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71.
Two recombinant barley cystatins, HvCPI5 and HvCPI6, have been tested in vitro against promastigotes and intracellular amastigotes of Leishmania infantum in the J774 monocytic cell line. Toxicity of cystatins for J774 cells was also determined. In addition, a comparison between direct counts of intracellular amastigotes and quantitation of burden by Q-PCR was carried out. Low concentrations (2 μM) from both cystatins were unable to inhibit promastigote replication. HvCPI5 was toxic for mammalian cells; 0.1 μM reduced by more than 50% the cell viability. On the contrary, HvCPI6 did not exhibit any toxicity for J774 cells up to 6 μM and inhibited the intracellular amastigote multiplication. Dose-response analysis showed that 4.8 μM HvCPI6 reduced by >90% the intracellular parasite load and had an approximate IC50 value of 1.5 μM. Comparable results were obtained by direct counting of intracellular amastigotes and Q-PCR. Results point towards the direct inhibition of amastigote multiplication by HvCPI6 and the interest of this recombinant cystatin in the chemotherapy of leishmaniasis. 相似文献
72.
Wilkinson B Gregory MA Moss SJ Carletti I Sheridan RM Kaja A Ward M Olano C Mendez C Salas JA Leadlay PF vanGinckel R Zhang MQ 《Bioorganic & medicinal chemistry letters》2006,16(22):5814-5817
A set of novel borrelidin analogues have been prepared by precursor-directed biosynthesis. Structure-activity relationship analysis suggests that steric structural arrangement within the C17 side chain is important for differentiating cytotoxic and anti-angiogenic activities. A C17-cyclobutyl analogue 3 was found to have markedly increased selectivity for in vitro angiogenesis inhibition over cytotoxicity and is therefore potentially useful as an anticancer agent. 相似文献
73.
Incidental entanglement in fishing gear is arguably the most serious threat to many populations of small cetaceans, judging by the alarming number of captured animals. However, other aspects of this threat, such as the potential capture of mother-offspring pairs or reproductive pairs, could be equally or even more significant but have rarely been evaluated. Using a combination of demographic and genetic data we provide evidence that i) Franciscana dolphin pairs that are potentially reproductive and mother-offspring pairs form temporal bonds, and ii) are entangled simultaneously. Our results highlight potential demographic and genetic impacts of by-catch to cetacean populations: the joint entanglement of mother-offspring or reproductive pairs, compared to random individuals, might exacerbate the demographic consequences of by-catch, and the loss of groups of relatives means that significant components of genetic diversity could be lost together. Given the social nature of many odontocetes (toothed cetaceans), we suggest that these potential impacts could be rather general to the group and therefore by-catch could be more detrimental than previously considered. 相似文献
74.
75.
Mendez M Gross KW Glenn ST Garvin JL Carretero OA 《The Journal of biological chemistry》2011,286(32):28608-28618
Renin is essential for blood pressure control. Renin is stored in granules in juxtaglomerular (JG) cells, located in the pole of the renal afferent arterioles. The second messenger cAMP stimulates renin release. However, it is unclear whether fusion and exocytosis of renin-containing granules is involved. In addition, the role of the fusion proteins, SNAREs (soluble N-ethylmaleimide-sensitive factor attachment proteins), in renin release from JG cells has not been studied. The vesicle SNARE proteins VAMP2 (vesicle associated membrane protein 2) and VAMP3 mediate cAMP-stimulated exocytosis in other endocrine cells. Thus, we hypothesized that VAMP2 and/or -3 mediate cAMP-stimulated renin release from JG cells. By fluorescence-activated cell sorting, we isolated JG cells expressing green fluorescent protein and compared the relative abundance of VAMP2/3 in JG cells versus total mouse kidney mRNA by quantitative PCR. We found that VAMP2 and VAMP3 mRNA are expressed and enriched in JG cells. Confocal imaging of primary cultures of JG cells showed that VAMP2 (but not VAMP3) co-localized with renin-containing granules. Cleavage of VAMP2 and VAMP3 with tetanus toxin blocked cAMP-stimulated renin release from JG cells by ~50% and impaired cAMP-stimulated exocytosis by ~50%, as monitored with FM1-43. Then we specifically knocked down VAMP2 or VAMP3 by adenoviral-mediated delivery of short hairpin silencing RNA. We found that silencing VAMP2 blocked cAMP-induced renin release by ~50%. In contrast, silencing VAMP3 had no effect on basal or cAMP-stimulated renin release. We conclude that VAMP2 and VAMP3 are expressed in JG cells, but only VAMP2 is targeted to renin-containing granules and mediates the stimulatory effect of cAMP on renin exocytosis. 相似文献
76.
Mendez FL Karafet TM Krahn T Ostrer H Soodyall H Hammer MF 《Human biology; an international record of research》2011,83(1):39-53
Increasing phylogenetic resolution of the Y chromosome haplogroup tree has led to finer temporal and spatial resolution for studies of human migration. Haplogroup T, initially known as K2 and defined by mutation M70, is found at variable frequencies across West Asia, Africa, and Europe. While several SNPs were recently discovered that extended the length of the branch leading to haplogroup T, only two SNPs are known to mark internal branches of haplogroup T. This low level of phylogenetic resolution has hindered studies of the origin and dispersal of this interesting haplogroup, which is found in Near Eastern non-Jewish populations, Jewish populations from several communities, and in the patrilineage of President Thomas Jefferson. Here we map 10 new SNPs that, together with the previously known SNPs, mark 11 lineages and two large subclades (T1a and T1b) of haplogroup T. We also report a new SNP that links haplogroups T and L within the major framework of Y chromosome evolution. Estimates of the timing of the branching events within haplogroup T, along with a comprehensive geographic survey of the major T subclades, suggest that this haplogroup began to diversify in the Near East -25 kya. Our survey also points to a complex history of dispersal of this rare and informative haplogroup within the Near East and from the Near East to Europe and sub-Saharan Africa. The presence of T1a2 chromosomes in Near Eastern Jewish and non-Jewish populations may reflect early exiles between the ancient lands of Israel and Babylon. The presence of different subclades of T chromosomes in Europe may be explained by both the spread of Neolithic farmers and the later dispersal of Jews from the Near East. Finally, the moderately high frequency (-18%) of T1b* chromosomes in the Lemba of southern Africa supports the hypothesis of a Near Eastern, but not necessarily a Jewish, origin for their paternal line. 相似文献
77.
The marine-estuarine bacterium Vibrio harveyi is an important pathogen of invertebrates, most significantly, the larvae of commercially important shrimp Penaeus monodon. In this study, we analyzed V. harveyi isolated from shrimp hatchery environments for understanding the distribution of putative virulence genes and antimicrobial
drug resistance. The putative genes targeted for PCR detection included four reversible toxin (Rtx)/hemolysin genes, a gene
encoding homologue of Vibrio
cholerae zonula occludens toxin (Zot) and a hemolysin-coregulated protein gene (hcp) by polymerase chain reaction (PCR). Of the four putative reversible toxin genes, vhh-1 was detected in 31% of the isolates, vhh-2 in 46%, vhh-3 in 23% and vhh-4 was detected in 27% of the isolates. A zot-like sequence of bacteriophage f237 was present in 15%, while hcp sequence was detected in 48% of the isolates. The antimicrobial susceptibility test revealed resistance to several groups
of antibiotics including β-lactams, cephalosporins, macrolides, quinolones, nitrofurantoin and tetracycline. 相似文献
78.
Sebastián Manzano Cesar H. Zambrano Miguel Angel Mendez Eric E. Dueno Robert A. Cazar 《Molecular simulation》2014,40(4):327-334
We report a theoretical study of the structural and electronic properties of the rccc and rctt conformers of several pyrogallol[4]arenes, R-Pyg[4]arenes (i.e. R = fluoroethyl, methyl, t-butyl, phenyl, tolyl and p-fluorophenyl) carried out by employing the HF-DFT hybrid B3LYP functional. Comparison of the B3LYP energies of the two stereoisomers showed that the rccc conformer is more stable than its rctt counterpart for all the derivatives considered. However, calculations made with the double-hybrid Grimme's B97D functional confirmed the experimental observation that the relative stability depends on the type of the R substituents. These results clearly suggest that the B97D functional together with large enough basis sets (i.e. split-valence plus polarisation and diffuse functions) is sufficiently accurate for the purpose of describing the conformational features of these compounds. Computed electrostatic potential maps of the rccc of the different R-Pyg[4]arenes showed that a negative potential is present within the cavity of these compounds. In addition, it is observed that the size of this negative electrostatic potential depends on the electron-donating or electron-withdrawing character of the R substituents. 相似文献
79.
Ram Krishna Thakur Vinod Kumar Yadav Akinchan Kumar Ankita Singh Krishnendu Pal Luke Hoeppner Dhurjhoti Saha Gunjan Purohit Richa Basundra Anirban Kar Rashi Halder Pankaj Kumar Aradhita Baral MJ Mahesh Kumar Alfonso Baldi Bruno Vincenzi Laura Lorenzon Rajkumar Banerjee Praveen Kumar Viji Shridhar Debabrata Mukhopadhyay Shantanu Chowdhury 《Nucleic acids research》2014,42(18):11589-11600
80.
Marieke?Pingen Ramin?Sarrami-Forooshani Annemarie?MJ?Wensing Petra?van Ham Agata?Drewniak Charles?AB?Boucher Teunis?BH?GeijtenbeekEmail author Monique?NijhuisEmail author 《Retrovirology》2014,11(1):113