723 research outputs found
Examining the Role of Placental-derived MicroRNA Secretions in Response to Gestational Hypoxia on Foetal Neurodevelopment
Structural connectivity and white matter health in adults born very low birthweight.
Children born very preterm or with a very low birthweight (VLBW), are at a significantly elevated risk of brain injury from inflammation or hypoxic-ischaemic events. Resulting damage to pre-myelinating cells and other issues, commonly lead to diffuse and acute white matter injury with long term impacts on cognitive and motor function. On average, over one in ten births are now preterm. Mortality rates for preterm births have declined, but unfortunately, neurological disorders remain a major impairment for this group.
The New Zealand VLBW cohort enrolled all infants born VLBW in 1986, and has undergone several multi-disciplinary follow up studies. Most recently, this included comprehensive cranial MRI scans at an age between 26 and 30 years. The MRI session included diffusion-weighted imaging, to examine white matter health in early adulthood. Probabilistic tractography has been used to isolate whole white matter tracts and to construct structural networks.
Of the 42 tracts identified, 12 showed significantly reduced volumes in the VLBW cohort (n= 141) compared to controls born normal birthweight (n = 49). These included the acoustic radiations, left cortico-spinal tract, left superior thalamic radiation, forceps major and minor, and the inferior longitudinal fasciculi. This indicates that the impact of an early birth remains as smaller WM volumes in early adulthood. Only three tracts showed altered diffusion properties. The forceps major and left temporal cingulum subsection showed a reduction in fractional anisotropy; these two tracts, along with the right optic radiation, also show an increase in radial diffusivity. These diffusion properties indicate poorer white matter health for these tracts, but this is much less pronounced than is commonly reported in child and adolescent studies. Taken together, these results suggest that the white matter of VLBW individuals may eventually mature similarly to their term born peers, but with lasting reductions in volume.
Structural network analysis used: AAL3 parcellation; FSL’s probabilistic tractography; and two normalisations, a standard approach (waytotal) and a novel algorithm developed for this thesis (node strength normalisation). This analysis found the VLBW group had marginally increased global efficiency, with an unchanged characteristic path length, suggesting that the short paths may be shorter in the VLBW group. Mean clustering coefficient was significantly decreased, and node-wise clustering generally reflected this trend. Notably, the cerebellum showed a slightly higher clustering in the VLBW group potentially in relating to impaired motor function. Modularity was higher, indicating a stronger community structure in the scale of 20-40 nodes.This thesis also introduced a novel normalisation algorithm: node strength normalisation (NSN). This algorithm allows nodes to have their strengths estimated and scaled relative to each other, allowing meaningful comparisons between subjects, with minimal underlying assumptions. It is the hope that NSN will be applicable more broadly, improving the validity of structural network analyses across a wide range of neuroimaging applications
Fractal-like Distributions over the Rational Numbers in High-throughput Biological and Clinical Data
Recent developments in extracting and processing biological and clinical data are allowing quantitative approaches to studying living systems. High-throughput sequencing, expression profiles, proteomics, and electronic health records are some examples of such technologies. Extracting meaningful information from those technologies requires careful analysis of the large volumes of data they produce. In this note, we present a set of distributions that commonly appear in the analysis of such data. These distributions present some interesting features: they are discontinuous in the rational numbers, but continuous in the irrational numbers, and possess a certain self-similar (fractal-like) structure. The first set of examples which we present here are drawn from a high-throughput sequencing experiment. Here, the self-similar distributions appear as part of the evaluation of the error rate of the sequencing technology and the identification of tumorogenic genomic alterations. The other examples are obtained from risk factor evaluation and analysis of relative disease prevalence and co-mordbidity as these appear in electronic clinical data. The distributions are also relevant to identification of subclonal populations in tumors and the study of the evolution of infectious diseases, and more precisely the study of quasi-species and intrahost diversity of viral populations
Returning to an old question: What do television actors do when they act?
This article argues for acknowledging and exploring actors’ processes in critical considerations of television drama. Theatre Studies boasts a tradition of research privileging the actor, including a century’s worth of actor-training manuals, academic works observing rehearsals and performances, and actor accounts. However, such considerations within Television Studies are relatively nascent. Drawing upon continuing drama as a fertile case study for investigating the specificities of television acting, the article concludes that the only way to understand television acting is through the analysis of insights from actors themselves, in combination with the well-established practices of analysing the textual end-products of television acting
Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process
Breakage-Fusion-Bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. The process has parallels with paper folding sequences that arise when a piece of paper is folded several times and then unfolded. Here we adapt such methods to study the breakage-fusion-bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are 2^(n(n-1)/2) qualitatively distinct evolutions involving n breakage-fusion-bridge cycles. Secondly we consider the stochastic nature of the fold positions, to determine evolution likelihoods, and also describe how amplicons become localised. Finally we highlight these methods by inferring the evolution of breakage-fusion-bridge cycles with data from primary tissue cancer samples
A catalogue of ULX coincidences with FIRST radio sources
We search for ultra luminous X-ray source (ULXs) radio counterparts located
in nearby galaxies in order to constrain their physical nature. Our work is
based on a systematic cross-identification of the most recent and extensive
available ULX catalogues and archival radio data. A catalogue of 70 positional
coincidences is reported. Most of them are located within the galaxy nucleus.
Among them, we find 11 new cases of non-nuclear ULX sources with possibly
associated radio emission.Comment: Accepted for publication in A&A; 17 pages, 9 figure
Genotyping and annotation of Affymetrix SNP arrays
In this paper we develop a new method for genotyping Affymetrix single nucleotide polymorphism (SNP) array. The method is based on (i) using multiple arrays at the same time to determine the genotypes and (ii) a model that relates intensities of individual SNPs to each other. The latter point allows us to annotate SNPs that have poor performance, either because of poor experimental conditions or because for one of the alleles the probes do not behave in a dose–response manner. Generally, our method agrees well with a method developed by Affymetrix. When both methods make a call they agree in 99.25% (using standard settings) of the cases, using a sample of 113 Affymetrix 10k SNP arrays. In the majority of cases where the two methods disagree, our method makes a genotype call, whereas the method by Affymetrix makes a no call, i.e. the genotype of the SNP is not determined. By visualization it is indicated that our method is likely to be correct in majority of these cases. In addition, we demonstrate that our method produces more SNPs that are in concordance with Hardy–Weinberg equilibrium than the method by Affymetrix. Finally, we have validated our method on HapMap data and shown that the performance of our method is comparable to other methods
Amplification and Overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in Medulloblastoma
Medulloblastoma is the most common malignant brain tumour of childhood. The identification of critical genes involved in its pathogenesis will be central to advances in our understanding of its molecular basis, and the development of improved therapeutic approaches.We performed a SNP-array based genome-wide copy number analysis in medulloblastoma cell lines, to identify regions of genomic amplification and homozygous deletion, which may harbour critical disease genes. A series of novel and established medulloblastoma defects were detected (MYC amplification (n = 4), 17q21.31 high-level gain (n = 1); 9p21.1-p21.3 (n = 1) and 6q23.1 (n = 1) homozygous deletion). Most notably, a novel recurrent region of genomic amplification at 8q24.22-q24.23 was identified (n = 2), and selected for further investigation. Additional analysis by interphase fluorescence in situ hybridisation (iFISH), PCR-based mapping and SNP-array revealed this novel amplification at 8q24.22-q24.23 is independent of MYC amplification at 8q24.21, and is unique to medulloblastoma in over 800 cancer cell lines assessed from different tumour types, suggesting it contains key genes specifically involved in medulloblastoma development. Detailed mapping identified a 3Mb common minimal region of amplification harbouring 3 coding genes (ZFAT1, LOC286094, KHDRBS3) and two genes encoding micro-RNAs (hsa-miR-30b, hsa-miR-30d). Of these, only expression of hsa-miR-30b, hsa-miR-30d and KHDRBS3 correlated with copy number status, and all three of these transcripts also displayed evidence of elevated expression in sub-sets of primary medulloblastomas, measured relative to the normal cerebellum.These data implicate hsa-miR-30b, hsa-miR-30d and KHDRBS3 as putative oncogenic target(s) of a novel recurrent medulloblastoma amplicon at 8q24.22-q24.23. Our findings suggest critical roles for these genes in medulloblastoma development, and further support the contribution of micro-RNA species to medulloblastoma pathogenesis
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