Molecular models for the core components of the flagellar type-III secretion complex

We show that by using a combination of computational methods, consistent three-dimensional molecular models can be proposed for the core proteins of the type-III secretion system. We employed a variety of approaches to reconcile disparate, and sometimes inconsistent, data sources into a coherent picture that for most of the proteins indicated a unique solution to the constraints. The range of difficulty spanned from the trivial (FliQ) to the difficult (FlhA and FliP). The uncertainties encountered with FlhA were largely the result of the greater number of helix packing possibilities allowed in a large protein, however, for FliP, there remains an uncertainty in how to reconcile the large displacement predicted between its two main helical hairpins and their ability to sit together happily across the bacterial membrane. As there is still no high resolution structural information on any of these proteins, we hope our predicted models may be of some use in aiding the interpretation of electron microscope images and in rationalising mutation data and experiments

Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity

BACKGROUND: Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP) and its counterpart long-term depression (LTD) of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP. RESULTS: We find that when LTP involves an increase in unitary conductance, subsequent depotentiation invariably involves the return of unitary conductance to pre-LTP values. In contrast, when LTP does not involve a change in unitary conductance then depotentiation also occurs in the absence of any change in unitary conductance, indicating a reduction in the number of activated receptors as the most likely mechanism. CONCLUSIONS: These data show that unitary conductance can be bi-directionally modified by synaptic activity. Furthermore, there are at least two distinct mechanisms to restore synaptic strength from a potentiated state, which depend upon the mechanism of the previous potentiation

Tizanidine does not affect the linear relation of stretch duration to the long latency M2 response of m. flexor carpi radialis

The long latency M2 electromyographic response of a suddenly stretched active muscle is stretch duration dependent of which the nature is unclear. We investigated the influence of the group II afferent blocker tizanidine on M2 response characteristics of the m. flexor carpi radialis (FCR). M2 response magnitude and eliciting probability in a group of subjects receiving 4 mg of tizanidine orally were found to be significantly depressed by tizanidine while tizanidine did not affect the significant linear relation of the M2 response to stretch duration. The effect of tizanidine on the M2 response of FCR is supportive of a group II afferent contribution to a compound response of which the stretch duration dependency originates from a different mechanism, e.g., rebound Ia firing

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

DP can occur without alterations in γ (DP) but only when preceded by LTP that does not involve a change in γ (LTP)

<p><b>Copyright information:</b></p><p>Taken from "Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity"</p><p>BMC Neuroscience 2004;5():44-44.</p><p>Published online 11 Nov 2004</p><p>PMCID:PMC535344.</p><p>Copyright © 2004 Lüthi et al; licensee BioMed Central Ltd.</p> (A) Plot of amplitude . time from a representative experiment. Black bar represents LTP pairing, grey bar DP pairing protocol. Throughout the figure, green represents baseline, red LTP and blue DP. (B) Current-variance relationship for baseline, LTP and DP (γ values for this cell (pS): baseline = 6.5, LTP = 6.7, DP = 6.0). (C) Mean EPSCs (average of all responses used for non-SFA) superimposed (left) and peak scaled (right). (D) Amplitude histogram (bin width = 2 pA; N = 151 for baseline, N = 211 for LTP, N = 513 for DP) for baseline, LTP and DP. Inset: 10 consecutive responses for baseline, LTP and DP

Bi-directional modification of AMPA receptor conductance (γ) during LTP (LTPγ) and DP (DP)

<p><b>Copyright information:</b></p><p>Taken from "Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity"</p><p>BMC Neuroscience 2004;5():44-44.</p><p>Published online 11 Nov 2004</p><p>PMCID:PMC535344.</p><p>Copyright © 2004 Lüthi et al; licensee BioMed Central Ltd.</p> (A1,2) Plot of amplitude . time from two representative experiments. Black bar represents LTP pairing, grey bar DP pairing protocol. Throughout the figure, green represents baseline, red LTP and blue DP. (B1,2) Current-variance relationship for baseline, LTP and DP (γ values for the same cells (pS): cell 1:baseline = 2.2, LTP = 6.5, DP = 3.7; cell 2: baseline = 4.5, LTP = 7.4, DP = 3.2). For this figure and in Figure 3, lines are parabolic fits of the data (see Methods). (C1,2) Inset. Mean EPSCs (average of all responses used for non-SFA) superimposed (left) and peak scaled (right). Amplitude histograms (bin width = 2 pA; number of trials: cell 1: N = 130 for baseline, N = 245 for LTP, N = 533 for DP; cell 2: N = 150 for baseline, N = 267 for LTP, N = 337 for DP; frequency normalised to the data set with the smallest number of observations for baseline, LTP and DP)