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  • 1
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    Invaders' control on post-disturbance succession in coastal mangroves (2012)
    Oxford University Press
    Details
    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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  • 2
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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
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    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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  • 3
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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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  • 4
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    A distribution-free two-sample run test applicable to high-dimensional data (2014)
    Oxford University Press
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    Publication Date: 2014-11-25
    Description: We propose a multivariate generalization of the univariate two-sample run test based on the shortest Hamiltonian path. The proposed test is distribution-free in finite samples. While most existing two-sample tests perform poorly or are even inapplicable to high-dimensional data, our test can be conveniently used in high-dimension, low-sample-size situations. We investigate its power when the sample size remains fixed and the dimension of the data grows to infinity. Simulated and real datasets demonstrate our method’s superiority over existing nonparametric two-sample tests.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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  • 5
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    On the Zariski-Lipman Conjecture for normal algebraic surfaces (2014)
    Oxford University Press
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    Publication Date: 2014-07-17
    Description: We consider the Zariski–Lipman Conjecture on a free module of derivations for algebraic surfaces. Using the theory of non-complete algebraic surfaces, and some basic results about ruled surfaces, we will prove the conjecture for several classes of affine and projective surfaces.
    Print ISSN: 0024-6107
    Electronic ISSN: 1469-7750
    Topics: Mathematics
    Published by Oxford University Press
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  • 6
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    Atomic force microscopy in biofilm study (2014)
    Oxford University Press
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    Publication Date: 2014-08-03
    Description: Biofilms have been classically visualized by Scanning Electron Microscopy (SEM). The complex operating procedure of SEM restricts its use in routine practice. There is a need of newer visualizing techniques for examining surfaces of biofilms, in particular under ambient conditions. We have presented the unique advantages of atomic force microscopy (AFM) in studying surfaces of biofilms through analyses of the height images obtained on biofilms of two gram positive and one gram negative bacteria, namely Staphylococcus aureus , Nocardia brasiliensis and Pseudomonas aeruginosa , respectively. Biofilm quality of the three different bacteria, ageing effects on Nocardia spp. biofilm surface and effects of the antibiotic ciprofloxacin at different doses on Staphylococcus and Pseudomonas biofilm surfaces have been investigated under ambient conditions and distinctive features have been observed.
    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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  • 7
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    The hnRNP F/H homologue of Trypanosoma brucei is differentially expressed in the two life cycle stages of the parasite and regulates splicing and mRNA stability (2013)
    Oxford University Press
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    Publication Date: 2013-07-16
    Description: Trypanosomes are protozoan parasites that cycle between a mammalian host (bloodstream form) and an insect host, the Tsetse fly (procyclic stage). In trypanosomes, all mRNAs are trans -spliced as part of their maturation. Genome-wide analysis of trans -splicing indicates the existence of alternative trans -splicing, but little is known regarding RNA-binding proteins that participate in such regulation. In this study, we performed functional analysis of the Trypanosoma brucei heterogeneous nuclear ribonucleoproteins (hnRNP) F/H homologue, a protein known to regulate alternative splicing in metazoa. The hnRNP F/H is highly expressed in the bloodstream form of the parasite, but is also functional in the procyclic form. Transcriptome analyses of RNAi-silenced cells were used to deduce the RNA motif recognized by this protein. A purine rich motif, AAGAA, was enriched in both the regulatory regions flanking the 3' splice site and poly (A) sites of the regulated genes. The motif was further validated using mini-genes carrying wild-type and mutated sequences in the 3' and 5' UTRs, demonstrating the role of hnRNP F/H in mRNA stability and splicing. Biochemical studies confirmed the binding of the protein to this proposed site. The differential expression of the protein and its inverse effects on mRNA level in the two lifecycle stages demonstrate the role of hnRNP F/H in developmental regulation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Infinitely divisible metrics and curvature inequalities for operators in the Cowen-Douglas class (2013)
    Oxford University Press
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    Publication Date: 2013-11-27
    Description: The curvature K T ( w ) of a contraction T in the Cowen–Douglas class B 1 (D) is bounded above by the curvature K S * ( w ) of the backward shift operator. However, in general, an operator satisfying the curvature inequality need not be contractive. In this paper, we characterize a slightly smaller class of contractions using a stronger form of the curvature inequality. Along the way, we find conditions on the metric of the holomorphic Hermitian vector bundle E T corresponding to the operator T in the Cowen–Douglas class B 1 (D) which ensures negative definiteness of the curvature function. We obtain a generalization for commuting tuples of operators in the class B 1 () for a bounded domain in C m .
    Print ISSN: 0024-6107
    Electronic ISSN: 1469-7750
    Topics: Mathematics
    Published by Oxford University Press
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  • 9
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    Accurate computational prediction of the transcribed strand of CRISPR non-coding RNAs (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-27
    Description: Motivation: CRISPR RNAs (crRNAs) are a type of small non-coding RNA that form a key part of an acquired immune system in prokaryotes. Specific prediction methods find crRNA-encoding loci in nearly half of sequenced bacterial, and three quarters of archaeal, species. These Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) arrays consist of repeat elements alternating with specific spacers. Generally one strand is transcribed, producing long pre-crRNAs, which are processed to short crRNAs that base pair with invading nucleic acids to facilitate their destruction. No current software for the discovery of CRISPR loci predicts the direction of crRNA transcription. Results: We have developed an algorithm that accurately predicts the strand of the resulting crRNAs. The method uses as input CRISPR repeat predictions. CRISPRDirection uses parameters that are calculated from the CRISPR repeat predictions and flanking sequences, which are combined by weighted voting. The prediction may use prior coding sequence annotation but this is not required. CRISPRDirection correctly predicted the orientation of 94% of a reference set of arrays. Availability and implementation: The Perl source code is freely available from http://bioanalysis.otago.ac.nz/CRISPRDirection . Contact: chris.brown@otago.ac.nz Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 10
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    MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension (2013)
    Oxford University Press
    Details
    Publication Date: 2013-08-23
    Description: Hypertension is a common hereditary syndrome with unclear pathogenesis. Chromogranin A (Chga), which catalyzes formation and cargo storage of regulated secretory granules in neuroendocrine cells, contributes to blood pressure homeostasis centrally and peripherally. Elevated Chga occurs in spontaneously hypertensive rat (SHR) adrenal glands and plasma, but central expression is unexplored. In this report, we measured SHR and Wistar–Kyoto rat (control) Chga expression in central and peripheral nervous systems, and found Chga protein to be decreased in the SHR brainstem, yet increased in the adrenal and the plasma. By re-sequencing, we systematically identified five promoter, two coding and one 3'-untranslated region (3'-UTR) polymorphism at the SHR (versus WKY or BN) Chga locus. Using HXB/BXH recombinant inbred (RI) strain linkage and correlations, we demonstrated genetic determination of Chga expression in SHR, including a cis-quantitative trait loci (QTLs) (i.e. at the Chga locus), and such expression influenced biochemical determinants of blood pressure, including a cascade of catecholamine biosynthetic enzymes, catecholamines themselves and steroids. Luciferase reporter assays demonstrated that the 3'-UTR polymorphism (which disrupts a microRNA miR-22 motif) and promoter polymorphisms altered gene expression consistent with the decline in SHR central Chga expression. Coding region polymorphisms did not account for changes in Chga expression or function. Thus, we hypothesized that the 3'-UTR and promoter mutations lead to dysregulation ( diminution ) of Chga in brainstem cardiovascular control nuclei, ultimately contributing to the pathogenesis of hypertension in SHR. Accordingly, we demonstrated that in vivo administration of miR-22 antagomir to SHR causes substantial (~18 mmHg) reductions in blood pressure, opening a novel therapeutic avenue for hypertension.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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