Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection

Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

The Escherichia coli O157:H7 EhaB autotransporter protein binds to laminin and collagen I and induces a serum IgA response in O157:H7 challenged cattle

Enterohaemorrhagic Escherichia coli (EHEC) are a subgroup of Shiga toxin-producing E. coli that cause gastrointestinal disease with the potential for life-threatening sequelae. Cattle serve as the natural reservoir for EHEC and outbreaks occur sporadically as a result of contaminated beef and other farming products. While certain EHEC virulence mechanisms have been extensively studied, the factors that mediate host colonization are poorly defined. Previously, we identified four proteins (EhaA,B,C,D) from the prototypic EHEC strain EDL933 that belong to the autotransporter (AT) family. Here we characterize the EhaB AT protein. EhaB was shown to be located at the cell surface and overexpression in E. coli K-12 resulted in significant biofilm formation under continuous flow conditions. Overexpression of EhaB in E. coli K12 and EDL933 backgrounds also promoted adhesion to the extracellular matrix proteins collagen I and laminin. An EhaB-specific antibody revealed that EhaB is expressed in E. coli EDL933 following in vitro growth. EhaB also cross-reacted with serum IgA from cattle challenged with E. coli O157:H7, indicating that EhaB is expressed in vivo and elicits a host IgA immune response.

Chinese EFL students' response to an assessment policy change

In light of its documented potential for enhancing learning, formative assessment has been adopted across a range of educational contexts to improve the quality of education. The assessment innovation that the Chinese Ministry of Education (CMoE) proposed to College English in 2007 via the College English Curriculum Requirements (CECR) (CMoE, 2007), is an initiative of this kind. Considering the acknowledged influence of assessment on students’ learning, it is instructive to explore the ways in which Chinese university students respond to an assessment policy change of this magnitude, particularly as it positions them as more active learners, having the potential for increased agency and engagement in their English language learning and assessment practices. In order to explore the response of students to this assessment initiative, a case study was conducted in the context of a College English classroom. Data included an interview with a College English teacher and four students from her classes, and classroom observations and a survey of her two classes of 100 students. Analysis of the data reveals that Chinese students’ responses to the assessment policy change are influenced by a variety of sociocultural factors, including their previous English language learning and assessment experience and the extent to which they are willing to play the ‘assessment game’. These findings have implications for policy and practice.

Building resilient communities : creating effective multi-channel communication during disaster response and recovery

Aim: To examine evidence-based strategies that motivate appropriate action and increase informed decision-making during the response and recovery phases of disasters.

Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Author response to : Brough et al. in response to the recently published article : Lottering,N., MacGregor,D.M.,Barry,M.D.,Reynolds,M.S., Gregory,L.S., 2014. Introducing standardized protocols for anthropological measurement of virtual sub-adult crania using computed tomography 2(1),34–38

Firstly, we would like to thank Ms. Alison Brough and her colleagues for their positive commentary on our published work [1] and their appraisal of our utility of the “off-set plane” protocol for anthropometric analysis. The standardized protocols described in our manuscript have wide applications, ranging from forensic anthropology and paleodemographic research to clinical settings such as paediatric practice and orthopaedic surgical design. We affirm that the use of geometrically based reference tools commonly found in computer aided design (CAD) programs such as Geomagic Design X® are imperative for more automated and precise measurement protocols for quantitative skeletal analysis. Therefore we stand by our recommendation of the use of software such as Amira and Geomagic Design X® in the contexts described in our manuscript...

Physical mechanism of the compressive response of F-actin networks : significance of crosslinker unbinding events

A model of crosslinker unbinding is implemented in a highly coarsegrained granular model of F-actin cytoskeleton. We employ this specific granular model to study the mechanisms of the compressive responses of F-actin networks. It is found that the compressive response of F-actin cytoskeleton has dependency on the strain rate. The evolution of deformation energy in the network indicates that crosslinker unbinding events can induce the remodelling of F-actin cytoskeleton in response to external loadings. The internal stress in F-actin cytoskeleton can efficiently dissipate with the help of crosslinker unbinding, which could lead to the spontaneous relaxation of living cells.

Metabolic response to a mixed meal in obese and lean women from two South African populations

Objective Lower lipid and insulin levels are found during a glucose-tolerance test in obese black than obese white South African women. Therefore, β-cell function and lipid metabolism were compared in these populations during a mixed meal. Research Methods and Procedures Blood concentrations of glucose, free fatty acids (FFAs), insulin, lipograms, and in vivo FFA oxidation were determined at fasting and for 7 hours after oral administration of a mixed emulsion containing glucose-casein-sucrose-lipid and [1-13C] palmitic acid in 8 lean black women (LBW), 10 obese black women (OBW), 9 lean white women (LWW), and 10 obese white women (OWW). Subcutaneous and visceral fat mass was assessed by computerized tomography. Results Visceral fat area was higher in OWW (152.7 ± 17.0 cm2) than OBW (80.0 ± 6.7 cm2; p < 0.01). In OBW, 30-minute insulin levels were higher (604.3 ± 117.6 pM) than OWW (311.0 ± 42.9 pM; p < 0.05). Total triglyceride was higher in OWW (706.7 ± 96.0 mM × 7 hours) than OBW (465.7 ± 48.2 mM × 7 hours; p < 0.05) and correlated with visceral fat area (β = 0.38, p = 0.05). Palmitate oxidation was higher in lean than obese women in both ethnic groups and correlated negatively with fat mass (β = −0.58, p < 0.005). Discussion The higher 30-minute insulin response in OBW may reflect a higher insulinotropic effect of FFAs or glucose. The elevated triglyceride level of OWW may be due to their higher visceral fat mass and possibly reduced clearance by adipose tissue.

Triphasic pattern in the ex vivo response of human proliferative phase endometrium to oestrogens

The aim of this study was to evaluate the ex vivo oestrogen responsiveness of human proliferative phase endometrium using short-term explant cultures. The effects of oestrogen (17beta-E2) on proliferation and the expression of oestrogen-responsive genes known to be involved in regulating endometrial function were evaluated. Three distinct response patterns could be distinguished: (1) the menstrual (M) phase pattern (cycle days 2-5), which is characterised by a complete lack in the proliferative response to 17beta-E2, while an increased expression of AR (2.6-fold, P<0.01), PR (2.7-fold, P<0.01) and COX-2 (3.5-fold, P<0.01) at the mRNA level was observed and a similar upregulation was also found for AR, PR and COX-2 at the protein level; (2) the early proliferative (EP) phase pattern (cycle days 6-10) with 17beta-E2 enhanced proliferation in the stroma (1.7-fold, P<0.05), whereas the expression of AR, PR and COX-2 were not affected at the mRNA and protein levels and ER-a mRNA and protein levels were significantly reduced by 17beta-E2; (3) the late proliferative (LP) phase pattern (cycle days 11-14), which is characterised by a moderate stimulation of proliferation (1.4-fold, P<0.05) and PR mRNA expression (1.7-fold, P<0.01) by 17beta-E2. In conclusion, three distinct response patterns to 17beta-E2 could be identified with respect to proliferation and the expression of known oestrogen-responsive genes in human proliferative phase endometrium explant cultures.

A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity

Introduction: In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not. Materials and Methods: Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU. Results: We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1 and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1a and IP-10. Conclusion: The marker panel is ready to be verified in a validation study with or without therapeutic intervention.

Understanding public response to a congestion charge : a random-effects ordered logit approach

Public acceptance is consistently listed as having an enormous impact on the implementation and success of a congestion charge scheme. This paper investigates public acceptance of such a scheme in Australia. Surveys were conducted in Brisbane and Melbourne, the two fastest growing Australian cities. Using an ordered logit modeling approach, the survey data including stated preferences were analyzed to pinpoint the important factors influencing people’s attitudes to a congestion charge and, in turn, to their transport mode choices. To accommodate the nature of, and to account for the resulting heterogeneity of the panel data, random effects were considered in the models. As expected, this study found that the amount of the congestion charge and the financial benefits of implementing it have a significant influence on respondents’ support for the charge and on the likelihood of their taking a bus to city areas. However, respondents’ current primary transport mode for travelling to the city areas has a more pronounced impact. Meanwhile, respondents’ perceptions of the congestion charge’s role in protecting the environment by reducing vehicle emissions, and of the extent to which the charge would mean that they travelled less frequently to the city for shopping or entertainment, also have a significant impact on their level of support for its implementation. We also found and explained notable differences across two cities. Finally, findings from this study have been fully discussed in relation to the literature.

The Cressbrook Creek alluvial aquifer system, Southeast Queensland : hydrochemistry and isotopes to determine hydrological processes and response to floods

This study developed an understanding of hydrological processes within the Cressbrook Creek catchment of the upper Brisbane River, in particular for the alluvial aquifers. Those aquifers within the lower catchment are used for intensive irrigation, and have been impacted by long-term drought followed by flooding. The study utilised water chemistry, isotopic characters and hydraulic measurements to determine factors such as recharge, links between creeks and groundwater, and variations in water quality. The catchment-wide study will enable improved management of the local water resources.

Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults

CONTEXT AND OBJECTIVE: Suboptimal vitamin D status can be corrected by vitamin D supplementation, but individual responses to supplementation vary. We aimed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D (25(OH)D) after supplementation. DESIGN AND PARTICIPANTS: We used data from a pilot randomized controlled trial in which 644 adults aged 60 to 84 years were randomly assigned to monthly doses of placebo, 30 000 IU, or 60 000 IU vitamin D3 for 12 months. Baseline characteristics were obtained from a self-administered questionnaire. Eighty-eight single-nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray technology. Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay. We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels. RESULTS: Supplement dose and baseline 25(OH)D level explained 24% of the variability in response to supplementation. Body mass index, self-reported health status, and ambient UV radiation made a small additional contribution. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6, and HERC2 were associated with change in 25(OH)D level, although only CYP2R1 was significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors. CONCLUSION: Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation, perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of 25(OH)D.

Power and paradigms : the Dutch response to pressures for shareholder value

In recent years, research aimed at identifying and relating the antecedents and consequences of diffusing organizational practices/ideas has turned its attention to debating the international adoption and implementation of the Anglo-American model of corporate governance, i.e., a shareholder-value-orientation (SVO). While financial economists characterize the adoption of an SVO as necessary and performance-enhancing, behavioral scientists have disputed such claims, invoking institutional contingencies in the appropriateness of an SVO. Our study seeks to provide some resolution to the debate by developing an overarching socio-political perspective that links the antecedents and consequences of the adoption of the contested practice of SVO. We test our framework using extensive longitudinal data from 1992-2006 from the largest listed corporations in the Netherlands, and we find a negative relationship between SVO adoption and subsequent firm performance, although this effect is attenuated when accompanied by greater SVO-alignment among major owners and a firm’s visible commitment to an SVO. This study extends prior research on the diffusion of contested organizational practices that has taken a socio-political perspective by offering an original contingency perspective that addresses how and why the misaligned preferences of corporate owners will affect (i) a company’s inclination to espouse an SVO, and (ii) the performance consequences of such misalignment.This study suggests when board members are considering the adoption of new ideas/practices (e.g., SVO), they should consider the contextual fitness of the idea/practice with the firm’s owners and their interests.

Characterisation of cytokine response to Chlamydia pecorum infection in the koala, Phascolarctos cinereus

This thesis aimed at identifying cytokine markers associated with chlamydial infection and disease in koalas which is facing many threats to its survival, Chlamydia pecorum infections being a major one. To identify immunological markers associated with chlamydial infection and disease in koalas, key cytokines such as TNF alpha, IL10, IFN gamma and IL17A were cloned and sequenced and subsequently developed Quantitative Real Time PCR (qrtPCR) assays. The thesis provides preliminary data on the role of these cytokines in koala chlamydial disease and further longitudinal studies are required to confirm the role played by cytokines in pathology and protection against C. pecorum infection in the koala.