Effects of Exercise Training on Neuromuscular Junction Morphology and Pre- to Post-Synaptic Coupling in Young and Aged Rats

The objective of this study was to determine whether pre- to post-synaptic coupling of the neuromuscular junction (NMJ) could be maintained in the face of significant morphological remodeling brought about by exercise training, and whether aging altered this capacity. Eighteen young adult (8 mo) and eighteen aged (24 mo) Fischer 344 rats were randomly assigned to either endurance trained (treadmill running) or untrained control conditions resulting in four groups (N = 9 / group). After the 10-week intervention rats were euthanized and hindlimb muscles were surgically removed, quickly frozen at approximate resting length and stored at - 85 degrees C. The plantaris and EDL muscles were selected for study as they have different functions (ankle extensor and ankle flexor, respectively) but both are similarly and overwhelmingly comprised of fast-twitch myofibers. NMJs were stained with immunofluorescent procedures and images were collected with confocal microscopy. Each variable of interest was analyzed with a 2-way ANOVA with main effects of age and endurance training; in all cases significance was set at P \u3c = 0.05. Results showed that no main effects of aging were detected in NMJs of either the plantaris or the EDL. Similarly, endurance training failed to alter any synaptic parameters of EDL muscles. The same exercise stimulus in the plantaris however, resulted in significant pre- and post-synaptic remodeling, but without altering pre- to post-synaptic coupling of the NMJs. Myofiber profiles of the same plantaris and EDL muscles were also analyzed. Unlike NMJs, myofibers displayed significant age-related atrophy in both the plantaris and EDL muscles. Overall, these results confirm that despite significant training-induced reconfiguration of NMJs, pre- to post-synaptic coupling remains intact underscoring the importance of maintaining proper apposition of neurotransmitter release and binding sites so that effective nerve to muscle communication is assured. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved

Teashirt 1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons in mouse

Feeding and breathing are essential motor functions and rely on the activity of hypoglossal and phrenic motor neurons that innervate the tongue and diaphragm, respectively. Little is known about the genetic programs that control the development of these neuronal subtypes. The transcription factor Tshz1 is strongly and persistently expressed in developing hypoglossal and phrenic motor neurons. We used conditional mutation of Tshz1 in the progenitor zone of motor neurons (Tshz1(MNΔ)) to show that Tshz1 is essential for survival and function of hypoglossal and phrenic motor neurons. Hypoglossal and phrenic motor neurons are born in correct numbers, but many die between embryonic day 13.5 and 14.5 in Tshz1(MNΔ) mutant mice. In addition, innervation and electrophysiological properties of phrenic and hypoglossal motor neurons are altered. Severe feeding and breathing problems accompany this developmental deficit. Although motor neuron survival can be rescued by elimination of the pro-apoptotic factor Bax, innervation, feeding and breathing defects persist in Bax(-/-); Tshz1(MNΔ) mutants. We conclude that Tshz1 is an essential transcription factor for the development and physiological function of phrenic and hypoglossal motor neurons

The Generic Short Patient Experiences Questionnaire (GS-PEQ): identification of core items from a survey in Norway

<p>Abstract</p> <p>Background</p> <p>Questionnaires are commonly used to collect patient, or user, experiences with health care encounters; however, their adaption to specific target groups limits comparison between groups. We present the construction of a generic questionnaire (maximum of ten questions) for user evaluation across a range of health care services.</p> <p>Methods</p> <p>Based on previous testing of six group-specific questionnaires, we first constructed a generic questionnaire with 23 items related to user experiences. All questions included a "not applicable" response option, as well as a follow-up question about the item's importance. Nine user groups from one health trust were surveyed. Seven groups received questionnaires by mail and two by personal distribution. Selection of core questions was based on three criteria: applicability (proportion "not applicable"), importance (mean scores on follow-up questions), and comprehensiveness (content coverage, maximum two items per dimension).</p> <p>Results</p> <p>1324 questionnaires were returned providing subsample sizes ranging from 52 to 323. Ten questions were excluded because the proportion of "not applicable" responses exceeded 20% in at least one user group. The number of remaining items was reduced to ten by applying the two other criteria. The final short questionnaire included items on outcome (2), clinician services (2), user involvement (2), incorrect treatment (1), information (1), organisation (1), and accessibility (1).</p> <p>Conclusion</p> <p>The Generic Short Patient Experiences Questionnaire (GS-PEQ) is a short, generic set of questions on user experiences with specialist health care that covers important topics for a range of groups. It can be used alone or with other instruments in quality assessment or in research. The psychometric properties and the relevance of the GS-PEQ in other health care settings and countries need further evaluation.</p

923-6 Intravenous Adenosine and Lidocaine to Limit Reperfusion Injury During Acute Myocardial Infarction: Preliminary Data

Adenosine (ADO) and lidocaine (LDO) given prior to restoration of blood flow reduces reperfusion injury in animals. We conducted a pilot study of intravenous ADO and LDO in pts undergoing direct angioplasty for acute myocardial infarction (AMI). Pts with ≤12 hours of chest pain and electrocardiographic evidence of AMI were given LDO 1mg/kg iv bolus and 2mg/min iv infusion beginning at the time of recruitment, and ADO 70mcg/kg iv infusion beginning when coronary occlusion (TIMI grade 0–1 blood flow) was confirmed angiographically. Pts with bronchospasm, blood pressure &lt;100mmHg, or&lt;1° heart block were excluded. ADO and LDO were given for 1 hour after vessel patency was restored. Myocardial area at risk and final infarction area were measured with serial Tc-99m-sestamibi perfusion studies (prior to angioplasty, before hospital discharge and 6 weeks after discharge). A salvage index (S1) was constructed by correcting the change in sestamibi perfusion defect for the mass of myocardium at risk. Analysis of 25 patients completing the protocol revealed a mean (±SD) salvage of 20±17% and S1=0.55. Salvage and S1 were 25±18% and 0.54 for anterior infarctions, 13±5% and 0.57 for inferior infarctions, respectively. These data were compared to an historical control group consisting of 50 patients undergoing direct angioplasty for AMI without adjunctive ADO/LDO. After adjustment for time to treatment and perfusion nadir, analysis of covariance revealed a similar degree of early salvage in the study and control groups (p=0.3). However, at 6 weeks, the median infarct size for study pts was 0. Using logistic regression analysis, significantly more study pts had no final measureable infarction at 6 weeks than control pts at hospital discharge (p=0.007). After adjusting for infarct size, location and time to treatment, this difference persisted (p=0.04).ConclusionsAdjunctive ADO and LDO during angioplasty for AMI may favorably affect late final infarction size. Randomized studies assessing 6 week final infarction size are needed

A comprehensive study on the relation between the metal enrichment of ionised and atomic gas in star-forming galaxies

We study the relation between the metallicities of ionised and neutral gas in star-forming galaxies at z=0-3 using the EAGLE cosmological, hydrodynamical simulations. This is done by constructing a dense grid of sightlines through the simulated galaxies and obtaining the star formation rate- and HI column density-weighted metallicities, Z_{SFR} and Z_{HI}, for each sightline as proxies for the metallicities of ionised and neutral gas, respectively. We find Z_{SFR} > Z_{HI} for almost all sightlines, with their difference generally increasing with decreasing metallicity. The stellar masses of galaxies do not have a significant effect on this trend, but the positions of the sightlines with respect to the galaxy centres play an important role: the difference between the two metallicities decreases when moving towards the galaxy centres, and saturates to a minimum value in the central regions of galaxies, irrespective of redshift and stellar mass. This implies that the mixing of the two gas phases is most efficient in the central regions of galaxies where sightlines generally have high column densities of HI. However, a high HI column density alone does not guarantee a small difference between the two metallicities. In galaxy outskirts, the inefficiency of the mixing of star-forming gas with HI seems to dominate over the dilution of heavy elements in HI through mixing with the pristine gas. We find good agreement between the available observational data and the ZSFR-ZHI relation predicted by the EAGLE simulations. Though, observed regions with a nuclear starburst mode of star formation appear not to follow the same relation.Comment: Under review with Ap

Dibromidobis(1-ethyl-2,6-dimethyl­pyridinium-4-olate-κO)zinc(II)

In the bioactive title compound, [ZnBr2(C9H13NO)2], the ZnII atom is coordinated in a distorted tetra­hedral arrangement by two Br− anions and the O atoms of two zwitterionic organic ligands. The pyridinium rings are almost planar [maximum deviations = 0.004 (4) and 0.003 (4) Å]. The ethyl groups are approximately perpendicular to the corresponding pyridinium ring planes [N—C—C—C = 88.8 (4)° in each ligand]. The packing of the mol­ecules is controlled by π–π inter­actions, with centroid–centroid distances of 3.625 (3) and 3.711 (2) Å, forming chains approximately parallel to (102). The crystal studied was non-merohedrally twinned (twin relationship between the domains 1 0 0, 0 1 0, −0.4672 −0.1864 −1 and batch scale factor of 7.39%)

Re-examining the consumption-wealth relationship : the role of model uncertainty

This paper discusses the consumption-wealth relationship. Following the recent influential workof Lettau and Ludvigson [e.g. Lettau and Ludvigson (2001), (2004)], we use data on consumption, assets andlabor income and a vector error correction framework. Key …ndings of their work are that consumption doesrespond to permanent changes in wealth in the expected manner, but that most changes in wealth are transitoryand have no e¤ect on consumption. We investigate the robustness of these results to model uncertainty andargue for the use of Bayesian model averaging. We …nd that there is model uncertainty with regards to thenumber of cointegrating vectors, the form of deterministic components, lag length and whether the cointegratingresiduals a¤ect consumption and income directly. Whether this uncertainty has important empirical implicationsdepends on the researcher's attitude towards the economic theory used by Lettau and Ludvigson. If we workwith their model, our findings are very similar to theirs. However, if we work with a broader set of models andlet the data speak, we obtain somewhat di¤erent results. In the latter case, we …nd that the exact magnitudeof the role of permanent shocks is hard to estimate precisely. Thus, although some support exists for the viewthat their role is small, we cannot rule out the possibility that they have a substantive role to play

Toward an Autonomous Lunar Landing Based on Low-Speed Optic Flow Sensors

International audienceFor the last few decades, growing interest has returned to the quite chal-lenging task of the autonomous lunar landing. Soft landing of payloads on the lu-nar surface requires the development of new means of ensuring safe descent with strong final conditions and aerospace-related constraints in terms of mass, cost and computational resources. In this paper, a two-phase approach is presented: first a biomimetic method inspired from the neuronal and sensory system of flying insects is presented as a solution to perform safe lunar landing. In order to design an au-topilot relying only on optic flow (OF) and inertial measurements, an estimation method based on a two-sensor setup is introduced: these sensors allow us to accu-rately estimate the orientation of the velocity vector which is mandatory to control the lander's pitch in a quasi-optimal way with respect to the fuel consumption. Sec-ondly a new low-speed Visual Motion Sensor (VMS) inspired by insects' visual systems performing local angular 1-D speed measurements ranging from 1.5 • /s to 25 • /s and weighing only 2.8 g is presented. It was tested under free-flying outdoor conditions over various fields onboard an 80 kg unmanned helicopter. These pre-liminary results show that the optic flow measured despite the complex disturbances encountered closely matched the ground-truth optic flow

The enrichment of an alkaliphilic biofilm consortia capable of the anaerobic degradation of isosaccharinic acid from cellulosic materials incubated within an anthropogenic, hyperalkaline environment.

Anthropogenic hyper-alkaline sites provide an environment that is analogous to proposed cementitious geological disposal facilities (GDF) for radioactive waste. Under anoxic, alkaline conditions cellulosic wastes will hydrolyse to a range of cellulose degradation products (CDP) dominated by isosaccharinic acids (ISA). In order to investigate the potential for microbial activity in a cementitious GDF, cellulose samples were incubated in the alkaline (∼pH 12), anaerobic zone of a lime kiln waste site. Following retrieval, these samples had undergone partial alkaline hydrolysis and were colonised by a Clostridia dominated biofilm community, where hydrogenotrophic, alkaliphilic methanogens were also present. When these samples were used to establish an alkaline CDP fed microcosm, the community shifted away from Clostridia, methanogens became undetectable and a flocculate community dominated by Alishewanella sp. established. These flocs were composed of bacteria embedded in polysaccharides and protein stabilised by extracellular DNA. This community was able to degrade all forms of ISA with >60% of the carbon flow being channelled into extracellular polymeric substance (EPS) production. This study demonstrated that alkaliphilic microbial communities can degrade the CDP associated with some radioactive waste disposal concepts at pH 11. These communities divert significant amounts of degradable carbon to EPS formation, suggesting that EPS has a central role in the protection of these communities from hyper-alkaline conditions