An ABC transporter containing a forkhead-associated domain interacts with a serine-threonine protein kinase and is required for growth of Mycobacterium tuberculosis in mice

Forkhead-associated (FHA) domains are modular phosphopeptide recognition motifs with a striking preference for phosphothreonine-containing epitopes. FHA domains have been best characterized in eukaryotic signaling pathways but have been identified in six proteins in Mycobacterium tuberculosis, the causative organism of tuberculosis. One of these, coded by gene Rv1747, is an ABC transporter and the only one to contain two such modules. A deletion mutant of Rv1747 is attenuated in a mouse intravenous injection model of tuberculosis where the bacterial load of the mutant is 10-fold lower than that of the wild type in both lungs and spleen. In addition, growth of the mutant in mouse bone marrow-derived macrophages and dendritic cells is significantly impaired. In contrast, growth of this mutant in vitro was indistinguishable from that of the wild type. The mutant phenotype was lost when the mutation was complemented by the wild-type allele, confirming that it was due to mutation of Rv1747. Using yeast two-hybrid analysis, we have shown that the Rv1747 protein interacts with the serine-threonine protein kinase PknF. This interaction appears to be phospho-dependent since it is abrogated in a kinase-dead mutant and by mutations in the presumed activation loop of PknF and in the first FHA domain of Rv1747. These results demonstrate that the protein coded by Rv1747 is required for normal virulent infection by M. tuberculosis in mice and, since it interacts with a serine-threonine protein kinase in a kinase-dependent manner, indicate that it forms part of an important phospho-dependent signaling pathway

Non-monotonic size dependence of the elastic modulus of nanocrystalline ZnO embedded in a nanocrystalline silver matrix

We present the first high pressure Raman study on nanocrystalline ZnO films with different average crystallite sizes. The problem of low Raman signals from nano sized particles was overcome by forming a nanocomposite of Ag and ZnO nanoparticles. The presence of the nanodispersed Ag particles leads to a substantial surface enhancement of the Raman signal from ZnO. We find that the elastic modulus of nanocrystalline ZnO shows a non-monotonic dependence on the crystallite size. We suggest that the non-monotonicity arises from an interplay between the elastic properties of the individual grains and the intergranular region.Comment: 10 pages, 6 figure

Anesthetic efficacy and safety of ropivacaine 0.75% versus bupivacaine 0.5% for spinal anesthesia in patients undergoing lower limb orthopedic surgery

Background: Ropivacaine, a new amino-amide local anesthetic agent, is similar in chemical structure to bupivacaine. The low solubility of ropivacaine leads to greater sensory-motor differentiation by blocking sensory nerve fiber more readily than motor nervefibers. Early recovery of motor function is associated with decreased incidence of venous thromboembolism and early mobilization. Aims and Objectives: The present study aimed to compare the anesthetic efficacy and safety of hyperbaric ropivacaine 0.75% with hyperbaric bupivacaine 0.5% in spinal anesthesia in patients undergoing lower limb orthopedic surgery. Materials and Methods: A total of 60 patients aged between 18 and 60 years of either sex, ASA I and II, undergoing elective lower limb orthopedic surgery were randomly divided into two groups, ropivacaine (R) and bupivacaine (B) group. Group R received 3 mL of 0.75% hyperbaric ropivacaine and group B received 3 mL 0.5% hyperbaric bupivacaine intrathecally. The efficacy in terms of onset and duration of anesthesia, quality of anesthesia, and hemodynamic and safety in terms of complications were noted. Results: Group R produced faster onset of sensory block (ropivacaine 2.6±0.53 min; bupivacaine 3±0.56 min; P<0.006) and the mean duration of sensory block was significantly lesser compared to Group B (Ropivacaine 121.16±7.73 min; Bupivacaine 180.34±11.56 min; P<0.0001). Patients in Group R has significantly more rapid recovery of a motor blockade than Group B (ropivacaine 149.5±8.64 min; bupivacaine 210.17±13.19 min; P<0.0001). Conclusion: Hyperbaric ropivacaine 0.75% was found to be a comparable alternative to hyperbaric bupivacaine 0.5% in patients undergoing lower limb orthopedic surgery

Zonal flows and long-distance correlations during the formation of the edge shear layer in the TJ-II stellarator

A theoretical interpretation is given for the observed long-distance correlations in potential fluctuations in TJ-II. The value of the correlation increases above the critical point of the transition for the emergence of the plasma edge shear flow layer. Mean (i.e. surface averaged, zero-frequency) sheared flows cannot account for the experimental results. A model consisting of four envelope equations for the fluctuation level, the mean flow shear, the zonal flow amplitude shear, and the averaged pressure gradient is proposed. It is shown that the presence of zonal flows is essential to reproduce the main features of the experimental observations.Comment: 19 pages, 7 figure

Temperature study of Al0.52In0.48P detector photon counting X-ray spectrometer

A prototype 200 μm diameter Al0.52In0.48P p+-i-n+ mesa photodiode (2 μm i-layer) was characterised at temperatures from 100 °C to −20 °C for the development of a temperature tolerant photon counting X-ray spectrometer. At each temperature, X-ray spectra were accumulated with the AlInP detector reverse biased at 0 V, 5 V, 10 V, and 15 V and using different shaping times. The detector was illuminated by an 55Fe radioisotope X-ray source. The best energy resolution, as quantified by the full width at half maximum (FWHM) at 5.9 keV, was observed at 15 V for all the temperatures studied; at 100 °C, a FWHM of 1.57 keV was achieved, and this value improved to 770 eV FWHM at −20 °C. System noise analysis was also carried out, and the different noise contributions were computed as functions of temperature. The results are the first demonstration of AlInP's suitability for photon counting X-ray spectroscopy at temperatures other than ≈20 °C

A fast CCD detector for charge exchange recombination spectroscopy on the DIII-D tokamak

Charge Exchange Recombination (CER) spectroscopy has become a standard diagnostic for tokamaks. CER measurements have been used to determine spatially and temporally resolved ion temperature, toroidal and poloidal ion rotation speed, impurity density and radial electric field. Knowledge of the spatial profile and temporal evolution of the electric field shear in the plasma edge is crucial to understanding the physics of the L to H transition. High speed CER measurements are also valuable for Edge Localized Mode (ELM) studies. Since the 0.52 ms minimum time resolution of our present system is barely adequate to study the time evolution of these phenomena, we have developed a new CCD detector system with about a factor of two better time resolution. In addition, our existing system detects sufficient photons to utilize the shortest time resolution only under exceptional conditions. The new CCD detector has a quantum efficiency of about 0.65, which is a factor of 7 better than our previous image intensifier-silicon photodiode detector systems. We have also equipped the new system with spectrometers of lower f/number. This combination should allow more routine operation at the minimum integration time, as well as improving data quality for measurements in the divertor-relevant region outside of the separatrix. Construction details, benchmark data and initial tokamak measurements for the new system will be presented

Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism

Mitochondria house evolutionarily conserved pathways of carbon and nitrogen metabolism that drive cellular energy production. Mitochondrial bioenergetics is regulated by calcium uptake through the mitochondrial calcium uniporter (MCU), a multi-protein complex whose assembly in the inner mitochondrial membrane is facilitated by the scaffold factor MCUR1. Intriguingly, many fungi that lack MCU contain MCUR1 homologs, suggesting alternate functions. Herein, we characterize Saccharomyces cerevisiae homologs Put6 and Put7 of MCUR1 as regulators of mitochondrial proline metabolism. Put6 and Put7 are tethered to the inner mitochondrial membrane in a large hetero-oligomeric complex, whose abundance is regulated by proline. Loss of this complex perturbs mitochondrial proline homeostasis and cellular redox balance. Yeast cells lacking either Put6 or Put7 exhibit a pronounced defect in proline utilization, which can be corrected by the heterologous expression of human MCUR1. Our work uncovers an unexpected role of MCUR1 homologs in mitochondrial proline metabolism. Although some fungal mitochondria lack the calcium uniporter, many intriguingly encode homologs of the uniporter assembly factor MCUR1. Here, the authors show that in budding yeast, the MCUR1 homologs Put6 and Put7 regulate mitochondrial proline metabolism, a function also conserved in human MCUR1