Structure and Function of the Mycobacterial Type VII Secretion Systems

Bacteria have evolved intricate secretion machineries for the successful delivery of large molecules across their cell envelopes. Such specialized secretion systems allow a variety of bacteria to thrive in specific host environments. In mycobacteria, type VII secretion systems (T7SSs) are dedicated protein transport machineries that fulfill diverse and crucial roles, ranging from metabolite uptake to immune evasion and subversion to conjugation. Since the discovery of mycobacterial T7SSs about 15 y ago, genetic, structural, and functional studies have provided insight into the roles and functioning of these secretion machineries. Here, we focus on recent advances in the elucidation of the structure and mechanism of mycobacterial T7SSs in protein secretion. As many of these systems are essential for mycobacterial growth or virulence, they provide opportunities for the development of novel therapies to combat a number of relevant mycobacterial diseases

Learning to dislike alcohol: conditioning negative implicit attitudes toward alcohol and its effect on drinking behavior

Rationale: Since implicit attitudes toward alcohol play an important role in drinking behavior, a possible way to obtain a behavioral change is changing these implicit attitudes. Objectives: This study examined whether a change in implicit attitudes and in drinking behavior can be achieved via evaluative conditioning. Methods: Participants were randomly assigned to an experimental condition and a control condition. In the experimental condition, participants were subjected to an evaluative conditioning procedure that consistently pairs alcohol-related cues with negative stimuli. In the control condition, alcohol-related cues were consistently paired with neutral stimuli during the evaluative conditioning phase. Implicit attitudes, explicit attitudes, and drinking behavior were measured before and after the evaluative conditioning phase. Results: Following the evaluative conditioning procedure, participants in the experimental condition showed stronger negative implicit attitudes toward alcohol and consumed less alcohol compared to participants in the control condition. However, this effect was only found when the evaluative conditioning task paired alcohol-related cues with general negative pictures, but not when using pictures of frowning faces. Conclusions: These results demonstrate that evaluative conditioning can effectively change implicit attitudes toward alcohol and also suggest that this procedure can be used to change drinking behavior. Hence, evaluative conditioning may be a useful new intervention tool to combat alcohol misuse

An Evaluation of Laminated Offset Jawed Traps for Reducing Injuries to Coyotes

Increasing public concern about injuries caused by foothold traps has resulted in a considerable amount of research for more humane traps. Much of this research effort has focused on evaluating the Victor No. 3 Soft-Catch trap manufactured by Woodstream Corporation, Lititz, Pennsylvania (Linhart and Dasch 1992). Research has concentrated on two major areas: (1) efficiency and selectivity of different trap types and modifications used for capturing coyotes (Canis latrans) and (2) reducing animal injuries associated with trapping (Phillips and Mullis 1991). The Soft-Catch trap has been shown to reduce foot injury sustained by most captured furbearers (Tullar 1984, Olsen et al. 1986, Linhart et al. 1988, Olsen et al. 1988, Onderka et al. 1990)

Measurements of total odd nitrogen (NOy) aboard MOZAIC in-service aircraft: instrument design, operation and performance

A small system for the unattended measurement of total odd nitrogen (NOy, i.e., the sum of NO and its atmospheric oxidation products) aboard civil in-service aircraft in the framework of MOZAIC is described. The instrument employs the detection of NO by its chemiluminescence with O-3 in combination with catalytic conversion of the other NOy compounds to NO at 300degreesC on a gold surface in the presence of H-2. The instrument has a sensitivity of 0.4-0.7 cps/ppt and is designed for unattended operation during 1-2 service cycles of the aircraft (400-800 flight hours). The total weight is 50 kg, including calibration system, compressed gases, mounting, and safety measures. The layout and inlet configuration are governed by requirements due to the certification for passenger aircraft. Laboratory tests are described regarding the conversion efficiency for NO2 and HNO3 (both > 98%). Interference by non-NOy species is <1% for CH3CN and NH3, <5 x 10(-5) % for N2O (corresponding to <0.2 ppt fake NOy from ambient N2O) and 100% for HCN. The time response of the instrument is <1 s (90% change) for NO2. The response for HNO3 is nonlinear: 20 s for 67%, 60 s for 80%, and 150 s for 90% response, respectively

Outmigration Pathways of Stocked Juvenile European Sturgeon (Acipenser Sturio L., 1758) in the Lower Rhine River, as Revealed by Telemetry

International audienceWorking towards a future Rhine Sturgeon Action Plan the outmigration pathways of stocked juvenile European sturgeon (Acipenser sturio L., 1758) were studied in the River Rhine in 2012 and 2015 using the NEDAP Trail system. A total of 87 sturgeonof 3 to 5 years old (n = 43 in 2012, n = 44 in 2015) were implanted with transponders and released in May and June in the river Rhine at the Dutch‐German border, approximately 160 km from the sea. In total three sturgeons (3%) were found dead on river banks within seven days after the release. Based upon their wounds these sturgeons were likely hit by ship‐propellers. Tracking results were obtained from 57 (66%) of the sturgeons, of which 39 (45%) indicated movement into the Port of Rotterdam. Here the sturgeons remained for an average of two weeks, which suggests they spent time to acclimatize to higher salinities before entering the North Sea. Of the 45 (52%) sturgeons that were confirmed to have entered the North Sea, ten (22%) were recaptured (mainly by shrimpers and gill‐nets) close to the Dutch coastline; nine were alive and were released. From the results we obtained the preferred outmigration pathways, movement speeds and an indication of impacting factors (i.e. ship propellers and bycatch). Bycatches provided also localisations information in the coastal area. A next step to complete this work would be to assess habitat selection in freshwater and downstream migration of young of the year (YOY sturgeons) in the Lower Rhine

The Implementation of the Feedback Principle in Science and Technics

In this study positive and negative influence of the feedback have been examined. A feedback principle in the alternating current amplifier and in the speed regulator of the turbine rotation was described. The main conclusion of the positive and negative effect was obtained. Negative feedback worsens the properties of an object, reducing a strengthening factor, delaying regulatory action. Positive feedback considerably raises device work stability. This research will enable to identify the importance and effectiveness of the feedback principle in science and technics

Modeling of Novel Diagnostic Strategies for Active Tuberculosis – A Systematic Review: Current Practices and Recommendations

Introduction: The field of diagnostics for active tuberculosis (TB) is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB. Methods: Pubmed, personal libraries and reference lists were searched to identify eligible papers. We extracted data on a wide variety of model structure, parameter choices, sensitivity analyses and study conclusions, which were discussed during a meeting of content experts. Results & Discussion From 5619 records a total of 36 papers were included in the analysis. Sixteen papers included population impact/transmission modeling, 5 were health systems models, and 24 included estimates of cost-effectiveness. Transmission and health systems models included specific structure to explore the importance of the diagnostic pathway (n = 4), key determinants of diagnostic delay (n = 5), operational context (n = 5), and the pre-diagnostic infectious period (n = 1). The majority of models implemented sensitivity analysis, although only 18 studies described multi-way sensitivity analysis of more than 2 parameters simultaneously. Among the models used to make cost-effectiveness estimates, most frequent diagnostic assays studied included Xpert MTB/RIF (n = 7), and alternative nucleic acid amplification tests (NAATs) (n = 4). Most (n = 16) of the cost-effectiveness models compared new assays to an existing baseline and generated an incremental cost-effectiveness ratio (ICER). Conclusion: Although models have addressed a small number of important issues, many decisions regarding implementation of TB diagnostics are being made without the full benefits of insight from mathematical models. Further models are needed that address a wider array of diagnostic and epidemiological settings, that explore the inherent uncertainty of models and that include additional epidemiological data on transmission implications of false-negative diagnosis and the pre-diagnostic period

Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata

Background Candida glabrata is an opportunistic yeast pathogen thought to have a large genetic and phenotypic diversity and a highly plastic genome. However, the lack of chromosome-level genome assemblies representing this diversity limits our ability to accurately establish how chromosomal structure and gene content vary across strains. Results Here, we expanded publicly available assemblies by using long-read sequencing technologies in twelve diverse strains, obtaining a final set of twenty-one chromosome-level genomes spanning the known C. glabrata diversity. Using comparative approaches, we inferred variation in chromosome structure and determined the pan-genome, including an analysis of the adhesin gene repertoire. Our analysis uncovered four new adhesin orthogroups and inferred a rich ancestral adhesion repertoire, which was subsequently shaped through a still ongoing process of gene loss, gene duplication, and gene conversion. Conclusions C. glabrata has a largely stable pan-genome except for a highly variable subset of genes encoding cell wall-associated functions. Adhesin repertoire was established for each strain and showed variability among clades.TG group acknowledges support from the Spanish Ministry of Science and Innovation (MCIN) for grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); from the Catalan Research Agency (AGAUR) SGR423; from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742); from the “La Caixa” foundation (Grant LCF/PR/HR21/00737), and from the Instituto de Salud Carlos III (IMPACT Grant IMP/00019 and CIBERINFEC CB21/13/00061- ISCIII-SGEFI/ERDF). PWJG acknowledges support by grants SBPLY/19/180501/000114 and SBPLY/19/180501/000356 funded by the Regional government of Castilla-La Mancha and grants SAF2013-47570-P and PID2020-117983RB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF a way of making Europe.Peer ReviewedPostprint (author's final draft