Managerial Overconfidence And Going-Concern Modified Audit Opinion Decisions

We examine how auditors perceive managerial overconfidence during audit reporting by testing the relationship between managerial overconfidence and the likelihood of issuing a first-time going-concern modified audit opinion to financially distressed firms. After controlling for the factors affecting auditor’s going-concern modified audit opinion decision, we find that the likelihood of issuing a first-time going-concern modified audit opinion is positively associated with managerial overconfidence, suggesting that auditors adversely value overconfident management in financially distressed firms and thus tend to issue a first-time going-concern modified audit opinion to them. We also find that the positive association above is reinforced with capital market uncertainty

Regeneration of a full-thickness defect of rotator cuff tendon with freshly thawed umbilical cord-derived mesenchymal stem cells in a rat model

Background It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an off-the-shelf usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model. Methods We evaluated morphology, viability, and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs, respectively. Two and 4 weeks later, macroscopic, histological, biomechanical, and cell trafficking were evaluated. T test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant. Results T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was more recovered at 2 and 4 weeks such as inflammation, defect size, neighboring tendon, swelling/redness, the connecting surrounding tissue and slidability. Histologically, the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization, and fiber coherence were improved by 33.33%, 42.75%, 1.86-fold, and 1.99-fold at 4 weeks, and GAG-rich area decreased by 88.13% and 94.70% at 2 and 4 weeks respectively. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both 2 and 4 weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Moreover, T-UC MSCs remained 8.77% at 4 weeks after injury, and there was no significant difference between C-UC MSCs and T-UC MSCs. Conclusions The morphology, viability, and proliferation of T-UC MSCs were comparable to those of C-UC MSCs. Treatment with T-UC MSCs could induce tendon regeneration of FTD at the macroscopic, histological, and biomechanical levels comparable to treatment with C-UC MSCs.This study was supported by a grant (NRF-2015M3A9E6028412) of the Bio & Medical Technology Development Program and a grant (NRF2017R1A2B2010995) awarded by the Basic Science Research Program of the National Research Foundation of Korea

LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding

The four members of the LRRTM family (LRRTM1-4) are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG) granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.Peer reviewe

Ultra-pH-Sensitive Small Molecule Probe Showing a Ratiometric Fluorescence Color Change

We synthesized an amphiphilic small molecule 1 by attaching oligo(ethylene glycol) (OEG) and N,N-diethylamine (DEA) units to a fluorescent dicyanodistyrylbenzene (DCS) core. The molecule is fully soluble in aqueous solution at low pH (pH&lt;4.3) by protonation of the DEA groups; but, above pH 4.3, it self-assembles to form nanoparticles due to increased hydrophobicity upon deprotonation, leading to a ratiometric fluorescence color change from green emission in the monomeric form (lambda(em,max)=538 nm) to red emission in the aggregated form (lambda(em,max)=646 nm). It should be noted that the ratio of emission intensities at 538 nm and 646 nm (R=I-538/I-646) changes drastically about 42-fold within a very narrow pH range of 4.3-4.6.Y

Climate Change Projections over CORDEX East Asia Domain using Multi-RCMs

In this study, global climate change scenario by HadGEM2-AO is dynamically downscaled using 5 Regional Climate Models (RCMs) for the Coordinated Regional Downscaling Experiment (CORDEX) - East Asia. All RCMs with 50-km horizontal resolution are integrated for continuous 71 years (1979-2049). In the evaluation of historical runs, all models tend to overestimate precipitation over the subtropical western North Pacific. For the surface air temperature, all models have cold biases over the East Asian continent compared to the observation. In the future projections, all models show similar changes in precipitation such as increasing precipitation over the tropical oceans and slightly decreasing precipitation over the East China Sea. In the mid-latitudes, convective precipitation tends to increase due to the enhanced convective instability, while non-convective precipitation tends to decrease slightly due to the changes in subtropical high and monsoon circulation. For surface air temperature, the warming tendency over the entire domain is captured by all models and it is larger in high latitude regions. The warming temperature is related to the increase in longwave radiation, which leads to prominent increase in minimum surface air temperature.clos

Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion

Synaptic adhesion molecules orchestrate synaptogenesis. The presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) regulate synapse development by interacting with postsynaptic Slit- and Trk-like family proteins (Slitrks), which harbour two extracellular leucine-rich repeats (LRR1 and LRR2). Here we identify the minimal regions of the LAR-RPTPs and Slitrks, LAR-RPTPs Ig1–3 and Slitrks LRR1, for their interaction and synaptogenic function. Subsequent crystallographic and structureguided functional analyses reveal that the splicing inserts in LAR-RPTPs are key molecular determinants for Slitrk binding and synapse formation. Moreover, structural comparison of the two Slitrk1 LRRs reveal that unique properties on the concave surface of Slitrk1 LRR1 render its specific binding to LAR-RPTPs. Finally, we demonstrate that lateral interactions between adjacent trans-synaptic LAR-RPTPs/Slitrks complexes observed in crystal lattices are critical for Slitrk1-induced lateral assembly and synaptogenic activity. Thus, we propose a model in which Slitrks mediate synaptogenic functions through direct binding to LAR-RPTPs and the subsequent lateral assembly of LAR-RPTPs/Slitrks complexes.133351sciescopu

Chloroplast and mitochondrial DNA editing in plants

Plant organelles including mitochondria and chloroplasts contain their own genomes, which encode many genes essential for respiration and photosynthesis, respectively. Gene editing in plant organelles, an unmet need for plant genetics and biotechnology, has been hampered by the lack of appropriate tools for targeting DNA in these organelles. In this study, we developed a Golden Gate cloning system(1), composed of 16 expression plasmids (8 for the delivery of the resulting protein to mitochondria and the other 8 for delivery to chloroplasts) and 424 transcription activator-like effector subarray plasmids, to assemble DddA-derived cytosine base editor (DdCBE)(2) plasmids and used the resulting DdCBEs to efficiently promote point mutagenesis in mitochondria and chloroplasts. Our DdCBEs induced base editing in lettuce or rapeseed calli at frequencies of up to 25% (mitochondria) and 38% (chloroplasts). We also showed DNA-free base editing in chloroplasts by delivering DdCBE mRNA to lettuce protoplasts to avoid off-target mutations caused by DdCBE-encoding plasmids. Furthermore, we generated lettuce calli and plantlets with edit frequencies of up to 99%, which were resistant to streptomycin or spectinomycin, by introducing a point mutation in the chloroplast 16S rRNA gene.

Neurotrophin-3 regulates synapse development by modulating TrkC-PTPσ synaptic adhesion and intracellular signaling pathways

Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10–25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semiquantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 μW) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 μW) further triggered the activation of phospholipase C-γ1 and CREB independently of PTPσ. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTPσ complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes. © 2016 the authors115141sciescopu

The influence of in vitro pectin fermentation on the human fecal microbiome

Abstract Pectin is a complex dietary fiber and a prebiotic. To investigate pectin-induced changes in the gut microbiome and their effects on the short chain fatty acids (SCFAs) production, we performed in vitro pectin fermentation using the feces of three Korean donors. The pectin degradations in all three donors were observed. While the donors displayed differences in baseline gut microbiota composition, commonly increased bacteria after pectin fermentation included Lachnospira, Dorea, Clostridium, and Sutterella. Regarding SCFAs, acetate levels rapidly increased with incubation with pectin, and butyrate levels also increased after 6 h of incubation. The results suggest that pectin fermentation increases bacterial species belonging to Clostridium cluster XIV (Lachnospira, Dorea, and Clostridium), with Lachnospira displaying the greatest increase. The results also confirm that pectin fermentation leads to the production of acetate and butyrate

Regeneration of a full-thickness defect in rotator cuff tendon with umbilical cord-derived mesenchymal stem cells in a rat model.

Although rotator cuff disease is a common cause of shoulder pain, there is still no treatment method that could halt or reveres its development and progression. The purpose of this study was to investigate the efficacy of umbilical cord-derived mesenchymal stem cells (UC MSCs) on the regeneration of a full-thickness rotator cuff defect (FTD) in a rat model. We injected either UC MSCs or saline to the FTD and investigated macroscopic, histological and biomechanical results and cell trafficking. Treatment with UC MSCs improved macroscopic appearance in terms of tendon thickness at two weeks, and inflammation, defect size, swelling/redness and connection surrounding tissue and slidability at four weeks compared to the saline group. Histologically, UC MSCs induced the tendon matrix formation recovering collagen organization, nuclear aspect ratio and orientation angle of fibroblast as well as suppressing cartilage-related glycosaminoglycan compared to saline group at four weeks. The UC MSCs group also improved ultimate failure load by 25.0% and 19.0% and ultimate stress by 27.3% and 26.8% at two and four weeks compared to saline group. UC MSCs labeled with PKH26 exhibited 5.3% survival at four weeks compared to three hours after injection. This study demonstrated that UC MSCs regenerated the FTD with tendon tissue similar properties to the normal tendon in terms of macroscopic, histological and biomechanical characteristics in a rat model