Thin-shell instability in collisionless plasma

Thin-shell instability is one process which can generate entangled structures in astrophysical plasma on collisional (fluid) scales. It is driven by a spatially varying imbalance between the ram pressure of the inflowing upstream plasma and the downstream's thermal pressure at a nonplanar shock. Here we show by means of a particle-in-cell simulation that an analog process can destabilize a thin shell formed by two interpenetrating, unmagnetized, and collisionless plasma clouds. The amplitude of the shell's spatial modulation grows and saturates after about ten inverse proton plasma frequencies, when the shell consists of connected piecewise linear patches.

Maintaining and reprogramming genomic androgen receptor activity in prostate cancer

Prostate cancer treatment is dominated by strategies to control androgen receptor (AR) activity. AR has an impact on prostate cancer development through the regulation of not only transcription networks but also genomic stability and DNA repair, as manifest in the emergence of gene fusions. Whole-genome maps of AR binding sites and transcript profiling have shown changes in the recruitment and regulatory effect of AR on transcription as prostate cancer progresses. Defining other factors that are involved in this reprogramming of AR function gives various opportunities for cancer detection and therapeutic intervention.

New androgen receptor genomic targets show an interaction with the ETS1 transcription factor

The androgen receptor (AR) initiates important developmental and oncogenic transcriptional pathways. The AR is known to bind as a homodimer to 15-base pair bipartite palindromic androgen-response elements; however, few direct AR gene targets are known. To identify AR promoter targets, we used chromatin immunoprecipitation with on-chip detection of genomic fragments. We identified 1,532 potential AR-binding sites, including previously known AR gene targets. Many of the new AR target genes show altered expression in prostate cancer. Analysis of sequences underlying AR-binding sites showed that more than 50% of AR-binding sites did not contain the established 15 bp AR-binding element. Unbiased sequence analysis showed 6-bp motifs, which were significantly enriched and were bound directly by the AR in vitro. Binding sequences for the avian erythroblastosis virus E26 homologue (ETS) transcription factor family were also highly enriched, and we uncovered an interaction between the AR and ETS1 at a subset of AR promoter targets.

Gender-specific genomic profiling in metastatic colorectal cancer patients treated with 5-fluorouracil and oxaliplatin

AIMS: Survival and response rates in metastatic colorectal cancer remain poor, despite advances in drug development. There is increasing evidence to suggest that gender-specific differences may contribute to poor clinical outcome. We tested the hypothesis that genomic profiling of metastatic colorectal cancer is dependent on gender.

MATERIALS & METHODS: A total of 152 patients with metastatic colorectal cancer who were treated with oxaliplatin and continuous infusion 5-fluorouracil were genotyped for 21 polymorphisms in 13 cancer-related genes by PCR. Classification and regression tree analysis tested for gender-related association of polymorphisms with overall survival, progression-free survival and tumor response.

RESULTS: Classification and regression tree analysis of all polymorphisms, age and race resulted in gender-specific predictors of overall survival, progression-free survival and tumor response. Polymorphisms in the following genes were associated with gender-specific clinical outcome: estrogen receptor β, EGF receptor, xeroderma pigmentosum group D, voltage-gated sodium channel and phospholipase A2.

CONCLUSION: Genetic profiling to predict the clinical outcome of patients with metastatic colorectal cancer may depend on gender.

Using geotechnical and LIDAR spatial monitoring to determine key environmental slope instability thresholds of a Jurassic coastal landslide: Straidkilly Point, Northern Ireland, UK.

The Antrim Coast Road stretching from the seaport of Larne in the East of Northern Ireland to the famous Giant’s Causeway in the North has a well-deserved reputation for being one of the most spectacular roads in Europe (Day, 2006). At various locations along the route, fluid interactions between the problematic geology, Jurassic Lias Clay and Triassic Mudstone overlain by Cretaceous Limestone and Tertiary Basalt, and environmental variables result in frequent instances of slope instability within the vadose zone. During such instances of instability, debris flows and composite mudflows encroach on the carriageway posing a hazard to road users. This paper examines the site investigative, geotechnical and spatial analysis techniques currently being implemented to monitor slope stability for one site at Straidkilly Point, Glenarm, Northern Ireland. An in-depth understanding of the geology was obtained via boreholes, resistivity surveys and laboratory testing. Environmental variables recorded by an on-site weather station were correlated with measured pore water pressure and soil moisture infiltration dynamic data.
Terrestrial LiDAR (TLS) was applied to the slope for the monitoring of failures, with surveys carried out on a bi-monthly basis. TLS monitoring allowed for the generation of Digital Elevation Models (DEMs) of difference, highlighting areas of recent movement, erosion and deposition. Morphology parameters were generated from the DEMs and include slope, curvature and multiple measures of roughness. Changes in the structure of the slope coupled with morphological parameters are characterised and linked to progressive failures from the temporal monitoring. In addition to TLS monitoring, Aerial LiDARi datasets were used for the spatio-morphological characterisation of the slope on a macro scale. Results from the geotechnical and environmental monitoring were compared with spatial data obtained through Terrestrial and Airborne LiDAR, providing a multi-faceted approach to slope stability characterization, which facilitates more informed management of geotechnical risk by the Northern Ireland Roads Service.

Genomic Resources Notes Accepted 1 June 2015 - 31 July 2015

This article documents the public availability of (i) microbiomes in diet and gut of larvae from the dipteran Dilophus febrilis using massive parallel sequencing, (ii) SNP and SSR discovery and characterization in the transcriptome of the Atlantic mackerel (Scomber scombrus, L) and (iii) assembled transcriptome for an endangered, endemic Iberian cyprinid fish (Squalius pyrenaicus).

A genomic island linked to ecotype divergence in Atlantic cod

The genomic architecture underlying ecological divergence and ecological speciation with gene flow is still largely unknown for most organisms. One central question is whether divergence is genome-wide or localized in 'genomic mosaics' during early stages when gene flow is still pronounced. Empirical work has so far been limited, and the relative impacts of gene flow and natural selection on genomic patterns have not been fully explored. Here, we use ecotypes of Atlantic cod to investigate genomic patterns of diversity and population differentiation in a natural system characterized by high gene flow and large effective population sizes, properties which theoretically could restrict divergence in local genomic regions. We identify a genomic region of strong population differentiation, extending over approximately 20 cM, between pairs of migratory and stationary ecotypes examined at two different localities. Furthermore, the region is characterized by markedly reduced levels of genetic diversity in migratory ecotype samples. The results highlight the genomic region, or 'genomic island', as potentially associated with ecological divergence and suggest the involvement of a selective sweep. Finally, we also confirm earlier findings of localized genomic differentiation in three other linkage groups associated with divergence among eastern Atlantic populations. Thus, although the underlying mechanisms are still unknown, the results suggest that 'genomic mosaics' of differentiation may even be found under high levels of gene flow and that marine fishes may provide insightful model systems for studying and identifying initial targets of selection during ecological divergence.

Genomic markers for decision making:What is preventing us from using markers?

The advent of novel genomic technologies that enable the evaluation of genomic alterations on a genome-wide scale has significantly altered the field of genomic marker research in solid tumors. Researchers have moved away from the traditional model of identifying a particular genomic alteration and evaluating the association between this finding and a clinical outcome measure to a new approach involving the identification and measurement of multiple genomic markers simultaneously within clinical studies. This in turn has presented additional challenges in considering the use of genomic markers in oncology, such as clinical study design, reproducibility and interpretation and reporting of results. This Review will explore these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the use of putative genomic markers in the clinic. Despite these rapid technological advances there is still a paucity of genomic markers in routine clinical use at present. A rational and focused approach to the evaluation and validation of genomic markers is needed, whereby analytically validated markers are investigated in clinical studies that are adequately powered and have pre-defined patient populations and study endpoints. Furthermore, novel adaptive clinical trial designs, incorporating putative genomic markers into prospective clinical trials, will enable the evaluation of these markers in a rigorous and timely fashion. Such approaches have the potential to facilitate the implementation of such markers into routine clinical practice and consequently enable the rational and tailored use of cancer therapies for individual patients. © 2010 Macmillan Publishers Limited. All rights reserved.

Genomic meningococcal load in the nasopharynx of children with meningococcal disease

This study demonstrates the feasibility of using quantitative real time PCR to measure genomic bacterial load in the nasopharynx of children with invasive meningococcal disease and shows that these loads are exceptionally high (median 6.6 x 105 (Range 1.2 x 105 to 1.1 x 108) genome copies of Neisseria meningitidis per swab).

The impact of hydrogeology on the instability of a road cutting through a drumlin in the North of Ireland

This paper describes the hydrogeological processes which caused unexpected instability and quick conditions during the excavation of a 25m deep cutting through a drumlin in County Down, Northern Ireland. A conceptual hydrogeological model of the cutting, based on pore pressures monitored during and after the excavation demonstrates how quick conditions at the toe of the cutting caused liquefaction of the till. Stability of the cutting was re-established by draining the highly permeable, weathered Greywacke which underlies the drumlin, through the use of a deep toe drain. In spite of this drainage, the cutting was only marginally stable due to the presence of a low permeability zone in the till above the bedrock which limits the reduction of elevated pore pressures within the upper to mid-depths of the drumlin. The factor of safety has been further improved by the addition of vertical relief drains at the crest and berm of the cutting to relieve the pore-pressures within the upper till by intercepting the weathered bedrock. The paper also highlights the importance of carrying out an adequate site investigation compliant with Eurocode 7 and additional monitoring in excavations in stiff, low permeability till.

Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer

Development of colorectal cancer occurs via a number of key pathways, with the clinicopathological features of specific subgroups being driven by underlying molecular changes. Mutations in key genes within the network of signalling pathways have been identified; however, therapeutic strategies to target these aberrations remain limited. As understanding of the biology of colorectal cancer has improved, this has led to a move toward broader genomic testing, collaborative research and innovative, adaptive clinical trial design. Recent developments in therapy include the routine adoption of wider mutational spectrum testing prior to use of targeted therapies and the first promise of effective immunotherapy for colorectal cancer patients. This review details current biomarkers in colorectal cancer for molecular stratification and for treatment allocation purposes, including open and planned precision medicine trials. Advances in our understanding, therapeutic strategy and technology will also be outlined.

Genomic structure and expression of parathyroid hormone-related protein gene (PTHrP) in a teleost, Fugu rubripes

In this study we describe the isolation and characterisation of the parathyroid hormone-related protein (PTHrP) gene from the teleost Fugu rubripes. The gene has a relatively simple structure, compared with tetrapod PTHrP genes, composed of three exons and two introns, encompassing 2.25 kb of genomic DNA. The gene encodes a protein of 163 amino acids, with a putative signal peptide of 37 amino acids and a mature peptide of 126 amino acids. The overall homology with known tetrapod PTHrP proteins is low (36%), with a novel sequence inserted between positions 38 and 65, the absence of the conserved pentapeptide (TRSAW) and shortened C-terminal domain. The N-terminus shows greater conservation (62%), suggesting that it may have a hypercalcaemic function similar to that of tetrapod PTHrP. In situ localisation and RT–PCR have demonstrated the presence of PTHrP in a wide range of tissues with varying levels of expression. Sequence scanning of overlapping cosmids has identified three additional genes, TMPO, LDHB and KCNA1, which map to human chromosome 12, with the latter two mapping to 12p12-11.2. PTHrP in human also maps to this chromosome 12 sub-region, thus demonstrating conservation of synteny between human and Fugu.

Phylogenetic insights of Avena genus based on genomic analysis of 45S rDNA molecular organization

Tese de mestrado. Biologia (Biologia Molecular e Genética). Universidade de Lisboa, Faculdade de Ciências, 2014

Affective Instability, Childhood Trauma and Major Affective Disorders

BACKGROUND: Affective instability (AI), childhood trauma, and mental illness are linked, but evidence in affective disorders is limited, despite both AI and childhood trauma being associated with poorer outcomes. Aims were to compare AI levels in bipolar disorder I (BPI) and II (BPII), and major depressive disorder recurrent (MDDR), and to examine the association of AI and childhood trauma within each diagnostic group. METHODS: AI, measured using the Affective Lability Scale (ALS), was compared between people with DSM-IV BPI (n=923), BPII (n=363) and MDDR (n=207) accounting for confounders and current mood. Regression modelling was used to examine the association between AI and childhood traumas in each diagnostic group. RESULTS: ALS scores in descending order were BPII, BPI, MDDR, and differences between groups were significant (p<0.05). Within the BPI group any childhood abuse (p=0.021), childhood physical abuse (p=0.003) and the death of a close friend in childhood (p=0.002) were significantly associated with higher ALS score but no association was found between childhood trauma and AI in BPII and MDDR. LIMITATIONS: The ALS is a self-report scale and is subject to retrospective recall bias. CONCLUSIONS: AI is an important dimension in bipolar disorder independent of current mood state. There is a strong link between childhood traumatic events and AI levels in BPI and this may be one way in which exposure and disorder are linked. Clinical interventions targeting AI in people who have suffered significant childhood trauma could potentially change the clinical course of bipolar disorder.