Meta-analysis of the normal diffusion tensor imaging values of the median nerve and how they change in carpal tunnel syndrome

Carpal tunnel syndrome (CTS) leads to distortion of axonal architecture, demyelination and fibrosis within the median nerve. Diffusion tensor imaging (DTI) characterises tissue microstructure and generates reproducible proxy measures of nerve ‘health’ which are sensitive to myelination, axon diameter, fiber density and organisation. This meta-analysis summarises the normal DTI values of the median nerve, and how they change in CTS. This systematic review included studies reporting DTI of the median nerve at the level of the wrist in adults. The primary outcome was to determine the normal fractional anisotropy (FA) and mean diffusivity (MD) of the median nerve. Secondarily, we show how the FA and MD differ between asymptomatic adults and patients with CTS, and how these differences are independent of the acquisition methods. We included 32 studies of 2643 wrists, belonging to 1575 asymptomatic adults and 1068 patients with CTS. The normal FA was 0.58 (95% CI 0.56, 0.59) and the normal MD was 1.138 × 10–3 mm2/s (95% CI 1.101, 1.174). Patients with CTS had a significantly lower FA than controls (mean difference 0.12 [95% CI 0.09, 0.16]). Similarly, the median nerve of patients with CTS had a significantly higher mean diffusivity (mean difference 0.16 × 10–3 mm2/s [95% CI 0.05, 0.27]). The differences were independent of experimental factors. We provide summary estimates of the normal FA and MD of the median nerve in asymptomatic adults. Furthermore, we show that diffusion throughout the length of the median nerve becomes more isotropic in patients with CTS

Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM

The β-barrel assembly machinery (BAM) is a ~203 kDa complex of five proteins (BamA-E) which is essential for viability in E. coli. BAM promotes the folding and insertion of β-barrel proteins into the outer membrane via a poorly understood mechanism. Several current models suggest that BAM functions through a ‘lateral gating’ motion of the β-barrel of BamA. Here we present a cryo-EM structure of the BamABCDE complex, at 4.9 Å resolution. The structure is in a laterally open conformation showing that gating is independent of BamB binding. We describe conformational changes throughout the complex, and interactions between BamA, B, D, and E and the detergent micelle that suggest communication between BAM and the lipid bilayer. Finally, using an enhanced reconstitution protocol and functional assays, we show that for the outer membrane protein OmpT, efficient folding in vitro requires lateral gating in BAM

Trauma patients have reduced ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model of vessel injury

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

Surface water numerical modelling for the Clarence-Moreton bioregion. Product 2.6.1 from the Clarence-Moreton Bioregional Assessment

No abstract available

Surface water numerical modelling for the Clarence-Moreton bioregion. Product 2.6.1 from the Clarence-Moreton Bioregional Assessment

No abstract available

Recent Developments and Applications of the HYDRUS Computer Software Packages

The HYDRUS-1D and HYDRUS (2D/3D) computer software packages are widely used finite-element models for simulating the one- and two- or three-dimensional movement of water, heat, and multiple solutes in variably saturated media, respectively. In 2008, Šimůnek et al. (2008b) described the entire history of the development of the various HYDRUS programs and related models and tools such as STANMOD, RETC, ROSETTA, UNSODA, UNSATCHEM, HP1, and others. The objective of this manuscript is to review selected capabilities of HYDRUS that have been implemented since 2008. Our review is not limited to listing additional processes that were implemented in the standard computational modules, but also describes many new standard and nonstandard specialized add-on modules that significantly expanded the capabilities of the two software packages. We also review additional capabilities that have been incorporated into the graphical user interface (GUI) that supports the use of HYDRUS (2D/3D). Another objective of this manuscript is to review selected applications of the HYDRUS models such as evaluation of various irrigation schemes, evaluation of the effects of plant water uptake on groundwater recharge, assessing the transport of particle-like substances in the subsurface, and using the models in conjunction with various geophysical methods

Directional porin binding of intrinsically disordered protein sequences promotes colicin epitope display in the bacterial periplasm

Protein bacteriocins are potent narrow spectrum antibiotics that exploit outer membrane porins to kill bacteria by poorly understood mechanisms. Here, we determine how colicins, bacteriocins specific for Escherichia coli, engage the trimeric porin OmpF to initiate toxin entry. The N-terminal ∼80 residues of the nuclease colicin ColE9 are intrinsically unstructured and house two OmpF binding sites (OBS1 and OBS2) that reside within the pores of OmpF and which flank an epitope that binds periplasmic TolB. Using a combination of molecular dynamics simulations, chemical trimerization, isothermal titration calorimetry, fluorescence microscopy, and single channel recording planar lipid bilayer measurements, we show that this arrangement is achieved by OBS2 binding from the extracellular face of OmpF, while the interaction of OBS1 occurs from the periplasmic face of OmpF. Our study shows how the narrow pores of oligomeric porins are exploited by colicin disordered regions for direction-specific binding, which ensures the constrained presentation of an activating signal within the bacterial periplasm