The VgrG Proteins Are "à la Carte" Delivery Systems for Bacterial Type VI Effectors

The bacterial type VI secretion system (T6SS) is a supra-molecular complex akin to bacteriophage tails, with VgrG proteins acting as a puncturing device. The Pseudomonas aeruginosa H1-T6SS has been extensively characterized. It is involved in bacterial killing and in the delivery of three toxins, Tse1–3. Here, we demonstrate the independent contribution of the three H1-T6SS co-regulated vgrG genes, vgrG1abc, to bacterial killing. A putative toxin is encoded in the vicinity of each vgrG gene, supporting the concept of specific VgrG/toxin couples. In this respect, VgrG1c is involved in the delivery of an Rhs protein, RhsP1. The RhsP1 C terminus carries a toxic activity, from which the producing bacterium is protected by a cognate immunity. Similarly, VgrG1a-dependent toxicity is associated with the PA0093 gene encoding a two-domain protein with a putative toxin domain (Toxin_61) at the C terminus. Finally, VgrG1b-dependent killing is detectable upon complementation of a triple vgrG1abc mutant. The VgrG1b-dependent killing is mediated by PA0099, which presents the characteristics of the superfamily nuclease 2 toxin members. Overall, these data develop the concept that VgrGs are indispensable components for the specific delivery of effectors. Several additional vgrG genes are encoded on the P. aeruginosa genome and are not linked genetically to other T6SS genes. A closer inspection of these clusters reveals that they also encode putative toxins. Overall, these associations further support the notion of an original form of secretion system, in which VgrG acts as the carrier

Influence of a 12.8-km military load carriage activity on lower limb gait mechanics and muscle activity

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The high stress fracture occurrence in military populations has been associated with frequent load carriage activities. This study aimed to assess the influence of load carriage and of completing a load carriage training activity on gait characteristics. Thirty-two Royal Marine recruits completed a 12.8-km load carriage activity as part of their military training. Data were collected during walking in military boots, pre and post-activity, with and without the additional load (35.5 kg). Ground contact time, lower limb sagittal plane kinematics and kinetics, and electromyographic variables were obtained for each condition. When carrying load, there was increased ground contact time, increased joint flexion and joint moments, and increased plantar flexor and knee extensor muscle activity. Post-activity, there were no changes to kinematic variables, knee extensor moments were reduced, and there was evidence of plantar flexor muscle fatigue. The observed gait changes may be associated with stress fracture development. Practitioner Summary: This study identified gait changes due to load carriage and after a military load carriage training activity. Such activities are associated with lower limb stress fractures. A pre-post study design was used. Gait mechanics changed to a greater extent when carrying load, than after completion of the activity when assessed without load.This work was part-funded by the Institute of Naval Medicine

Strain evolution in GaN Nanowires: from free-surface objects to coalesced templates

Top-down fabricated GaN nanowires, 250 nm in diameter and with various heights, have been used to experimentally determine the evolution of strain along the vertical direction of 1-dimensional objects. X-ray diffraction and photoluminescence techniques have been used to obtain the strain profile inside the nanowires from their base to their top facet for both initial compressive and tensile strains. The relaxation behaviors derived from optical and structural characterizations perfectly match the numerical results of calculations based on a continuous media approach. By monitoring the elastic relaxation enabled by the lateral free-surfaces, the height from which the nanowires can be considered strain-free has been estimated. Based on this result, NWs sufficiently high to be strain-free have been coalesced to form a continuous GaN layer. X-ray diffraction, photoluminescence and cathodoluminescence clearly show that despite the initial strain-free nanowires template, the final GaN layer is strained

Facet recovery and light emission from GaN/InGaN/GaN core-shell structures grown by metal organic vapour phase epitaxy on etched GaN nanorod arrays

The use of etched nanorods from a planar template as a growth scaffold for a highly regular GaN/InGaN/GaN core-shell structure is demonstrated. The recovery of m-plane non-polar facets from etched high-aspect-ratio GaN nanorods is studied with and without the introduction of a hydrogen silsesquioxane passivation layer at the bottom of the etched nanorod arrays. This layer successfully prevented c-plane growth between the nanorods, resulting in vertical nanorod sidewalls (∼89.8°) and a more regular height distribution than re-growth on unpassivated nanorods. The height variation on passivated nanorods is solely determined by the uniformity of nanorod diameter, which degrades with increased growth duration. Facet-dependent indium incorporation of GaN/InGaN/GaN core-shell layers regrown onto the etched nanorods is observed by high-resolution cathodoluminescence imaging. Sharp features corresponding to diffracted wave-guide modes in angle-resolved photoluminescence measurements are evidence of the uniformity of the full core-shell structure grown on ordered etched nanorods

Calibrating whole building energy model: a case study using BEMS data

This paper describes a Calibration methodology which is specifically configured to best match actual building performance, based on a case study conducted to calibrate whole building energy model using Building Energy Management System (BEMS) measured data. It details the calibration approach which was designed to meet the specific characteristic of the spaces, systems and energy use in the pilot school building. Two calibration methods were developed; one is for electrical and the other is for thermal energy along with calibrated weather file. The result shows excellent correlation with the measured electricity and room air temperature and demonstrates the effectiveness of the methodology. Mean Bias Error (MBE) and Cumulative Variation of Root Mean Squared Error (CVRMSE) for electricity consumption is 6% and 14% respectively and -5 and 7% for air temperature

A narrow bimalleolar width is a risk factor for ankle inversion injury in male military recruits: A prospective study

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Background: Ankle inversion injuries are one of the most common and burdensome injuries in athletic populations. Research that prospectively identifies characteristics associated with this injury is lacking. This prospective study compared baseline anthropometric and biomechanical gait characteristics of military recruits who sustained an ankle inversion injury during training, with those who remained injury-free. Methods: Bilateral plantar pressure and three-dimensional lower limb kinematics were recorded in 1065 male, injury-free military recruits, during barefoot running. Injuries that occurred during the 32-week recruit training programme were subsequently recorded. Data were compared between recruits who sustained an ankle inversion injury during training (n=27) and a sample (n=120) of those who completed training injury-free. A logistic regression analysis was used to identify risk factors for this injury. Findings: A narrower bimalleolar width and an earlier peak pressure under the fifth metatarsal were predictors of ankle inversion injury. Those who sustained an ankle inversion injury also had a lower body mass, body mass index, and a smaller calf girth than those who completed training injury-free. Interpretation: Anthropometric and dynamic gait characteristics have been identified that may predispose recruits to an ankle inversion injury during Royal Marine recruit training, allowing identification of recruits at higher risk at the start of training

Functional heterogeneity of the UpaH autotransporter protein from uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) are responsible for the majority of urinary tract infections(UTI). To cause UTI, UPEC must adhere to epithelial cells of the urinary tract and overcome the shear flow forces of urine. This function is primarily mediated by fimbrial adhesins, which mediate specific attachment to host cell receptors. Another group of adhesins that contribute to UPEC mediated UTI are autotransporter (AT) proteins. AT proteins possess a range of virulence properties such as adherence, aggregation, invasion and biofilm formation. One recently characterized AT protein of UPEC is UpaH, a large AIDA-I type AT protein that contributes to biofilm formation and bladder colonization. In this study, we have characterized a series of naturally occurring variants of UpaH. We demonstrate that extensive sequence variation exists within the passenger-encoding domain of UpaH variants from different UPEC strains. This sequence variation is associated with functional heterogeneity with respect to the ability of UpaH to mediate biofilm formation. In contrast, all of the UpaH variants examined retained a conserved ability to mediate binding to extracellular matrix (ECM) proteins. Bioinformatic analysis of the UpaH passenger domain identified a conserved region (UpaHCR) and hydrophobic region (UpaHHR). Deletion of these domains reduced biofilm formation but not binding to ECM proteins. Despite variation in upaH sequence, the transcription of upaH was repressed by a conserved mechanism involving the global regulator H-NS, and mutation of the hns gene relieved this repression. Overall, our findings shed new light on the regulation and function of the UpaH AT protein

The Interaction between the ISM and Star Formation in the Dwarf Starburst Galaxy NGC 4214

We present the first interferometric study of the molecular gas in the metal-poor dwarf starburst galaxy NGC 4214. Our map of the 12CO(1-0) emission, obtained at the OVRO millimeter array, reveals an unexpected structural wealth. We detected three regions of molecular emission in the north-west (NW), south-east (SE) and centre of NGC 4214 which are in very different and distinct evolutionary stages (total molecular mass: 5.1 x 10^6 M_sun). These differences are apparent most dramatically when the CO morphologies are compared to optical ground based and HST imaging: massive star formation has not started yet in the NW region; the well-known starburst in the centre is the most evolved and star formation in the SE complex started more recently. We derive a star formation efficiency of 8% for the SE complex. Using high--resolution VLA observations of neutral hydrogen HI and our CO data we generated a total gas column density map for NGC 4214 (HI + H_2). No clear correlation is seen between the peaks of HI, CO and the sites of ongoing star formation. This emphasizes the irregular nature of dwarf galaxies. The HI and CO velocities agree well, so do the H-alpha velocities. In total, we cataloged 14 molecular clumps in NGC 4214. Our results from a virial mass analysis are compatible with a Galactic CO-to-H_2 conversion factor for NGC 4214 (lower than what is usually found in metal-poor dwarf galaxies).Comment: accepted for publication in the AJ (February 2001), full ps file at: ftp://ftp.astro.caltech.edu/users/fw/ngc4214/walter_prep.p

Sign of the crossed conductances at a FSF double interface

Crossed conductance in hybrid Ferromagnet / Superconductor / Ferromagnet (FSF) structures results from the competition between normal transmission and Andreev reflection channels. Crossed Andreev reflection (CAR) and elastic cotunneling (EC) between the ferromagnets are dressed by local Andreev reflections, which play an important role for transparent enough interfaces and intermediate spin polarizations. This modifies the simple result previously obtained at lowest order, and can explain the sign of the crossed resistances in a recent experiment [D. Beckmann {\sl et al.}, cond-mat/0404360]. This holds both in the multiterminal hybrid structure model (where phase averaging over the Fermi oscillations is introduced ``by hand'' within the approximation of a single non local process) and for infinite planar interfaces (where phase averaging naturally results in the microscopic solution with multiple non local processes).Comment: 9 pages, 7 figure