Synthase of Escherichia coli Reconstituted into Liposomes
No full textThe H+‐translocating F0F1‐ATPase from Escherichia coli (EF0F1) was purified and reconstituted into preformed reverse‐phase liposomes prepared from egg yolk phosphatidylcholine/phosphatidic acid. The EF0F1 liposomes were energized by an acid/base transition (pHout= 8.3; pHin= 5.0) and a superimposed K+/valinomycin diffusion potential ([K+]out= 100 mM; [K+]in= 0.6 mM) yielding a maximum rate (turnover number) of ATP synthesis of 27±8 mol ATP · molEF0F1−1· s−1), i.e. 27±8 s−1 This reaction was inhibited by NH4Cl or by addition of the F0F1, inhibitor N,N′‐dicyclohexylcarbodiimide. The rate of ATP synthesis measured as a function of the phosphate and ADP concentrations, can be described by Michaelis‐Menten kinetics with a Km of 0.7±0.2 mM for phosphate ([ADP] = 200 μM) and a Km, of 27±7 μM for ADP ([phosphate] = 5 mM), respectively. Copyright © 1994, Wiley Blackwell. All rights reserve
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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