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  • 1
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    Replication of single-stranded DNA templates by primase-polymerase complexes of the yeast,Saccharomyces cerevisiae (1988)
    Oxford University Press
    Details
    Publication Date: 1988-01-01
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Comparison of haplotype-based statistical tests for disease association with rare and common variants (2016)
    Oxford University Press
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    Publication Date: 2016-07-16
    Description: Recent literature has highlighted the advantages of haplotype association methods for detecting rare variants associated with common diseases. As several new haplotype association methods have been proposed in the past few years, a comparison of new and standard methods is important and timely for guidance to the practitioners. We consider nine methods—Haplo.score, Haplo.glm, Hapassoc, Bayesian hierarchical Generalized Linear Model (BhGLM), Logistic Bayesian LASSO (LBL), regularized GLM (rGLM), Haplotype Kernel Association Test, wei-SIMc-matching and Weighted Haplotype and Imputation-based Tests. These can be divided into two types—individual haplotype-specific tests and global tests depending on whether there is just one overall test for a haplotype region (global) or there is an individual test for each haplotype in the region. Haplo.score is the only method that tests for both; Haplo.glm, Hapassoc, BhGLM and LBL are individual haplotype-specific, while the rest are global tests. For comparison, we also apply a popular collapsing method—Sequence Kernel Association Test (SKAT) and its two variants—SKAT-O (Optimal) and SKAT-C (Combined). We carry out an extensive comparison on our simulated data sets as well as on the Genetic Analysis Workshop (GAW) 18 simulated data. Further, we apply the methods to GAW18 real hypertension data and Dallas Heart Study sequence data. We find that LBL, Haplo.score (global test) and rGLM perform well over the scenarios considered here. Also, haplotype methods are more powerful (albeit more computationally intensive) than SKAT and its variants in scenarios where multiple causal variants act interactively to produce haplotype effects.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
    Published by Oxford University Press
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  • 3
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    SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKC{beta} (2016)
    Oxford University Press
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    Publication Date: 2016-05-27
    Description: Emergence of drug resistance during visceral leishmaniasis (VL) is a major obstacle imposed during successful therapy. An effective vaccine strategy against this disease is therefore necessary. Our present study exploited the SLA (soluble leishmanial antigen) and PGN (peptidoglycan) stimulated bone marrow-derived dendritic cells (DCs) as a suitable vaccine candidate during experimental VL. SLA-PGN-stimulated DCs showed a significant decrease in hepatic and splenic parasite burden, which were associated with increased production of nitric oxide and pro-inflammatory cytokines such as IL-12, IFN- and IL-17. Elevated level of IL-17 was accompanied with the generation of more Th17 cells. Further studies on DC provided the evidence that these SLA-PGN-stimulated DCs played an important role in providing necessary cytokines such as IL-6, IL-23 and TGF-β for the generation of Th17 cells. Interestingly, inhibition of protein kinase C-β (PKCβ) in DCs led to decreased production of Th17 polarizing cytokines, causing reduction of the Th17 population size. Altogether, our finding highlighted the important role of DC-based PKCβ in regulation of the function and generation of Th17 cells.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 4
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    Scanning electron microscopy of scale microstructures in Channa barca, a poorly known snake head fish in regard to taxonomy (2015)
    Oxford University Press
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    Publication Date: 2015-10-10
    Description: Scanning electron microscopy has been identified as an important approach in studying scale microstructures in fish with reference to taxonomy. In this article, a detailed microstructural analysis of the scales of Channa barca , a poorly known snakehead fish was carried out the location of focus, inter-radial distance, average width and inter-circular space of anterior circulii; inter-circular distance and dentition in lateral circulii; the shape, spacing, length of lepidonts in anterior circulii and the number and width of radii were compared with those of a related species, Channa aurantimaculata . The location of the focus was found to be similar to those of the gachua group of the genus Channa but was different from those of the marulius group. There were major similarities—though with a few notable differences—in scale microstructures between C. barca and the aforementioned closely related species C. aurantimaculata , indicating that scale microstructure analysis has the potential to distinguish even closely related fish species . While several of the microstructural features of the scale were found to be similar to those of the gachua group, others were closer in nature to those of the marulius group. Some microstructural characteristics, however, were found to be totally different from those of both gachua and marulius groups. All of these characteristic features of scale microstructure in C. barca are discussed with reference to taxonomic significance.
    Print ISSN: 0022-0744
    Electronic ISSN: 1477-9986
    Topics: Electrical Engineering, Measurement and Control Technology , Natural Sciences in General , Physics
    Published by Oxford University Press on behalf of The Japanese Electron Microscopy Society.
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  • 5
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    ISQuest: finding insertion sequences in prokaryotic sequence fragment data (2015)
    Oxford University Press
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    Publication Date: 2015-10-21
    Description: Motivation: Insertion sequences (ISs) are transposable elements present in most bacterial and archaeal genomes that play an important role in genomic evolution. The increasing availability of sequenced prokaryotic genomes offers the opportunity to study ISs comprehensively, but development of efficient and accurate tools is required for discovery and annotation. Additionally, prokaryotic genomes are frequently deposited as incomplete, or draft stage because of the substantial cost and effort required to finish genome assembly projects. Development of methods to identify IS directly from raw sequence reads or draft genomes are therefore desirable. Software tools such as Optimized Annotation System for Insertion Sequences and IScan currently identify IS elements in completely assembled and annotated genomes; however, to our knowledge no methods have been developed to identify ISs from raw fragment data or partially assembled genomes. We have developed novel methods to solve this computationally challenging problem, and implemented these methods in the software package ISQuest. This software identifies bacterial ISs and their sequence elements—inverted and direct repeats—in raw read data or contigs using flexible search parameters. ISQuest is capable of finding ISs in hundreds of partially assembled genomes within hours, making it a valuable high-throughput tool for a global search of IS elements. We tested ISQuest on simulated read libraries of 3810 complete bacterial genomes and plasmids in GenBank and were capable of detecting 82% of the ISs and transposases annotated in GenBank with 80% sequence identity. Contact : abiswas@cs.odu.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 6
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    Invaders' control on post-disturbance succession in coastal mangroves (2012)
    Oxford University Press
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    Publication Date: 2012-04-13
    Description: Aims In recent years, coastal mangroves have been frequently affected by large disturbances (cyclones, hurricanes, flooding and tsunamis) and post-disturbance vegetation is often dominated by small stature mangrove, mangrove-associate and non-mangrove species potentially affecting ecosystem functioning. Knowledge on the processes of mangrove vegetation development and recovery (succession) following normal and large disturbances will benefit practitioners in designing robust ecosystem management/restoration plans. Here we propose a conceptual model of disturbance-mediated succession in mangroves. Methods Based on field observations and species’ life history traits, we develop conceptual models of mangrove succession under normal disturbance regime and recently experienced increased frequency of large disturbances. We evaluate our conceptual models by conducting a scenario testing experiment. Important Findings We suggest two predominant processes affecting mangrove succession after disturbance: propagule limitation due to damage of seed producing mature trees and dispersal barrier resulting from biological invasion associated with large disturbance. We argue that large disturbances affect mature trees more than the small-stature non-tree (shrubs, herbs and climbers) species creating a larger propagule shortage for mangrove tree species than non-tree species. Secondly, large disturbances facilitate invasion of free-floating aquatics, which may interfere with the flow-facilitated propagule dispersal and seedling establishment of mangrove species. In a scenario testing experiment, we have shown that similar levels of disturbance impact vegetation development and recovery differently depending on the presence or absence of invasive species. We conclude that since biological invasion is one of the major drivers of post-disturbance mangrove succession, the dimension of biological invasion should be included in prediction, management and restoration of mangrove forests.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Stability of Curcuma longa rhizome lectin: Role of N-linked glycosylation (2016)
    Oxford University Press
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    Publication Date: 2016-02-26
    Description: Curcuma longa rhizome lectin, a mannose-binding protein of non-seed portions of turmeric, is known to have antifungal, antibacterial and α-glucosidase inhibitory activities. We studied the role of complex-type glycans attached to asparagine (Asn) 66 and Asn 110 to elucidate the role of carbohydrates in lectin activity and stability. Apart from the native lectin, the characteristics of a deglycosylated Escherichia coli expressed lectin, high-mannose oligosaccharides at both asparagines and its glycosylation mutants N66Q and N110Q expressed in Pichia pastoris , were compared to understand the relationship between glycosylation and activity. Far UV circular dichroism (CD) spectra, fluorescence emission maximum, hemagglutination assay show no change in secondary or tertiary structures or sugar-binding properties between wild-type and aforementioned recombinant lectins under physiological pH. But reduced agglutination activity and loss of tertiary structure are observed in the acidic pH range for the deglycosylated and the N110Q protein. In thermal and guanidine hydrochloride (GdnCl)-induced unfolding, the wild-type and high-mannose lectins possess higher stability compared with the deglycosylated recombinant lectin and both mutants, as measured by a higher T m of denaturation or a greater free energy change, respectively. Reversibility experiments after thermal denaturation reveal that deglycosylated proteins tend to aggregate during thermal inactivation but the wild type shows a much greater recovery to the native state upon refolding. These results suggest that N-glycosylation in turmeric lectin is important for the maintenance of its proper folding upon changes in pH, and that the oligosaccharides help in maintaining the active conformation and prevent aggregation in unfolded or partially folded molecules.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    Pseudo-real principal G-bundles over a real curve (2016)
    Oxford University Press
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    Publication Date: 2016-01-24
    Description: We consider stable and semistable principal bundles over a smooth projective real algebraic curve, equipped with a real or pseudo-real structure in the sense of Atiyah. After fixing appropriate topological invariants, one can build a suitable gauge theory, and show that the resulting moduli spaces of pseudo-real bundles are connected. This in turn allows one to describe the various fixed point varieties on the complex moduli spaces under the action of the real involutions on the curve and the structure group.
    Print ISSN: 0024-6107
    Electronic ISSN: 1469-7750
    Topics: Mathematics
    Published by Oxford University Press
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  • 9
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    Functional evaluation of BRCA2 variants mapping to the PALB2-binding and C-terminal DNA-binding domains using a mouse ES cell-based assay (2012)
    Oxford University Press
    Details
    Publication Date: 2012-08-28
    Description: Single-nucleotide substitutions and small in-frame insertions or deletions identified in human breast cancer susceptibility genes BRCA1 and BRCA2 are frequently classified as variants of unknown clinical significance (VUS) due to the availability of very limited information about their functional consequences. Such variants can most reliably be classified as pathogenic or non-pathogenic based on the data of their co-segregation with breast cancer in affected families and/or their co-occurrence with a pathogenic mutation. Biological assays that examine the effect of variants on protein function can provide important information that can be used in conjunction with available familial data to determine the pathogenicity of VUS. In this report, we have used a previously described mouse embryonic stem (mES) cell-based functional assay to characterize eight BRCA2 VUS that affect highly conserved amino acid residues and map to the N-terminal PALB2-binding or the C-terminal DNA-binding domains. For several of these variants, very limited co-segregation information is available, making it difficult to determine their pathogenicity. Based on their ability to rescue the lethality of Brca2- deficient mES cells and their effect on sensitivity to DNA-damaging agents, homologous recombination and genomic integrity, we have classified these variants as pathogenic or non-pathogenic. In addition, we have used homology-based modeling as a predictive tool to assess the effect of some of these variants on the structural integrity of the C-terminal DNA-binding domain and also generated a knock-in mouse model to analyze the physiological significance of a residue reported to be essential for the interaction of BRCA2 with meiosis-specific recombinase, DMC1.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway (2014)
    Oxford University Press
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    Publication Date: 2014-03-20
    Description: Neuronal ceroid lipofuscinosis (NCL) comprises ~13 genetically distinct lysosomal disorders primarily affecting the central nervous system. Here we report successful reprograming of patient fibroblasts into induced pluripotent stem cells (iPSCs) for the two most common NCL subtypes: classic late-infantile NCL, caused by TPP1(CLN2) mutation, and juvenile NCL, caused by CLN3 mutation. CLN2/TPP1- and CLN3-iPSCs displayed overlapping but distinct biochemical and morphological abnormalities within the endosomal–lysosomal system. In neuronal derivatives, further abnormalities were observed in mitochondria, Golgi and endoplasmic reticulum. While lysosomal storage was undetectable in iPSCs, progressive disease subtype-specific storage material was evident upon neural differentiation and was rescued by reintroducing the non-mutated NCL proteins. In proof-of-concept studies, we further documented differential effects of potential small molecule TPP1 activity inducers. Fenofibrate and gemfibrozil, previously reported to induce TPP1 activity in control cells, failed to increase TPP1 activity in patient iPSC-derived neural progenitor cells. Conversely, nonsense suppression by PTC124 resulted in both an increase of TPP1 activity and attenuation of neuropathology in patient iPSC-derived neural progenitor cells. This study therefore documents the high value of this powerful new set of tools for improved drug screening and for investigating early mechanisms driving NCL pathogenesis.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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