Charge transport through perylene bisimide molecular junctions: An electrochemical approach

Single molecular junction conductances of a family of five symmetric and two unsymmetric perylene tetracarboxylic bisimides (PBI) with variable bay-area substituents were studied employing a scanning tunneling microscope (STM)-based break junction technique. The stretching experiments provide clear evidence for the formation of single molecular junctions and π–π stacked dimers. Electrolyte gating demonstrates a distinct gating effect in symmetric molecular junctions, which strongly depends on molecular structure and properties of the solvent/electrolyte. Weak π–π-coupling in the unsymmetric dimers prevents rectification.

Charge Transport in Photoswitchable Dimethyldihydropyrene-Type Single-Molecule Junctions

The conductance properties of a photoswitchable dimethyldihydropyrene (DHP) derivative have been investigated for the first time in single-molecule junctions using the mechanically controllable break junction technique. We demonstrate that the reversible structure changes induced by isomerization of a single bispyridine-substituted DHP molecule are correlated with a large drop of the conductance value. We found a very high ON/OFF ratio (>104) and an excellent reversibility of conductance switching.

Neuromuscular disuse and atrophy: {\it In vivo\/} magnetic resonance studies of intramuscular lipid metabolism and fluid shift changes

We postulated that neuromuscular disuse results in deleteriously affected tissue-vascular fluid exchange processes and subsequently damages the important oxidative bioenergetic process of intramuscular lipid metabolism. The in-depth research reported in the literature is somewhat limited by the ex vivo nature and sporadic time-course characterization of disuse atrophy and recovery. Thus, an in vivo controlled, localized animal model of disuse atrophy was developed in one of the hindlimbs of laboratory rabbits (employing surgically implanted tetrodotoxin (TTX)-filled mini-osmotic pump-sciatic nerve superfusion system) and tested repeatedly with magnetic resonance (MR) throughout the 2-week period of temporarily induced disuse and during the recovery period (following explantation of the TTX-filled pump) for a period of 3 weeks. Controls consisted of saline/"sham"-implanted rabbit hindlimbs. The validity of this model was established with repeated electrophysiologic nerve conduction testing using a clinically appropriate protocol and percutaneously inserted small needle stimulating and recording electrodes. Evoked responses recorded from proximal (P) and distal (D) sites to the sciatic nerve cuff in the TTX-implanted group revealed significantly decreased (p $<$ 0.001) proximal-to-distal (P/D) amplitude ratios (as much as 50-70% below Baseline/pre-implanted and sham-implanted group values) and significantly increased (p $<$ 0.01) differential latency (PL-DL) values (as much as 1.5 times the pre- and sham-implanted groups). By Day 21 of recovery, observed P/D and PL-DL levels matched Baseline/sham-implemented levels. MRI-determined cross-sectional area (CSA) values of Baseline/pre-implanted, sham- or TTX-implanted, and recovering/explanted and the corresponding contralateral hindlimb tibialis anterior (TA) muscles normalized to tibial bone (TB) CSA (in TA/TB ratios) revealed that there was a significant decline (indicative of atrophic response) from pre- and sham-implanted controls by as much as 20% (p $<$ 0.01) at Day 7 and 50-55% (p $<$ 0.001) at Day 13 of TTX-implantation. In the non-implanted contralaterals, a significant increase (indicative of hypertrophic response) by as much as 10% (p $<$ 0.025) at Day 7 and 27% (p $<$ 0.001) at Day 13 + TTX was found. The induced atrophic/hypertrophic TA muscles were observed to be fully recovered by Day 21 post-explantation as evidenced by image TA/TB ratios. End-point biopsy results from a small group of rabbits revealed comprehensive atrophy of both Type I and Type II fibers, although the heterogeneity of the response supports the use of image-guided, volume-localized proton magnetic resonance spectroscopy (MRS) to noninvasively assess tissue-level metabolic changes. MRS-determined results of a 0.25cc volume of tissue within implanted limb TA muscles under resting/pre-ischemic, ischemic-stressed, and post-ischemic conditions at timepoints during and following disuse atrophy/recovery revealed significantly increased intramuscular spectral lipid levels, as much as 2-3 times (p $<$ 0.01) the Baseline/pre-implanted values at Day 7 and 6-7 times (p $<$ 0.001) at Day 13 + TTX, which approached normal levels (compared to pre- and sham-implanted groups) by Day 21 of post-explanation recovery. (Abstract shortened by UMI.) ^

Expression of neuromuscular junction messenger RNAs and protein in aged rats

The loss of skeletal muscle mass is believed to be the dominant reason for reduced strength in aging humans. The purpose of this investigation was to gain some information as to why skeletal muscles lose mass as we age. Since nervous system innervation is essential for skeletal muscle fiber viability, incomplete regional reinnervation during normal synaptic junction turnover has been hypothesized to result in selective muscle fiber loss. Examined here was the age-related association in skeletal muscle between atrophy and the expression of mRNAs encoding the γ- and ϵ-subunits of the nicotinic acetylcholine receptor, myogenin, and muscle specific receptor kinase (MuSK). Gastrocnemius and biceps brachii muscles were collected from young (2 month), adult (18 month), and old (31 month) Fischer 344 cross brown Norway F 1 male rats. In the gastrocnemius, muscles of old vs. young and adult rats, lower muscle mass was accompanied by significantly elevated acetylcholine receptor γ-subunit, myogenin, and MuSK mRNA levels. In contrast, the biceps brachii muscle in the same animals exhibited neither atrophy nor a change in acetylcholine receptor γ-subunit, myogenin, or MuSK mRNA levels. Expression of the acetylcholine receptor ϵ-subunit mRNA did not change with age in either gastrocnemius or biceps brachii muscles. Since acetylcholine receptor γ-subunit, myogenin, and MuSK mRNA levels are upregulated in surgically denervated skeletal muscles of young rats while expression of the acetylcholine receptor ϵ-subunit does not change, the findings of the current investigation suggest that a select fiber population within atrophied skeletal muscles of old rats may be in a denervated-like state. I speculate that increases in γ-subunit, myogenin, and MuSK mRNA levels in atrophied muscles of old rats are compensatory responses to nerve terminal retraction. Indeed, a prolongation of denervation in these muscle fibers would subsequently result in their atrophy and death, ultimately leading to a decline in the number of force generating elements present in the muscle. ^

Highly-effective gating of single-molecule junctions: an electrochemical approach

We report an electrochemical gating approach with [similar]100% efficiency to tune the conductance of single-molecule 4,4′-bipyridine junctions using scanning-tunnelling-microscopy break junction technique. Density functional theory calculation suggests that electrochemical gating aligns molecular frontier orbitals relative to the electrode Fermi-level, switching the molecule from an off resonance state to “partial” resonance.

The Synthesis of Functionalised Diaryltetraynes and Their Transport Properties in Single-Molecule Junctions

The synthesis and characterisation is described of six diaryltetrayne derivatives [Ar-(C[TRIPLE BOND]C)4-Ar] with Ar=4-NO2-C6H4- (NO24), 4-NH(Me)C6H4- (NHMe4), 4-NMe2C6H4- (NMe24), 4-NH2-(2,6-dimethyl)C6H4- (DMeNH24), 5-indolyl (IN4) and 5-benzothienyl (BTh4). X-ray molecular structures are reported for NO24, NHMe4, DMeNH24, IN4 and BTh4. The stability of the tetraynes has been assessed under ambient laboratory conditions (20 °C, daylight and in air): NO24 and BTh4 are stable for at least six months without observable decomposition, whereas NHMe4, NMe24, DMeNH24 and IN4 decompose within a few hours or days. The derivative DMeNH24, with ortho-methyl groups partially shielding the tetrayne backbone, is considerably more stable than the parent compound with Ar=4-NH2C6H4 (NH24). The ability of the stable tetraynes to anchor in Au|molecule|Au junctions is reported. Scanning-tunnelling-microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques are employed to investigate single-molecule conductance characteristics.

The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions

Barrier characteristics of brain endothelial cells forming the blood-brain barrier (BBB) are tightly regulated by cellular and acellular components of the neurovascular unit. During embryogenesis, the accumulation of the heparan sulfate proteoglycan agrin in the basement membranes ensheathing brain vessels correlates with BBB maturation. In contrast, loss of agrin deposition in the vasculature of brain tumors is accompanied by the loss of endothelial junctional proteins. We therefore wondered whether agrin had a direct effect on the barrier characteristics of brain endothelial cells. Agrin increased junctional localization of vascular endothelial (VE)-cadherin, β-catenin, and zonula occludens-1 (ZO-1) but not of claudin-5 and occludin in the brain endothelioma cell line bEnd5 without affecting the expression levels of these proteins. This was accompanied by an agrin-induced reduction of the paracellular permeability of bEnd5 monolayers. In vivo, the lack of agrin also led to reduced junctional localization of VE-cadherin in brain microvascular endothelial cells. Taken together, our data support the notion that agrin contributes to barrier characteristics of brain endothelium by stabilizing the adherens junction proteins VE-cadherin and β-catenin and the junctional protein ZO-1 to brain endothelial junctions.

Resolving Atomic Connectivity in Graphene Nanostructure Junctions

We report on the structural characterization of junctions between atomically well-defined graphene nanoribbons (GNRs) by means of low-temperature, noncontact scanning probe microscopy. We show that the combination of simultaneously acquired frequency shift and tunneling current maps with tight binding (TB) simulations allows a comprehensive characterization of the atomic connectivity in the GNR junctions. The proposed approach can be generally applied to the investigation of graphene nanomaterials and their interconnections and is thus expected to become an important tool in the development of graphene-based circuitry.

Brain barriers: Crosstalk between complex tight junctions and adherens junctions

Unique intercellular junctional complexes between the central nervous system (CNS) microvascular endothelial cells and the choroid plexus epithelial cells form the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB), respectively. These barriers inhibit paracellular diffusion, thereby protecting the CNS from fluctuations in the blood. Studies of brain barrier integrity during development, normal physiology, and disease have focused on BBB and BCSFB tight junctions but not the corresponding endothelial and epithelial adherens junctions. The crosstalk between adherens junctions and tight junctions in maintaining barrier integrity is an understudied area that may represent a promising target for influencing brain barrier function.