The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, ...here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1β, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anyons are exotic quasiparticles obeying fractional statistics, whose behavior can be emulated in artificially designed spin systems. Here we present an experimental emulation of creating anyonic ...excitations in a superconducting circuit that consists of four qubits, achieved by dynamically generating the ground and excited states of the toric code model, i.e., four-qubit Greenberger-Horne-Zeilinger states. The anyonic braiding is implemented via single-qubit rotations: a phase shift of π related to braiding, the hallmark of Abelian 1/2 anyons, has been observed through a Ramsey-type interference measurement.
The newly emerging monolayer phosphorene was recently predicted to be a promising thermoelectric material. In this work, we propose to further enhance the thermoelectric performance of phosphorene ...using the strain-induced band convergence. The effect of the uniaxial strain on the thermoelectric properties of phosphorene was investigated by using the first-principles calculations combined with the semiclassical Boltzmann theory. When the zigzag-direction strain is applied, the Seebeck coefficient and electrical conductivity in the zigzag direction can simultaneously be greatly enhanced at the critical strain of 5%, at which the band convergence is achieved. The largest ZT value of 1.65 at 300 K is then conservatively estimated by using the bulk lattice thermal conductivity. When the armchair-direction strain of 8% is applied, the room-temperature ZT value can reach 2.12 in the armchair direction of phosphorene. Our results indicate that strain-induced band convergence could be an effective method to enhance the thermoelectric performance of phosphorene.
The nodal-line semimetals have attracted immense interest due to the unique electronic structures such as the linear dispersion and the vanishing density of states as the Fermi energy approaching the ...nodes. Here, we report temperature-dependent transport and scanning tunneling microscopy (spectroscopy) STM(S) measurements on nodal-line semimetal ZrSiSe. Our experimental results and theoretical analyses consistently demonstrate that the temperature induces Lifshitz transitions at 80 and 106 K in ZrSiSe, which results in the transport anomalies at the same temperatures. More strikingly, we observe a V-shaped dip structure around Fermi energy from the STS spectrum at low temperature, which can be attributed to co-effect of the spin-orbit coupling and excitonic instability. Our observations indicate the correlation interaction may play an important role in ZrSiSe, which owns the quasi-two-dimensional electronic structures.
The super τ-charm facility (STCF) is an electron−positron collider proposed by the Chinese particle physics community. It is designed to operate in a center-of-mass energy range from 2 to 7 GeV with ...a peak luminosity of 0.5 × 10 35 cm −2·s −1 or higher. The STCF will produce a data sample about a factor of 100 larger than that of the present τ-charm factory - the BEPCII, providing a unique platform for exploring the asymmetry of matter-antimatter (charge-parity violation), in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions, as well as searching for exotic hadrons and physics beyond the Standard Model. The STCF project in China is under development with an extensive R&D program. This document presents the physics opportunities at the STCF, describes conceptual designs of the STCF detector system, and discusses future plans for detector R&D and physics case studies.
Aims: To optimize the transformation conditions and improve the transformation efficiency of Bacillus subtilis WB800 and DB104. Methods and Results: Trehalose, which could decrease the damage of ...electric shock to the cells, was added to the electroporation medium containing sorbitol and mannitol. The factors affecting the transformation efficiency, such as the growth phase of bacteria, cell concentration, electric field strength and plasmid variety, were examined and improved. The new method increased the transformation efficiency of B. subtilis by nearly 100‐fold compared with the conventional one. Conclusions: With the optimized method, the transformation efficiency came up to 3·64 × 105 transformants μg−1 DNA for WB800, and 2·10 × 105 transformants μg−1 DNA for DB104. Significance and Impact of the Study: This improvement in transformation efficiency will be largely attributed to the research of expression of exogenous genes in B. subtilis, gene library construction for directed evolution and transformation of wild‐type B. subtilis strains.
The ability of droplet digital PCR (ddPCR) to accurately determine the concentrations of amplifiable targets makes it a promising platform for measuring copy number alterations (CNAs) in genomic ...biomarkers. However, its application to clinical samples, particularly formalin-fixed paraffin-embedded specimens, will require strategies to reliably determine CNAs in DNA of limited quantity and quality. When applied to cancerous tissue, those methods must also account for global genetic instability and the associated probability that the abundance(s) of one or more chosen reference loci do not represent the average ploidy of cells comprising the specimen. Here we present an experimental design strategy and associated data analysis tool that enables accurate determination of CNAs in a panel of biomarkers using multiplexed ddPCR. The method includes strategies to optimize primer and probes design to cleanly segregate droplets in the data output from reaction wells amplifying multiple independent templates, and to correct for bias from artifacts such as DNA fragmentation. We demonstrate how a panel of reference loci can be used to determine a stable CNA-neutral benchmark. These innovations, when taken together, provide a comprehensive strategy that can be used to reliably detect biomarker CNAs in DNA extracted from either frozen or FFPE tissue biopsies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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