Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from \u3cem\u3eShigella flexneri\u3c/em\u3e

Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents

A revised edition of the readiness to change questionnaire (treatment version)

The UK Alcohol Treatment Trial provided an opportunity to examine the factor structure of the Readiness to Change Questionnaire-Treatment Version (RCQ[TV]) in a large sample (N = 742) of individuals in treatment for alcohol problems who were given the RCQ[TV] at baseline, 3-months and 12-months follow-up. Confirmatory factor analysis of the previously reported factor structure (5 items for each of Precontemplation, Contemplation and Action scales) resulted in a relatively poor fit to the data. Removal of one item from each of the scales resulted in a 12-item instrument for which goodness-of-fit indices were improved, without loss of internal consistency of the three scales, on all three measurement occasions. Inspection of relationships between stage allocation by the new instrument and negative alcohol outcome expectancies provided evidence of improved construct validity for the revised edition of the RCQ[TV]. There was also a strong relationship between stage allocation at 3-months follow-up and outcome of treatment at 12 months. The revised edition of the RCQ[TV] offers researchers and clinicians a shorter and improved measurement of stage of change in the alcohol treatment population

Can consumers learn to ask three questions to improve shared decision making? A feasibility study of the ASK (AskShareKnow) Patient–Clinician Communication Model® intervention in a primary health-care setting

Funded by Informed Medical Decisions Foundation. Grant Number: #0175-1 National Health and Medical Research Council Public Health Training Fellowship. Grant Number: 568962Peer reviewedPublisher PD

Ethnicity as a Moderator of Treatment Effects on Parent-Child Interaction for Children With ADHD

Objective: To examine ethnic differences in observed parenting and child behavior and the moderating effects of ethnicity on the relationship between treatment and parent and child behavior. Method: Observations of 508 children with ADHD (ages 7–9) and their caregivers, collected during the Multimodal Treatment Study of ADHD, were analyzed using univariate and mixed-model ANOVAs. Results: Although baseline parenting practices differed by ethnic group, ethnicity did not moderate the relationship between treatment and either parenting or child behavior. Conclusion: Consistent with data from normative samples, parents of children with ADHD differed by ethnicity in their utilization of certain parenting strategies. However, different ethnic groups did not differ on benefit received from treatments for ADHD, measured by parent and child behavior. Although ethnicity did not emerge as a moderator, ethnic minority family engagement in treatment may be increased by recognizing different parenting strategies and modifying interventions accordingly. (J. of Att. Dis. 2010; 13(6) 592-600

Assimilation of Oil-Derived Elements by Oysters Due to the Deepwater Horizon Oil Spill

During and after the Deepwater Horizon Oil Spill (DWHOS), oysters (Crassostrea virginica) were exposed to oil and susceptible to incidental consumption of surface and subsurface oil materials. We determined the contribution of oil materials from the DWHOS to diet of oysters by comparing carbon (C) and nitrogen (N) stable isotope ratios in oyster shell to ratios in suspended particulate matter (SPM) and in fresh and weathered oil. Average δ13C and δ15N values in oyster shell (−21 ± 1‰ and 9−11‰, respectively) were consistent with consumption of naturally available SPM as opposed to values in oil (−27 ± 0.2‰, 1.6 ± 0.4‰). Stable isotope ratios in oyster adductor muscle were similar to shell for δ15N but not δ13C, suggesting either a recent shift in diet composition or differential assimilation of C between tissue types. We found no evidence of assimilation of oil-derived C and N and, therefore, no evidence of an oyster-based conduit to higher trophic levels. Trace elements in shell were inconclusive to corroborate oil exposure. These findings are not an indication that oysters were not exposed to oil; rather they imply oysters either did not consume oil-derived materials or consumed too little to be detectable compared to natural diet

Are there valid proxy measures of clinical behaviour?

Background: Accurate measures of health professionals' clinical practice are critically important to guide health policy decisions, as well as for professional self-evaluation and for research-based investigation of clinical practice and process of care. It is often not feasible or ethical to measure behaviour through direct observation, and rigorous behavioural measures are difficult and costly to use. The aim of this review was to identify the current evidence relating to the relationships between proxy measures and direct measures of clinical behaviour. In particular, the accuracy of medical record review, clinician self-reported and patient-reported behaviour was assessed relative to directly observed behaviour. Methods: We searched: PsycINFO; MEDLINE; EMBASE; CINAHL; Cochrane Central Register of Controlled Trials; science/social science citation index; Current contents (social & behavioural med/clinical med); ISI conference proceedings; and Index to Theses. Inclusion criteria: empirical, quantitative studies; and examining clinical behaviours. An independent, direct measure of behaviour (by standardised patient, other trained observer or by video/audio recording) was considered the 'gold standard' for comparison. Proxy measures of behaviour included: retrospective self-report; patient-report; or chart-review. All titles, abstracts, and full text articles retrieved by electronic searching were screened for inclusion and abstracted independently by two reviewers. Disagreements were resolved by discussion with a third reviewer where necessary. Results: Fifteen reports originating from 11 studies met the inclusion criteria. The method of direct measurement was by standardised patient in six reports, trained observer in three reports, and audio/video recording in six reports. Multiple proxy measures of behaviour were compared in five of 15 reports. Only four of 15 reports used appropriate statistical methods to compare measures. Some direct measures failed to meet our validity criteria. The accuracy of patient report and chart review as proxy measures varied considerably across a wide range of clinical actions. The evidence for clinician self-report was inconclusive. Conclusion: Valid measures of clinical behaviour are of fundamental importance to accurately identify gaps in care delivery, improve quality of care, and ultimately to improve patient care. However, the evidence base for three commonly used proxy measures of clinicians' behaviour is very limited. Further research is needed to better establish the methods of development, application, and analysis for a range of both direct and proxy measures of behaviour

The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2

Osteoblasts are responsible for the formation and mineralization of the skeleton. To identify novel regulators of osteoblast differentiation, we conducted an unbiased forward genetic screen using a lentiviral-based shRNA library. This functional genomics analysis led to the identification of the microtubule-associated protein DCAMKL1 (Doublecortin-like and CAM kinase–like 1) as a novel regulator of osteogenesis. Mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts. Molecular experiments demonstrated that DCAMKL1 represses osteoblast activation by antagonizing Runx2, the master transcription factor in osteoblasts. Key elements of the cleidocranial dysplasia phenotype observed in Runx2+/− mice are reversed by the introduction of a Dcamkl1-null allele. Our results establish a genetic linkage between these two proteins in vivo and demonstrate that DCAMKL1 is a physiologically relevant regulator of anabolic bone formation

Teaching the Three E’s of Sustainability Through Service‐Learning in a Professional Program

Using seven established course design principles for effective service‐learning, this chapter discusses the lessons learned in teaching the three E’s of sustainability: environmental; economic; and (social) equity, in a professional program at an American Midwestern public university.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154652/1/tl20374_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154652/2/tl20374.pd

Effect of HIV-infection and menopause status on raltegravir pharmacokinetics in the blood and genital tract

This study describes first dose and steady state pharmacokinetics of raltegravir (RAL) in cervicovaginal fluid (CVF) and blood plasma (BP)

Comparative genomics of mutualistic viruses of Glyptapanteles parasitic wasps

Comparative genome analysis of two endosymbiotic polydnaviruses from Glyptapanteles parasitic wasps reveals new insights into the evolutionary arms race between host and parasite