Characterisation of the effects of salicylidene acylhydrazide compounds on type three secretion in Escherichia coli O157:H7

Recent work has highlighted a number of compounds that target bacterial virulence by affecting gene regulation. In this work, we show that small-molecule inhibitors affect the expression of the type III secretion system (T3SS) of <i>Escherichia coli</i> O157:H7 in liquid culture and when the bacteria are attached to bovine epithelial cells. The inhibition of T3SS expression resulted in a reduction in the capacity of the bacteria to form attaching and effacing lesions. Our results show a marked variation in the ability of four structurally-related compounds to inhibit the T3SS of a panel of isolates. Using transcriptomics, we provide a comprehensive analysis of the conserved- and inhibitor-specific transcriptional responses to the four compounds. These analyses of gene expression show that numerous virulence genes, located on horizontally-acquired DNA elements, are affected by the compounds but the number of genes significantly affected varied markedly between the compounds. Overall, we highlight the importance of assessing the effect of such "anti-virulence" agents on a range of isolates and discuss the possible mechanisms which may lead to the co-ordinate down-regulation of horizontally acquired virulence genes

Disfluency in dialogue:an intentional signal from the speaker?

Disfluency is a characteristic feature of spontaneous human speech, commonly seen as a consequence of problems with production. However, the question remains open as to why speakers are disfluent: Is it a mechanical by-product of planning difficulty, or do speakers use disfluency in dialogue to manage listeners' expectations? To address this question, we present two experiments investigating the production of disfluency in monologue and dialogue situations. Dialogue affected the linguistic choices made by participants, who aligned on referring expressions by choosing less frequent names for ambiguous images where those names had previously been mentioned. However, participants were no more disfluent in dialogue than in monologue situations, and the distribution of types of disfluency used remained constant. Our evidence rules out at least a straightforward interpretation of the view that disfluencies are an intentional signal in dialogue. © 2012 Psychonomic Society, Inc

Construction of probabilistic event trees for eruption forecasting at Sinabung volcano, Indonesia 2013-14

Eruptions of Sinabung volcano, Indonesia have been ongoing since 2013. Since that time, the character of eruptions has changed, from phreatic to phreatomagmatic to magmatic explosive eruptions, and from production of a lava dome that collapsed to a subsequent thick lava flow that slowly ceased to be active, and later, to a new lava dome. As the eruption progressed, event trees were constructed to forecast eruptive behavior six times, with forecast windows that ranged from 2. weeks to 1. year: November 7-10, December 12-14, and December 27, 2013; and January 9-10, May 13, and October 7, 2014. These event trees were successful in helping to frame the forecast scenarios, to collate current monitoring information, and to document outstanding questions and unknowns. The highest probability forecasts closely matched outcomes of eruption size (including extrusion of the first dome), production of pyroclastic density currents, and pyroclastic density current runout distances. Events assigned low probabilities also occurred, including total collapse of the lava dome in January 2014 and production of a small blast pyroclastic density current in February 2014

School-Based Services for Children with Attention-Deficit/Hyperactivity Disorder

This study was designed to present descriptive data from a survey of 201 school psychologists. Psychologists completed a survey addressing current practices for determining placement for students with ADHD including the role of school psychologists in determining placement, how often and who monitors services, where students are served, and what services are provided in each setting. Findings indicated that psychologists were involved less frequently in placement decisions and evaluation for Section 504 than in Special Education. Students with 504 plans received less frequent follow-up than students in Special Education. Results indicated that schools were generally following federal guidelines and recommendations from researchers for placement decisions, at least when the school psychologist was involved. Overall, service patterns for Section 504 and Special Education were similar; however, all interventions were reported more frequently in Special Education. Data indicated that empirically supported interventions may be underutilized in both settings for students with ADHD

The need for multidisciplinarity in specialist training to optimize future patient care

Harmonious interactions between radiation, medical, interventional and surgical oncologists, as well as other members of multidisciplinary teams, are essential for the optimization of patient care in oncology. This multidisciplinary approach is particularly important in the current landscape, in which standard-of-care approaches to cancer treatment are evolving towards highly targeted treatments, precise image guidance and personalized cancer therapy. Herein, we highlight the importance of multidisciplinarity and interdisciplinarity at all levels of clinical oncology training. Potential deficits in the current career development pathways and suggested strategies to broaden clinical training and research are presented, with specific emphasis on the merits of trainee involvement in functional multidisciplinary teams. Finally, the importance of training in multidisciplinary research is discussed, with the expectation that this awareness will yield the most fertile ground for future discoveries. Our key message is for cancer professionals to fulfil their duty in ensuring that trainees appreciate the importance of multidisciplinary research and practice

Filled pauses in Hungarian: Their phonetic form and function

Filled pauses are natural occurrences in spontaneous speech and they may turn up at any level of the speech planning process and in a number of functions. The aim of this paper is to find out whether the diverse functions of filled pauses correlate with diverse articulations resulting in diverse acoustic structures. Spontaneous narratives are used as research material. The duration of the filled pauses and the frequency values of their first two formants are analyzed. The most frequent form, schwa, shows function-dependent realizations as confirmed by the durational values and by the second formant values of these vowel-like sounds

A Test of Feasibility and Acceptability of Online Mindfulness-Based Stress Reduction for Lesbian, Gay, and Bisexual Women and Men at Risk for High Stress: Pilot Study

Background: In conservative and rural areas, where antidiscrimination laws do not exist, lesbian, gay, and bisexual (LGB) people are at risk for excess stress arising from discrimination. Stress-reducing interventions delivered via innovative channels to overcome access barriers are needed. Objective: This study aimed to investigate the feasibility and acceptability of online mindfulness-based stress reduction (OMBSR) with LGB people in Appalachian Tennessee at high risk for stress. Methods: In 2 pilot studies involving pre-post test designs, participants completed 8 weeks of OMBSR, weekly activity logs, semistructured interviews, and surveys of perceived and minority stress. Results: Overall, 24 LGB people enrolled in the study and 17 completed OMBSR. In addition, 94% completed some form of mindfulness activities daily, including meditation. Participants enjoyed the program and found it easy to use. Perceived stress (Cohen, perceived stress scale-10) decreased by 23% in women (mean 22.73 vs mean 17.45; t10=3.12; P=.01) and by 40% in men (mean 19.83 vs mean 12.00; t5=3.90; P=.01) between baseline and postprogram. Women demonstrated a 12% reduction in overall minority stress (Balsam, Daily Experiences with Heterosexism Questionnaire) from baseline to 12-week follow-up (mean 1.87 vs mean 1.57; t10=4.12; P=.002). Subscale analyses indicated that women’s stress due to vigilance and vicarious trauma decreased by 21% and 20%, respectively. Conclusions: OMBSR may be a useful tool to help LGB people reduce general and minority-specific stress in socially conservative regions lacking antidiscrimination policies

Regulatory T cell dysfunction in type 1 diabetes:what's broken and how can we fix it?

Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4(+) and CD8(+) T cells with specificity for islet autoantigens. In health, these potentially pathogenic T cells are held in check by multiple regulatory mechanisms, known collectively as 'immunological tolerance'. This raises the question as to whether type 1 diabetes develops, at least in part, as a result of a defect in one or more of these control mechanisms. Immunological tolerance includes both central mechanisms (purging of the T cell repertoire of high-affinity autoreactive T cells in the thymus) and peripheral mechanisms, a major component of which is the action of a specialised subpopulation of T cells, known as regulatory T cells (Tregs). In this review, we highlight the evidence suggesting that a reduction in the functional capacity of different Treg populations contributes to disease development in type 1 diabetes. We also address current controversies regarding the putative causes of this defect and discuss strategies to correct it as a means to reduce or prevent islet destruction in a clinical setting.</p

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Kinerja Implementasi Program Pendaftaran Tanah Sistematis Lengkap di Desa Soddara Kecamatan Pasongsongan Kabupaten Sumenep

This study aims to describe the implementation’s performance of Complete Systematic Land Registration (PTSL) program in Soddara Village Pasongsongan Subdistrict Sumenep Regency. The basis for this research is the problem of the land area owned by the community, which is not yet legally documented and raises land disputes. The Village Government is trying to solve the problem by proposing the implementation of the Comprehensive Systematic Land Registration (PTSL) program to the Sumenep Regency Land Office. The approach and research method used is qualitative with the type of data consisting of primary data and secondary data obtained through interview, observation, and documentation techniques. The validity of data was tested using the data triangulation technique. Analysis of the data using the interactive model of Miles, Huberman, and Saldana. The result showed that out of eight implementation’s performance described by Ripley, only accountability aspects were not found in this study. Keywords: Implementation; PTS