Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis

BACKGROUND: Nitrogen is an essential element for bacterial growth and an important component of biological macromolecules. Consequently, responding to nitrogen limitation is critical for bacterial survival and involves the interplay of signalling pathways and transcriptional regulation of nitrogen assimilation and scavenging genes. In the soil dwelling saprophyte Mycobacterium smegmatis the OmpR-type response regulator GlnR is thought to mediate the transcriptomic response to nitrogen limitation. However, to date only ten genes have been shown to be in the GlnR regulon, a vastly reduced number compared to other organisms. RESULTS: We investigated the role of GlnR in the nitrogen limitation response and determined the entire GlnR regulon, by combining expression profiling of M. smegmatis wild type and glnR deletion mutant, with GlnR-specific chromatin immunoprecipitation and high throughput sequencing. We identify 53 GlnR binding sites during nitrogen limitation that control the expression of over 100 genes, demonstrating that GlnR is the regulator controlling the assimilation and utilisation of nitrogen. We also determine a consensus GlnR binding motif and identify key residues within the motif that are required for specific GlnR binding. CONCLUSIONS: We have demonstrated that GlnR is the global nitrogen response regulator in M. smegmatis, directly regulating the expression of more than 100 genes. GlnR controls key nitrogen stress survival processes including primary nitrogen metabolism pathways, the ability to utilise nitrate and urea as alternative nitrogen sources, and the potential to use cellular components to provide a source of ammonium. These studies further our understanding of how mycobacteria survive nutrient limiting conditions

Anatomical and diffusion MRI of deep gray matter in pediatric spina bifida

AbstractIndividuals with spina bifida myelomeningocele (SBM) exhibit brain abnormalities in cortical thickness, white matter integrity, and cerebellar structure. Little is known about deep gray matter macro- and microstructure in this population. The current study utilized volumetric and diffusion-weighted MRI techniques to examine gray matter volume and microstructure in several subcortical structures: basal ganglia nuclei, thalamus, hippocampus, and amygdala. Sixty-six children and adolescents (ages 8–18; M = 12.0, SD = 2.73) with SBM and typically developing (TD) controls underwent T1- and diffusion-weighted neuroimaging. Microstructural results indicated that hippocampal volume was disproportionately reduced, whereas the putamen volume was enlarged in the group with SBM. Microstructural analyses indicated increased mean diffusivity (MD) and fractional anisotropy (FA) in the gray matter of most examined structures (i.e., thalamus, caudate, hippocampus), with the putamen exhibiting a unique pattern of decreased MD and increased FA. These results provide further support that SBM differentially disrupts brain regions whereby some structures are volumetrically normal whereas others are reduced or enlarged. In the hippocampus, volumetric reduction coupled with increased MD may imply reduced cellular density and aberrant organization. Alternatively, the enlarged volume and significantly reduced MD in the putamen suggest increased density

Estimating oceanic primary production using vertical irradiance and chlorophyll profiles from ocean gliders in the North Atlantic

An autonomous underwater vehicle (Seaglider) has been used to estimate marine primary production (PP) using a combination of irradiance and fluorescence vertical profiles. This method provides estimates for depth-resolved and temporally evolving PP on fine spatial scales in the absence of ship-based calibrations. We describe techniques to correct for known issues associated with long autonomous deployments such as sensor calibration drift and fluorescence quenching. Comparisons were made between the Seaglider, stable isotope (13C), and satellite estimates of PP. The Seaglider-based PP estimates were comparable to both satellite estimates and stable isotope measurements

The Australian Corneal Graft Registry 2015 Report

The Australian Corneal Graft Registry (ACGR) opened in May 1985 and has now been operating for 30 years. Over the years, we have collected information on more than 30,000 corneal grafts. At registration, we seek information on the donor, eye bank practices, the recipient, the surgeon, the graft type and the operative procedure. Follow-up then occurs at approximately yearly intervals for an indefinite period, and ceases upon graft failure, or the death or loss-to-follow-up of the patient. At each round of follow-up, we request information on the survival of the graft, the visual outcomes, and any relevant post-operative events and treatments. The data are entered into an Access database and checked for consistency. Descriptive, univariate and multivariate analyses are subsequently performed using SPSS and Stata software, and the report is eventually collated.Eye Bank of South Australia, Lions New South Wales Eye Bank, Lions Eye Bank of Western Australia, Lions Eye Donation Service, Victoria, Queensland Eye Bank, The Australian Government Organ and Tissue Authority (DonateLife

Evaluating the feasibility of complex interventions in mental health services: standardised measure and reporting guidelines

Aims: To develop a) an empirically-based standardised measure of the feasibility of complex interventions for use within mental health services and b) reporting guidelines to facilitate feasibility assessment. Method: A focussed narrative review of studies assessing implementation blocks and enablers was conducted with thematic analysis and vote counting used to determine candidate items for the measure. Twenty purposively sampled studies (15 trial reports, 5 protocols) were included in the psychometric evaluation, spanning different interventions types. Cohen’s Kappa was calculated for inter-rater reliability and test-retest reliability. Results: 95 influences on implementation were identified from 299 reviewed references. The final measure - Structured Assessment of Feasibility (SAFE) - comprises 16 items rated on a Likert scale. SAFE demonstrated excellent inter-rater (kappa 0.84, 95% CI 0.79 - 0.89) and test re-test reliability (kappa 0.89, 95% CI 0.85 - 0.93). Cost information and training time were the two influences least likely to be reported in intervention papers. SAFE Reporting Guidelines include 16 items organised into 3 categories (Intervention, Resource consequences, Evaluation). Conclusion: SAFE is a novel approach to evaluating interventions, and supplements efficacy and health economic evidence. SAFE Reporting Guidelines will allow feasibility of an intervention to be systematically assessed

Changing Attitudes About Being a Bystander to Violence: Translating an In-Person Sexual Violence Prevention Program to a New Campus

Bystander approaches to reducing sexual violence train community members in prosocial roles to interrupt situations with risk of sexual violence and be supportive community allies after an assault. This study employs a true experimental design to evaluate the effectiveness of Bringing in the Bystander™ through 1-year post-implementation with first-year students from two universities (one rural, primarily residential; one urban, heavily commuter). We found significant change in bystander attitudes for male and female student program participants compared with the control group on both campuses, although the pattern of change depended on the combination of gender and campus

Changing Attitudes About Being a Bystander to Violence: Translating an In-Person Sexual Violence Prevention Program to a New Campus

Bystander approaches to reducing sexual violence train community members in prosocial roles to interrupt situations with risk of sexual violence and be supportive community allies after an assault. This study employs a true experimental design to evaluate the effectiveness of Bringing in the Bystander™ through 1-year post-implementation with first-year students from two universities (one rural, primarily residential; one urban, heavily commuter). We found significant change in bystander attitudes for male and female student program participants compared with the control group on both campuses, although the pattern of change depended on the combination of gender and campus

SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer

The oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in several human cancer types, but has not been investigated in human endometrial cancer. In a model of hormonal carcinogenesis, mice neonatally exposed to the soy phytoestrogen genistein (GEN) or the synthetic estrogen diethylstilbestrol (DES) develop endometrial cancer as adults. Previously, we demonstrated that SIX1 becomes aberrantly expressed in the uteri of these mice. Here we used this mouse model to investigate the role of SIX1 expression in endometrial carcinoma development and used human tissue microarrays to explore the utility of SIX1 as a biomarker in human endometrial cancer. In mice neonatally exposed to GEN or DES, the Six1 transcript level increased dramatically over time in uteri at 6, 12, and 18 months of age and was associated with development of endometrial carcinoma. SIX1 protein localized within abnormal basal cells and all atypical hyperplastic and neoplastic lesions. These findings indicate that developmental estrogenic chemical exposure induces persistent endometrial SIX1 expression that is strongly associated with abnormal cell differentiation and cancer development. In human endometrial tissue specimens, SIX1 was not present in normal endometrium but was expressed in a subset of endometrial cancers in patients who were also more likely to have late-stage disease. These findings identify SIX1 as a disease biomarker in a model of hormonal carcinogenesis and suggest that SIX1 plays a role in endometrial cancer development in both mice and women