128 research outputs found

    Study on microstructure mechanism of sandstone based on complex network theory

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    Rock contains a large number of micro-pores, which are of different shapes and complex structures. The structure information of sandstones is extracted based on different porosities through X-ray CT (Computer Tomography) scanning, photo processing techniques and complex network method to explore the topological structure of sandstone seepage network. The results show that sandstone seepage network has scale-free property. The minute quantities of pores with more throat connections have vital functions of overall connectivity of sandstone seepage network, while sandstone seepage network has strong robustness with random error. This research can provide reference for across scales research of porous seepage and multi-disciplinary application of complex network theory

    Exciting Complexity: The Role of Motor Circuit Elements in ALS Pathophysiology

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    Amyotrophic lateral sclerosis (ALS) is a fatal disease, characterized by the degeneration of both upper and lower motor neurons. Despite decades of research, we still to date lack a cure or disease modifying treatment, emphasizing the need for a much-improved insight into disease mechanisms and cell type vulnerability. Altered neuronal excitability is a common phenomenon reported in ALS patients, as well as in animal models of the disease, but the cellular and circuit processes involved, as well as the causal relevance of those observations to molecular alterations and final cell death, remain poorly understood. Here, we review evidence from clinical studies, cell type-specific electrophysiology, genetic manipulations and molecular characterizations in animal models and culture experiments, which argue for a causal involvement of complex alterations of structure, function and connectivity of different neuronal subtypes within the cortical and spinal cord motor circuitries. We also summarize the current knowledge regarding the detrimental role of astrocytes and reassess the frequently proposed hypothesis of glutamate-mediated excitotoxicity with respect to changes in neuronal excitability. Together, these findings suggest multifaceted cell type-, brain area- and disease stage- specific disturbances of the excitation/inhibition balance as a cardinal aspect of ALS pathophysiology

    A new reference genome assembly for the microcrustacean Daphnia pulex

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    Comparing genomes of closely related genotypes from populations with distinct demographic histories can help reveal the impact of effective population size on genome evolution. For this purpose, we present a high quality genome assembly of Daphnia pulex (PA42), and compare this with the first sequenced genome of this species (TCO), which was derived from an isolate from a population with >90% reduction in nucleotide diversity. PA42 has numerous similarities to TCO at the gene level, with an average amino acid sequence identity of 98.8 and >60% of orthologous proteins identical. Nonetheless, there is a highly elevated number of genes in the TCO genome annotation, with similar to 7000 excess genes appearing to be false positives. This view is supported by the high GC content, lack of introns, and short length of these suspicious gene annotations. Consistent with the view that reduced effective population size can facilitate the accumulation of slightly deleterious genomic features, we observe more proliferation of transposable elements (TEs) and a higher frequency of gained introns in the TCO genome

    Study on microstructure mechanism of sandstone based on complex network theory

    Get PDF
    Rock contains a large number of micro-pores, which are of different shapes and complex structures. The structure information of sandstones is extracted based on different porosities through X-ray CT (Computer Tomography) scanning, photo processing techniques and complex network method to explore the topological structure of sandstone seepage network. The results show that sandstone seepage network has scale-free property. The minute quantities of pores with more throat connections have vital functions of overall connectivity of sandstone seepage network, while sandstone seepage network has strong robustness with random error. This research can provide reference for across scales research of porous seepage and multi-disciplinary application of complex network theory

    Joint testing of genotypic and gene-environment interaction identified novel association for BMP4 with non-syndromic CL/P in an Asian population using data from an International Cleft Consortium

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    Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10(-5)) and 0.0065 (asymptotic P = 5.54*10(-5)), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs.Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies

    The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating drosha activity.

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    Here we show that a major muscle specific isoform of the murine LINC complex protein SUN1 is required for efficient muscle regeneration. The nucleoplasmic domain of the isoform specifically binds to and inhibits Drosha, a key component of the microprocessor complex required for miRNA synthesis. Comparison of the miRNA profiles between wildtype and SUN1 null myotubes identified a cluster of miRNAs encoded by a non-translated retrotransposon-like one antisense (Rtl1as) transcript that are decreased in the WT myoblasts due to SUN1 inhibition of Drosha. One of these miRNAs miR-127 inhibits the translation of the Rtl1 sense transcript, that encodes the retrotransposon-like one protein (RTL1), which is also required for muscle regeneration and is expressed in regenerating/dystrophic muscle. The LINC complex may therefore regulate gene expression during muscle regeneration by controlling miRNA processing. This provides new insights into the molecular pathology underlying muscular dystrophies and how the LINC complex may regulate mechanosignaling

    Oral Administration of Skin Gelatin Isolated from Chum Salmon (Oncorhynchus keta) Enhances Wound Healing in Diabetic Rats

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    Care for diabetic wounds remains a significant clinical problem. The present study was aimed at investigating the effect of skin gelatin from Chum Salmon on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 48 rats, of which 32 were diabetes. The diabetic rats were orally treated daily for 14 days with skin gelatin from Chum Salmon (2 g/kg) or its vehicle. Sixteen non-diabetic control rats received the same amount of water as vehicle-treated non-diabetic rats. Rats were killed to assess the rate of wound closure, microvessel density (MVD), vascular endothelial growth factor (VEGF), hydroxyproline (HP) contents in wound tissues and nitrate in plasma and wound tissue at 7 and 14 days after wounding. Skin gelatin-treated diabetic rats showed a better wound closure, increased MVD, VEGF, hyproxyproline and NO contents and a reduced extent of inflammatory response. All parameters were significant (P < 0.05) in comparison to vehicle-treated diabetic group. In light of our finding that skin gelatin of Chum Salmon promotes skin wound repair in diabetic rats, we propose that oral administration of Chum Salmon skin gelatin might be a beneficial method for treating wound disorders associated with diabetes

    Early molecular layer interneuron hyperactivity triggers Purkinje neuron degeneration in SCA1.

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    Toxic proteinaceous deposits and alterations in excitability and activity levels characterize vulnerable neuronal populations in neurodegenerative diseases. Using in vivo two-photon imaging in behaving spinocerebellar ataxia type 1 (Sca1) mice, wherein Purkinje neurons (PNs) degenerate, we identify an inhibitory circuit element (molecular layer interneurons [MLINs]) that becomes prematurely hyperexcitable, compromising sensorimotor signals in the cerebellum at early stages. Mutant MLINs express abnormally elevated parvalbumin, harbor high excitatory-to-inhibitory synaptic density, and display more numerous synaptic connections on PNs, indicating an excitation/inhibition imbalance. Chemogenetic inhibition of hyperexcitable MLINs normalizes parvalbumin expression and restores calcium signaling in Sca1 PNs. Chronic inhibition of mutant MLINs delayed PN degeneration, reduced pathology, and ameliorated motor deficits in Sca1 mice. Conserved proteomic signature of Sca1 MLINs, shared with human SCA1 interneurons, involved the higher expression of FRRS1L, implicated in AMPA receptor trafficking. We thus propose that circuit-level deficits upstream of PNs are one of the main disease triggers in SCA1
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