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1.
Srđan Đ. Stojanović Božidarka L. Zarić Snežana D. Zarić 《Journal of molecular modeling》2010,16(11):1743-1751
The distinguishing property of Sm protein associations is very high stability. In order to understand this property, we analyzed
the interfaces and compared the properties of Sm protein interfaces with those of a test set, the Binding Interface Database
(BID). The comparison revealed that the main differences between the interfaces of Sm proteins and those of the BID set are
the content of charged residues, the coordination numbers of the residues, knowledge-based pair potentials, and the conservation
scores of hot spots. In Sm proteins, the interfaces have more hydrophobic and fewer charged residues than the surfaces, which
is also the case for the BID test set and other proteins. However, in the interfaces, the content of charged residues in Sm
proteins (26%) is substantially larger than that in the BID set (22%). Hot spots are residues that make up a small fraction
of the interfaces, but they contribute most of the binding energy. These residues are critical to protein–protein interactions.
Analyses of knowledge-based pair potentials of hot spot and non-hot spot residues in Sm proteins show that they are significantly
different; their mean values are 31.5 and 11.3, respectively. In the BID set, this difference is smaller; in this case, the
mean values for hot spot and non-hot spot residues are 20.7 and 12.4, respectively. Hence, the pair potentials of hot spots
differ significantly for the Sm and BID data sets. In the interfaces of Sm proteins, the amino acids are tightly packed, and
the coordination numbers are larger in Sm proteins than in the BID set for both hot spots and non-hot spots. At the same time,
the coordination numbers are higher for hot spots; the average coordination number of the hot spot residues in Sm proteins
is 7.7, while it is 6.1 for the non-hot spot residues. The difference in the calculated average conservation score for hot
spots and non-hot spots in Sm proteins is significantly larger than it is in the BID set. In Sm proteins, the average conservation
score for the hot spots is 7.4. Hot spots are surrounded by residues that are moderately conserved (5.9). The average conservation
score for the other interface residues is 5.6. The conservation scores in the BID set do not show a significant distinction
between hot and non-hot spots: the mean values for hot and non-hot spot residues are 5.5 and 5.2, respectively. These data
show that structurally conserved residues and hot spots are significantly correlated in Sm proteins. 相似文献
2.
The resting metabolic rate (RMR) of seasonally-acclimated Mabuya brevicollis of various body masses was determined at 20, 25, 30, 35 and 40 °C, using open-flow respirometry. RMR (ml g−1 h−1) decreased with increasing mass at each temperature. RMRs increaProd. Type: FTPsed as temperature increased. The highest and lowest Q10 values were obtained for the temperature ranges 20–25 °C and 30–35 °C for the summer-acclimated lizards. The exponent of mass “b” in the metabolism-body mass relation ranged from 0.41 to 0.61. b values were lower in the autumn and winter-acclimated lizards than in spring and summer-acclimated lizards. Seasonal acclimation effects were evident at all temperatures (20–40 °C) for M. brevicollis. Winter-acclimated skinks had the lowest metabolic rates at different temperatures. The pattern of acclimation exhibited by M. brevicollis may represent a useful adaptation for lizards inhabiting subtropical deserts to promote activity during their active seasons. 相似文献
3.
Nesaei Abolfazl Naderi Ghale-noie Zari Khorshid Shamshiri Asma Afzaljavan Fahimeh Rivandi Mahdi Tajbakhsh Amir Homaei Shandiz Fatemeh Pasdar Alireza 《Molecular biology reports》2022,49(5):3549-3557
Molecular Biology Reports - Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease... 相似文献
4.
The investigation of associations between rare genetic variants and diseases or phenotypes has two goals. Firstly, the identification of which genes or genomic regions are associated, and secondly, discrimination of associated variants from background noise within each region. Over the last few years, many new methods have been developed which associate genomic regions with phenotypes. However, classical methods for high-dimensional data have received little attention. Here we investigate whether several classical statistical methods for high-dimensional data: ridge regression (RR), principal components regression (PCR), partial least squares regression (PLS), a sparse version of PLS (SPLS), and the LASSO are able to detect associations with rare genetic variants. These approaches have been extensively used in statistics to identify the true associations in data sets containing many predictor variables. Using genetic variants identified in three genes that were Sanger sequenced in 1998 individuals, we simulated continuous phenotypes under several different models, and we show that these feature selection and feature extraction methods can substantially outperform several popular methods for rare variant analysis. Furthermore, these approaches can identify which variants are contributing most to the model fit, and therefore both goals of rare variant analysis can be achieved simultaneously with the use of regression regularization methods. These methods are briefly illustrated with an analysis of adiponectin levels and variants in the ADIPOQ gene. 相似文献
5.
Woodland key habitat (WKH) inventories have been conducted in northern European countries, with the aim to create networks of minimally disturbed forest stands for protection. The goal of national forest inventory is to provide information relevant to forest management, such as on forest types, trees species composition, age structure and wood volume. The aim of this study was to link these two inventory databases to identify districts of Latvia most deficient in connectivity and habitat quality, in order to prioritize districts needing conservation effort. As an example, the area of deciduous forest with nemoral tree species (oak, ash, lime, maple and elm) and aspen was chosen. These forests provide habitat for a specific community of epiphytes. Using information in the WKH database, habitat quality in different districts of Latvia was estimated by the frequencies of occurrence of structural elements and selected indicator epiphyte species in nemoral tree species and aspen WKHs. Using digital data in the national forest inventory database, fragmentation metrics were determined for forests that, according to age and tree species composition, could potentially be nemoral tree and aspen WKHs. On a regional level, the lowest habitat quality in WKH occurred in districts that had the least fragmentation of potential WKH forest. In the less fragmented areas, the habitat quality of the existing WKH will likely increase in the future, and could be promoted by management to create structural elements typical of natural forests. The districts with the most fragmented nemoral and aspen forests, contained WKHs with the best habitat quality. A focus on protection should be given to these stands as they are the most likely to support source populations, and there is a need to improve spatial continuity of suitable tree substrate in these areas. 相似文献
6.
The role of rare genetic variation in the etiology of complex disease remains unclear. However, the development of next-generation sequencing technologies offers the experimental opportunity to address this question. Several novel statistical methodologies have been recently proposed to assess the contribution of rare variation to complex disease etiology. Nevertheless, no empirical estimates comparing their relative power are available. We therefore assessed the parameters that influence their statistical power in 1,998 individuals Sanger-sequenced at seven genes by modeling different distributions of effect, proportions of causal variants, and direction of the associations (deleterious, protective, or both) in simulated continuous trait and case/control phenotypes. Our results demonstrate that the power of recently proposed statistical methods depend strongly on the underlying hypotheses concerning the relationship of phenotypes with each of these three factors. No method demonstrates consistently acceptable power despite this large sample size, and the performance of each method depends upon the underlying assumption of the relationship between rare variants and complex traits. Sensitivity analyses are therefore recommended to compare the stability of the results arising from different methods, and promising results should be replicated using the same method in an independent sample. These findings provide guidance in the analysis and interpretation of the role of rare base-pair variation in the etiology of complex traits and diseases. 相似文献
7.
Dastani Z Hivert MF Timpson N Perry JR Yuan X Scott RA Henneman P Heid IM Kizer JR Lyytikäinen LP Fuchsberger C Tanaka T Morris AP Small K Isaacs A Beekman M Coassin S Lohman K Qi L Kanoni S Pankow JS Uh HW Wu Y Bidulescu A Rasmussen-Torvik LJ Greenwood CM Ladouceur M Grimsby J Manning AK Liu CT Kooner J Mooser VE Vollenweider P Kapur KA Chambers J Wareham NJ Langenberg C Frants R Willems-Vandijk K Oostra BA Willems SM Lamina C Winkler TW Psaty BM Tracy RP Brody J Chen I Viikari J Kähönen M 《PLoS genetics》2012,8(3):e1002607
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance. 相似文献
8.
Uribe A Zariñán T Pérez-Solis MA Gutiérrez-Sagal R Jardón-Valadez E Piñeiro A Dias JA Ulloa-Aguirre A 《Biology of reproduction》2008,78(5):869-882
The carboxyl-terminal segment of G protein-coupled receptors has one or more conserved cysteine residues that are potential sites for palmitoylation. This posttranslational modification contributes to membrane association, internalization, and membrane targeting of proteins. In contrast to other members of the glycoprotein hormone receptor family (the LH and thyroid-stimulating hormone receptors), it is not known whether the follicle-stimulating hormone receptor (FSHR) is palmitoylated and what are the effects of abolishing its potential palmitoylation sites. In the present study, a functional analysis of the FSHR carboxyl-terminal segment cysteine residues was carried out. We constructed a series of mutant FSHRs by substituting cysteine residues with alanine, serine, or threonine individually and together at positions 629 and 655 (conserved cysteines) and 627 (nonconserved). The results showed that all three cysteine residues are palmitoylated but that only modification at Cys629 is functionally relevant. The lack of palmitoylation does not appear to greatly impair coupling to G(s) but, when absent at position 629, does significantly impair cell surface membrane expression of the partially palmitoylated receptor. All FSHR Cys mutants were capable of binding agonist with the same affinity as the wild-type receptor and internalizing on agonist stimulation. Molecular dynamics simulations at a time scale of approximately 100 nsec revealed that replacement of Cys629 resulted in structures that differed significantly from that of the wild-type receptor. Thus, deviations from wild-type conformation may potentially contribute to the severe impairment in plasma membrane expression and the modest effects on signaling exhibited by the receptors modified in this particular position. 相似文献
9.
Saša N. Malkov Miodrag V. Živković Miloš V. Beljanski Srđan Đ. Stojanović Snežana D. Zarić 《The protein journal》2009,28(2):74-86
Using the data from Protein Data Bank the correlations of primary and secondary structures of proteins were analyzed. The
correlation values of the amino acids and the eight secondary structure types were calculated, where the position of the amino
acid and the position in sequence with the particular secondary structure differ at most 25. The diagrams describing these
results indicate that correlations are significant at distances between −9 and 10. The results show that the substituents
on Cβ or Cγ atoms of amino acid play major role in their preference for particular secondary structure at the same position
in the sequence, while the polarity of amino acid has significant influence on α-helices and strands at some distance in the
sequence. The diagrams corresponding to polar amino acids are noticeably asymmetric. The diagrams point out the exchangeability
of residues in the proteins; the amino acids with similar diagrams have similar local folding requirements.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
10.
Jamal S. M. Sabir Dhivya Arasappan Ahmed Bahieldin Salah Abo-Aba Sameera Bafeel Talal A. Zari Sherif Edris Ahmed M. Shokry Nour O. Gadalla Ahmed M. Ramadan Ahmed Atef Magdy A. Al-Kordy Fotoh M. El-Domyati Robert K. Jansen 《PloS one》2014,9(4)
Date palm is a very important crop in western Asia and northern Africa, and it is the oldest domesticated fruit tree with archaeological records dating back 5000 years. The huge economic value of this crop has generated considerable interest in breeding programs to enhance production of dates. One of the major limitations of these efforts is the uncertainty regarding the number of date palm cultivars, which are currently based on fruit shape, size, color, and taste. Whole mitochondrial and plastid genome sequences were utilized to examine single nucleotide polymorphisms (SNPs) of date palms to evaluate the efficacy of this approach for molecular characterization of cultivars. Mitochondrial and plastid genomes of nine Saudi Arabian cultivars were sequenced. For each species about 60 million 100 bp paired-end reads were generated from total genomic DNA using the Illumina HiSeq 2000 platform. For each cultivar, sequences were aligned separately to the published date palm plastid and mitochondrial reference genomes, and SNPs were identified. The results identified cultivar-specific SNPs for eight of the nine cultivars. Two previous SNP analyses of mitochondrial and plastid genomes identified substantial intra-cultivar ( = intra-varietal) polymorphisms in organellar genomes but these studies did not properly take into account the fact that nearly half of the plastid genome has been integrated into the mitochondrial genome. Filtering all sequencing reads that mapped to both organellar genomes nearly eliminated mitochondrial heteroplasmy but all plastid SNPs remained heteroplasmic. This investigation provides valuable insights into how to deal with interorganellar DNA transfer in performing SNP analyses from total genomic DNA. The results confirm recent suggestions that plastid heteroplasmy is much more common than previously thought. Finally, low levels of sequence variation in plastid and mitochondrial genomes argue for using nuclear SNPs for molecular characterization of date palm cultivars. 相似文献