Unwrapped : Readiness-to-eat in food images affects cravings

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors would like to thank Karcher Cox for help with stimulus selection and data collection.Peer reviewedPostprin

Light social drinkers are more distracted by irrelevant information from an induced attentional bias than heavy social drinkers

It is well established that alcoholics and heavy social drinkers show a bias of attention towards alcohol-related items. Previous research suggests that there is a shared foundation of attentional bias, which is linked to attentional control settings. Specifically, attentional bias relates to a persistent selection of a Feature Search Mode which prioritises attentional bias-related information for selection and processing. However, no research has yet examined the effect of pre-existing biases on the development of an additional attentional bias. This paper seeks to discover how pre-existing biases affect the formation of a new, additional attentional bias. Twenty-five heavy and 25 light social drinkers, with and without a pre-existing bias to alcohol-related items, respectively, had an attentional bias towards the colour green induced via an information sheet. They then completed a series of one-shot change detection tasks. In the critical task, green items were present but task-irrelevant. Irrelevant green items caused significantly more interference for light than heavy social drinkers. This somewhat counter intuitive result is likely due to heavy drinkers having more experience in exerting cognitive control over attentional biases, something not previously observed in investigations of the effects of holding an attentional bias. Our findings demonstrate for the first time that an established attentional bias significantly modulates future behaviour

Fearing the wurst : Robust approach bias towards non-vegetarian food images in a sample of young female vegetarian eaters

Peer reviewedPostprin

The Role of the Left Dorsolateral Prefrontal Cortex in Attentional Bias

The DLPFC is thought to be critically involved in maintaining attention away from behaviourally irrelevant information, and in the establishment of attentional control settings. These play an important role in the phenomenon of top-down bias to features in the visual field – also known as attentional bias. This paper probes the involvement of the left DLPFC in attentional bias by manipulating its cortical excitability via tDCS and then analysing these effects following an induced attentional bias towards the colour green. Although both anodal and cathodal tDCS over the left DLPFC decrease distractibility caused by biased but irrelevant objects, further interrogation of our data reveals theoretically differential mechanisms for each type of stimulation. Anodal tDCS appears to increase cognitive control over attentional bias-related items that are behaviourally irrelevant, allowing for their efficient disregard. In contrast, cathodal tDCS appears to lessen the overall effect of the induced attentional bias, potentially by reducing the influence of top-down modulated attentional control settings thus preventing the implementation of the control setting favouring green items. These results suggest a potential causal role of the left DLPFC in the cognitive mechanism underlying attentional bias

Distinct Transcriptional and Anti-Mycobacterial Profiles of Peripheral Blood Monocytes Dependent on the Ratio of Monocytes: Lymphocytes.

The ratio of monocytes and lymphocytes (ML ratio) in peripheral blood is associated with tuberculosis and malaria disease risk and cancer and cardiovascular disease outcomes. We studied anti-mycobacterial function and the transcriptome of monocytes in relation to the ML ratio. Mycobacterial growth inhibition assays of whole or sorted blood were performed and mycobacteria were enumerated by liquid culture. Transcriptomes of unstimulated CD14 + monocytes isolated by magnetic bead sorting were characterised by microarray. Transcript expression was tested for association with ML ratio calculated from leucocyte differential counts by linear regression. The ML ratio was associated with mycobacterial growth in vitro (β = 2.23, SE 0.91, p = 0.02). Using sorted monocytes and lymphocytes, in vivo ML ratio (% variance explained R(2) = 11%, p = 0.02) dominated over in vitro ratios (R(2) = 5%, p = 0.10) in explaining mycobacterial growth. Expression of 906 genes was associated with the ML ratio and 53 with monocyte count alone. ML-ratio associated genes were enriched for type-I and -II interferon signalling (p = 1.2 × 10(− 8)), and for genes under transcriptional control of IRF1, IRF2, RUNX1, RELA and ESRRB. The ML-ratio-associated gene set was enriched in TB disease (3.11-fold, 95% CI: 2.28-4.19, p = 5.7 × 10(− 12)) and other inflammatory diseases including atopy, HIV, IBD and SLE. The ML ratio is associated with distinct transcriptional and anti-mycobacterial profiles of monocytes that may explain the disease associations of the ML ratio

The role of micrornas in the development of hospital acquired infection in polytrauma patients

Introduction Traumatic injury is associated with immunosuppression and an increased risk of developing nosocomial infections. However, the immune regulatory mechanisms involved remain unclear. Objectives 1) To describe genome-wide alterations in micro RNA (miRNA) expression following severe trauma. 2) To explore the potential role of miRNAs in mediating the post-traumatic immunosuppressive phenotype and their potential role in enhancing the risk of nosocomial infections. Methods Patients requiring ICU care following traumatic injury were recruited. Whole blood was collected within 2 hours of injury and 24 hours later. Total RNA (containing miRNAs) was isolated utilising PAX Gene and RNA extraction kits (Qiagen). miRNA-sequencing was performed with the Illumina HiSeq2500, and sequences were aligned to the human GRCh37 reference genome. Data analysis was carried out using the DESEQ2 package in R, and miRNAs were considered significantly altered with an adjusted p value of < 0.05. Functional enrichment analysis was performed using Ingenuity Pathway Analysis (IPA) on all miRNAs reaching an adjusted p value of < 0.1. mRNA targets of interest were identified using miRBase and TargetScan (http://www.mirbase.org, http://www.targetscan.org). Results 49 patients were recruited and 25 patients developed nosocomial infections. Expression of 139 miRNAs was significantly altered between 2 hours and 24 hours following injury, with miR-146b, a key inhibitor of pro-inflammatory pathways[1], upregulated to the greatest degree. Figure 1 presents miRNAs that differ between those patients who developed nosocomial infections and those who did not. miR-144-5p was significantly different between the two groups at both time points. a large percentage of mRNA targets for miR-144 are involved the Cell-mediated Immune Response (Figure 2), including the B-cell receptor complex, p38MAPK, GATA3, IgG, BCL6 and the T-cell receptor. in addition, we have previously shown that the miR-374 family of miRNAs is linked to increased IL-10 expression in trauma patients[2]. IPA highlights Cancer, Haematological Disease, Immunological and Inflammatory Disease and Organismal Injury and Abnormalities as important pathways altered between infected and non-infected patients. Conclusions These data provide a miRNA signature of severely injured trauma patients who develop hospital acquired infection compared to those who do not, and identify the miR-144 and miR-374b families as being of particular interest for future studies of trauma-induced immune dysfunction

Strength in diversity: enhancing learning in vocationally-orientated, master's level courses

Postgraduate education in geography, especially at the Master’s level, is undergoing significant changes in the developed world. There is an expansion of vocationally-oriented degree programmes, increasing recruitment of international students, integration of work place skills, and the engagement of non-traditional postgraduate students as departments respond to policies for a more ‘inclusive’ higher education. This paper sets the context by outlining some programmatic changes in selected countries (Australia, the UK, and the USA). We briefly reflect on how postgraduate ‘bars’ or ‘levels’ are defined and explore in detail what ‘diversity’ or ‘heterogeneity’ means in these new postgraduate settings. The paper then explores some examples of practice drawn from our own experiences, whilst recognising that relevance will vary in other contexts. Finally we consider how diversity can be harnessed as a strength that has potential to enhance taught elements of contemporary postgraduate education in and beyond the discipline

A novel nonsense CDK5RAP2 mutation in a Somali child with primary microcephaly and sensorineural hearing loss

Primary microcephaly is a genetically heterogeneous condition characterized by reduced head circumference (-3 SDS or more) and mild-to-moderate learning disability. Here, we describe clinical and molecular investigations of a microcephalic child with sensorineural hearing loss. Although consanguinity was unreported initially, detection of 13.7 Mb of copy neutral loss of heterozygosity (cnLOH) on chromosome 9 implicated the CDK5RAP2 gene. Targeted sequencing identified a homozygous E234X mutation, only the third mutation to be described in CDK5RAP2, the first in an individual of non-Pakistani descent. Sensorineural hearing loss is not generally considered to be consistent with autosomal recessive microcephaly and therefore it seems likely that the deafness in this individual is caused by the co-occurrence of a further gene mutation, independent of CDK5RAP2. Nevertheless, further detailed clinical descriptions of rare CDK5RAP2 patients, including hearing assessments will be needed to resolve fully the phenotypic range associated with mutations in this gene. This study also highlights the utility of SNP-array testing to guide disease gene identification where an autosomal recessive condition is plausible

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma

Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethiON platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans