Burkholderia Hep_Hag autotransporter (BuHA) proteins elicit a strong antibody response during experimental glanders but not human melioidosis

Background The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei. Results Using bacteriophage-mediated immunoscreening we identified genes expressed in vivo during experimental equine glanders infection. A family of immunodominant antigens were identified that share protein domain architectures with hemagglutinins and invasins. These have been designated Burkholderia Hep_Hag autotransporter (BuHA) proteins. A total of 110/207 positive clones (53%) of a B. mallei expression library screened with sera from two infected horses belonged to this family. This contrasted with 6/189 positive clones (3%) of a B. pseudomallei expression library screened with serum from 21 patients with culture-proven melioidosis. Conclusion Members of the BuHA proteins are found in other Gram-negative bacteria and have been shown to have important roles related to virulence. Compared with other bacterial species, the genomes of both B. mallei and B. pseudomallei contain a relative abundance of this family of proteins. The domain structures of these proteins suggest that they function as multimeric surface proteins that modulate interactions of the cell with the host and environment. Their effect on the cellular immune response to B. mallei and their potential as diagnostics for glanders requires further study

MEMS based hair flow-sensors as model systems for acoustic perception studies

Arrays of MEMS fabricated flow sensors inspired by the acoustic flow-sensitive hairs found on the cerci of crickets, have been designed, fabricated and characterized. The hairs consist of up to 1 mm long SU-8 structures mounted on suspended membranes with normal translational and rotational degrees of freedom. Electrodes on the membrane and on the substrate form variable capacitors allowing for capacitive read-out. Capacitance versus voltage, frequency dependency and directional sensitivity measurements have been successfully carried out on fabricated sensor arrays, showing the viability of the concept. The sensors form a model-system allowing for investigations on sensory acoustics by their arrayed nature, their adaptivity via electrostatic interaction (frequency tuning and parametric amplifica- tion) and their susceptibility to noise (stochastic resonance

Cell wall elongation mode in Gram-negative bacteria is determined by peptidoglycan architecture

Cellular integrity and morphology of most bacteria is maintained by cell wall peptidoglycan, the target of antibiotics essential in modern healthcare. It consists of glycan strands, cross-linked by peptides, whose arrangement determines cell shape, prevents lysis due to turgor pressure and yet remains dynamic to allow insertion of new material, and hence growth. The cellular architecture and insertion pattern of peptidoglycan have remained elusive. Here we determine the peptidoglycan architecture and dynamics during growth in rod-shaped Gram-negative bacteria. Peptidoglycan is made up of circumferentially oriented bands of material interspersed with a more porous network. Super-resolution fluorescence microscopy reveals an unexpected discontinuous, patchy synthesis pattern. We present a consolidated model of growth via architecture-regulated insertion, where we propose only the more porous regions of the peptidoglycan network that are permissive for synthesis

The feasibility and efficacy of a brief integrative treatment for adults with depression and/or anxiety: A randomized controlled trial

The aim of this study was to investigate the efficacy and suitability of a brief integrative intervention, Personalized Integrative Therapy (PI Therapy), for the treatment of adult depression and/or anxiety. In this 6-week, 3-arm, parallel-group, randomized trial, PI Therapy delivered alone or with nutritional supplements (PI Therapy + Supps) was compared to cognitive behavior therapy (CBT) in 48 adults with depression and/or anxiety. All treatments were delivered as a 1-day workshop plus 6 weeks of reminder phone text messages to reinforce topics and skills covered in the workshop. Affective symptoms decreased significantly and to the same extent in all 3 conditions. At the end of treatment, 33% to 58% of participants reported levels of depressive symptoms in the normal range, and 50% to 58% reported nonclinical levels of anxiety. Compared to CBT and PI Therapy, PI Therapy + Supps was associated with significantly greater improvements in sleep quality. These findings suggest that a brief integrative intervention with or without supplements was comparable to CBT in reducing affective symptoms in adults with depression and/or anxiety. However, sleep quality improved only in the PI Therapy + Supps condition. These findings will require replication with a larger cohort

Учебная программа для специальности 1–24 01 01 Международное право

«Защита населения и объектов от чрезвычай-ных ситуаций. Радиационная безопасность» –– учебная дисциплина, изучающая чрезвычайные ситуации мирного и военного времени, влияние их поражающих факторов на жизнь и здоровье людей, объекты народного хозяйства и окружаю-щую среду, а также меры по предотвращению и ликвидации чрезвычайных си-туаций с целью сохранения здоровья нации, уменьшения ущерба природной сре-де и экономическому развитию страны

The Cost of Stability in Coalitional Games

A key question in cooperative game theory is that of coalitional stability, usually captured by the notion of the \emph{core}--the set of outcomes such that no subgroup of players has an incentive to deviate. However, some coalitional games have empty cores, and any outcome in such a game is unstable. In this paper, we investigate the possibility of stabilizing a coalitional game by using external payments. We consider a scenario where an external party, which is interested in having the players work together, offers a supplemental payment to the grand coalition (or, more generally, a particular coalition structure). This payment is conditional on players not deviating from their coalition(s). The sum of this payment plus the actual gains of the coalition(s) may then be divided among the agents so as to promote stability. We define the \emph{cost of stability (CoS)} as the minimal external payment that stabilizes the game. We provide general bounds on the cost of stability in several classes of games, and explore its algorithmic properties. To develop a better intuition for the concepts we introduce, we provide a detailed algorithmic study of the cost of stability in weighted voting games, a simple but expressive class of games which can model decision-making in political bodies, and cooperation in multiagent settings. Finally, we extend our model and results to games with coalition structures.Comment: 20 pages; will be presented at SAGT'0

Identification of a quorum sensing-dependent communication pathway mediating bacteria-gut-brain cross talk

Despite recently established contributions of the intestinal microbiome to human health and disease, our understanding of bacteria-host communication pathways with regard to the gut-brain axis remains limited. Here we provide evidence that intestinal neurons are able to “sense” bacteria independently of the host immune system. Using supernatants from cultures of the opportunistic pathogen Staphylococcus aureus (S. aureus) we demonstrate the release of mediators with neuromodulatory properties at high population density. These mediators induced a biphasic response in extrinsic sensory afferent nerves, increased membrane permeability in cultured sensory neurons, and altered intestinal motility and secretion. Genetic manipulation of S. aureus revealed two key quorum sensing-regulated classes of pore forming toxins that mediate excitation and inhibition of extrinsic sensory nerves, respectively. As such, bacterial mediators have the potential to directly modulate gut-brain communication to influence intestinal symptoms and reflex function in vivo, contributing to homeostatic, behavioral, and sensory consequences of infection

Intra-Articular Fms-Like Tyrosine Kinase 3 Ligand Expression Is a Driving Force in Induction and Progression of Arthritis

Background: One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. Methodology/Principal Findings: To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). Conclusions/Significance: Our findings indicate that Flt3-L is strongly expressed at the site of inflammation in human RA. It exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. Owing to these properties, treatment attempts to neutralize this molecule should be considered in RA

Differential localization of LTA synthesis proteins and their interaction with the cell division machinery in Staphylococcus aureus

Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria. In Staphylococcus aureus it consists of a polyglycerolphosphate-chain that is retained within the membrane via a glycolipid. Using an immunofluorescence approach, we show here that the LTA polymer is not surface exposed in S. aureus, as it can only be detected after digestion of the peptidoglycan layer. S. aureus mutants lacking LTA are enlarged and show aberrant positioning of septa, suggesting a link between LTA synthesis and the cell division process. Using a bacterial two-hybrid approach, we show that the three key LTA synthesis proteins, YpfP and LtaA, involved in glycolipid production, and LtaS, required for LTA backbone synthesis, interact with one another. All three proteins also interacted with numerous cell division and peptidoglycan synthesis proteins, suggesting the formation of a multi-enzyme complex and providing further evidence for the co-ordination of these processes. When assessed by fluorescence microscopy, YpfP and LtaA fluorescent protein fusions localized to the membrane while the LtaS enzyme accumulated at the cell division site. These data support a model whereby LTA backbone synthesis proceeds in S. aureus at the division site in co-ordination with cell division, while glycolipid synthesis takes place throughout the membrane

The effect of skin fatty acids on Staphylococcus aureus

Staphylococcus aureus is a commensal of the human nose and skin. Human skin fatty acids, in particular cis-6-hexadecenoic acid (C-6-H), have high antistaphylococcal activity and can inhibit virulence determinant production. Here, we show that sub-MIC levels of C-6-H result in induction of increased resistance. The mechanism(s) of C-6-H activity was investigated by combined transcriptome and proteome analyses. Proteome analysis demonstrated a pleiotropic effect of C-6-H on virulence determinant production. In response to C-6-H, transcriptomics revealed altered expression of over 500 genes, involved in many aspects of virulence and cellular physiology. The expression of toxins (hla, hlb,hlgBC) was reduced, whereas that of host defence evasion components (cap, sspAB, katA) was increased. In particular, members of the SaeRS regulon had highly reduced expression, and the use of specific mutants revealed that the effect on toxin production is likely mediated via SaeRS