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61.
M. Shahar Yar M. Mustaqeem Abdullah A. Husain M. Afroz Bhakht Erik De Clercq 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):949-956
3-Chlorobenzofuran-2-carbaldehyde was condensed with substituted acetophenone by using the Claisen-Schmidt condensation to obtain 3-(3-chlorobenzofuran-2-yl)-1-(substituted phenyl)-2-propen-1-one (2a-m) which upon further treatment with hydrazine hydrate gave 2-[3-(substituted phenyl)-4,5-dihydro-1H-5- pyrazolyl)benzofuran-3-yl chloride derivatives (3a-m). All the newly synthesized derivatives were evaluated in vitro for cytotoxicity and antiviral activity in Crandell-Rees Feline Kidney cell, human embryonic lung (HEL) cell, HeLa cell and Vero cell cultures against different viruses. Several compounds, i.e. 2f, 2g, 2i, 2m, 3b, 3d, 3g, 3h and 3m proved quite cytotoxic to the host cells (minimum cytotoxic concentration: 1-10 μg/mL). No specific antiviral activity [50% antivirally effective concentration (EC50) ≥ 5-fold lower than the minimum cytototoxic concentration] was observed for any of the compounds. 相似文献
62.
Medaka (O. latipes) and zebrafish (D. rerio) are two teleost fish increasingly used as models to study human skeletal diseases. Although they are similar in size, swimming pattern and many other characteristics, these two species are very distant from an evolutionary point of view (by at least 100 million years). A prominent difference between the skeletons of medaka and zebrafish is the total absence of osteocytes in medaka (anosteocytic), while zebrafish bone contains numerous osteocytes (osteocytic). This fundamental difference suggests the possibility that the bony elements of their skeleton may be different in a variety of other aspects, structural, mechanical or both, particularly in heavily loaded bones like the vertebrae. Here we report on the results of a comparative study that aimed to determine the similarities and differences in medaka and zebrafish vertebrae in terms of their macro- to nanostructure, composition and mechanical properties. Our results reveal many similarities between medaka and zebrafish vertebrae, making the lack or presence of osteocytes the only major difference between the bones of these two species. 相似文献
63.
Most sexually reproducing animal species are characterized by two morphologically and behaviorally distinct sexes. The genetic, molecular and cellular processes that produce sexual dimorphisms are phylogenetically diverse, though in most cases they are thought to occur early in development. In some species, however, sexual dimorphisms are manifested after development is complete, suggesting the intriguing hypothesis that sex, more generally, might be considered a continuous trait that is influenced by both developmental and postdevelopmental processes. Here, we explore how biological sex is defined at the genetic, neuronal and behavioral levels, its effects on neuronal development and function, and how it might lead to sexually dimorphic behavioral traits in health and disease. We also propose a unifying framework for understanding neuronal and behavioral sexual dimorphisms in the context of both developmental and postdevelopmental, physiological timescales. Together, these two temporally separate processes might drive sex‐specific neuronal functions in sexually mature adults, particularly as it pertains to behavior in health and disease. 相似文献
64.
Or David Shahar Ronen Gabizon Oren Feine Raphael Alhadeff Assaf Ganoth Liron Argaman Elee Shimshoni Assaf Friedler Michal Goldberg 《PloS one》2013,8(10)
Occurrence of DNA damage in a cell activates the DNA damage response, a survival mechanism that ensures genomics stability. Two key members of the DNA damage response are the tumor suppressor p53, which is the most frequently mutated gene in cancers, and MDC1, which is a central adaptor that recruits many proteins to sites of DNA damage. Here we characterize the in vitro interaction between p53 and MDC1 and demonstrate that p53 and MDC1 directly interact. The p53-MDC1 interaction is mediated by the tandem BRCT domain of MDC1 and the C-terminal domain of p53. We further show that both acetylation of lysine 382 and phosphorylation of serine 392 in p53 enhance the interaction between p53 and MDC1. Additionally, we demonstrate that the p53-MDC1 interaction is augmented upon the induction of DNA damage in human cells. Our data suggests a new role for acetylation of lysine 382 and phosphorylation of serine 392 in p53 in the cellular stress response and offers the first evidence for an interaction involving MDC1 that is modulated by acetylation. 相似文献
65.
66.
Berdichevsky Y Mizrahi A Ugolev Y Molshanski-Mor S Pick E 《The Journal of biological chemistry》2007,282(30):22122-22139
The superoxide-generating NADPH oxidase is converted to an active state by the assembly of a membrane-localized cytochrome b(559) with three cytosolic components: p47(phox), p67(phox), and GTPase Rac1 or Rac2. Assembly involves two sets of protein-protein interactions: among cytosolic components and among cytosolic components and cytochrome b(559) within its lipid habitat. We circumvented the need for interactions among cytosolic components by constructing a recombinant tripartite chimera (trimera) consisting of the Phox homology (PX) and Src homology 3 (SH3) domains of p47(phox), the tetratricopeptide repeat and activation domains of p67(phox), and full-length Rac1. Upon addition to phagocyte membrane, the trimera was capable of oxidase activation in vitro in the presence of an anionic amphiphile. The trimera had a higher affinity (lower EC(50)) for and formed a more stable complex (longer half-life) with cytochrome b(559) compared with the combined individual components, full-length or truncated. Supplementation of membrane with anionic but not neutral phospholipids made activation by the trimera amphiphile-independent. Mutagenesis, truncations, and domain replacements revealed that oxidase activation by the trimera was dependent on the following interactions: 1) interaction with anionic membrane phospholipids via the poly-basic stretch at the C terminus of the Rac1 segment; 2) interaction with p22(phox) via Trp(193) in the N-terminal SH3 domain of the p47(phox) segment, supplementing the electrostatic attraction; and 3) an intrachimeric bond among the p67(phox) and Rac1 segments complementary to their physical fusion. The PX domain of the p47(phox) segment and the insert domain of the Rac1 segment made only minor contributions to oxidase assembly. 相似文献
67.
Shahar R Zaslansky P Barak M Friesem AA Currey JD Weiner S 《Journal of biomechanics》2007,40(2):252-264
Young's modulus and Poisson's ratios of 6mm-sized cubes of equine cortical bone were measured in compression using a micro-mechanical loading device. Surface displacements were determined by electronic speckle pattern-correlation interferometry. This method allows for non-destructive testing of very small samples in water. Analyses of standard materials showed that the method is accurate and precise for determining both Young's modulus and Poisson's ratio. Material properties were determined concurrently in three orthogonal anatomic directions (axial, radial and transverse). Young's modulus values were found to be anisotropic and consistent with values of equine cortical bone reported in the literature. Poisson's ratios were also found to be anisotropic, but lower than those previously reported. Poisson's ratios for the radial-transverse and transverse-radial directions were 0.15+/-0.02, for the axial-transverse and axial-radial directions 0.19+/-0.04, and for the transverse-axial and radial-axial direction 0.09+/-0.02 (mean+/-SD). Cubes located only millimetres apart had significantly different elastic properties, showing that significant spatial variation occurs in equine cortical bone. 相似文献
68.
Songlei Liu Sukanya Punthambaker Eswar P R Iyer Thomas Ferrante Daniel Goodwin Daniel Fürth Andrew C Pawlowski Kunal Jindal Jenny M Tam Lauren Mifflin Shahar Alon Anubhav Sinha Asmamaw T Wassie Fei Chen Anne Cheng Valerie Willocq Katharina Meyer King-Hwa Ling Conor
K Camplisson Richie E Kohman John Aach Je Hyuk Lee Bruce
A Yankner Edward S Boyden George M Church 《Nucleic acids research》2021,49(10):e58
69.
Overripe ova and twinning. 总被引:4,自引:2,他引:2
Multiple births were studied in a sample of orthodox Jewesses for whom an estimate could be made of the day of ovulation and the earliest possible day of conception. The overall rate of twinning was 14.5/1,000 deliveries, and of triplets, 0.40/1,000. Twinning rates varied significantly from 11.4 in the 5,976 "early" conceptions (day -1 or earlier relative to the estimated day of ovulation) to 26.9 in the 1,498 "late" conceptions (day 0 or later). Triplets varied significantly from 0 to 2.01 in early and late conceptions, respectively, and unlike-sexed multiple sets, 2.8 and 12.8, respectively. The excess of multiple births in late conceptions was seen within different ages and origin groups, in women with different menstrual characteristics, and in those with and without treatment for anovulation. While the excess of unlike-sexed sets seems to lead to the conclusion that late conceptions are associated with dizygosity, polar body twinning and uniovular dispermatic twinning should also be considered. 相似文献
70.
The Transient Receptor Potential (TRP) proteins constitute a large and diverse family of channel proteins, which is conserved through evolution. TRP channel proteins have critical functions in many tissues and cell types, but their gating mechanism is an enigma. In the present study patch-clamp whole-cell recordings was applied to measure the TRP- and TRP-like (TRPL)-dependent currents in isolated Drosophila ommatidia. Also, voltage responses to light and to metabolic stress were recorded from the eye in vivo. We report new insight into the gating of the Drosophila light-sensitive TRP and TRPL channels, by which both Ca2+ and protein dephosphorylation are required for channel activation. ATP depletion or inhibition of protein kinase C activated the TRP channels, while photo-release of caged ATP or application of phorbol ester antagonized channels openings in the dark. Furthermore, Mg(2+)-dependent stable phosphorylation event by ATPgammaS or protein phosphatase inhibition by calyculin A abolished activation of the TRP and TRPL channels. While a high reduction of cellular Ca2+ abolished channel activation, subsequent application of Ca2+ combined with ATP depletion induced a robust dark current that was reminiscent of light responses. The results suggest that the combined action of Ca2+ and protein dephosphorylation activate the TRP and TRPL channels, while protein phosphorylation by PKC antagonized channels openings. 相似文献