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71.
The low activity variant of the monoamine oxidase A (MAOA) functional promoter polymorphism, MAOA‐LPR, in interaction with adverse environments (G × E) is associated with child and adult antisocial behaviour disorders. MAOA is expressed during foetal development so in utero G × E may influence early neurodevelopment. We tested the hypothesis that MAOA G × E during pregnancy predicts infant negative emotionality soon after birth. In an epidemiological longitudinal study starting in pregnancy, using a two stage stratified design, we ascertained MAOA‐LPR status (low vs. high activity variants) from the saliva of 209 infants (104 boys and 105 girls), and examined predictions to observed infant negative emotionality at 5 weeks post‐partum from life events during pregnancy. In analyses weighted to provide estimates for the general population, and including possible confounders for life events, there was an MAOA status by life events interaction (P = 0.017). There was also an interaction between MAOA status and neighbourhood deprivation (P = 0.028). Both interactions arose from a greater effect of increasing life events on negative emotionality in the MAOA‐LPR low activity, compared with MAOA‐LPR high activity infants. The study provides the first evidence of moderation by MAOA‐LPR of the effect of the social environment in pregnancy on negative emotionality in infancy, an early risk for the development of child and adult antisocial behaviour disorders . 相似文献
72.
Dong Zhang Ana B. Asenjo Michaela Greenbaum Luping Xie David J. Sharp Hernando Sosa 《PloS one》2013,8(8)
Kinesin-13s are microtubule (MT) depolymerases different from most other kinesins that move along MTs. Like other kinesins, they have a motor or head domain (HD) containing a tubulin and an ATP binding site. Interestingly, kinesin-13s have an additional binding site (Kin-Tub-2) on the opposite side of the HD that contains several family conserved positively charged residues. The role of this site in kinesin-13 function is not clear. To address this issue, we investigated the in-vitro and in-vivo effects of mutating Kin-Tub-2 family conserved residues on the Drosophila melanogaster kinesin-13, KLP10A. We show that the Kin-Tub-2 site enhances tubulin cross-linking and MT bundling properties of KLP10A in-vitro. Disruption of the Kin-Tub-2 site, despite not having a deleterious effect on MT depolymerization, results in abnormal mitotic spindles and lagging chromosomes during mitosis in
Drosophila
S2 cells. The results suggest that the additional Kin-Tub-2 tubulin biding site plays a direct MT attachment role in-vivo. 相似文献
73.
Rudicell RS Piel AK Stewart F Moore DL Learn GH Li Y Takehisa J Pintea L Shaw GM Moore J Sharp PM Hahn BH 《Journal of virology》2011,85(19):9918-9928
Simian immunodeficiency virus of chimpanzees (SIVcpz) has a significant negative impact on the health, reproduction, and life span of chimpanzees, yet the prevalence and distribution of this virus in wild-living populations are still only poorly understood. Here, we show that savanna chimpanzees, who live in ecologically marginal habitats at 10- to 50-fold lower population densities than forest chimpanzees, can be infected with SIVcpz at high prevalence rates. Fecal samples were collected from nonhabituated eastern chimpanzees (Pan troglodytes schweinfurthii) in the Issa Valley (n = 375) and Shangwa River (n = 6) areas of the Masito-Ugalla region in western Tanzania, genotyped to determine the number of sampled individuals, and tested for SIVcpz-specific antibodies and nucleic acids. None of 5 Shangwa River apes tested positive for SIVcpz; however, 21 of 67 Issa Valley chimpanzees were SIVcpz infected, indicating a prevalence rate of 31% (95% confidence interval, 21% to 44%). Two individuals became infected during the 14-month observation period, documenting continuing virus spread in this community. To characterize the newly identified SIVcpz strains, partial and full-length viral sequences were amplified from fecal RNA of 10 infected chimpanzees. Phylogenetic analyses showed that the Ugalla viruses formed a monophyletic lineage most closely related to viruses endemic in Gombe National Park, also located in Tanzania, indicating a connection between these now separated communities at some time in the past. These findings document that SIVcpz is more widespread in Tanzania than previously thought and that even very low-density chimpanzee populations can be infected with SIVcpz at high prevalence rates. Determining whether savanna chimpanzees, who face much more extreme environmental conditions than forest chimpanzees, are more susceptible to SIVcpz-associated morbidity and mortality will have important scientific and conservation implications. 相似文献
74.
Depth is a term frequently applied to the shape and surface of macromolecules, describing for example the grooves in DNA, the shape of an enzyme active site, or the binding site for a small molecule in a protein. Yet depth is a difficult property to define rigorously in a macromolecule, and few computational tools exist to quantify this notion, to visualize it, or analyze the results. We present our notion of travel depth, simply put the physical distance a solvent molecule would have to travel from a surface point to a suitably defined reference surface. To define the reference surface, we use the limiting form of the molecular surface with increasing probe size: the convex hull. We then present a fast, robust approximation algorithm to compute travel depth to every surface point. The travel depth is useful because it works for pockets of any size and complexity. It also works for two interesting special cases. First, it works on the grooves in DNA, which are unbounded in one direction. Second, it works on the case of tunnels, that is pockets that have no "bottom", but go through the entire macromolecule. Our algorithm makes it straightforward to quantify discussions of depth when analyzing structures. High-throughput analysis of macromolecule depth is also enabled by our algorithm. This is demonstrated by analyzing a database of protein-small molecule binding pockets, and the distribution of bound magnesium ions in RNA structures. These analyses show significant, but subtle effects of depth on ligand binding localization and strength. 相似文献
75.
Jrme Goudeau Catherine S Sharp Jonathan Paw Laura Savy Manuel D Leonetti Andrew G York Dustin L Updike Cynthia Kenyon Maria Ingaramo 《Genetics》2021,217(4)
We create and share a new red fluorophore, along with a set of strains, reagents and protocols, to make it faster and easier to label endogenous Caenorhabditis elegans proteins with fluorescent tags. CRISPR-mediated fluorescent labeling of C. elegans proteins is an invaluable tool, but it is much more difficult to insert fluorophore-size DNA segments than it is to make small gene edits. In principle, high-affinity asymmetrically split fluorescent proteins solve this problem in C. elegans: the small fragment can quickly and easily be fused to almost any protein of interest, and can be detected wherever the large fragment is expressed and complemented. However, there is currently only one available strain stably expressing the large fragment of a split fluorescent protein, restricting this solution to a single tissue (the germline) in the highly autofluorescent green channel. No available C. elegans lines express unbound large fragments of split red fluorescent proteins, and even state-of-the-art split red fluorescent proteins are dim compared to the canonical split-sfGFP protein. In this study, we engineer a bright, high-affinity new split red fluorophore, split-wrmScarlet. We generate transgenic C. elegans lines to allow easy single-color labeling in muscle or germline cells and dual-color labeling in somatic cells. We also describe a novel expression strategy for the germline, where traditional expression strategies struggle. We validate these strains by targeting split-wrmScarlet to several genes whose products label distinct organelles, and we provide a protocol for easy, cloning-free CRISPR/Cas9 editing. As the collection of split-FP strains for labeling in different tissues or organelles expands, we will post updates at doi.org/10.5281/zenodo.3993663 相似文献
76.
77.
The isolation,characterization and application in the Triticeae of a set of wheat RFLP probes identifying each homoeologous chromosome arm 总被引:8,自引:0,他引:8
P. J. Sharp S. Chao S. Desai M. D. Gale 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1989,78(3):342-348
Summary To investigate the use of RFLP analysis in the Triticeae, a set of low copy number probes has been isolated from a wheat cDNA library. The probes identify each of the 14 homoeologous chromosome arms of wheat as determined by analysis of DNA fragments hybridizing to the probes in aneuploid lines of Chinese Spring. These probes can be used in RFLP analyses both for the assignment of homoeology of alien chromosomes or arms added to wheat, and for the determination of chromosome dosage in wheat aneuploids. Different chromosomes from various Triticeae species can therefore be followed in a wheat genetic background using a single technique. The potential uses of the set in facilitating the transfer of alien segments into wheat are outlined. 相似文献
78.
The question of whether abscisic acid (ABA) acts as an inhibitor or promoter of shoot growth in plants growing in drying soil is examined, drawing on current understanding of the role of ABA in root growth maintenance. Particular consideration is given to studies of endogenous ABA deficiency, which have shown that an important role of ABA is to limit ethylene production, and that this interaction is involved in the effects of ABA status on shoot and root growth. 相似文献
79.
Carol A. Sheppard Peter B. Simpson Alan H. Sharp Frederick C. Nucifora Christopher A. Ross †G. David Lange James T. Russell 《Journal of neurochemistry》1997,68(6):2317-2327
Abstract: We have examined the mechanisms that underlie Ca2+ wave propagation in cultured cortical astrocytes. Norepinephrine evoked Ca2+ waves in astrocytes that began at discrete initiation loci and propagated throughout the cell by regenerative amplification at a number of cellular sites, as shown by very high Ca2+ release rates at these regions. We have hypothesized previously that domains displaying elevated Ca2+ release kinetics in astrocytes may correspond to sites of high inositol 1,4,5-trisphosphate receptor (InsP3 R) density. To examine this possibility, we compared the distribution pattern of endoplasmic reticulum (ER) and InsP3 Rs with Ca2+ release kinetics in subcellular regions during propagation of norepinephrine-evoked waves. 3,3'-Dihexyloxacarbocyanine iodide staining revealed that the ER in astrocytes exists as a meshwork of membranes extending throughout the cells, including fine processes. A specific antibody directed against type 2 InsP3 Rs (InsP3 R2) detected a 260-kDa band in western blotting of astrocyte membranes. Immunocytochemistry using this antibody stained the entire ER system in a punctate, variegated manner. When Ca2+ responses and InsP3 R2 immunofluorescence were compared in the same cell, domains of elevated Ca2+ response kinetics (high amplitude and rapid rate of rise) showed significant positive correlation with high local intensity of InsP3 R2 staining. It appears, therefore, that specializations in the ER responsible for discrete local Ca2+ release sites that support regenerative wave propagation include increased levels of InsP3 R2 expression. 相似文献
80.
Coral Reefs - Coral reefs in the Florida Keys have degraded in recent decades, prompting efforts to re-establish populations of staghorn coral, Acropora cervicornis, to restore structure and... 相似文献