4,107 research outputs found
Cadmium Induces the Expression of Grp78, an Endoplasmic Reticulum Molecular Chaperone, in LLC-PK1 Renal Epithelial Cells
To reveal the effects of cadmium exposure on the endoplasmic reticulum (ER) stress response, we examined the expression and function of 78-kDa glucose-regulated protein (Grp78), an ER-resident molecular chaperone, in LLC-PK1 cells. In cells treated with 10 μM cadmium chloride, Grp78 protein levels increased after 6 hr and remained elevated at 24 hr. When cells were incubated with 1–20 μM CdCl(2) for 6 hr, Grp78 increased in a dose-dependent manner. In addition, Grp78 mRNA levels were elevated in response to CdCl(2) exposure. After exposure to 10 μM CdCl(2), the levels of activating transcription factor 4 (ATF4) were increased at 2 hr, with a further enhancement after that; this accumulation followed the transient but marked phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α) on serine 51. Although ATF4 mRNA levels increased mildly by CdCl(2) exposure, treatment with actinomycin D did not suppress CdCl(2)-induced accumulation of ATF4 protein, suggesting the involvement of posttranscriptional and, in part, transcriptional mechanisms. Compared with other heavy-metal compounds such as manganese chloride, zinc chloride, mercuric chloride, and lead chloride, CdCl(2) could increase the levels of Grp78, ATF4, and the phosphorylated form of eIF2α more markedly without definite cellular damage. The silencing of Grp78 expression using short-interference RNA enhanced CdCl(2)-induced cellular damage. These results show that cadmium induces the expression of Grp78 probably via phosphorylation of eIF2α and resultant translation of ATF4, and this ER stress response plays a role in protection against cadmium cytotoxicity in this renal epithelial cell
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The optical microscopy with virtual image breaks a record: 50-nm resolution imaging is demonstrated
We demonstrate a new 'microsphere nanoscope' that uses ordinary SiO2
microspheres as superlenses to create a virtual image of the object in near
field. The magnified virtual image greatly overcomes the diffraction limit. We
are able to resolve clearly 50-nm objects under a standard white light source
in both transmission and reflection modes. The resolution achieved for white
light opens a new opportunity to image viruses, DNA and molecules in real time
Near-Infrared Super Resolution Imaging with Metallic Nanoshell Particle Chain Array
We propose a near-infrared super resolution imaging system without a lens or
a mirror but with an array of metallic nanoshell particle chain. The imaging
array can plasmonically transfer the near-field components of dipole sources in
the incoherent and coherent manners and the super resolution images can be
reconstructed in the output plane. By tunning the parameters of the metallic
nanoshell particle, the plasmon resonance band of the isolate nanoshell
particle red-shifts to the near-infrared region. The near-infrared super
resolution images are obtained subsequently. We calculate the field intensity
distribution at the different planes of imaging process using the finite
element method and find that the array has super resolution imaging capability
at near-infrared wavelengths. We also show that the image formation highly
depends on the coherence of the dipole sources and the image-array distance.Comment: 15 pages, 6 figure
Photonic Analogue of Two-dimensional Topological Insulators and Helical One-Way Edge Transport in Bi-Anisotropic Metamaterials
Recent progress in understanding the topological properties of condensed
matter has led to the discovery of time-reversal invariant topological
insulators. Because of limitations imposed by nature, topologically non-trivial
electronic order seems to be uncommon except in small-band-gap semiconductors
with strong spin-orbit interactions. In this Article we show that artificial
electromagnetic structures, known as metamaterials, provide an attractive
platform for designing photonic analogues of topological insulators. We
demonstrate that a judicious choice of the metamaterial parameters can create
photonic phases that support a pair of helical edge states, and that these edge
states enable one-way photonic transport that is robust against disorder.Comment: 13 pages, 3 figure
Near-field examination of perovskite-based superlenses and superlens-enhanced probe-object coupling
A planar slab of negative index material works as a superlens with
sub-diffraction-limited imaging resolution, since propagating waves are focused
and, moreover, evanescent waves are reconstructed in the image plane. Here, we
demonstrate a superlens for electric evanescent fields with low losses using
perovskites in the mid-infrared regime. The combination of near-field
microscopy with a tunable free-electron laser allows us to address precisely
the polariton modes, which are critical for super-resolution imaging. We
spectrally study the lateral and vertical distributions of evanescent waves
around the image plane of such a lens, and achieve imaging resolution of
wavelength/14 at the superlensing wavelength. Interestingly, at certain
distances between the probe and sample surface, we observe a maximum of these
evanescent fields. Comparisons with numerical simulations indicate that this
maximum originates from an enhanced coupling between probe and object, which
might be applicable for multifunctional circuits, infrared spectroscopy, and
thermal sensors.Comment: 20 pages, 6 figures, published as open access article in Nature
Communications (see http://www.nature.com/ncomms/
Signalling, trafficking and glucoregulatory properties of glucagon-like peptide-1 receptor agonists exendin-4 and lixisenatide.
BACKGROUND AND PURPOSE: Amino acid substitutions at the N-termini of glucagon-like peptide-1 receptor agonist (GLP-1RA) peptides result in distinct patterns of intracellular signalling, sub-cellular trafficking and efficacy in vivo. Here we aimed to determine whether sequence differences at the ligand C-termini of clinically approved GLP-1RAs exendin-4 and lixisenatide lead to similar phenomena. EXPERIMENTAL APPROACH: Exendin-4, lixisenatide, and N-terminally substituted analogues with biased signalling characteristics were compared across a range of in vitro trafficking and signalling assays in different cell types. Fluorescent ligands and new time-resolved FRET approaches were developed to study agonist behaviours at the cellular and sub-cellular level. Anti-hyperglycaemic and anorectic effects of each parent ligand, and their biased derivatives, were assessed in mice. KEY RESULTS: Lixisenatide and exendin-4 showed equal binding affinity, but lixisenatide was 5-fold less potent for cAMP signalling. Both peptides induced extensive GLP-1R clustering in the plasma membrane and were rapidly endocytosed, but the GLP-1R recycled more slowly to the cell surface after lixisenatide treatment. These combined deficits resulted in reduced maximal sustained insulin secretion and reduced anti-hyperglycaemic and anorectic effects in mice with lixisenatide. N-terminal substitution of His1 by Phe1 to both ligands had favourable effects on their pharmacology, resulting in improved insulin release and lowering of blood glucose. CONCLUSION AND IMPLICATIONS: Changes to the C-terminus of exendin-4 affect signalling potency and GLP-1R trafficking via mechanisms unrelated to GLP-1R occupancy. These differences were associated with changes in their ability to control blood glucose and therefore may be therapeutically relevant
Mechanical Metamaterials with Negative Compressibility Transitions
When tensioned, ordinary materials expand along the direction of the applied
force. Here, we explore network concepts to design metamaterials exhibiting
negative compressibility transitions, during which a material undergoes
contraction when tensioned (or expansion when pressured). Continuous
contraction of a material in the same direction of an applied tension, and in
response to this tension, is inherently unstable. The conceptually similar
effect we demonstrate can be achieved, however, through destabilisations of
(meta)stable equilibria of the constituents. These destabilisations give rise
to a stress-induced solid-solid phase transition associated with a twisted
hysteresis curve for the stress-strain relationship. The strain-driven
counterpart of negative compressibility transitions is a force amplification
phenomenon, where an increase in deformation induces a discontinuous increase
in response force. We suggest that the proposed materials could be useful for
the design of actuators, force amplifiers, micro-mechanical controls, and
protective devices.Comment: Supplementary information available at
http://www.nature.com/nmat/journal/v11/n7/abs/nmat3331.htm
Beating the channel capacity limit for linear photonic superdense coding
Dense coding is arguably the protocol that launched the field of quantum
communication. Today, however, more than a decade after its initial
experimental realization, the channel capacity remains fundamentally limited as
conceived for photons using linear elements. Bob can only send to Alice three
of four potential messages owing to the impossibility of carrying out the
deterministic discrimination of all four Bell states with linear optics,
reducing the attainable channel capacity from 2 to log_2 3 \approx 1.585 bits.
However, entanglement in an extra degree of freedom enables the complete and
deterministic discrimination of all Bell states. Using pairs of photons
simultaneously entangled in spin and orbital angular momentum, we demonstrate
the quantum advantage of the ancillary entanglement. In particular, we describe
a dense-coding experiment with the largest reported channel capacity and, to
our knowledge, the first to break the conventional linear-optics threshold. Our
encoding is suited for quantum communication without alignment and satellite
communication.Comment: Letter: 6 pages, 4 figures. Supplementary Information: 4 pages, 1
figur
Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons
Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated.
Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope.
Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes.
Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron
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