The Immunological Synapse: a Dynamic Platform for Local Signaling

The immunological synapse (IS) as a concept has evolved from a static view of the junction between T cells and their antigen-presenting cell partners. The entire process of IS formation and extinction is now known to entail a dynamic reorganization of membrane domains and proteins within and adjacent to those domains. Discussion The entire process is also intricately tied to the motility machinery—both as that machinery directs “scanning” prior to T-cell receptor engagement and as it is appropriated during the ongoing developments at the IS. While the synapse often remains dynamic in order to encourage surveillance of new antigen-presenting surfaces, cytoskeletal forces also regulate the development of signals, likely including the assembly of ion channels. In both neuronal and immunological synapses, localized Ca 2+ signals and accumulation or depletion of ions in microdomains accompany the concentration of signaling molecules in the synapse. Such spatiotemporal signaling in the synapse greatly accelerates kinetics and provides essential checkpoints to validate effective cell–cell communication

Evolution of the germline mutation rate across vertebrates

The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself1. However, little is known about what determines its evolution, as most studies of mutation rates have focused on single species with different methodologies2. Here we quantify germline mutation rates across vertebrates by sequencing and comparing the high-coverage genomes of 151 parent–offspring trios from 68 species of mammals, fishes, birds and reptiles. We show that the per-generation mutation rate varies among species by a factor of 40, with mutation rates being higher for males than for females in mammals and birds, but not in reptiles and fishes. The generation time, age at maturity and species-level fecundity are the key life-history traits affecting this variation among species. Furthermore, species with higher long-term effective population sizes tend to have lower mutation rates per generation, providing support for the drift barrier hypothesis3. The exceptionally high yearly mutation rates of domesticated animals, which have been continually selected on fecundity traits including shorter generation times, further support the importance of generation time in the evolution of mutation rates. Overall, our comparative analysis of pedigree-based mutation rates provides ecological insights on the mutation rate evolution in vertebrates

The Antibody Targeting the E314 Peptide of Human Kv1.3 Pore Region Serves as a Novel, Potent and Specific Channel Blocker

Selective blockade of Kv1.3 channels in effector memory T (TEM) cells was validated to ameliorate autoimmune or autoimmune-associated diseases. We generated the antibody directed against one peptide of human Kv1.3 (hKv1.3) extracellular loop as a novel and possible Kv1.3 blocker. One peptide of hKv1.3 extracellular loop E3 containing 14 amino acids (E314) was chosen as an antigenic determinant to generate the E314 antibody. The E314 antibody specifically recognized 63.8KD protein stably expressed in hKv1.3-HEK 293 cell lines, whereas it did not recognize or cross-react to human Kv1.1(hKv1.1), Kv1.2(hKv1.2), Kv1.4(hKv1.4), Kv1.5(hKv1.5), KCa3.1(hKCa3.1), HERG, hKCNQ1/hKCNE1, Nav1.5 and Cav1.2 proteins stably expressed in HEK 293 cell lines or in human atrial or ventricular myocytes by Western blotting analysis and immunostaining detection. By the technique of whole-cell patch clamp, the E314 antibody was shown to have a directly inhibitory effect on hKv1.3 currents expressed in HEK 293 or Jurkat T cells and the inhibition showed a concentration-dependence. However, it exerted no significant difference on hKv1.1, hKv1.2, hKv1.4, hKv1.5, hKCa3.1, HERG, hKCNQ1/hKCNE1, L-type Ca2+ or voltage-gated Na+ currents. The present study demonstrates that the antibody targeting the E314 peptide of hKv1.3 pore region could be a novel, potent and specific hKv1.3 blocker without affecting a variety of closely related Kv1 channels, KCa3.1 channels and functional cardiac ion channels underlying central nervous systerm (CNS) disorders or drug-acquired arrhythmias, which is required as a safe clinic-promising channel blocker

Green Financing Efficiency and Influencing Factors of Chinese Listed Construction Companies against the Background of Carbon Neutralization: A Study Based on Three-Stage DEA and System GMM

This paper combines the green industrial strategy and green financial policies for the construction industry implemented in China in the context of carbon neutrality. A total of 67 listed companies in the construction industry from 2017 to 2020 were taken as the research sample, the green financing efficiency was measured, and its influencing factors were identified based on the three-stage DEA and systematic GMM method. The findings show that the green financing efficiency of listed companies in the construction industry is not high overall, although it is increasing. There are obvious differences in subsectors, among which, the efficiency of architectural design and service industries is relatively high. Overall, the financial environment, and the interaction between the government and the financial market, significantly and positively influence the green financing efficiency. In addition, the macroeconomic environment and the government–enterprise relationship has a complex impact on the green financing efficiency. The ownership concentration and having corporate executives with a financial background have a significant positive impact on the green financing efficiency, and the enterprise size, the debt maturity structure, and the R&D and innovation capability have a significant negative impact. The findings of this paper have implications for the improvement of the policy system that supports green development in the construction industry, and provide guidance for the strategic adjustment of the construction industry itself

Green Financing Efficiency and Influencing Factors of Chinese Listed Construction Companies against the Background of Carbon Neutralization: A Study Based on Three-Stage DEA and System GMM

This paper combines the green industrial strategy and green financial policies for the construction industry implemented in China in the context of carbon neutrality. A total of 67 listed companies in the construction industry from 2017 to 2020 were taken as the research sample, the green financing efficiency was measured, and its influencing factors were identified based on the three-stage DEA and systematic GMM method. The findings show that the green financing efficiency of listed companies in the construction industry is not high overall, although it is increasing. There are obvious differences in subsectors, among which, the efficiency of architectural design and service industries is relatively high. Overall, the financial environment, and the interaction between the government and the financial market, significantly and positively influence the green financing efficiency. In addition, the macroeconomic environment and the government–enterprise relationship has a complex impact on the green financing efficiency. The ownership concentration and having corporate executives with a financial background have a significant positive impact on the green financing efficiency, and the enterprise size, the debt maturity structure, and the R&D and innovation capability have a significant negative impact. The findings of this paper have implications for the improvement of the policy system that supports green development in the construction industry, and provide guidance for the strategic adjustment of the construction industry itself

Facile preparation of polymer-based heat dissipation composite coating with enhanced thermal conductivity via optimizing synergistic effect of multi-scale fillers

Aluminum radiator plays a significant role in thermal managing system of passive heat dissipation for high power consuming microelectronic devices. Although inspiring strategies have been proposed to design and prepare polymer-based composites with high thermal conductivity in previous reports, it remains urgent to develop practical techniques for economically fabricating thermally conductive composite coatings in large-scale. To construct efficient heat dissipation film, two-dimensional (2D) graphene nanoplatelets (GNPs)/hexagonal boron nitride nanoplatelets (BNNPs) hybrid fillers are dispersed in polydimethylsiloxane (PDMS) solution with branch-like porous magnéli-phase Ti4O7 microparticles as heat conducting paths, and fabricated via convenient spray-coating. Thermal conductivity of the cured coating presents two-fold increase to 5.339 W m−1 K−1 as compared to the coating without Ti4O7, and a heat dissipation ratio of 13.96 %. Furthermore, the composite coating demonstrates excellent corrosion resistance under neutral salt solution spray. The as-prepared composite coating is of great potential to be applied as protective coating for aluminum radiators

External K Activation of Kir1.1 Depends on the pH Gate

The inward rectifier Kir1.1 (ROMK) family is gated by both internal pH and external K, where the putative pH gate is formed by the convergence of leucine side chains, near the inner helical bundle crossing at L160-Kir1.1. However, it is unclear whether K activation is mediated at the pH gate or by another gate in the permeation path. In this study, we used the whole-cell conductance increase during rapid K elevation as a measure of K activation, assuming that activation is inherently slower than changes in channel conduction. Results indicate that structural disruption of the Kir1.1 bundle-crossing pH gate prevents both inactivation by low external K and reactivation by high external K