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1.
Past studies have suggested that a key feature of the mechanism of heparin allosteric activation of the anticoagulant serpin, antithrombin, is the release of the reactive center loop P14 residue from a native state stabilizing interaction with the hydrophobic core. However, more recent studies have indicated that this structural change plays a secondary role in the activation mechanism. To clarify this role, we expressed and characterized 15 antithrombin P14 variants. The variants exhibited basal reactivities with factors Xa and IXa, heparin affinities and thermal stabilities that were dramatically altered from wild type, consistent with the P14 mutations perturbing native state stability and shifting an allosteric equilibrium between native and activated states. Rapid kinetic studies confirmed that limiting rate constants for heparin allosteric activation of the mutants were altered in conjunction with the observed shifts of the allosteric equilibrium. However, correlations of the P14 mutations'' effects on parameters reflecting the allosteric activation state of the serpin were inconsistent with a two-state model of allosteric activation and suggested multiple activated states. Together, these findings support a minimal three-state model of allosteric activation in which the P14 mutations perturb equilibria involving distinct native, intermediate, and fully activated states wherein the P14 residue retains an interaction with the hydrophobic core in the intermediate state but is released from the core in the fully activated state, and the bulk of allosteric activation has occurred in the intermediate.  相似文献   
2.
目的:探讨颈围用于筛选糖调节受损人群的临床价值。方法:选取哈尔滨市第一医院2017年3月至11月收治的糖调节受损患者共100例,男性颈围以38 cm为临界值,女性以35 cm为临界值,分为颈围正常组和颈围异常组,比较两组患者空腹及餐后血糖、空腹胰岛素、糖化血红蛋白、总胆固醇、甘油三酯、低密度脂蛋白等相关指标水平,并分析颈围与以上指标的相关性。结果:颈围异常组患者的餐后2 h血糖、空腹胰岛素、糖化血红蛋白、总胆固醇、甘油三酯、低密度脂蛋白数值高于颈围正常组,尤以甘油三酯明显,高密度脂蛋白数值低于颈围正常组,差异有统计学意义(P0.05)。颈围与餐后2 h血糖、总胆固醇、甘油三酯、低密度脂蛋白水平呈正相关,差异均有统计学意义(P0.05),颈围与高密度脂蛋白水平呈负相关,差异均有统计学意义(P0.05)。结论:颈围可以作为临床预测、评估糖调节受损患者的早期指标,为早期社区筛查及诊断提供相关的参考依据。  相似文献   
3.
经过多年探索,对肝脏疾病的研究已取得重大进展,但其发病机制复杂,目前仍未完全阐明。长链非编码RNA(long noncoding RNA,lnc RNA)是非编码RNA中的一种,不具有蛋白编码功能。研究发现,lnc RNA参与调控多种肝脏疾病的生理和病理过程,能在表观遗传、转录和转录后水平发挥重要的调节作用,提示我们lnc RNA可能成为一个新的治疗突破口。本文针对当前lnc RNA在肝疾病中的功能及作用机制进行综述。首先介绍了lnc RNA的功能,再将计算机与生物学相结合概括lnc RNA的四个研究步骤,包括筛选、鉴定、预测及验证,重点阐述lnc RNA与肝纤维化、肝硬化、肝癌及肝移植的近期研究成果,并进一步探讨未来lnc RNA在肝病中的研究方向和应用前景。充分了解肝病的研究现状以及与肝病发生发展有关的lnc RNA分子和生物学功能,为后续研究肝病的机制和治疗提供理论依据和借鉴。  相似文献   
4.
Groucho (Gro) is a Drosophila co-repressor that regulates the expression of a large number of genes, many of which are involved in developmental control. Previous studies have shown that its central region is essential for function even though its three domains are poorly conserved and intrinsically disordered. Using these disordered domains as affinity reagents, we have now identified multiple embryonic Gro-interacting proteins. The interactors include protein complexes involved in chromosome organization, mRNA processing, and signaling. Further investigation of the interacting proteins using a reporter assay showed that many of them modulate Gro-mediated repression either positively or negatively. The positive regulators include components of the spliceosomal subcomplex U1 small nuclear ribonucleoprotein (U1 snRNP). A co-immunoprecipitation experiment confirms this finding and suggests that a sizable fraction of nuclear U1 snRNP is associated with Gro. The use of RNA-seq to analyze the gene expression profile of cells subjected to knockdown of Gro or snRNP-U1-C (a component of U1 snRNP) showed a significant overlap between genes regulated by these two factors. Furthermore, comparison of our RNA-seq data with Gro and RNA polymerase II ChIP data led to a number of insights, including the finding that Gro-repressed genes are enriched for promoter-proximal RNA polymerase II. We conclude that the Gro central domains mediate multiple interactions required for repression, thus functioning as a regulatory hub. Furthermore, interactions with the spliceosome may contribute to repression by Gro.  相似文献   
5.
The European pond turtle, Emys orbicularis (Linnaeus, 1758), is one of the world's most widely distributed chelonian species. We investigated its mitochondrial phylogeography and demography using ∼1300 cyt b sequences from the entire range, with a focus on the eastern part, in particular on Turkey, where the species currently suffers massive losses. Coloration data from >1450 turtles were compared with mtDNA differentiation to assess the validity of the currently accepted subspecies from Turkey, the Black Sea Region, the Transcaucasus, and Iran. Our study region harbors considerable part of the mtDNA diversity of Emys, including a newly discovered lineage and 16 new haplotypes. In this area corresponding to approximately one-third of the entire distribution range, six out of the ten mitochondrial lineages and about half of all 72 haplotypes occur. Two mitochondrial lineages (VIII, X) are confined to small ranges along the southern coast of Turkey, another lineage (I) occupies the remainder of Turkey, the entire Black Sea Region, and the north-eastern part of the species’ range. In the south-western corner of the Black Sea and in the Aegean Region, two lineages (II, IV) occur that have their main distribution areas farther west. In the Transcaucasus and northern Iran, another endemic lineage (VII) is found. Lineage I is the largest and most diverse of all lineages and has its greatest diversity in Anatolia. Phylogeographic and demographic data suggest Anatolia as an ancient glacial refuge for turtles harboring mitochondrial lineages I, VIII and X, and that Anatolia and the Black Sea coasts constitute a hotspot for a younger burst of diversification within lineage I. These two regions correspond to the glacial refuge from which lineage I turtles recolonized more northerly parts of the range in the Holocene; lineage II represents an off-shoot of lineage I that became isolated in a westward-located refuge in the south-eastern Balkans during a previous Pleistocene glacial. Our data on coloration indicate that such characters have only limited value for delineating evolutionarily significant units. We propose to reduce the number of subspecies using mtDNA lineages as arbiter, and to recognize three subspecies as valid in Turkey, the Black Sea Region, the Transcaucasus and Iran: Emys orbicularis orbicularis (mtDNA lineage I); E. o. eiselti Fritz et al., 1998 (X); and E. o. persica Eichwald, 1831 (VII). However, the southern Turkish lineage VIII most probably represents an additional undescribed subspecies. Both southern Turkish endemics are critically endangered, with only three surviving populations of fewer than 30 adults each. We recommend establishing sanctuaries for them, and including them in the IUCN Red List.  相似文献   
6.
Genetic and morphological structure of tub gurnard Chelidonichthys lucerna populations in Turkish marine waters were investigated with mtDNA sequencing of 16S rRNA and morphological characters. C. lucerna samples were collected from the Black Sea, Marmara, Aegean and northeastern Mediterranean coasts of Turkey. The lowest genetic diversity was found in the northeastern Mediterranean (Iskenderun Bay) population, while the highest was in the Marmara population with overall average value of genetic diversity within populations. A total of 14 haplotypes was found, and the highest haplotype diversity was in the Black Sea whereas the lowest was in the northeastern Mediterranean population (Iskenderun Bay). The Black Sea and Iskenderun Bay populations showed the least genetic divergence (0.001081), while the highest was between the Marmara Sea and northeastern Mediterranean (Antalya Bay) populations (0.002067). Pairwise comparisons of genetic distance revealed statistically significant differences (P < 0.05) between the Marmara and both the Aegean and northeastern Mediterranean (Antalya Bay) samples. Neighbour joining tree analyses clustered the northeastern Mediterranean populations (Antalya Bay and Iskenderun Bay) as genetically more interrelated populations, whereas the Aegean Sea population was clustered as most isolated one. Discriminant function analysis of morphological characters showed that only the Black Sea population is differentiated from the other populations.  相似文献   
7.
We characterized fifteen microsatellite markers for the butterfly Maniola jurtina. For the six studied populations (96 samples) the total number of alleles per locus ranged from 3 to 55 and mean overall expected heterozygosity across all loci was 0.74. In spite of a high frequency of null alleles detected in part of the loci, a recurrent phenomenon in Lepidopteron, the estimation of pairwise FST seems rather insensitive to the presence of these null alleles as shown by the high correlation between FST calculated after correction for the presence of null alleles and non-corrected FST, indicating that the loci may be usable in population genetics, more specifically for the study of populations genetics structure.  相似文献   
8.
Manila clam Ruditapes philippinarum – synonym Venerupis philippinarum (Adams and Reeve, 1850) – is one of the most successful marine invaders, being introduced worldwide for aquaculture and fisheries. Genetic diversity and structure of its populations are largely unknown, especially in the invaded environments. Herein we present molecular genetic data on 12 introduced Manila clam populations in Italy, Spain, and Portugal from both Mediterranean (Adriatic) and Atlantic sampling sites. The phylogenetic information was investigated by the direct sequencing of 16S mitochondrial DNA. Results of mtDNA analyses showed the occurrence of 11 haplotypes for European introduced populations, as a consequence of multiple founder effects from different source populations. Rp hap1 was the most frequent, shared among all populations. The other 10 haplotypes were rare and distributed at local scale, in agreement with what was observed in other invasive bivalves. Biogeographic and phylogenetic analyses based on 16S rDNA of introduced Manila clam populations showed a complex scenario, dominated by multiple pools of individuals coming from different sources, as a consequence of multiple introductions.  相似文献   
9.
  1. Top‐down population regulation can influence the success of biological control agents when they are released into the field. Entomopathogenic nematodes (EPNs) are used commonly in biological control programmes, but their efficacy suffers from poor persistence. Although abiotic soil conditions have been shown to reduce EPN persistence, consumption of infected insects by scavengers and of infective juvenile (IJ) nematodes by predators may also regulate these populations. In the present study, the effects of different soil arthropods on EPNs in laboratory conditions were measured. It was hypothesised that arthropods commonly found in soil communities where EPNs are applied would consume cadavers of insects parasitised by the nematodes and the IJs themselves.
  2. Some species of scavengers consume EPN‐infected insects. Crickets (Gryllus bimaculatus De Geer), American cockroaches [Periplaneta Americana (Linnaeus)], ants [Tetramorium chefketi Forel and Pheidole pallidula (Nylander)], earwigs (Labidura riparia Pallas), mites (Sancassania polyphyllae Zachvatkin), and springtails (Sinella curviseta Brook and Folsomia candida Willem) have different responses to nematode‐killed insects. Results suggested that ants (T. chefketi), cockroaches, mites, and earwigs fed on Steinernema‐killed insects whereas neither crickets nor springtails consumed them.
  3. In the second part of the study, experiments were conducted to determine whether mites and springtails consumed IJ EPNs. Results showed that S. polyphyllae mites do not consume infective juveniles in soil, whereas both springtail species consumed significant numbers of the IJs.
  4. Top‐down regulatory processes can be a limiting factor for EPN populations under laboratory conditions. Both host cadavers and IJs are consumed (albeit by different arthropods), so these results may help explain the difficulties associated with the persistence of EPN application to soil.
  相似文献   
10.
在高中生物教学中,血糖平衡的调节一直是重要的教学内容。以往的教学设计思路主要是依靠教师讲述,学生被动接受,因此学生在学习上缺乏主动性。且由于内容比较抽象,学生很难真正理解。教师如何依据现代教育理论,通过组织和引导学生模拟血糖的调节机制,建构和不断修正动态的物理模型,再建构抽象的血糖调节的图解式概念模型,从而使学生深入理解血糖调节的机制,更好地理解体内激素对生命活动进行的调节,不仅是突破教学难点有效途径,对学生建立科学思维方式也具有重要的意义。结合课堂教学实际,介绍“建立血糖调节模型”的教学设计和“概念模型”的教学组织策略两个方面研究成果。  相似文献   
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