Structure of HrcQ(B)-C, a conserved component of the bacterial type III secretion systems

Type III secretion systems enable plant and animal bacterial pathogens to deliver virulence proteins into the cytosol of eukaryotic host cells, causing a broad spectrum of diseases including bacteremia, septicemia, typhoid fever, and bubonic plague in mammals, and localized lesions, systemic wilting, and blights in plants. In addition, type III secretion systems are also required for biogenesis of the bacterial flagellum. The HrcQ(B) protein, a component of the secretion apparatus of Pseudomonas syringae with homologues in all type III systems, has a variable N-terminal and a conserved C-terminal domain (HrcQ(B)-C). Here, we report the crystal structure of HrcQ(B)-C and show that this domain retains the ability of the full-length protein to interact with other type III components. A 3D analysis of sequence conservation patterns reveals two clusters of residues potentially involved in protein–protein interactions. Based on the analogies between HrcQ(B) and its flagellum homologues, we propose that HrcQ(B)-C participates in the formation of a C-ring-like assembly

Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients

© 2020, Hellenic Endocrine Society. Purpose: Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. The aim of this study was to systematically review and conduct a meta-analysis of the available observational studies reporting the effect of diabetes on mortality among hospitalized patients with COVID-19. Methods: The Medline, Embase, Google Scholar, and medRxiv databases were reviewed for identification of eligible studies. A random effects model meta-analysis was used, and I2 was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed. Results: A total of 18,506 patients were included in this meta-analysis (3713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared with patients without diabetes (OR 1.65; 95% CI 1.35–1.96; I2 77.4%). The heterogeneity was high. A study-level meta-regression analysis was performed for all the important covariates, and no significant interactions were found between the covariates and the outcome of mortality. Conclusion: This meta-analysis shows that that the likelihood of death seems to be higher in diabetic patients hospitalized with COVID-19 compared with non-diabetic patients. Further studies are needed to assess whether this association is independent or not, as well as to investigate the role of adequate glycemic control prior to infection with COVID-19

Becoming invisible: The ethics and politics of imperceptibility

This speculative essay examines ‘invisible’ social identities and the processes by which they are manifested and occasionally sought. Using various literary and academic sources, and loosely informed by an unlikely combination of Stoic philosophy and post-structuralist politics, we argue that invisibility is conventionally viewed as undesirable or ‘suffered’ by individuals or groups that are disadvantaged or marginalised within society. Whilst appreciating this possibility, we argue that social invisibility can also be the result of strategies carefully conceived and consciously pursued. We suggest that forms of social invisibility can be acquired by ethically informed personal action as well as by politically informed collective action. In this context, invisibility can be seen as a strategy of escaping from institutionalised and organisational judgements and which presents a challenge to common notions of voice and identity

GBR 12909 administration as a mouse model of bipolar disorder mania: mimicking quantitative assessment of manic behavior

Mania is a core feature of bipolar disorder (BD) that traditionally is assessed using rating scales. Studies using a new human behavioral pattern monitor (BPM) recently demonstrated that manic BD patients exhibit a specific profile of behavior that differs from schizophrenia and is characterized by increased motor activity, increased specific exploration, and perseverative locomotor patterns as assessed by spatial d. It was hypothesized that disrupting dopaminergic homeostasis by inhibiting dopamine transporter (DAT) function would produce a BD mania-like phenotype in mice as assessed by the mouse BPM. We compared the spontaneous locomotor and exploratory behavior of C57BL/6J mice treated with the catecholamine transporter inhibitor amphetamine or the selective DAT inhibitor GBR 12909 in the mouse BPM. We also assessed the duration of the effect of GBR 12909 by testing mice in the BPM for 3 h and its potential strain dependency by testing 129/SvJ mice. Amphetamine produced hyperactivity and increased perseverative patterns of locomotion as reflected in reduced spatial d values but reduced exploratory activity in contrast to the increased exploration observed in BD patients. GBR 12909 increased activity and reduced spatial d in combination with increased exploratory behavior, irrespective of inbred strain. These effects persisted for at least 3 h. Thus, selectively inhibiting the DAT produced a long-lasting cross-strain behavioral profile in mice that was consistent with that observed in manic BD patients. These findings support the use of selective DAT inhibition in animal models of the impaired dopaminergic homeostasis putatively involved in the pathophysiology of BD mania

Integration operators for generating RDF/OWL-based user defined mediator views in a grid environment

Research and development activities relating to the grid have generally focused on applications where data is stored in files. However, many scientific and commercial applications are highly dependent on Information Servers (ISs) for storage and organization of their data. A data-information system that supports operations on multiple information servers in a grid environment is referred to as an interoperable grid system. Different perceptions by end-users of interoperable systems in a grid environment may lead to different reasons for integrating data. Even the same user might want to integrate the same distributed data in various ways to suit different needs, roles or tasks. Therefore multiple mediator views are needed to support this diversity. This paper describes our approach to supporting semantic interoperability in a heterogeneous multi-information server grid environment. It is based on using Integration Operators for generating multiple semantically rich RDF/OWL-based user defined mediator views above the grid participating ISs. These views support different perceptions of the distributed and heterogeneous data available. A set of grid services are developed for the implementation of the mediator views

Organizing solidarity initiatives : a socio-spatial conceptualization of resistance

This paper offers a spatial conceptualization of resistance by focusing on the practices through which solidarity initiatives constitute new resistance socio-spatialities. We discuss two solidarity initiatives in Greece, WCNA and Vio.Me.SI, and explore how they institute distinctive local and translocal organizational practices that make the production of new forms of resistance possible. In particular, we adopt a productive and transformative view of resistance. First, we identify three local practices of organizing solidarity initiatives, namely, the organization of general assembly meetings, the constitution of resistance laboratories and the (re)articulation of socio-spatial relations in local sites. Then, we turn to flows, movements and translocal social formations, and examine the role of solidarity mobilizations, the material and symbolic co-production of resources and members’ mobility in the production of resistance. We conclude that new resistance socio-spatialities become constitutive of a broader reconfiguration of political agencies, a creative process that challenges existing relations and invites alternative ways of working and organizing

At What Stage of Neural Processing Does Cocaine Act to Boost Pursuit of Rewards?

Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s) of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the KM of an enzyme) whereas gain determines the maximum intensity attainable (a measure analogous to the vmax of an enzyme-catalyzed reaction). To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood

Cold adaptation of a psychrophilic chitinase: a mutagenesis study

The gene encoding chitinase ArChiB from the Antarctic Arthrobacter sp. TAD20 has been expressed in Escherichia coli and the recombinant enzyme purified to homogeneity. In an effort to engineer cold-adapted biocatalysts through rational redesign to operate at elevated temperatures, we performed several mutations aiming to increase the rigidity of the molecular edifice of the selected psychrophilic chitinase. The mutations were designed on the basis of a homology-based three-dimensional model of the enzyme, and included an attempt to introduce a salt bridge (mutant N198K) and replacements of selected Gly residues by either Pro (mutants G93P, G254P) or Gln (G406Q). Mutant N198K resulted in a more stable protein (DeltaT(m)=0.6degreesC). Mutant G93P exhibited a DeltaT(m) of 1.2degreesC, while mutants G254P and G406Q exhibited decreased stability. We conclude that the effect of mutating Gly residues on enzyme stability is rather complex and can only be understood in the context of the structural environment. Kinetic and spectroscopic analysis of these enzyme variants revealed that the kinetic parameters k(cat) and K-m have been significantly modified