An informatic pipeline for the data capture and submission of quantitative proteomic data using iTRAQ(TM)

BACKGROUND: Proteomics continues to play a critical role in post-genomic science as continued advances in mass spectrometry and analytical chemistry support the separation and identification of increasing numbers of peptides and proteins from their characteristic mass spectra. In order to facilitate the sharing of this data, various standard formats have been, and continue to be, developed. Still not fully mature however, these are not yet able to cope with the increasing number of quantitative proteomic technologies that are being developed. RESULTS: We propose an extension to the PRIDE and mzData XML schema to accommodate the concept of multiple samples per experiment, and in addition, capture the intensities of the iTRAQ(TM )reporter ions in the entry. A simple Java-client has been developed to capture and convert the raw data from common spectral file formats, which also uses a third-party open source tool for the generation of iTRAQ(TM) reported intensities from Mascot output, into a valid PRIDE XML entry. CONCLUSION: We describe an extension to the PRIDE and mzData schemas to enable the capture of quantitative data. Currently this is limited to iTRAQ(TM) data but is readily extensible for other quantitative proteomic technologies. Furthermore, a software tool has been developed which enables conversion from various mass spectrum file formats and corresponding Mascot peptide identifications to PRIDE formatted XML. The tool represents a simple approach to preparing quantitative and qualitative data for submission to repositories such as PRIDE, which is necessary to facilitate data deposition and sharing in public domain database. The software is freely available from

Apoptosis is a prominent feature of acute anterior uveitis in the Fischer 344 rat

AIMS: To examine the hypothesis that apoptosis of infiltrating cells contributes to spontaneous resolution of uveitis in clinically relevant rodent models. METHODS: Experimental melanin induced uveitis (EMIU) was induced in Fischer 344 rats by immunisation with 250 microg bovine ocular melanin. Endotoxin induced uveitis (EIU) was induced by injection of 200 microg Escherichia coli lipopolysaccharide. Formalin fixed, paraffin embedded ocular cross sections were stained by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) to identify apoptotic cells. Indirect immunoperoxidase staining of paraformaldehyde lysine periodate fixed tissue cross sections was used to demonstrate expression of inducible nitric oxide synthase (iNOS). RESULTS: TUNEL positive mononuclear cells were observed in the anterior uvea during both EMIU and EIU at all selected time points. However, whereas the majority of mononuclear cells appeared apoptotic from the outset of disease, neutrophils were notably TUNEL negative at all time points examined. Many infiltrating neutrophils expressed iNOS. CONCLUSION: Apoptosis occurs early in the course of rat EMIU and EIU, and may contribute to resolution of these diseases. In general, infiltrating mononuclear cells die rapidly, while neutrophils survive, producing inducible nitric oxide synthase which may contribute to disease pathogenesis

Efficacy of infant simulator programmes to prevent teenage pregnancy: a school-based cluster randomised trial in Western Australia

Background: Infant simulator-based programmes seek to prevent teenage pregnancy. They are utilised in western and developing countries but, despite growing popularity, there is no published evidence of their long-term impact. The aim of this trial was to investigate the effect of such a programme, the Virtual Infant Parenting (VIP) Programme, on the pregnancy outcomes of birth and induced abortion. Methods: Fifty-seven of 66 eligible schools (86%) in Perth, Western Australia enrolled in the pragmatic clustered (by school) randomised trial (ISRCTN24952438) with even randomisation to the intervention and control groups. Between 2003 and 2006, the VIP programme was administered to 1,267 girls in the intervention schools, while 1,567 girls in the control schools received the standard health education curriculum. Participants were aged 13-15 years and were followed until age 20 via data linkage to hospital medical and abortion clinic records. Log binomial and Cox proportional hazards regression was used to test for differences in pregnancy rates between study groups. Findings: Compared to girls Findings: Compared to girls in the control group, a higher proportion of girls in the intervention group recorded at least one birth (7.6%, n=97; 4·3%, n=67) or at least one abortion as the first pregnancy event (8.9%, n=113; 6.4%, n=101). After adjustment for potential confounding, the intervention group had a higher overall pregnancy risk (RR = 1·36, 95% CI 1.10–1·67, p=0.003) compared to the control group. Similar results were obtained using proportional hazard models (HR = 1.35, 95% CI 1.10–1·67, p=0·016). Interpretation: The infant-simulator based VIP Programme did not achieve its aim of reducing teenage pregnancy. Girls in the intervention group were more likely to experience a birth or an induced abortion than those in the control group before turning 20 years of age. Funding: The Health Promotion Research Foundation of Western Australia (Healthway), Lotteries WA, the Western Australian Department of Education and Training and the Western Australian Department of Health

Attainment and maintenance of pubertal cyclicity may predict reproductive longevity in beef heifers

We hypothesized the manner that heifers achieve puberty may indicate their future reproductive longevity. Heifers with discontinued or delayed cyclicity during puberty attainment may have irregular reproductive cycles, anovulation, and infertility in their first breeding season contributing to a shorter reproductive lifespan. Therefore, plasma progesterone (P4) was measured from weaning to breeding on 611 heifers born 2012–2017 and four pubertal classifications were identified: (1) Early; P4 ≥ 1 ng/ml \u3c March 12 with continued cyclicity, (2) Typical; P4 ≥ 1 ng/ml ≥ March 12 with continued cyclicity, (3) Start-Stop; P4 ≥ 1 ng/ml but discontinued cyclicity, and (4) Non-Cycling; no P4 ≥ 1 ng/ml. Historical herd records indicated that 25% of heifers achieved puberty prior to March 12th in the 10 years prior to the study. Start-Stop and Non-Cycling yearling heifers were lighter indicating reduced growth and reproductive maturity traits compared with Early/Typical heifers. In addition, Non-Cycling/Start-Stop heifers were less responsive to prostaglandin F2 alpha (PGF2α) to initiate estrous behavior and ovulation to be artificially inseminated. Non-Cycling heifers had fewer reproductive tract score-5 and reduced numbers of calves born in the first 21-days-ofcalving during their first breeding season. Within the Start-Stop classification, 50% of heifers reinitiated cyclicity with growth traits and reproductive parameters that were similar to heifers in the Early/Typical classification while those that remained non-cyclic were more similar to heifers in the Non-Cycling group. Thus, heifers with discontinued cyclicity or no cyclicity during puberty attainment had delayed reproductive maturity resulting in subfertility and potentially a shorter reproductive lifespan

Emotional priming effects during Stroop task performance

The ability to make decisions within an emotional context requires a balance between two functionally integrated neural systems that primarily support executive control and affective processing. Several studies have demonstrated effects of emotional interference presented during an ongoing cognitive task, but it is unclear how activating the emotional circuitry prior to a cognitive task may enhance or disrupt the executive system. In this study we used fMRI to examine the effects of emotional priming on executive processing during a number Stroop task. Our results indicated that during trials with less executive requirements, there was a greater aversive emotional attenuation effect in a network of regions including the ventrolateral prefrontal cortex (vlPFC), insula and cingulate gyrus. This attenuation effect was counteracted during trials with increased executive demand, suggesting that while pre-activation of the emotional system may lead to an automatic attenuation of activity in multiple regions, requirements for executive function may override the aversive emotional attenuation effect. Furthermore, this override effect was found to be associated with faster reaction times during executive processing. These findings demonstrate that activity in the vlPFC, cingulate and insula is dynamically adjusted in order to optimize performance, and illustrate the importance of the timing of each system’s engagement in determining how competing cognitive and emotional information is processed

Comparison of the Standardized Video Interview and Interview Assessments of Professionalism and Interpersonal Communication Skills in Emergency Medicine

ObjectivesThe Association of American Medical Colleges Standardized Video Interview (SVI) was recently added as a component of emergency medicine (EM) residency applications to provide additional information about interpersonal communication skills (ICS) and knowledge of professionalism (PROF) behaviors. Our objective was to ascertain the correlation between the SVI and residency interviewer assessments of PROF and ICS. Secondary objectives included examination of 1) inter‐ and intrainstitutional assessments of ICS and PROF, 2) correlation of SVI scores with rank order list (ROL) positions, and 3) the potential influence of gender on interview day assessments.MethodsWe conducted an observational study using prospectively collected data from seven EM residency programs during 2017 and 2018 using a standardized instrument. Correlations between interview day PROF/ICS scores and the SVI were tested. A one‐way analysis of variance was used to analyze the association of SVI and ROL position. Gender differences were assessed with independent‐groups t‐tests.ResultsA total of 1,264 interview‐day encounters from 773 unique applicants resulted in 4,854 interviews conducted by 151 interviewers. Both PROF and ICS demonstrated a small positive correlation with the SVI score (r = 0.16 and r = 0.17, respectively). ROL position was associated with SVI score (p < 0.001), with mean SVI scores for top‐, middle‐, and bottom‐third applicants being 20.9, 20.5, and 19.8, respectively. No group differences with gender were identified on assessments of PROF or ICS.ConclusionsInterview assessments of PROF and ICS have a small, positive correlation with SVI scores. These residency selection tools may be measuring related, but not redundant, applicant characteristics. We did not identify gender differences in interview assessments.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150548/1/aet210346_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150548/2/aet210346.pd

Visuospatial executive function in Turner syndrome: functional MRI and neurocognitive findings

Turner syndrome is a genetic disorder that results from an abnormal or missing X chromosome in females and is typically associated with impairments in visuospatial, but not verbal, information processing. These visuospatial processing impairments may be exacerbated with increased task demands, such as those engaged during working memory (WM). While previous studies have examined spatial WM function in Turner syndrome, none have directly compared the neural correlates of spatial and verbal WM processes across the encoding, maintenance and retrieval phases. We employed both neurocognitive assessments and functional MRI (fMRI) to examine the neural circuitry underlying both verbal and visuospatial WM functions in individuals with Turner syndrome and normal controls. We furthermore examined the vulnerability of task-related fMRI activation to distracters presented during WM maintenance. Fifteen healthy female volunteers and eight individuals with Turner syndrome performed a delayed-response WM task during fMRI scanning. Neurocognitive tests revealed impaired performance across both verbal and spatial domains in Turner syndrome, with greater impairment on tasks with WM demands. Frontoparietal regions in controls showed significantly sustained levels of activation during visuospatial WM. This sustained activation was significantly reduced in the group with Turner syndrome. Domain-specific activation of temporal regions, in contrast, did not differ between the two groups. Sensory distraction during the WM maintenance phase did not differentially alter frontoparietal activation between the two groups. The results reveal impaired frontoparietal circuitry recruitment during visuospatial executive processing in Turner syndrome, suggesting a significant role for the X chromosome in the development of these pathways

Changes in Depression and Stress after Release from a Tobacco-Free Prison in the United States

Prior research has found high levels of depression and stress among persons who are incarcerated in the United States (U.S.). However, little is known about changes in depression and stress levels among inmates post-incarceration. The aim of this study was to examine changes in levels of depression and stress during and after incarceration in a tobacco-free facility. Questionnaires that included valid and reliable measures of depression and stress were completed by 208 male and female inmates approximately eight weeks before and three weeks after release from a northeastern U.S. prison. Although most inmates improved after prison, 30.8% had a worsening in levels of depression between baseline and the three-week follow-up. In addition, 29.8% had a worsening in levels of stress after release than during incarceration. While it is not surprising that the majority of inmates reported lower levels of depression and stress post-incarceration, a sizable minority had an increase in symptoms, suggesting that environmental stressors may be worse in the community than in prison for some inmates. Further research is needed to address depression and stress levels during and after incarceration in order for inmates to have a healthier transition back into the community and to prevent repeat incarcerations