941 research outputs found
Localized Joule heating produced by ion current focusing through micron-size holes
We provide an experimental demonstration that the focusing of ionic currents
in a micron size hole connecting two chambers can produce local temperature
increases of up to C with gradients as large as K. We find a good agreement between the measured temperature profiles and
a finite elements-based numerical calculation. We show how the thermal
gradients can be used to measure the full melting profile of DNA duplexes
within a region of 40 m. The possibility to produce even larger gradients
using sub-micron pores is discussed.Comment: 3 pages, accepted to Appl. Phys. Lett
Anisotropic coarse-grained statistical potentials improve the ability to identify native-like protein structures
We present a new method to extract distance and orientation dependent
potentials between amino acid side chains using a database of protein
structures and the standard Boltzmann device. The importance of orientation
dependent interactions is first established by computing orientational order
parameters for proteins with alpha-helical and beta-sheet architecture.
Extraction of the anisotropic interactions requires defining local reference
frames for each amino acid that uniquely determine the coordinates of the
neighboring residues. Using the local reference frames and histograms of the
radial and angular correlation functions for a standard set of non-homologue
protein structures, we construct the anisotropic pair potentials. The
performance of the orientation dependent potentials was studied using a large
database of decoy proteins. The results demonstrate that the new distance and
orientation dependent residue-residue potentials present a significantly
improved ability to recognize native folds from a set of native and decoy
protein structures.Comment: Submitted to "The Journal of Chemical Physics
Representations for Three-Body T-Matrix on Unphysical Sheets: Proofs
A proof is given for the explicit representations which have been formulated
in the author's previous work (nucl-th/9505028) for the Faddeev components of
three-body T-matrix continued analytically on unphysical sheets of the energy
Riemann surface. Also, the analogous representations for analytical
continuation of the three-body scattering matrices and resolvent are proved. An
algorithm to search for the three-body resonances on the base of the Faddeev
differential equations is discussed.Comment: 98 Kb; LaTeX; Journal-ref was added (the title changed in the
journal
Representations for Three-Body T-Matrix on Unphysical Sheets
Explicit representations are formulated for the Faddeev components of
three-body T-matrix continued analytically on unphysical sheets of the energy
Riemann surface. According to the representations, the T-matrix on unphysical
sheets is obviously expressed in terms of its components taken on the physical
sheet only. The representations for T-matrix are used then to construct similar
representations for analytical continuation of three-body scattering matrices
and resolvent. Domains on unphysical sheets are described where the
representations obtained can be applied.Comment: 123 Kb; LaTeX; Journal-ref was added (the title changed in the
journal
Dynamics of forced biopolymer translocation
We present results from our simulations of biopolymer translocation in a
solvent which explain the main experimental findings. The forced translocation
can be described by simple force balance arguments for the relevant range of
pore potentials in experiments and biological systems. Scaling of translocation
time with polymer length varies with pore force and friction. Hydrodynamics
affects this scaling and significantly reduces translocation times.Comment: Published in:
http://www.iop.org/EJ/article/0295-5075/85/5/58006/epl_85_5_58006.htm
Comprehensive Identification and Modified-Site Mapping of S-Nitrosylated Targets in Prostate Epithelial Cells
Although overexpression of nitric oxide synthases (NOSs) has been found associated with prostate diseases, the underlying mechanisms for NOS-related prostatic diseases remain unclear. One proposed mechanism is related to the S-nitrosylation of key regulatory proteins in cell-signaling pathways due to elevated levels of NO in the prostate. Thus, our primary objective was to identify S-nitrosylated targets in an immortalized normal prostate epithelial cell line, NPrEC.We treated NPrEC with nitroso-cysteine and used the biotin switch technique followed by gel-based separation and mass spectrometry protein identification (using the LTQ-Orbitrap) to discover S-nitrosylated (SNO) proteins in the treated cells. In parallel, we adapted a peptide pull-down methodology to locate the site(s) of S-nitrosylation on the protein SNO targets identified by the first technique. This combined approach identified 116 SNO proteins and determined the sites of modification for 82 of them. Over 60% of these proteins belong to four functional groups: cell structure/cell motility/protein trafficking, protein folding/protein response/protein assembly, mRNA splicing/processing/transcriptional regulation, and metabolism. Western blot analysis validated a subset of targets related to disease development (proliferating cell nuclear antigen, maspin, integrin beta4, alpha-catenin, karyopherin [importin] beta1, and elongation factor 1A1). We analyzed the SNO sequences for their primary and secondary structures, solvent accessibility, and three-dimensional structural context. We found that about 80% of the SNO sites that can be mapped into resolved structures are buried, of which approximately half have charged amino acids in their three-dimensional neighborhood, and the other half residing within primarily hydrophobic pockets.We here identified 116 potential SNO targets and mapped their putative SNO sites in NPrEC. Elucidation of how this post-translational modification alters the function of these proteins should shed light on the role of NO in prostate pathologies. To our knowledge, this is the first report identifying SNO targets in prostate epithelial cells
Driven polymer translocation through a nanopore: a manifestation of anomalous diffusion
We study the translocation dynamics of a polymer chain threaded through a
nanopore by an external force. By means of diverse methods (scaling arguments,
fractional calculus and Monte Carlo simulation) we show that the relevant
dynamic variable, the translocated number of segments , displays an {\em
anomalous} diffusive behavior even in the {\em presence} of an external force.
The anomalous dynamics of the translocation process is governed by the same
universal exponent , where is the Flory
exponent and - the surface exponent, which was established recently
for the case of non-driven polymer chain threading through a nanopore. A closed
analytic expression for the probability distribution function , which
follows from the relevant {\em fractional} Fokker - Planck equation, is derived
in terms of the polymer chain length and the applied drag force . It is
found that the average translocation time scales as . Also the corresponding time dependent
statistical moments, and reveal unambiguously the anomalous nature of the translocation
dynamics and permit direct measurement of in experiments. These
findings are tested and found to be in perfect agreement with extensive Monte
Carlo (MC) simulations.Comment: 6 pages, 4 figures, accepted to Europhys. Lett; some references were
supplemented; typos were correcte
Microglia Control Vascular Architecture via a TGFβ1 Dependent Paracrine Mechanism Linked to Tissue Mechanics
© 2020, The Author(s). Tissue microarchitecture and mechanics are important in development and pathologies of the Central Nervous System (CNS); however, their coordinating mechanisms are unclear. Here, we report that during colonization of the retina, microglia contacts the deep layer of high stiffness, which coincides with microglial bipolarization, reduction in TGFβ1 signaling and termination of vascular growth. Likewise, stiff substrates induce microglial bipolarization and diminish TGFβ1 expression in hydrogels. Both microglial bipolarization in vivo and the responses to stiff substrates in vitro require intracellular adaptor Kindlin3 but not microglial integrins. Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling, excessive TGFβ1 expression and abnormally-patterned vasculature with severe malformations in the area of photoreceptors. Both excessive TGFβ1 signaling and vascular defects caused by Kindlin3-deficient microglia are rescued by either microglial depletion or microglial knockout of TGFβ1 in vivo. This mechanism underlies an interplay between microglia, vascular patterning and tissue mechanics within the CNS
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