Origin of Discrepancies in Inelastic Electron Tunneling Spectra of Molecular Junctions

We report inelastic electron tunneling spectroscopy (IETS) of multilayer molecular junctions with and without incorporated metal nano-particles. The incorporation of metal nanoparticles into our devices leads to enhanced IET intensity and a modified line-shape for some vibrational modes. The enhancement and line-shape modification are both the result of a low lying hybrid metal nanoparticle-molecule electronic level. These observations explain the apparent discrepancy between earlier IETS measurements of alkane thiolate junctions by Kushmerick \emph{et al.} [Nano Lett. \textbf{4}, 639 (2004)] and Wang \emph{et al.} [Nano Lett. \textbf{4}, 643 (2004)].Comment: 4 pages, 4 figures accepted for publication in Physical Review Letter

Large-Scale Atomistic Simulations of Environmental Effects on the Formation and Properties of Molecular Junctions

Using an updated simulation tool, we examine molecular junctions comprised of benzene-1,4-dithiolate bonded between gold nanotips, focusing on the importance of environmental factors and inter-electrode distance on the formation and structure of bridged molecules. We investigate the complex relationship between monolayer density and tip separation, finding that the formation of multi-molecule junctions is favored at low monolayer density, while single-molecule junctions are favored at high density. We demonstrate that tip geometry and monolayer interactions, two factors that are often neglected in simulation, affect the bonding geometry and tilt angle of bridged molecules. We further show that the structures of bridged molecules at 298 and 77 K are similar.Comment: To appear in ACS Nano, 30 pages, 5 figure

Novel Strains of Mice Deficient for the Vesicular Acetylcholine Transporter: Insights on Transcriptional Regulation and Control of Locomotor Behavior

Defining the contribution of acetylcholine to specific behaviors has been challenging, mainly because of the difficulty in generating suitable animal models of cholinergic dysfunction. We have recently shown that, by targeting the vesicular acetylcholine transporter (VAChT) gene, it is possible to generate genetically modified mice with cholinergic deficiency. Here we describe novel VAChT mutant lines. VAChT gene is embedded within the first intron of the choline acetyltransferase (ChAT) gene, which provides a unique arrangement and regulation for these two genes. We generated a VAChT allele that is flanked by loxP sequences and carries the resistance cassette placed in a ChAT intronic region (FloxNeo allele). We show that mice with the FloxNeo allele exhibit differential VAChT expression in distinct neuronal populations. These mice show relatively intact VAChT expression in somatomotor cholinergic neurons, but pronounced decrease in other cholinergic neurons in the brain. VAChT mutant mice present preserved neuromuscular function, but altered brain cholinergic function and are hyperactive. Genetic removal of the resistance cassette rescues VAChT expression and the hyperactivity phenotype. These results suggest that release of ACh in the brain is normally required to “turn down” neuronal circuits controlling locomotion

Reliability and precision of the mouse calyx of Held synapse

Traditionally, the calyx of Held synapse is viewed as a highly reliable relay in the sound localization circuit of the auditory brainstem, with every presynaptic action potential triggering a postsynaptic action potential in vivo. However, this view is at odds with slice recordings that report large short-term depression (STD). To investigate the reliability and precision of this synapse, we compared slice and in vivo recordings from medial nucleus of the trapezoid body neurons of young adult mice. We show that the extracellularly recorded complex waveform can be used to estimate both presynaptic release and postsynaptic excitability. Whereas under standard slice conditions the synapse underwent large STD, both extracellular and whole-cell recordings indicated that in vivo the size of the EPSPs was independent of recent history. The estimated quantal content was typically <20 in vivo, much lower than in the resting synapse under standard slice conditions. However, due to the large quantal size and summation of EPSPs, the safety factor of this synapse was generally still sufficiently large and postsynaptic failures were observed only infrequently in vivo. When present, failures were typically due to stochastic fluctuations in EPSP size or postsynaptic spike depression. In vivo, the calyx of Held synapse thus functions as a tonic synapse. The price it pays for its low release probability is an increase in jitter and synaptic latency and occasional postsynaptic failures

Vagus nerve stimulation improves coagulopathy in hemorrhagic shock: a thromboelastometric animal model study

Abstract Introduction Inflammation plays a major role in the multifactorial process of trauma associated coagulopathy. The vagus nerve regulates the cholinergic anti-inflammatory pathway. We hypothesized that efferent vagus nerve stimulation (VNS) can improve coagulopathy by modulating the inflammatory response to hemorrhage. Methods Wistar rats (n = 24) were divided in 3 groups: Group (G1) Sham hemorrhagic shock (HS); (G2) HS w/o VNS; (G3) HS followed by division of the vagus nerves and VNS of the distal stumps. Hemorrhage (45% of baseline MAPx15 minutes) was followed by normotensive resuscitation with LR. Vagus nerves were stimulated (3.5 mA, 5 Hz) for 30 sec 7 times. Samples were obtained at baseline and at 60 minutes for thromboelastometry (Rotem®) and cytokine assays (IL-1 and IL-10). ANOVA was used for statistical analysis; significance was set at p < 0.05. Results Maximum clot firmness (MCF) significantly decreased in G2 after HS (71.5 ± 1.5 vs. 64 ± 1.6) (p < 0.05). MCF significantly increased in G3 compared to baseline (67.3 ± 2.7 vs. 71.5 ± 1.2) (p < 0.05). G3 also showed significant improvement in Alfa angle, and Clot Formation Time (CFT) compared to baseline. IL-1 increased significantly in group 2 and decrease in group 3, while IL-10 increased in group 3 (p < 0.05). Conclusions Electrical stimulation of efferent vagus nerves, during resuscitation (G3), decreases inflammatory response to hemorrhage and improves coagulation

Antiarrhythmogenic effects of a neurotoxin from the spider Phoneutria nigriventer.

In this study, we evaluated the effects of PhKv, a 4584 Da peptide isolated from the spider Phoneutria nigriventer venom, in the isolated rat heart and in isolated ventricular myocytes. Ventricular arrhythmias were induced by occlusion of the left anterior descending coronary artery for 15 min followed by 30 min of reperfusion. Administration of native PhKv (240 nM) 1 min before or after reperfusion markedly reduced the duration of arrhythmias. This effect was blocked by atropine, thereby indicating the participation of muscarinic receptors in the antiarrhythmogenic effect of PhKv. Notably, recombinant PhKv (240 nM) was also efficient to attenuate the arrhythmias (3.8 0.9 vs. 8.0 1.2 arbitrary units in control group). Furthermore, PhKv induced a significant reduction in heart rate. This bradycardia was partially blunted by atropine and potentiated by pyridostigmine. To further evaluate the participation of acetylcholine on the PhKv effects, we examined the release of this neurotransmitter from neuromuscular junctions. It was found that Phkv (200 nM) significantly increased the release of acetylcholine in this preparation. Moreover, PhKv (250 nM) did not cause any significant change in action potential or Ca2þ transient parameters in isolated cardiomyocytes. Altogether, these findings show an important acetylcholine-mediated antiarrhythmogenic effect of the spider PhKv toxin in isolated hearts