Functional inhibition of deep brain non-visual opsins facilitates acute long day induction of reproductive recrudescence in male Japanese quail :Deep brain photoreceptors in birds

For nearly a century, we have known that brain photoreceptors regulate avian seasonal biology. Two photopigments, vertebrate ancient opsin (VA) and neuropsin (OPN5), provide possible molecular substrates for these photoreceptor pathways. VA fulfills many criteria for providing light input to the reproductive response, but a functional link has yet to be demonstrated. This study examined the role of VA and OPN5 in the avian photoperiodic response of Japanese quail (Coturnix japonica). Non-breeding male quail were housed under short days (6L:18D) and received an intracerebroventricular infusion of adeno-associated viral vectors with shRNAi that selectively inhibited either VA or OPN5. An empty viral vector acted as a control. Quail were then photostimulated (16L:8D) to stimulate gonadal growth. Two long days significantly increased pituitary thyrotrophin-stimulating hormone β-subunit (TSHβ) and luteinizing hormone β-subunit (LHβ) mRNA of VA shRNAi treated quail compared to controls. Furthermore, at one week there was a significant increase, compared to controls, in both hypothalamic gonadotrophin releasing hormone-I (GnRH-I) mRNA and paired testicular mass in VA shRNAi birds. Opn5 shRNAi facilitated the photoinduced increase in TSHβ mRNA at 2 days, but no other differences were identified compared to controls. Contrary to our expectations, the silencing of deep brain photoreceptors enhanced the response of the reproductive axis to photostimulation rather than preventing it. In addition, we show that VA opsin plays a dominant role in the light-dependent neuroendocrine control of seasonal reproduction in birds. Together our findings suggest the photoperiodic response involves at least two photoreceptor types and populations working together with VA opsin playing a dominant role

A novel class of CoA-transferase involved in short-chain fatty acid metabolism in butyrate-producing human colonic bacteria

Peer reviewedPublisher PD

α6ß4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of α3ß1 integrin

Growth factor-induced cell migration and proliferation are essential for epithelial wound repair. Cell migration during wound repair also depends upon expression of laminin-5, a ligand for α6ß4 integrin. We investigated the role of α6ß4 integrin in laminin-5-dependent keratinocyte migration by re-expressing normal or attachment-defective ß4 integrin in ß4 integrin null keratinocytes. We found that expression of ß4 integrin in either a ligand bound or ligand unbound state was necessary and sufficient for EGF-induced cell migration. In a ligand bound state, ß4 integrin supported EGF-induced cell migration though sustained activation of Rac1. In the absence of α6ß4 integrin ligation, Rac1 activation became tempered and EGF chemotaxis proceeded through an alternate mechanism that depended upon α3ß1 integrin and was characterized by cell scattering. α3ß1 integrin also relocalated from cell-cell contacts to sites of basal clustering where it displayed increased conformational activation. The aberrant distribution and activation of α3ß1 integrin in attachment-defective ß4 cells could be reversed by the activation of Rac1. Conversely, in WT ß4 cells the normal cell-cell localization of α3ß1 integrin became aberrant after the inhibition of Rac1. These studies indicate that the extracellular domain of ß4 integrin, through its ability to bind ligand, functions to integrate the divergent effects of growth factors on the cytoskeleton and adhesion receptors so that coordinated keratinocyte migration can be achieved

Individual-Based Measure of Socio-Economic Disadvantage: Making Identification "Agile"

This project aimed to develop an individual-based measure of socio-economic disadvantage that can assist Australian universities to identify socio-economic disadvantage at the level of the individual student. A mixed-methods design was used. Phase 1 comprised an online questionnaire distributed to staff working in the area of widening participation and student support at each of the 42 universities in Australia (n = 256) and an online questionnaire for undergraduate students at three universities (one a member of the Group of Eight and the other two members of the Innovative Research Universities group – one a multi-campus metropolitan university and one a rural university) (n = 4,114). In Phase 2, five focus groups were conducted with staff and six with students to further explore the issues raised in Phase 1. Phase 3 consisted of a desk audit of university websites to provide data on the information publicly available to students experiencing socio-economic disadvantage. In the final phase, Phase 4, a possible approach to measuring disadvantage was evaluated through its presentation to students at two universities which had been part of Phase 1 (n = 91). The following factors were found to be indicators of socio-economic disadvantage. Whether the student: provides financially for their family; is the first in family to attend university; is experiencing financial hardship; and/or is in receipt of Youth Allowance, Austudy or ABSTUDY during Years 11 and/or 12 (or another Centrelink income and asset-tested entitlement) for a period of at least three months during Years 11 and/or 12 or equivalent. These were found to be questions that students were willing to answer and which would lead to effective and efficient identification

Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

Functional network dysconnectivity as a biomarker of treatment resistance in schizophrenia.

Schizophrenia may develop from disruptions in functional connectivity regulated by neurotransmitters such as dopamine and acetylcholine. The modulatory effects of these neurotransmitters might explain how antipsychotics attenuate symptoms of schizophrenia and account for the variable response to antipsychotics observed in clinical practice. Based on the putative mechanisms of antipsychotics and evidence of disrupted connectivity in schizophrenia, we hypothesised that functional network connectivity, as assessed using network-based statistics, would exhibit differences between treatment response subtypes of schizophrenia and healthy controls. Resting-state functional MRI data were obtained from 17 healthy controls as well as individuals with schizophrenia who responded well to first-line atypical antipsychotics (first-line responders; FLR, n=18), had failed at least two trials of antipsychotics but responded to clozapine (treatment-resistant schizophrenia; TRS, n=18), or failed at least two trials of antipsychotics and a trial of clozapine (ultra-treatment-resistant schizophrenia; UTRS, n=16). Data were pre-processed using the Advanced Normalization Toolkit and BrainWavelet Toolbox. Network connectivity was assessed using the Network-Based Statistics toolbox in Matlab. ANOVA revealed a significant difference in functional connectivity between groups that extended between cerebellar and parietal regions to the frontal cortex (p<0.05). Post-hoc t-tests revealed weaker network connectivity in individuals with UTRS compared with healthy controls but no other differences between groups. Results demonstrated distinct differences in functional connectivity between individuals with UTRS and healthy controls. Future work must determine whether these changes occur prior to the onset of treatment and if they can be used to predict resistance to antipsychotics during first-episode psychosis

Uropathogenic Escherichia coli infection-induced epithelial trained immunity impacts urinary tract disease outcome

Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC infection, promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing to sustained cyclooxygenase-2 expression, bladder inflammation and mucosal wounding-responses associated with severe recurrent cystitis. Thus, UPEC infection acts as an epi-mutagen reprogramming the urothelial epigenome, leading to urothelial-intrinsic remodelling and training of the innate response to subsequent infection

The Wide-field Infrared Survey Explorer (WISE): Mission Description and Initial On-orbit Performance

The all sky surveys done by the Palomar Observatory Schmidt, the European Southern Observatory Schmidt, and the United Kingdom Schmidt, the InfraRed Astronomical Satellite and the 2 Micron All Sky Survey have proven to be extremely useful tools for astronomy with value that lasts for decades. The Wide-field Infrared Survey Explorer is mapping the whole sky following its launch on 14 December 2009. WISE began surveying the sky on 14 Jan 2010 and completed its first full coverage of the sky on July 17. The survey will continue to cover the sky a second time until the cryogen is exhausted (anticipated in November 2010). WISE is achieving 5 sigma point source sensitivities better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic in bands centered at wavelengths of 3.4, 4.6, 12 and 22 microns. Sensitivity improves toward the ecliptic poles due to denser coverage and lower zodiacal background. The angular resolution is 6.1, 6.4, 6.5 and 12.0 arc-seconds at 3.4, 4.6, 12 and 22 microns, and the astrometric precision for high SNR sources is better than 0.15 arc-seconds.Comment: 22 pages with 19 included figures. Updated to better match the accepted version in the A

The Wide-Field Infrared Survey Explorer (WISE): Mission Description and Initial On-Orbit Performance

The all sky surveys done by the Palomar Observatory Schmidt, the European Southern Observatory Schmidt, and the United Kingdom Schmidt, the InfraRed Astronomical Satellite and the 2 Micron All Sky Survey have proven to be extremely useful tools for astronomy with value that lasts for decades. The Wide-field Infrared Survey Explorer is mapping the whole sky following its launch on 14 December 2009. WISE began surveying the sky on 14 Jan 2010 and completed its first full coverage of the sky on July 17. The survey will continue to cover the sky a second time until the cryogen is exhausted (anticipated in November 2010). WISE is achieving 5 sigma point source sensitivities better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic in bands centered at wavelengths of 3.4, 4.6, 12 and 22 micrometers. Sensitivity improves toward the ecliptic poles due to denser coverage and lower zodiacal background. The angular resolution is 6.1", 6.4", 6.5" and 12.0" at 3.4, 4.6, 12 and 22 micrometers, and the astrometric precision for high SNR sources is better than 0.15"