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111.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):1274-1290
4-(4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylamino]phenyl)-4-oxo-butyric acid (V), 4-(3- & 4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylaminophenyl]-2-aryl-4-oxo-butyric acids (Xa–e) and 4-(2-alkyl-2-[N-3-(3,5-dibromo-4-hydroxyphenyl)-1-carboxy-3-oxo-propylamino]acetamido) benzoate esters (XVa–e) were designed, synthesized and biologically evaluated as anti-HCV for genotypes 1b and 4a. The design was based on their docking scores with HCV NS3/4A protease-binding site of the genotype 1b (1W3C), which is conserved in the genotype 4a structure. The docking scores predicted that most of these molecules have higher affinity to the HCV NS3/4A enzyme more than Indoline lead. These compounds were synthesized and evaluated for their cytopathic inhibitory activity against RAW HCV cell cultures of genotype 4a and also examined against Huh 5–2 HCV cell culture of genotype 1b, utilizing Luciferase and MTS assays. Compounds Xa and Xb have 95 and 80% of the activity of Ribavirin against genotype 4a and compounds XVa, XVb and XVd exerted high percentage inhibitory activity against genotype 1b equal 87.7, 84.3 and 82.8%, respectively, with low EC50 doses. 相似文献
112.
Lewis D. Pennington Douglas A. Whittington Michael D. Bartberger Steven R. Jordan Holger Monenschein Thomas T. Nguyen Bryant H. Yang Qiufen M. Xue Filisaty Vounatsos Robert C. Wahl Kui Chen Stephen Wood Martin Citron Vinod F. Patel Stephen A. Hitchcock Wenge Zhong 《Bioorganic & medicinal chemistry letters》2013,23(15):4459-4464
We describe a systematic study of how macrocyclization in the P1–P3 region of hydroxyethylamine-based inhibitors of β-site amyloid precursor protein (APP)-cleaving enzyme (BACE1) modulates in vitro activity. This study reveals that in a number of instances macrocyclization of bis-terminal dienes leads to improved potency toward BACE1 and selectivity against cathepsin D (CatD), as well as greater amyloid β-peptide (Aβ)-lowering activity in HEK293T cells stably expressing APPSW. However, for several closely related analogs the benefits of macrocyclization are attenuated by the effects of other structural features in different regions of the molecules. X-ray crystal structures of three of these novel macrocyclic inhibitors bound to BACE1 revealed their binding conformations and interactions with the enzyme. 相似文献
113.
石羊河流域武威绿洲春玉米水氮耦合效应 总被引:3,自引:0,他引:3
为探讨西北旱区春玉米最佳的水氮耦合模式,在甘肃石羊河流域武威绿洲边缘进行田间正交试验,研究不同生育阶段水量分配及施氮量对春玉米群体产量和水氮利用的影响.结果表明:石羊河流域武威绿洲春玉米籽粒产量随施氮量的增加而增加;施氮量为300 kg·hm-2、拔节期灌水136 mm时的籽粒产量最大.籽粒灌溉水利用效率随灌水量的增加而降低;全生育期灌水340 mm时增施氮肥可使籽粒产量和籽粒灌溉水利用效率同时提高;施氮量为300 kg·hm-2、苗期和灌浆期分别灌水34 mm时籽粒灌溉水利用效率最大.各因素对玉米植株全氮累积总量的影响由大到小依次为:施氮量、拔节期灌水、苗期灌水、灌浆期灌水和抽穗期灌水.石羊河流域武威绿洲春玉米水氮耦合最佳模式为:施氮量300 kg·hm-2,苗期、拔节期、抽穗期和灌浆期分别灌水34、136、68和102 mm. 相似文献
114.
AbstractThe Neogene Fortuna Basin (Murcia Region, SE Spain) is rich in microvertebrate sites. Its continental sections include localities extended from the middle Turolian (MN12) to the early Ruscinian (MN14). However, there are few works dealing with the taxonomy of these fossil assemblages. In this paper we provide a complete taxonomic study of the rodents and insectivores from three levels (ROM-2B, ROM-2C and ROM-3A) within the Romerales section. We infer a late Turolian age (late Messinian) for these levels, among which the richest and most diverse level is ROM-C, including at least 11 different taxa. In addition, the paleoecological analysis of these fossil assemblages suggests the dominance of open herbaceous meadows under temperate climate during the formation of these sites, with a slight decrease in temperature and humidity from ROM-2B to ROM-2C. 相似文献
115.
K. E. Mock J. C. Brim Box J. P. Chong J. Furnish J. K. Howard 《Molecular ecology》2013,22(24):6060-6073
We investigate population genetic structuring in Margaritifera falcata, a freshwater mussel native to western North America, across the majority of its geographical range. We find shallow rangewide genetic structure, strong population‐level structuring and very low population diversity in this species, using both mitochondrial sequence and nuclear microsatellite data. We contrast these patterns with previous findings in another freshwater mussel species group (Anodonta californiensis/A. nuttalliana) occupying the same continental region and many of the same watersheds. We conclude that differences are likely caused by contrasting life history attributes between genera, particularly host fish requirements and hermaphroditism. Further, we demonstrate the occurrence of a ‘hotspot’ for genetic diversity in both groups of mussels, occurring in the vicinity of the lower Columbia River drainage. We suggest that stream hierarchy may be responsible for this pattern and may produce similar patterns in other widespread freshwater species. 相似文献
116.
C-K Yang C-C Feng J-F Lo J-W Chen V. V Padma C-H Lai 《Biotechnic & histochemistry》2013,88(8):632-639
Mesenchymal stem cells are an attractive source of multipotent cells in part because they are easy to obtain. Several E3 ligases regulate the stability and functions of various factors in different adult stem cells through the ubiquitylation pathway. We investigated the C-terminus of Hsc70-interacting protein (CHIP) E3 ligase that regulates pluripotency of human Wharton’s jelly mesenchymal stem cells (hWJMSC). We found that CHIP increases protein kinase B (Akt) phosphorylation by decreased expression of phosphatase and tensin homolog (PTEN), which suggests improvement of the survival pathway by CHIP over-expression. We also found that increased CHIP expression induced Sox2 and NANOG, which can promote stem cell self-renewal and prevent oxidative stress-induced senescence of hWJMSC by decreased p21. We found that CHIP could be used to enhance the multiple functions of hWJMSC. 相似文献
117.
《Geobios》2019
The early Pleistocene travertines from Kocabaş in the Denizli Basin (SW Turkey), from which the only known Homo erectus from Anatolia derives, are covered by a succession of lake deposits. So far, the taphonomic history of the site has precluded a detailed palaeoecological analysis. This paper details the sedimentary succession and palaeoenvironmental conditions by analysing the micro- and macropalaeontological species compositions. These data provide direct evidence of the opportunities and limiting factors of the environment inhabited by hominins during the early Pleistocene. Four distinctive lithostratigraphic units are recognized in the Quaternary succession, consisting of: Lower Travertine, Lower Conglomerates, Upper Travertine, and Upper Conglomerates. These units correspond to an alternation of lacustrine limestone, fluvial-lacustrine siliciclastic deposits and subaerially precipitated travertine accumulations. The age of the succession is constrained by cosmogenic nuclide concentration, palaeomagnetic measurements and large mammal biostratigraphy which suggest deposition occurred between ∼1.6 and 1.2 Ma. The travertine succession contains a moderately diverse macromammal fauna, including Homo erectus, decapod crustaceans and leaf imprints. The herbivore association likely dwelled in a mixed landscape during temperate and humid climatic conditions, supported by negative δ18O values from analysed gastropod and bivalve shells. The presence of an anomalohaline lake is indicated by an abundant and well-preserved ostracod community, consisting of alkaline tolerant taxa and freshwater genera further supported by the presence of cardiid bivalves. 相似文献
118.
In arthropods, the large majority of studies on olfaction have been focused on insects, where most of the proteins involved have been identified. In particular, chemosensing in insects relies on two families of membrane receptors, olfactory/gustatory receptors (ORs/GRs) and ionotropic receptors (IRs), and two classes of soluble proteins, odorant-binding proteins (OBPs) and chemosensory proteins (CSPs). In other arthropods, such as ticks and mites, only IRs have been identified, while genes encoding for OBPs and CSPs are absent. A third class of soluble proteins, called Niemann-Pick C2 (NPC2) has been suggested as potential carrier for semiochemicals both in insects and other arthropods.Here we report the results of a proteomic analysis on olfactory organs (Haller's organ and palps) and control tissues of the tick Ixodes ricinus, and of immunostaining experiments targeting NPC2s. Adopting different extraction and proteomic approaches, we identified a large number of proteins, and highlighted those differentially expressed. None of the 13 NPC2s known for this species was found. On the other hand, using immunocytochemistry, we detected reaction against one NPC2 in the Haller's organ and palp sensilla. We hypothesized that the low concentration of such proteins in the tick's tissues could possibly explain the discrepant results. In ligand-binding assays the corresponding recombinant NPC2 showed good affinity to the fluorescent probe N-phenylnaphthylamine and to few organic compounds, supporting a putative role of NPC2s as odorant carriers. 相似文献
119.
Maxime Lasseron 《Comptes Rendus Palevol》2019,18(7):897-907
Two tooth morphotypes corresponding to one or two tetrapod species from the Late Jurassic or Earliest Cretaceous locality of Ksar Metlili (KM), Anoual Syncline (eastern Morocco), are reported and described. These teeth cannot be related to any of the identified vertebrate major groups of this site. They are tricusped and uniradiculate, with a high and large main central cusp mesio-distally surrounded by two smaller accessory cusps. Their morphology is reminiscent of several taxa such as pterosaurs, notosuchians and mammals, with which they are compared here. These morphotypes are tentatively referred to cf. Cynodontia indet. They would be the most recent non-mammaliaform cynodonts reported in Africa and among the latest described. The KM specimens display remarkable plesiomorphic dental features with respect to known contemporaneous non-mammaliaform cynodonts. They might indicate the survival of a relict lineage in a North African refugium. 相似文献
120.