86 research outputs found
Features of superexchange nonresonant tunneling conductance in anchored molecular wires
NAS Ukraine via Project No. 0116U002067A modified superexchange model is used to clarify the physical mechanisms for the formation of nonresonant tunneling conductance in terminated molecular wires. Due to the specific relationship between its key parameters, this model has wider areas of applicability compared to the flat-barrier model and the standard superexchange model, which are widely involved for the physical interpretation of experimental results. Moreover, the results obtained in the two latest models appear in the modified model as characteristic limiting cases. Our estimates show that the exponential decay of conductance, characterized by an attenuation factor β (per repeating unit), is limited by the conditions β ≤ 1.2 and β ≥ 3.7 for the flat-barrier and standard models, respectively. At the same time, the modified superexchange model yields β > 0, which, thus, allows us to analyze the tunneling conductance in molecular wires containing both saturated and conjugated bonds. We also show that for a small number of N repeating wire units (about 3-6 depending on the value of β), the exponential dependence of conductance on N is violated and, accordingly, contact conductance is not identical to conductance at N = 0. Formulas are found which, on the basis of experimental data, make it possible to establish the values of superexchange parameters as well as indicate the conditions of possible hybridization between the orbitals of the anchor groups and the adjacent end units belonging to the interior wire region. One example is the establishment of features in the tunneling conductance of terminated alkane chains caused by the nature of their anchor groups.publishersversionpublishe
The Coxsackievirus and Adenovirus Receptor Has a Short Half-Life in Epithelial Cells
The coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell adhesion, cell signaling, and viral infection. The 8-exon encoded isoform (CAREx8) resides at the apical surface of polarized epithelia, where it is accessible as a receptor for adenovirus entering the airway lumen. Given its pivotal role in viral infection, it is a target for antiviral strategies. To understand the regulation of CAREx8 and determine the feasibility of receptor down regulation, the half-life of total and apical localized CAREx8 was determined and correlated with adenovirus transduction. Total and apical CAREx8 has a relatively short half-life of approximately 2 h. The half-life of apical CAREx8 correlates well with adenovirus transduction. These results suggest that antiviral strategies that aim to degrade the primary receptor for apical adenovirus infection will be effective within a relatively short time frame after application
Insulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes–Associated Variants
International audienceObjective. Zinc ions are essential for the formation of hexameric insulin and hormone crystallisation. Correspondingly, a non-synonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. Here, we describe the effects of deleting the ZnT8 gene in mice and explore the action of the at-risk allele. Research Design and Methods. Slc30a8 null mice were generated and backcrossed at least twice onto a C57BL/6J background. Glucose and insulin tolerance were measured by intraperitoneal injection, or euglycemic clamp, respectively. Insulin secretion, electrophysiology, imaging, and the generation of adenoviruses encoding the low- (W325) or elevated- (R325) risk ZnT8 alleles, were undertaken using standard protocols. Results. ZnT8(-/-) mice displayed age, sex and diet-dependent abnormalities in glucose tolerance, insulin secretion and body weight. Islets isolated from null mice had reduced granule zinc content, and showed age-dependent changes in granule morphology, with markedly fewer dense cores but more rod-like crystals. Glucose-stimulated insulin secretion, granule fusion and insulin crystal dissolution, as assessed by total internal reflection fluorescence microscopy, were unchanged or enhanced in ZnT8(-/-) islets. Insulin processing was normal. Molecular modelling revealed that residue-325 was located at the interface between ZnT8 monomers. Correspondingly, the R325 variant displayed lower apparent Zn(2+) transport activity than W325 ZnT8 by fluorescence-based assay. Discussion and conclusions. ZnT8 is required for normal insulin crystallisation and insulin release in vivo but not, remarkably, in vitro. Defects in the former processes in carriers of the R allele may increase type 2 diabetes risk
Modeling the differentiation of A- and C-type baroreceptor firing patterns
The baroreceptor neurons serve as the primary transducers of blood pressure
for the autonomic nervous system and are thus critical in enabling the body to
respond effectively to changes in blood pressure. These neurons can be
separated into two types (A and C) based on the myelination of their axons and
their distinct firing patterns elicited in response to specific pressure
stimuli. This study has developed a comprehensive model of the afferent
baroreceptor discharge built on physiological knowledge of arterial wall
mechanics, firing rate responses to controlled pressure stimuli, and ion
channel dynamics within the baroreceptor neurons. With this model, we were able
to predict firing rates observed in previously published experiments in both A-
and C-type neurons. These results were obtained by adjusting model parameters
determining the maximal ion-channel conductances. The observed variation in the
model parameters are hypothesized to correspond to physiological differences
between A- and C-type neurons. In agreement with published experimental
observations, our simulations suggest that a twofold lower potassium
conductance in C-type neurons is responsible for the observed sustained basal
firing, whereas a tenfold higher mechanosensitive conductance is responsible
for the greater firing rate observed in A-type neurons. A better understanding
of the difference between the two neuron types can potentially be used to gain
more insight into the underlying pathophysiology facilitating development of
targeted interventions improving baroreflex function in diseased individuals,
e.g. in patients with autonomic failure, a syndrome that is difficult to
diagnose in terms of its pathophysiology.Comment: Keywords: Baroreflex model, mechanosensitivity, A- and C-type
afferent baroreceptors, biophysical model, computational mode
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Yb(III), Sm(III) and La(III) complexes of a tetradentate pyridoxal Schiff base ligand: their DNA-binding activity and bio-imaging applications
Yb(III), Sm(III) and La(III) complexes of a tetradentate Schiff base ligand, bis(pyridoxylidene)ethyelenediamine, are reported. Single crystal X-ray crystal structures of the complexes reveal that in all of them the Ln(III) ions are in a distorted dodecahedral geometry with N4O4-coordination environment provided by two coordinated ligands. Fluorescence spectroscopy shows that in the Yb(III) and Sm(III) complexes energy transfer from ligand centered excited state leads to population of emissive f-f excited states. The reported complexes bind to ct-DNA, with high binding constant (Kb) comparable to those which bind by intercalative mode. Cytotoxicity study shows that the complexes have quite low cytotoxicity towards HeLa cell. Further, they exhibited fast response, bright fluorescence and stability at physiological pH, making them suitable for use in fluorescence bio-imaging
Overshooting Cytosolic Ca2+ Signals Evoked By Capacitative Ca2+ Entry Result from Delayed Stimulation of a Plasma Membrane Ca2+ Pump
The effect of capacitative Ca2+ entry on cytosolic free Ca2+ concentration ([Ca2+](c)) was examined in calf pulmonary artery endothelial cells treated with thapsigargin. Restoration of extracellular Ca2+ evoked an overshoot in [Ca2+](c): the intial rate of Ca2+ influx was 12.4 ± 0.5 nM/s as [Ca2+](c) rose monoexponentially (time constant, τ = 36 ± 2 s) to a peak (322 ± 16 nM) before declining to 109 ± 14 nM after 2000 s. Rates of Ca2+ removal from the cytosol were measured throughout the overshoot by recording the monoexponential decrease in [Ca2+](c) after rapid removal of extracellular Ca2+. The time constant for recovery (τ(rec) decreased from 54 ± 4 s when Ca2+ was removed after 10 s to its limiting value of 8.8 ± 1.0 s when it was removed after 2000 s. The time dependence of the changes in τ(rec) indicate that an increase in [Ca2+](c) is followed by a delayed (τ = 408 s) stimulation of Ca2+ removal, which fully reverses (τ ~ 185 s) after Ca2+ entry ceases. Numerical simulation indicated that the changes in Ca2+ removal were largely responsible for the overshooting pattern of [Ca2+](c). Because prolonged (30 min) Ca2+ entry did not increase the total 45Ca2+ content of the cells, an increased rate of Ca2+ extrusion across the plasma membrane most likely mediates the Ca2+ removal, and since it persists in the absence of extracellular Na+, it probably results from stimulation of a plasma membrane Ca2+ pump. We conclude that delayed stimulation of a plasma membrane Ca2+ pump by capacitative Ca2+ entry may protect cells from excessive increases in [Ca2+](c) and contribute to oscillatory changes in [Ca2+](c)
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