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  • BioMed Central  (11)
  • Oxford University Press  (11)
  • Nature Publishing Group
  • 2010-2014  (22)
  • 1955-1959
  • 2014  (22)
  • 1
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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
    Details
    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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  • 2
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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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  • 3
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    A novel GPR40 agonist, CNX-011-67, suppresses glucagon secretion in pancreatic islets under chronic glucolipotoxic conditions in vitro (2014)
    BioMed Central
    Details
    Publication Date: 2014-09-04
    Description: Background: Elevated glucose concentrations lead to increased insulin secretion and suppression of glucagon secretion. In fact, insulin is a physiological inhibitor of glucagon secretion. Type 2 diabetes mellitus (T2DM) patients have defects in insulin secretion. In addition to this, lack of suppression of glucagon secretion under elevated glucose concentrations is also observed in T2DM patients. We have earlier shown that GPR40 activation by CNX-011-67 stimulates glucose stimulated insulin secretion (GSIS). Here we extended our studies to examine the impact of GPR40 activation by CNX-011-67 on glucagon secretion from intact islets under both normal and glucolipotoxic conditions.FindingsGlucagon secretion from intact rat islets was suppressed under elevated glucose concentration. Activation of GPR40 by CNX-011-67 further suppressed glucagon secretion. Culturing islets under chronic glucolipotoxic (GL) conditions, we have observed increased high glucose mediated glucagon secretion and content which were reduced with GPR40 activation by CNX-011-67. Interestingly, expression of pre-proglucagon gene (GCG) remained unchanged under glucolipotoxicity in the presence or absence of GPR40 activation. Conclusion: Activation of GPR40 by CNX-011-67 can reduce glucagon secretion from pancreatic islets.
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
    Published by BioMed Central
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  • 4
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    Molecular cloning and in-silico characterization of high temperature stress responsive pAPX gene isolated from heat tolerant Indian wheat cv. Raj 3765 (2014)
    BioMed Central
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    Publication Date: 2014-10-11
    Description: Background: Heat stress leads to accelerated production of reactive oxygen species (ROS) which causes a huge amount of oxidative damage to the cellular components of plants. A large number of heat stress related genes as HSPs, catalases, peroxidases are overexpressed at the time of stress. A potent stress responsive gene peroxisomal ascorbate peroxidase (TapAPX) obtained from heat stress (42[degree sign]C) responsive subtractive cDNA library from a thermo tolerant wheat cv. Raj3765 at anthesis stage was cloned, characterized and its role was validated under heat stress by proteomics and in-silico studies.. In the present study we report the characterization at molecular and in-silico level of peroxisomal TapAPX gene isolated from heat tolerant wheat cultivar of India. Results: qPCR studies of TapAPX gene displayed up to 203 fold level of expression at 42[degree sign]C heat stress exposure. A full length cDNA of 876 bp obtained by RACE deduced a protein of 292 amino acid residues which gives a complete 3D structure of pAPX by homology modeling. TapAPX cDNA was cloned in expression vector pET28 (a+) and the recombinant protein over-expressed in E. coli BL21 showed highest homology with APX protein as deduced by peptide mass fingerprinting. Conclusions: TapAPX gene from wheat cv Raj3765 has a distinct role in conferring thermo tolerance to the plants and thus can be used in crop improvement programmes for development of crops tolerant to high temperature.
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
    Published by BioMed Central
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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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    Procalcitonin as a prognostic marker for sepsis: a prospective observational study (2014)
    BioMed Central
    Details
    Publication Date: 2014-07-18
    Description: Background: Procalcitonin is useful for the diagnosis of sepsis but its prognostic value regarding mortality is unclear. This prospective observational study was designed to study the prognostic value of procalcitonin in prediction of 28 day mortality in patients of sepsis. Fifty-four consecutive patients of sepsis, severe sepsis and septic shock defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria from medical Intensive Care Unit (ICU) of a tertiary care center in New Delhi, India were enrolled from July 2011 to June 2013. Procalcitonin (PCT), C-reactive protein (CRP) measurements were recorded on day 1, day 7 and day 28 of follow up. Results: Procalcitonin value was a better predictor of all-cause short-term mortality than C-reactive protein. Those patients with Procalcitonin levels
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
    Published by BioMed Central
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  • 7
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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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  • 8
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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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  • 9
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    Scan for Motifs: a webserver for the analysis of post-transcriptional regulatory elements in the 3[prime] untranslated regions (3[prime] UTRs) of mRNAs (2014)
    BioMed Central
    Details
    Publication Date: 2014-06-09
    Description: Background: Gene expression in vertebrate cells may be controlled post-transcriptionally through regulatory elements in mRNAs. These are usually located in the untranslated regions (UTRs) of mRNA sequences, particularly the 3[prime]UTRs. Results: Scan for Motifs (SFM) simplifies the process of identifying a wide range of regulatory elements on alignments of vertebrate 3[prime]UTRs. SFM includes identification of both RNA Binding Protein (RBP) sites and targets of miRNAs. In addition to searching pre-computed alignments, the tool provides users the flexibility to search their own sequences or alignments. The regulatory elements may be filtered by expected value cutoffs and are cross-referenced back to their respective sources and literature. The output is an interactive graphical representation, highlighting potential regulatory elements and overlaps between them. The output also provides simple statistics and links to related resources for complementary analyses. The overall process is intuitive and fast. As SFM is a free web-application, the user does not need to install any software or databases. Conclusions: Visualisation of the binding sites of different classes of effectors that bind to 3[prime]UTRs will facilitate the study of regulatory elements in 3[prime] UTRs.
    Electronic ISSN: 1471-2105
    Topics: Biology , Computer Science
    Published by BioMed Central
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  • 10
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    Procalcitonin as a prognostic marker for sepsis: a prospective observational study (2014)
    BioMed Central
    Details
    Publication Date: 2014-07-22
    Description: Background: Procalcitonin is useful for the diagnosis of sepsis but its prognostic value regarding mortality is unclear. This prospective observational study was designed to study the prognostic value of procalcitonin in prediction of 28 day mortality in patients of sepsis. Fifty-four consecutive patients of sepsis, severe sepsis and septic shock defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria from medical Intensive Care Unit (ICU) of a tertiary care center in New Delhi, India were enrolled from July 2011 to June 2013. Procalcitonin (PCT), C-reactive protein (CRP) measurements were recorded on day 1, day 7 and day 28 of follow up. Results: Procalcitonin value was a better predictor of all-cause short-term mortality than C-reactive protein. Those patients with Procalcitonin levels
    Electronic ISSN: 1756-0500
    Topics: Biology , Medicine
    Published by BioMed Central
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