Microbial signaling and systems biology

A report of the symposium on Signaling and Systems Biology held during the Society for General Microbiology Spring Meeting, 29-30 March 2010, Edinburgh, U

Proalgebraic crossed modules of quasirational presentations

We introduce the concept of quasirational relation modules for discrete and pro-$p$ presentations of discrete and pro-$p$ groups and show that aspherical presentations and their subpresentations are quasirational. In the pro-$p$-case quasirationality of pro-$p$-groups with a single defining relation holds. For every quasirational (pro-$p$)relation module we construct the so called $p$-adic rationalization, which is a pro-fd-module $\overline{R}\widehat{\otimes}\mathbb{Q}_p= \varprojlim R/[R,R\mathcal{M}_n]\otimes\mathbb{Q}_p$. We provide the isomorphisms $\overline{R^{\wedge}_w}(\mathbb{Q}_p)=\overline{R}\widehat{\otimes}\mathbb{Q}_p$ and $\overline{R_u}(\mathbb{Q}_p)=\mathcal{O}(G_u)^*$, where $R^{\wedge}_w$ and $R^{\wedge}_u$ stands for continuous prounipotent completions and corresponding prounipotent presentations correspondingly. We show how $\overline{R^{\wedge}_{w}}$ embeds into a sequence of abelian prounipotent groups. This sequence arises naturally from a certain prounipotent crossed module, the latter bring concrete examples of proalgebraic homotopy types. The old-standing open problem of Serre, slightly corrected by Gildenhuys, in its modern form states that pro-$p$-groups with a single defining relation are aspherical. Our results give a positive feedback to the question of Serre.Comment: This is a corrected version of the paper which appeared in the Extended Abstracts Spring 2015, Interactions between Representation Theory, Algebraic Topology and Commutative Algebra, Research Perspectives CRM Barcelona, Vol.5, 201

Transmission of multidrug-resistant tuberculosis in the UK: a cross-sectional molecular and epidemiological study of clustering and contact tracing

BACKGROUND: Between 2000 and 2012 the number of multidrug-resistant (MDR) tuberculosis cases in the UK increased from 28 per year to 81 per year. We investigated the proportion of MDR tuberculosis cases arising from transmission in the UK and associated risk factors. METHOD: We identified patients with MDR tuberculosis notified in England, Wales, and Northern Ireland between Jan 1, 2004, and Dec 31, 2007, by linking national laboratory and surveillance data. Data for laboratory isolates, including drug sensitivities and 24-mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing were obtained routinely from the National Tuberculosis Reference laboratories as part of national tuberculosis surveillance. We investigated clusters of cases with indistinguishable MIRU-VNTR profiles to identify epidemiological links. We calculated transmission using the n-1 method and established associated risk factors by logistic regression. We also assessed the likelihood of transmission to additional secondary active tuberculosis cases, identified through conventional contact tracing. FINDINGS: 204 patients were diagnosed with MDR tuberculosis in the study period; 189 (92·6%) had an MIRU-VNTR profile. We identified 12 clusters containing 40 individuals and 149 unique strains. The proportion of cases attributable to recent transmission, on the basis of molecular data, was 15% (40 cases clustered-12 clusters/189 with a strain type). The proportion of cases attributable to recent transmission (ie, transmission within the UK) after adjustment for epidemiological links was 8·5% (22 cases with epidemiological links-six clusters/189 cases with a strain type). Being UK born (odds ratio 4·81; 95% CI 2·03-11·36, p=0·0005) and illicit drug use (4·75; 1·19-18·96, p=0·026) were significantly associated with clustering. The most common transmission setting was the household but 21 of 22 of epidemiological links were missed by conventional contact tracing. 13 secondary active tuberculosis cases identified by conventional contact tracing were mostly contacts of patients with MDR tuberculosis from countries of high tuberculosis burden. 11 (85%) of 13 shared the same country of birth as the index case, of whom ten did not share a strain type or drug resistance pattern. INTERPRETATION: Transmission of MDR tuberculosis in the UK is low and associated with being UK born or illicit drug use. MIRU-VNTR typing with cluster investigation was more successful at identifying transmission events than conventional contact tracing. Individuals with tuberculosis who have had contact with a known MDR tuberculosis source case from a country of high tuberculosis burden should have drug-sensitivity testing on isolates to ensure appropriate treatment is given. FUNDING: Public Health England

New method for the orthogonal labeling and purification of Toxoplasma gondii proteins while inside the host cell

oxoplasma gondii is an obligate intracellular protozoan parasite that is capable of causing severe disease in immunocompromised humans. How T. gondii is able to modulate the host cell to support itself is still poorly understood. Knowledge pertaining to the host-parasite interaction could be bolstered by developing a system to specifically label parasite proteins while the parasite grows inside the host cell. For this purpose, we have created a strain of T. gondii that expresses a mutant Escherichia coli methionyl-tRNA synthetase (MetRSNLL) that allows methionine tRNA to be loaded with the azide-containing methionine analog azidonorleucine (Anl). Anl-containing proteins are susceptible to a copper-catalyzed “click” reaction to attach affinity tags for purification or fluorescent tags for visualization. The MetRSNLL-Anl system labels nascent T. gondii proteins in an orthogonal fashion, labeling proteins only in MetRSNLL-expressing parasites. This system should be useful for nonradioactive pulse-chase studies and purification of nascently translated proteins. Although this approach allows labeling of a diverse array of parasite proteins, secreted parasite proteins appear to be only minimally labeled in MetRSNLL-expressing T. gondii. The minimal labeling of secreted proteins is likely a consequence of the selective charging of the initiator tRNA (and not the elongator methionine tRNA) by the heterologously expressed bacterial MetRS. IMPORTANCE Studying how T. gondii modifies the host cell to permit its survival is complicated by the complex protein environment of the host cell. The approach presented in this article provides the first method for specific labeling of T. gondii proteins while the parasite grows inside the host cell. We show that this approach is useful for pulse-chase labeling of parasite proteins during in vitro growth. It should also be applicable during in vivo infections and in other apicomplexan parasites, including Plasmodium spp

Multi-heme Cytochromes in Shewanella oneidensis MR-1:Structures, functions and opportunities

Multi-heme cytochromes are employed by a range of microorganisms to transport electrons over distances of up to tens of nanometers. Perhaps the most spectacular utilization of these proteins is in the reduction of extracellular solid substrates, including electrodes and insoluble mineral oxides of Fe(III) and Mn(III/IV), by species of Shewanella and Geobacter. However, multi-heme cytochromes are found in numerous and phylogenetically diverse prokaryotes where they participate in electron transfer and redox catalysis that contributes to biogeochemical cycling of N, S and Fe on the global scale. These properties of multi-heme cytochromes have attracted much interest and contributed to advances in bioenergy applications and bioremediation of contaminated soils. Looking forward there are opportunities to engage multi-heme cytochromes for biological photovoltaic cells, microbial electrosynthesis and developing bespoke molecular devices. As a consequence it is timely to review our present understanding of these proteins and we do this here with a focus on the multitude of functionally diverse multi-heme cytochromes in Shewanella oneidensis MR-1. We draw on findings from experimental and computational approaches which ideally complement each other in the study of these systems: computational methods can interpret experimentally determined properties in terms of molecular structure to cast light on the relation between structure and function. We show how this synergy has contributed to our understanding of multi-heme cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies

World caf\ue9 method to engage smart energy-district project partners in assessing urban co-benefits

Urban energy-district projects introduce outstanding technological innovation in buildings and energy systems increasing sustainability in city neighborhoods. Such projects generate additional co-benefits for the city beyond changes in physical elements and development of social and institutional relationships (e.g. local employment, environmental quality, public health, property values, innovation attitude, etc.). Since exceeding main declared goals or not always clearly foreseen in the early project phase, these co-benefits are often not properly understood and considered. However, only their explicit recognition will make possible their inclusion in the assessment of the whole project\u2019s performance. From these considerations, this study faces the issue of engaging project partners in assessing co-benefits in order to consider a broad spectrum of relevant, positive effects in the evaluation process. Group knowledge and group thinking of this complex topic are investigated through the world caf\ue9 method, providing an atmosphere of trust and open discussions among participants. This empirical work lays the foundations to go beyond the mere economic measure as the sole criterion for assessing project effects, also including changes in end-user behavior and intangible asset

The application of a management procedure to regulate the directed and bycatch fishery of South African sardine sardinops sagax

The South African sardine Sardinops sagax resource is subjected to both directed fishing that targets adult fish, and bycatch of both juvenile and adult fish taken in the directed fisheries for anchovy Engraulis capensisand round herring Etrumeus whiteheadi. Two separate TACs (Total Allowable Catch) for sardine are calculated in the management procedures considered. The first is a directed TAC linked to sardine abundance, and the second is a bycatch TAC with an “anchovy” component coupled to the anchovy population dynamics as a proportion of the anchovy TAC, plus a “round herring” component reflecting a fixed tonnage independent of round herring abundance. Requirements from the pelagic industry, such as a minimum economically viable annual directed catch and a maximum percentage decrease in the directed TAC that could be tolerated from year to year are also incorporated. The selection of a single management procedure for implementation is based on the comparison of performance statistics such as risk of severe depletion and average annual catch, which incorporate the consequences of random error in survey estimates of abundance and random fluctuations in recruitment from year to year. Sensitivity tests are carried out to ensure robustness over a range of alternative assumptions concerning resource dynamics. A description is given of the development of the management procedure for sardine thatwas implemented in 1994, and the rationale for its selection. A wide range of variants to this procedure, including those that consider alternative approaches for handling bycatch, are investigated. Performance of the management procedures considered demonstrates extreme sensitivity to the choice of the proportion of the anchovy TAC used in the sardine bycatch TAC calculation. A lack of robustness of the selected management procedure to possible bias in estimates of spawner biomass from hydroacoustic surveys, and poor precision of recruit survey estimatesare argued as justification for adopting a conservative approach for managing sardine