Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis

Oleoyl Coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in Mycobacteria

We have recently shown that RaaS (regulator of antimicrobial-assisted survival), encoded by Rv1219c in Mycobacterium tuberculosis and by bcg_1279c in Mycobacterium bovis bacillus Calmette-Guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. Here, we demonstrate that long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, palmitoyl-CoA) modulate RaaS binding to DNA and expression of the downstream genes that encode ATP-dependent efflux pumps. Moreover, exogenously added oleic acid influences RaaS-mediated mycobacterial improvement of survival and expression of the RaaS regulon. Our data suggest that long chain acyl-CoA derivatives serve as biological indicators of the bacterial metabolic state. Dysregulation of efflux pumps can be used to eliminate non-growing mycobacteria

Numerical analysis of the stress-strain state of osteotomies of the first metatarsal bone

Deviation of the first toe to the outside, interconnected with the deviation of the first metatarsal bone to the inside, occurs in 46% of patients of the older age group and is called valgus deformity of the first toe. The negative impact of this pathology on the quality of life of patients is the reason for seeking medical help, the gold standard of which is surgical correction, and the basic surgical technique is osteotomy (sawing the bone and fixing its fragments with implants) of the first metatarsal. At the same time, an ideal osteotomy should provide initial stability in the early postoperative period. However, a large number of ways to perform osteotomy, as well as the advantages and disadvantages of each of the surgical techniques, do not allow to consider one of them as the most successful. In this regard, the aim of the work was to develop and validate a biomechanical model of osteotomy of the first metatarsal bone to analyze its stability and reliability depending on the type of osteotomy, the degree of displacement of bone fragments, as well as the number of fastening screws. In this study, biomechanical modeling of the most commonly used variants of osteotomy of the first metatarsal bone of the foot in the surgical treatment of its valgus deformity was carried out. For this purpose, 10 models of osteotomies of a separate first metatarsal bone were created, which were then subjected to static loading to analyze their stress-strain state and assess their success. Successful (stable and reliable) treatment options were identified, as well as unsuccessful ones. Two of the ten options considered were unsuccessful – scarf type osteotomies with displacement of bone fragments by 2/3 of its diameter and fixed with a single screw. It was revealed that osteotomies of the chevron type showed higher stability in comparison with scarf osteotomies. As a result, we note that in this study, numerical experiments were conducted for the first time to compare the stability and strength of the most commonly used variants of osteotomies based on a single bone model. A biomechanical model of scarf osteotomy of the first metatarsal bone has been developed and validated on the basis of mechanical experiments

Pressure-induced symmetry changes in body-centred cubic zeolites

Previous work has shown a strong correlation between zeolite framework flexibility and the nature of structural symmetry and phase transitions. However, there is little experimental data regarding this relationship, in addition to how flexibility can be connected to the synthesis of these open framework materials. This is of interest for the synthesis of novel zeolites, which require organic additives to permutate the resulting geometry and symmetry of the framework. Here, we have used high pressure powder X-ray diffraction to study the three zeolites: Na-X, RHO and ZK-5, which can all be prepared using 18-crown-6 ether as an organic additive. We observe significant differences in how the occluded 18-crown-6 ether influences the framework flexibility – this being dependant on the geometry of the framework. We use these differences as an indicator to define the role of 18-crown-6 ether during zeolite crystallisation. Furthermore, in conjunction with previous work we predict that pressure-induced symmetry transitions are intrinsic to body-centred cubic zeolites. The high symmetry yields fewer degrees of freedom, meaning it is energetically favourable to lower the symmetry to facilitate further compression.Dataset for the article "Pressure-induced symmetry changes in body-centred cubic zeolites"This repository contains the data included in the article "Pressure-induced symmetry changes in body-centred cubic zeolites". The data consists of high pressure powder X-ray diffraction data collected at the ID15B beamline at the European Synchrotron Radiation Facility (ESRF).Cubic High-Pressure Repository.zi

Utilization of Staphylococcal Immune Evasion Protein Sbi as a Novel Vaccine Adjuvant

<p>Co-ligation of the B cell antigen receptor with complement receptor 2 on B-cells via a C3d-opsonised antigen complex significantly lowers the threshold required for B cell activation. Consequently, fusions of antigens with C3d polymers have shown great potential in vaccine design. However, these linear arrays of C3d multimers do not mimic the natural opsonisation of antigens with C3d. Here we investigate the potential of using the unique complement activating characteristics of Staphylococcal immune-evasion protein Sbi to develop a pro-vaccine approach that spontaneously coats antigens with C3 degradation products in a natural way. We show that Sbi rapidly triggers the alternative complement pathway through recruitment of complement regulators, forming tripartite complexes that act as competitive antagonists of factor H, resulting in enhanced complement consumption. These functional results are corroborated by the structure of the complement activating Sbi-III-IV:C3d:FHR-1 complex. Finally, we demonstrate that Sbi, fused with Mycobacterium tuberculosis antigen Ag85b, causes efficient opsonisation with C3 fragments, thereby enhancing the immune response significantly beyond that of Ag85b alone, providing proof of concept for our pro-vaccine approach.</p

Trust, control and knowledge transfer in small business networks

The ability to transfer knowledge effectively in the networks of small and medium-sized firms (SMEs) is paramount for supporting firm competitiveness. Our research is the first one that explores the joint effect of trust and control mechanisms on knowledge transfer in the case of networks of SMEs. We use a multiple case study approach based on six Italian networks of SMEs. We analyse the joint impact of different ethical based trustworthiness factors—namely benevolence and integrity—and the levers of control (LOCs)—namely, belief, boundary, diagnostic and interactive LOCs—on knowledge transfer between SMEs in networks. We find that trust substitutes for the implementation of boundary, diagnostic, and belief tools, while it works jointly with interactive tools in order to support knowledge transfer. These insights not only provide a rich foundation for follow-up research, but also inform SME managers about how to increase the effectiveness and efficiency of knowledge transfer with their network partners

Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria

We have recently shown that RaaS (regulator of antimicrobial-assisted survival), encoded by Rv1219c in Mycobacterium tuberculosis and by bcg_1279c in Mycobacterium bovis bacillus Calmette-Guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. Here, we demonstrate that long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, palmitoyl-CoA) modulate RaaS binding to DNA and expression of the downstream genes that encode ATP-dependent efflux pumps. Moreover, exogenously added oleic acid influences RaaS-mediated mycobacterial improvement of survival and expression of the RaaS regulon. Our data suggest that long chain acyl-CoA derivatives serve as biological indicators of the bacterial metabolic state. Dysregulation of efflux pumps can be used to eliminate non-growing mycobacteria

10681_2006_9321_Author.pdf

Abstract Sixty-six spring and winter common 11 wheat genotypes from Central Asian breeding 12 programs were evaluated for grain concentrations 13 of iron (Fe