The Exocyst Complex in Health and Disease

Exocytosis involves the fusion of intracellular secretory vesicles with the plasma membrane, thereby delivering integral membrane proteins to the cell surface and releasing material into the extracellular space. Importantly, exocytosis also provides a source of lipid moieties for membrane extension. The tethering of the secretory vesicle before docking and fusion with the plasma membrane is mediated by the exocyst complex, an evolutionary conserved octameric complex of proteins. Recent findings indicate that the exocyst complex also takes part in other intra-cellular processes besides secretion. These various functions seem to converge toward defining a direction of membrane growth in a range of systems from fungi to plants and from neurons to cilia. In this review we summarize the current knowledge of exocyst function in cell polarity, signaling and cell-cell communication and discuss implications for plant and animal health and disease

Electrically tunable multi-terminal SQUID-on-tip

We present a new nanoscale superconducting quantum interference device (SQUID) whose interference pattern can be shifted electrically in-situ. The device consists of a nanoscale four-terminal/four-junction SQUID fabricated at the apex of a sharp pipette using a self-aligned three-step deposition of Pb. In contrast to conventional two-terminal/two-junction SQUIDs that display optimal sensitivity when flux biased to about a quarter of the flux quantum, the additional terminals and junctions allow optimal sensitivity at arbitrary applied flux, thus eliminating the magnetic field "blind spots". We demonstrate spin sensitivity of 5 to 8 $\mu_B/\text{Hz}^{1/2}$ over a continuous field range of 0 to 0.5 T, with promising applications for nanoscale scanning magnetic imaging

An anaesthetic and intensive care perspective on infection control measures for the prevention of airborne transmission of SARS-CoV-2

No embargo required. Guidance regarding appropriate use of personal protective equipment in hospitals is in constant flux as research into SARS-COV-2 transmission continues to develop our understanding of the virus. The risk associated with procedures classed as ‘aerosol generating’ is under constant debate. Current guidance is largely based on pragmatic and cautious logic, as there is little scientific evidence of aerosolization and transmission of respiratory viruses associated with procedures. The physical properties of aerosol particles which may contain viable virus have implications for the safe use of personal protective equipment and infection control protocols. As elective work in the NHS is reinstated, it is important that the implications of the possibility of airborne transmission of the virus in hospitals are more widely understood. This will facilitate appropriate use of personal protective equipment and help direct further research into the true risks of aerosolization during these procedures to allow safe streamlining of services for staff and patients. </jats:p

The non-Abelian gauge theory of matrix big bangs

We study at the classical and quantum mechanical level the time-dependent Yang-Mills theory that one obtains via the generalisation of discrete light-cone quantisation to singular homogeneous plane waves. The non-Abelian nature of this theory is known to be important for physics near the singularity, at least as far as the number of degrees of freedom is concerned. We will show that the quartic interaction is always subleading as one approaches the singularity and that close enough to t=0 the evolution is driven by the diverging tachyonic mass term. The evolution towards asymptotically flat space-time also reveals some surprising features.Comment: 29 pages, 8 eps figures, v2: minor changes, references added: v3 small typographical changes

Posterior Bearing Overhang Following Medial and Lateral Mobile Bearing Unicompartmental Knee Replacements

This study explores the extent of bearing overhang following mobile bearing Oxford unicompartmental knee replacement (OUKR) (Oxford Phase 3, Zimmer Biomet). The Oxford components are designed to be fully congruent, however knee movements involve femoral rollback, which may result in bearing overhang at the posterior margin of the tibial implant, with potential implications for; pain, wear, and dislocation. Movement is known to be greater, and therefore posterior overhang more likely to occur, with; lateral compared to medial implants, anterior cruciate ligament deficiency, and at extremes of movement. 24 medial, and 20 domed lateral, OUKRs underwent sagittal plane knee fluoroscopy during step‐up and forward lunge exercises. The bearing position was inferred from the relative position of the femoral and tibial components. Based on the individual component sizes and geometry the extent the posterior part of the bearing which overhung the posterior part of the tibial component was calculated. There was no significant posterior overhang in knees with medial implants. Knees with lateral domed implants exhibited overhang at flexion angles beyond 60°, the magnitude of which increased with increasing flexion angle, reaching a maximum of 50% of the bearing length at 140° (range 0‐140°). This demonstrates a clear difference between the kinematics, and prevalence and extent of posterior bearing overhang between medial and lateral OUKRs

Adult respiratory distress syndrome secondary to end-stage liver disease—successful outcome following liver transplantation

The adult respiratory distress syndrome (ARDS) com­plicating liver failure carries a 100% mortality. Two cases of ARDS that resolved following liver transplantation have been reported, one associated with acute allograft rejection, and the second due to sepsis. There is, however, a great reluctance to transplant these very-high-risk patients. We report the first series of patients with ARDS secondary to liver failure who successfully underwent OLTX. No patient had sepsis or pneumonia. Posttransplant mechanical ventilation was required for a median of 14 days (range 6-37 days). All patients in this series are alive and well, with a follow-up of 6-15 months. This demonstrates that ARDS associated with liver failure, an otherwise uniformly lethal complica­tion, can respond dramatically to OLTX. © 1993 by William & Wilkins

Remarks on the method of comparison equations (generalized WKB method) and the generalized Ermakov-Pinney equation

The connection between the method of comparison equations (generalized WKB method) and the Ermakov-Pinney equation is established. A perturbative scheme of solution of the generalized Ermakov-Pinney equation is developed and is applied to the construction of perturbative series for second-order differential equations with and without turning points.Comment: The collective of the authors is enlarged and the calculations in Sec. 3 are correcte

Ordering phenomena in quasi one-dimensional organic conductors

Low-dimensional organic conductors could establish themselves as model systems for the investigation of the physics in reduced dimensions. In the metallic state of a one-dimensional solid, Fermi-liquid theory breaks down and spin and charge degrees of freedom become separated. But the metallic phase is not stable in one dimension: as the temperature is reduced, the electronic charge and spin tend to arrange themselves in an ordered fashion due to strong correlations. The competition of the different interactions is responsible for which broken-symmetry ground state is eventually realized in a specific compound and which drives the system towards an insulating state. Here we review the various ordering phenomena and how they can be identified by optic and magnetic measurements. While the final results might look very similar in the case of a charge density wave and a charge-ordered metal, for instance, the physical cause is completely different. When density waves form, a gap opens in the density of states at the Fermi energy due to nesting of the one-dimension Fermi surface sheets. When a one-dimensional metal becomes a charge-ordered Mott insulator, on the other hand, the short-range Coulomb repulsion localizes the charge on the lattice sites and even causes certain charge patterns. We try to point out the similarities and conceptional differences of these phenomena and give an example for each of them. Particular emphasis will be put on collective phenomena which are inherently present as soon as ordering breaks the symmetry of the system.Comment: Review article Naturwissenschaften 200

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1