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991.
Zhong-Wei Zhou Alicia Tapias Christopher Bruhn Ralph Gruber Mikhail Sukchev Zhao-Qi Wang 《DNA Repair》2013,12(8):645-655
MCPH1 encodes BRCT-containing protein MCPH1/Microcephalin/BRIT1, mutations of which in humans cause autosomal recessive disorder primary microcephaly type 1 (MCPH1), characterized by a congenital reduction of brain size particularly in the cerebral cortex. We have shown previously that a deletion of Mcph1 in mice results in microcephaly because of a premature switch from symmetric to asymmetric division of the neuroprogenitors, which is regulated by MCPH1's function in the centrosome. Because MCPH1 has been implicated in ATM and ATR-mediated DNA damage response (DDR) and defective DDR is often associated with neurodevelopmental diseases, we wonder whether the DDR-related function of MCPH1 prevents microcephaly. Here, we show that a deletion of Mcph1 results in a specific reduction of the cerebral cortex at birth, which is persistent through life. Due to an effect on premature neurogenic production, Mcph1-deficient progenitors give rise to a high level of early-born neurons that form deep layers (IV–VI), while generate less late-born neurons that form a thinner outer layer (II–III) of the cortex. However, neuronal migration seems to be unaffected by Mcph1 deletion. Ionizing radiation (IR) induces a massive apoptosis in the Mcph1-null neocortex and also embryonic lethality. Finally, Mcph1 deletion compromises homologous recombination repair and increases genomic instability. Altogether, our data suggest that MCPH1 ensures proper neuroprogenitor expansion and differentiation not only through its function in the centrosome, but also in the DDR. 相似文献
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993.
994.
Piotr Wysoczanski Robert J. Mart E. Joel Loveridge Christopher Williams Sara B.-M. Whittaker Matthew P. Crump Rudolf K. Allemann 《Biomolecular NMR assignments》2013,7(2):187-191
Here we report the 1H, 13C and 15N resonance assignments of free Bcl-xL and of Bcl-xL in complex with an azobenzene-modified peptide derived from the BH3 domain of the pro-apoptotic Bak. The spectra suggest predominantly folded proteins; chemical shift difference analysis provides a detailed view of the reorganization occurring on peptide binding. 相似文献
995.
Jamison M. Gove Gareth J. Williams Margaret A. McManus Scott F. Heron Stuart A. Sandin Oliver J. Vetter David G. Foley 《PloS one》2013,8(4)
Coral reef ecosystems are exposed to a range of environmental forcings that vary on daily to decadal time scales and across spatial scales spanning from reefs to archipelagos. Environmental variability is a major determinant of reef ecosystem structure and function, including coral reef extent and growth rates, and the abundance, diversity, and morphology of reef organisms. Proper characterization of environmental forcings on coral reef ecosystems is critical if we are to understand the dynamics and implications of abiotic–biotic interactions on reef ecosystems. This study combines high-resolution bathymetric information with remotely sensed sea surface temperature, chlorophyll-a and irradiance data, and modeled wave data to quantify environmental forcings on coral reefs. We present a methodological approach to develop spatially constrained, island- and atoll-scale metrics that quantify climatological range limits and anomalous environmental forcings across U.S. Pacific coral reef ecosystems. Our results indicate considerable spatial heterogeneity in climatological ranges and anomalies across 41 islands and atolls, with emergent spatial patterns specific to each environmental forcing. For example, wave energy was greatest at northern latitudes and generally decreased with latitude. In contrast, chlorophyll-a was greatest at reef ecosystems proximate to the equator and northern-most locations, showing little synchrony with latitude. In addition, we find that the reef ecosystems with the highest chlorophyll-a concentrations; Jarvis, Howland, Baker, Palmyra and Kingman are each uninhabited and are characterized by high hard coral cover and large numbers of predatory fishes. Finally, we find that scaling environmental data to the spatial footprint of individual islands and atolls is more likely to capture local environmental forcings, as chlorophyll-a concentrations decreased at relatively short distances (>7 km) from 85% of our study locations. These metrics will help identify reef ecosystems most exposed to environmental stress as well as systems that may be more resistant or resilient to future climate change. 相似文献
996.
Ethan A. Rossi Rebecca L. Achtman Arnaud Guidon David R. Williams Austin Roorda Daphne Bavelier Joseph Carroll 《PloS one》2013,8(2)
Carriers of blue cone monochromacy have fewer cone photoreceptors than normal. Here we examine how this disruption at the level of the retina affects visual function and cortical organization in these individuals. Visual resolution and contrast sensitivity was measured at the preferred retinal locus of fixation and visual resolution was tested at two eccentric locations (2.5° and 8°) with spectacle correction only. Adaptive optics corrected resolution acuity and cone spacing were simultaneously measured at several locations within the central fovea with adaptive optics scanning laser ophthalmoscopy (AOSLO). Fixation stability was assessed by extracting eye motion data from AOSLO videos. Retinotopic mapping using fMRI was carried out to estimate the area of early cortical regions, including that of the foveal confluence. Without adaptive optics correction, BCM carriers appeared to have normal visual function, with normal contrast sensitivity and visual resolution, but with AO-correction, visual resolution was significantly worse than normal. This resolution deficit is not explained by cone loss alone and is suggestive of an associated loss of retinal ganglion cells. However, despite evidence suggesting a reduction in the number of retinal ganglion cells, retinotopic mapping showed no reduction in the cortical area of the foveal confluence. These results suggest that ganglion cell density may not govern the foveal overrepresentation in the cortex. We propose that it is not the number of afferents, but rather the content of the information relayed to the cortex from the retina across the visual field that governs cortical magnification, as under normal viewing conditions this information is similar in both BCM carriers and normal controls. 相似文献
997.
Andrea Gottlieb Hans-Georg Müller Alicia N. Massa Humphrey Wanjugi Karin R. Deal Frank M. You Xiangyang Xu Yong Q. Gu Ming-Cheng Luo Olin D. Anderson Agnes P. Chan Pablo Rabinowicz Katrien M. Devos Jan Dvorak 《PloS one》2013,8(1)
Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands “gene insulae” to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes. 相似文献
998.
Nir Eynon Emiliya S. Nasibulina Lauren K. Banting Pawel Cieszczyk Agnieszka Maciejewska-Karlowska Marek Sawczuk Elvira A. Bondareva Roza R. Shagimardanova Maytal Raz Yael Sharon Alun G. Williams Ildus I. Ahmetov Alejandro Lucia Ruth Birk 《PloS one》2013,8(4)
Objective
The FTO A/T polymorphism (rs9939609) is a strong candidate to influence obesity-related traits. Elite athletes from many different sporting disciplines are characterized by low body fat. Therefore, the aim of this study was to assess whether athletic status is associated with the FTO A/T polymorphism.Subjects and Methods
A large cohort of European Caucasians from Poland, Russia and Spain were tested to examine the association between FTO A/T polymorphism (rs9939609) and athletic status. A total of 551 athletes were divided by type of sport (endurance athletes, n = 266 vs. sprint/power athletes, n = 285) as well as by level of competition (elite-level vs. national-level). The control group consisted of 1,416 ethnically-matched, non-athletic participants, all Europeans. Multinomial logistic regression analyses were conducted to assess the association between FTO A/T genotypes and athletic status/competition level.Results
There were no significantly greater/lesser odds of harbouring any type of genotype when comparing across athletic status (endurance athletes, sprint/power athletes or control participants). These effects were observed after controlling for sex and nationality. Furthermore, no significantly greater/lesser odds ratios were observed for any of the genotypes in respect to the level of competition (elite-level vs. national-level).Conclusion
The FTO A/T polymorphism is not associated with elite athletic status in the largest group of elite athletes studied to date. Large collaborations and data sharing between researchers, as presented here, are strongly recommended to enhance the research in the field of exercise genomics. 相似文献999.
Joshua M. Plotnik Jennifer J. Pokorny Titiporn Keratimanochaya Christine Webb Hana F. Beronja Alice Hennessy James Hill Virginia J. Hill Rebecca Kiss Caitlin Maguire Beckett L. Melville Violet M. B. Morrison Dannah Seecoomar Benjamin Singer Jehona Ukehaxhaj Sophia K. Vlahakis Dora Ylli Nicola S. Clayton John Roberts Emilie L. Fure Alicia P. Duchatelier David Getz 《PloS one》2013,8(4)
Recent research suggests that domesticated species – due to artificial selection by humans for specific, preferred behavioral traits – are better than wild animals at responding to visual cues given by humans about the location of hidden food. \Although this seems to be supported by studies on a range of domesticated (including dogs, goats and horses) and wild (including wolves and chimpanzees) animals, there is also evidence that exposure to humans positively influences the ability of both wild and domesticated animals to follow these same cues. Here, we test the performance of Asian elephants (Elephas maximus) on an object choice task that provides them with visual-only cues given by humans about the location of hidden food. Captive elephants are interesting candidates for investigating how both domestication and human exposure may impact cue-following as they represent a non-domesticated species with almost constant human interaction. As a group, the elephants (n = 7) in our study were unable to follow pointing, body orientation or a combination of both as honest signals of food location. They were, however, able to follow vocal commands with which they were already familiar in a novel context, suggesting the elephants are able to follow cues if they are sufficiently salient. Although the elephants’ inability to follow the visual cues provides partial support for the domestication hypothesis, an alternative explanation is that elephants may rely more heavily on other sensory modalities, specifically olfaction and audition. Further research will be needed to rule out this alternative explanation. 相似文献
1000.
Paul T. Williams Xue-Qiao Zhao Santica M. Marcovina B. Greg Brown Ronald M. Krauss 《PloS one》2013,8(2)