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281.
John A. Lawson Edward T. Uyeno John Nienow Gilda H. Loew Lawrence Toll 《Life sciences》1984,34(21):2007-2013
A number of β-carboline analogs have been obtained or synthesized, and their receptor affinities and antagonist activities determined. The choice of analogs was made in order to explore the importance of the N9-H, the aromatic nitrogen and the C3-ester moiety for high-receptor affinity and antagonist activity of this class of benzodiazepine antagonist. Among the analogs investigated, we describe the properties of 3-cyano-β-carboline (), the first potent β-carboline antagonist without a carbonyl at the C3-position.The results obtained indicate: (1) Specific interactions of the C3-substituent with key cationic receptor sites rather than electron-withdrawing properties are important for high-receptor affinity and antagonist activity. (2) Specific in-plane interactions of the atomatic nitrogen with a cationic receptor site, rather than stacking with neutral aromatic residues of the receptor are also important for high affinity and antagonist activity. (3) While the presence of an N9H enhances receptor affinity, interaction with an anionic receptor site does not appear essential for antagonist activity. 相似文献
282.
Scott Michael Taylor Ellis R. Loew Michael S. Grace 《Environmental Biology of Fishes》2011,92(4):513-523
The nature and distributions of photoreceptor cell types were investigated in the retinas of 12 species (5 families) of elopomorph
anguilliform leptocephalus larvae. Anti-opsin immunofluorescence, light microscopy and transmission electron microscopy (TEM)
were used to assess opsin distribution across the retinas and to associate photoreceptor morphology and opsin content. Retinas
of all species were immunoreactive with anti-rhodopsin throughout, while anti-cone opsin immunoreactivity was restricted only
to the ventral region of the retina in all specimens. Rod and cone photoreceptors were morphologically indistinguishable at
low magnifications; TEM revealed that nearly all photoreceptors had rod-like ultrastructure, with only rare examples of cone-like
cells identified in the ventral retina. These results indicate a rhodopsin/rod-dominated retina in leptocephalus larvae of
anguilliform eels in the teleost subdivision Elopomorpha, contrasting with the cone-dominated retinas of nearly all other
species of teleost larvae. This distinctive developmental pattern shared among elopomorph larvae has important evolutionary
and ecological implications, indicating a shared ancestor and/or ecological characteristics that are very different from most
other teleost larvae. 相似文献
283.
In the context of the bay region, K-region and radical cation hypotheses for polycyclic aromatic carcinogens, molecular properties were calculated for fourteen methyl derivatives of benz[a]anthracene (BA) related to (1) intrinsic substrate reactivities towards activating and detoxifying metabolism and (2)-the stabilities of the putative carbocation ultimate carcinogens. Allvalence electron methods were used, avoiding the inherent difficulties found in the π-electron methods. The calculated substrate reactivities were found to predict major metabolites sucessfully, supporting the validity of their use in attempted correlations with observed carcinogenic potencies. Positive correlations were found between observed carcinogenic potencies and (1) the reactivities of the parent polycyclic aromatic hydrocarbons (PAH) towards the initial distal bay region epoxidation and (2) the stabilities of the diol epoxide carbocations. This latter correlation holds when both the methyl derivatives of BA and previously studied unsubstituted PAH are considered together, indicating its potential usefulness as a screening parameter for carcinogenic activity. 相似文献
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Cristina Chiva Teresa Mendes Maia Christian Panse Karel Stejskal Thibaut Douch Mariette Matondo Damarys Loew Dominic Helm Mandy Rettel Karl Mechtler Francis Impens Paolo Nanni Anna Shevchenko Eduard Sabid 《EMBO reports》2021,22(6)
Proteomics research infrastructures and core facilities within the Core for Life alliance advocate for community policies for quality control to ensure high standards in proteomics services. Core facilities and research infrastructures have become an essential part of the scientific ecosystem. In the field of proteomics, national and international networks and research platforms have been established during the past decade that are supposed to set standards for high‐quality services, promote an exchange of professional information, and enable access to cutting‐edge, specialized proteomics technologies. Either centralized or distributed, these national and international proteomics infrastructures and technology platforms are generating massive amounts of data for the research community, and support a broad range of translational, computational and multi‐omics initiatives and basic research projects.By delegating part of their work to these services, researchers expect that the core facility adjusts their analytical protocols appropriately for their project to acquire data conforming best research practice of the scientific community. The implementation of quality assessment measures and commonly accepted quality controls in data generation is therefore crucially important for proteomics research infrastructures and the scientists who rely on them.However, current quality control and quality assessment procedures in proteomics core facilities and research infrastructures are a motley collection of protocols, standards, reference compounds and software tools. Proteomics relies on a customized multi‐step workflow typically consisting of sample preparation, data acquisition and data processing, and the implementation of each step differs among facilities. For example, sample preparation involves enzymatic digestion of the proteins, which can be performed in‐solution, in‐gel, or on‐beads, with often different proteolytic enzymes, chemicals, and conditions among laboratories. Data acquisition protocols are often customized to the particular instrument set up, and the acquired spectra and chromatograms are processed by different software tools provided by equipment vendors, third parties or developed in‐house.
…current quality control and quality assessment procedures in proteomics core facilities and research infrastructures are a motley collection of protocols, standards, reference compounds and software tools.Moreover, core facilities implement their own guidelines to monitor the performance and quality of the entire workflow, typically utilizing different commercially available standards such as pre‐digested cell lysates, recombinant proteins, protein mixtures, or isotopically labeled peptides. Currently, there is no clear consensus on if, when and how to perform quality control checks. There is even less quality control in walk‐in facilities, where the staff is only responsible for correct usage of the instruments and users select and execute the analytical workflow themselves. It is not surprising therefore that instrument stability and robustness of the applied analytical approach are often unclear, which compromises analytical rigor. 相似文献
288.
Properties of six chloroethylenes which could serve as indicators of their relative metabolic behavior and carcinogenic activity have been calculated using Modified Neglect of Diatomic Overlap (MNDO), a semiempirical, all valence electron, molecular orbital method. Possible pathways of transformation of parent compounds to acylchlorides, chloroaldehydes and epoxides — their putative ultimate carcinogens — were considered, and heats of formation and relative stabilities of intermediates were calculated. Our results indicate that carbonyl compounds could be formed with and without the intermediacy of epoxides, suggesting the possibility of more than one pathway in activation of parent compounds. Electronic properties of carbonyl products and epoxide carbocations, putative ultimate carcinogens which could serve as indicators of their relative electrophilicities, were also calculated. The results obtained indicated that the relative extent of metabolism to carbonyl products, rather than their electrophilicity, is a determinant of the relative carcinogenic activity of the parent compound. Of the various thermodynamic criteria investigated, four were found to be indicators of both relative metabolic behavior and carcinogenic activity. 相似文献
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