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991.
Siem Jakob Veenstra Heinrich Rueeger Markus Voegtle Rainer Lueoend Philipp Holzer Konstanze Hurth Marina Tintelnot-Blomley Mathias Frederiksen Jean-Michel Rondeau Laura Jacobson Matthias Staufenbiel Ulf Neumann Rainer Machauer 《Bioorganic & medicinal chemistry letters》2018,28(12):2195-2200
New amino-1,4-oxazine derived BACE-1 inhibitors were explored and various synthetic routes developed. The binding mode of the inhibitors was elucidated by co-crystallization of 4 with BACE-1 and X-ray analysis. Subsequent optimization led to inhibitors with low double digit nanomolar activity in a biochemical and single digit nanomolar potency in a cellular assays. To assess the inhibitors for their permeation properties and potential to cross the blood-brain-barrier a MDR1-MDCK cell model was successfully applied. Compound 8a confirmed the in vitro results by dose-dependently reducing Aβ levels in mice in an acute treatment regimen. 相似文献
992.
Gabriele Murineddu Francesco Deligia Giulio Ragusa Laura García-Toscano María Gómez-Cañas Battistina Asproni Valentina Satta Elena Cichero Ruth Pazos Paola Fossa Giovanni Loriga Javier Fernández-Ruiz Gerard A. Pinna 《Bioorganic & medicinal chemistry》2018,26(1):295-307
A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB1 receptors (Ki values of 44.6?nM for CB1 receptors and >40?μM for CB2 receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB1 receptors with Ki values of 75.5 and 73.2?nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB1 receptor in the [35S]-GTPγS binding assays, and none showed adequate predictive blood–brain barrier permeation, exhibiting low estimated LD50. However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB1 receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist. 相似文献
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995.
Two new species of Phyllonema (Rivulariaceae,Cyanobacteria) with an emendation of the genus 下载免费PDF全文
Laura González‐Resendiz Jeffrey R. Johansen Viviana Escobar‐Sánchez Claudia Segal‐Kischinevzky Luis F. Jiménez‐García Hilda León‐Tejera 《Journal of phycology》2018,54(5):638-652
Two untapered, heterocytous species were observed and collected from the intertidal and supratidal zones of the Mexican coastline of the Pacific Ocean near Oaxaca and from the Gulf of Mexico. These populations were highly similar in morphology to the freshwater taxon Petalonema incrustans in the Scytonemataceae. However, 16S rRNA sequence data and phylogenetic analysis indicated that they were sister taxa to the epiphyllic, Brazilian species Phyllonema aveceniicola in the Rivulariaceae, described from culture material. While genetic identity between the two new species was high, they differed significantly in morphology, 16S rRNA gene sequence identity, and sequence and structure of the 16S–23S ITS region. Their morphology differed markedly from the generitype of the previously monotypic Phyllonema, which has tapered, heteropolar, single‐false branched trichomes with very thin or absent sheath. The two new species, Phyllonema ansata and Phyllonema tangolundensis, described from both culture and environmental material, have untapered, isopolar, geminately false branched trichomes with thick, lamellated sheaths, differences so significant that the species would not be placed in Phyllonema without molecular corroboration. The morphological differences are so significant that a formal emendation of the genus is required. These taxa provide a challenge to algal taxonomy because the morphological differences are such that one would logically conclude that they represent different genera, but the phylogenetic evidence for including them all in the same genus is conclusive. This conclusion is counter to the current trend in algal taxonomy in which taxa with minor morphological differences have been repeatedly placed in separate genera based primarily upon DNA sequence evidence. 相似文献
996.
Biswapriya B. Misra Ram P. Upadhayay Laura A. Cox Michael Olivier 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):75
Introduction
Metabolomics is a promising approach for discovery of relevant biomarkers in cells, tissues, organs, and biofluids for disease identification and prediction. The field has mostly relied on blood-based biofluids (serum, plasma, urine) as non-invasive sources of samples as surrogates of tissue or organ-specific conditions. However, the tissue specificity of metabolites pose challenges in translating blood metabolic profiles to organ-specific pathophysiological changes, and require further downstream analysis of the metabolites.Objectives
As part of this project, we aim to develop and optimize an efficient extraction protocol for the analysis of kidney tissue metabolites representative of key primate metabolic pathways.Methods
Kidney cortex and medulla tissues of a baboon were homogenized and extracted using eight different extraction protocols including methanol/water, dichloromethane/methanol, pure methanol, pure water, water/methanol/chloroform, methanol/chloroform, methanol/acetonitrile/water, and acetonitrile/isopropanol/water. The extracts were analyzed by a two-dimensional gas chromatography time-of-flight mass-spectrometer (2D GC–ToF-MS) platform after methoximation and silylation.Results
Our analysis quantified 110 shared metabolites in kidney cortex and medulla tissues from hundreds of metabolites found among the eight different solvent extractions spanning low to high polarities. The results revealed that medulla is metabolically richer compared to the cortex. Dichloromethane and methanol mixture (3:1) yielded highest number of metabolites across both the tissue types. Depending on the metabolites of interest, tissue type, and the biological question, different solvents can be used to extract specific groups of metabolites.Conclusion
This investigation provides insights into selection of extraction solvents for detection of classes of metabolites in renal cortex and medulla, which is fundamentally important for identification of prognostic and diagnostic metabolic kidney biomarkers for future therapeutic applications.997.
Francisco J. García-De León Andrés I. Hernández Sandoval Fernando Contreras-Catala Laura Sánchez-Velasco Gorgonio Ruiz-Campos 《Environmental Biology of Fishes》2018,101(1):167-180
A priority issue in ecology and biogeography is understanding the patterns in species diversity and the causal factors of their distribution, which allows the generation of information for conservation strategies. The longitudinal distribution of fishes and their relationships with environmental variables were studied in the Guayalejo-Río Tamesí system (northeastern Mexico) from February 2000 to July 2001. A total of 5918 fish were caught in 27 collections along an altitudinal gradient in the main river course, from high mountain (1500 masl) to coastal plain near Tampico. Forty-three native and five exotic species, belonging to 35 genera in 23 families, were identified. Cluster analyses identified four major fish habitats in the river system. A distinctive euryhaline marine fish habitat (1) occurs near the mouth with native and two exotic species. Two other habitats consist essentially of freshwater fish species that are distributed along the longitudinal gradient. One of these habitats (habitat 4) shows greater diversity, as per the Shannon index value, and also includes amphidromous fish, in addition to two exotic freshwater fish; the other (habitat 2) includes freshwater, euryhaline and three exotic species. The changes in the frequency of occurrence and the abundance of Gambusia vittata, Astyanax mexicanus, and Xiphophorus variatus contribute to explaining differences between these habitats. Another habitat (3) is represented by two sampling sites located near the mouth and consist of freshwater and euryhaline fish and three exotic cyprinids with broad salinity tolerance. The low abundance and richness of exotic species suggest little impact on native fish fauna in this river. The fish assemblage of the Guayalejo-Tamesí river system species changes along a longitudinal gradient with the addition, replacement and presence of indicator species. Upstream fish fauna is mostly composed of freshwater species, some of them generalists that inhabit the entire longitudinal gradient, others that are restricted to certain sites, and the remainder of species is an assemblage composed of a mixture of euryhaline freshwater and marine species near the mouth. 相似文献
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999.
Margarita Stritzler Ana Diez Tissera Gabriela Soto Nicolás Ayub 《Biotechnology letters》2018,40(9-10):1419-1423
Objectives
Identification of novel microbial factors contributing to plant protection against abiotic stress.Results
The genome of plant growth-promoting bacterium Pseudomonas fluorescens FR1 contains a short mobile element encoding a novel type of extracellular polyhydroxybutyrate (PHB) polymerase (PhbC) associated with a type I secretion system. Genetic analysis using a phbC mutant strain and plants showed that this novel extracellular enzyme is related to the PHB production in planta and suggests that PHB could be a beneficial microbial compound synthesized during plant adaptation to cold stress.Conclusion
Extracellular PhbC can be used as a new tool for improve crop production under abiotic stress.1000.
Maternal Metabolic Health Parameters During Pregnancy in Relation to Early Childhood BMI Trajectories 下载免费PDF全文