Membrane-bound delta-like 1 homolog (Dlk1) promotes while soluble Dlk1 inhibits myogenesis in C2C12 cells

AbstractDelta-like 1 homolog (Dlk1) is important in myogenesis. However, the roles of different Dlk1 isoforms have not been investigated. In C2C12 cell lines producing different Dlk1 isoforms, membrane-bound Dlk1 promoted the hypertrophic phenotype and a higher fusion rate, whereas soluble Dlk1 inhibited myotube formation. Inversed expression patterns of genes related to myogenic differentiation further support these phenotypic changes. In addition, temporal expression and balance between the Dlk1 isoforms have a regulatory role in myogenesis in vivo. Collectively, Dlk1 isoforms have distinctive effects on myogenesis, and its regulation during myogenesis is critical for normal muscle development

iDML: Incentivized Decentralized Machine Learning

With the rising emergence of decentralized and opportunistic approaches to machine learning, end devices are increasingly tasked with training deep learning models on-devices using crowd-sourced data that they collect themselves. These approaches are desirable from a resource consumption perspective and also from a privacy preservation perspective. When the devices benefit directly from the trained models, the incentives are implicit - contributing devices' resources are incentivized by the availability of the higher-accuracy model that results from collaboration. However, explicit incentive mechanisms must be provided when end-user devices are asked to contribute their resources (e.g., computation, communication, and data) to a task performed primarily for the benefit of others, e.g., training a model for a task that a neighbor device needs but the device owner is uninterested in. In this project, we propose a novel blockchain-based incentive mechanism for completely decentralized and opportunistic learning architectures. We leverage a smart contract not only for providing explicit incentives to end devices to participate in decentralized learning but also to create a fully decentralized mechanism to inspect and reflect on the behavior of the learning architecture

Direct observation of DNA target searching and cleavage by CRISPR-Cas12a

Cas12a (also called Cpf1) is a representative type V-A CRISPR effector RNA-guided DNA endonuclease, which provides an alternative to type II CRISPR-Cas9 for genome editing. Previous studies have revealed that Cas12a has unique features distinct from Cas9, but the detailed mechanisms of target searching and DNA cleavage by Cas12a are still unclear. Here, we directly observe this entire process by using single-molecule fluorescence assays to study Cas12a from Acidaminococcus sp. (AsCas12a). We determine that AsCas12a ribonucleoproteins search for their on-target site by a one-dimensional diffusion along elongated DNA molecules and induce cleavage in the two DNA strands in a well-defined order, beginning with the non-target strand. Furthermore, the protospacer-adjacent motif (PAM) for AsCas12a makes only a limited contribution of DNA unwinding during R-loop formation and shows a negligible role in the process of DNA cleavage, in contrast to the Cas9 PAM.

Symmetry-Dependent Intramolecular Charge Transfer Dynamics of Pyrene Derivatives Investigated by Two-Photon Excitation

Intramolecular charge transfer (ICT) processes in two-photon (TP) allowed states were investigated using three pyrene derivatives <b>N1</b>, <b>N2C</b>, and <b>N2T</b>, which have different molecular symmetry depending on the number and position of <i>N</i>,<i>N</i>-dimethylaniline donating substituents. On the basis of steady-state and nondegenerate two-photon absorption measurements, we investigated femtosecond transient absorption (TA) spectra by one-photon (OPE) and two-photon excitation (TPE). In the analysis of TA spectra, we discovered that the transfer rate from locally excited state to the ICT state by TPE is slower than that by OPE, indicating that the energy barrier between the TP and ICT states is higher than that between the one-photon (OP) allowed and ICT states. Furthermore, we demonstrated that ICT dynamics in a TP state are affected by molecular symmetry through the disappearance of stimulated emission from the locally excited state in the TA spectra of <b>N2T</b> obtained by TPE. We believe that our findings will provide fundamental information for a better understanding of excited-state ICT dynamics

Regioselective phenylene-fusion reactions of Ni(II)-porphyrins controlled by an electron-withdrawing: Meso -substituent

Oxidation of 10, 15, 20-triaryl Ni(ii)-porphyrins bearing an electron-withdrawing substituent at the 5-position with DDQ and FeCl3 gave 10, 12- and 18, 20-doubly phenylene-fused Ni(ii)-porphyrins regioselectively. A doubly phenylene-fused meso-chloro porphyrin thus prepared was reductively coupled to give a meso-meso linked dimer, which was further converted to a quadruply phenylene-fused meso-meso, β-β, β-β triply linked Zn(ii)-diporphyrin via inner-metal exchange followed by oxidation with DDQ and Sc(OTf)3. As compared to the usual meso-meso, β-β, β-β triply linked Zn(ii)-diporphyrin, this π-extended porphyrin dyad exhibits a smaller HOMO-LUMO gap and a larger two-photon absorption cross-section

Skeletal muscle characterization of Japanese quail line selectively bred for lower body weight as an avian model of delayed muscle growth with hypoplasia.

This study was designed to extensively characterize the skeletal muscle development in the low weight (LW) quail selected from random bred control (RBC) Japanese quail in order to provide a new avian model of impaired and delayed growth in physically normal animals. The LW line had smaller embryo and body weights than the RBC line in all age groups (P<0.05). During 3 to 42 d post-hatch, the LW line exhibited approximately 60% smaller weight of pectoralis major muscle (PM), mainly resulting from lower fiber numbers compared to the RBC line (P<0.05). During early post-hatch period when myotubes are still actively forming, the LW line showed impaired PM growth with prolonged expression of Pax7 and lower expression levels of MyoD, Myf-5, and myogenin (P<0.05), likely leading to impairment of myogenic differentiation and consequently, reduced muscle fiber formation. Additionally, the LW line had delayed transition of neonatal to adult myosin heavy chain isoform, suggesting delayed muscle maturation. This is further supported by the finding that the LW line continued to grow unlike the RBC line; difference in the percentages of PMW to body weights between both quail lines diminished with increasing age from 42 to 75 d post-hatch. This delayed muscle growth in the LW line is accompanied by higher levels of myogenin expression at 42 d (P<0.05), higher percentage of centered nuclei at 42 d (P<0.01), and greater rate of increase in fiber size between 42 and 75 d post-hatch (P<0.001) compared to the RBC line. Analysis of physiological, morphological, and developmental parameters during muscle development of the LW quail line provided a well-characterized avian model for future identification of the responsible genes and for studying mechanisms of hypoplasia and delayed muscle growth

Trichosanthis Semen Suppresses Lipopolysaccharide-Induced Neuroinflammation by Regulating the NF-κB Signaling Pathway and HO-1 Expression in Microglia

Neuroinflammation, which is mediated by microglia that release various inflammatory cytokines, is a typical feature of neurodegenerative diseases (NDDs), such as Alzheimer’s disease and Parkinson’s disease. Hence, alleviating neuroinflammation by downregulating pro-inflammatory action, and upregulating anti-inflammatory action of microglia is an efficient therapeutic target for NDDs. In this study, we evaluated whether trichosanthis semen (TS), a dried ripe seed of Trichosanthes kirilowii Maximowicz, reduces lipopolysaccharide (LPS)-induced neuroinflammation by regulating microglial responses in vitro and in vivo. Our results presented that TS reduced the release of pro-inflammatory mediators, such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin-1β, and interleukin-6 via inhibition of the nuclear factor kappa B (NF-κB) signaling pathway in LPS-treated BV2 microglial cells. Moreover, TS induced anti-inflammatory mediators, such as interleukin-10, found in inflammatory zone 1, and chitinase 3-like 3 by the upregulation of heme oxygenase 1 (HO-1). We further confirmed that TS administration suppressed microglial activation, but enhanced HO-1 expression in LPS-injected mice. These results suggest that TS has anti-neuroinflammatory effects via inhibition of NF-κB signaling through the activation of HO-1, and that TS may be a therapeutical candidate for NDDs treatment

Analysis of a Tapered Rectangular Waveguide for V to W Millimeter Wavebands

An electromagnetic boundary-value problem of a tapered rectangular waveguide is rigorously solved based on eigenfunction expansion and the mode-matching method. Scattering parameters of the tapered rectangular waveguide are represented in a series form and calculated in terms of different rectangular waveguide combinations. Computation is performed to analyze reflection and transmission characteristics. Conductor loss by surface current density is also calculated and discussed