Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts

Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-β), a pro-fibrotic cytokine. Methods: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-β and was identified by the expression of smooth muscle actin. Results: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif­ferentiation. CFs treated with TGF-β demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it’s antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway. Conclusions: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway

Privacy-Preserving Machine Learning with Fully Homomorphic Encryption for Deep Neural Network

Fully homomorphic encryption (FHE) is one of the prospective tools for privacypreserving machine learning (PPML), and several PPML models have been proposed based on various FHE schemes and approaches. Although the FHE schemes are known as suitable tools to implement PPML models, previous PPML models on FHE encrypted data are limited to only simple and non-standard types of machine learning models. These non-standard machine learning models are not proven efficient and accurate with more practical and advanced datasets. Previous PPML schemes replace non-arithmetic activation functions with simple arithmetic functions instead of adopting approximation methods and do not use bootstrapping, which enables continuous homomorphic evaluations. Thus, they could not use standard activation functions and could not employ a large number of layers. The maximum classification accuracy of the existing PPML model with the FHE for the CIFAR-10 dataset was only 77% until now. In this work, we firstly implement the standard ResNet-20 model with the RNS-CKKS FHE with bootstrapping and verify the implemented model with the CIFAR-10 dataset and the plaintext model parameters. Instead of replacing the non-arithmetic functions with the simple arithmetic function, we use state-of-the-art approximation methods to evaluate these non-arithmetic functions, such as the ReLU, with sufficient precision [1]. Further, for the first time, we use the bootstrapping technique of the RNS-CKKS scheme in the proposed model, which enables us to evaluate a deep learning model on the encrypted data. We numerically verify that the proposed model with the CIFAR-10 dataset shows 98.67% identical results to the original ResNet-20 model with non-encrypted data. The classification accuracy of the proposed model is 90.67%, which is pretty close to that of the original ResNet-20 CNN model...Comment: 12 pages, 4 figure

Analysis of whole genome sequencing and virulence factors of Vibrio vulnificus 1908-10 isolated from sea water at Gadeok island coast

Vibrio vulnificus is an aquatic bacterium causing septicemia and wound infection in humans. To understand this pathogen at the genomic level, it was performed whole genome sequencing of a cefoxitin-resistant strain, V. vulnificus 1908-10 possessing virulence-related genes (vvhA, viuB, and vcgC) isolated from Gadeok island coastal seawater in South Korea. The genome of V. vulnificus 1908-10 consisted of two circular contigs and no plasmid. The total genome size was estimated to be 5,018,425 bp with a guanine-cytosine (GC) content of 46.9%. We found 119 tRNA and 34 rRNA genes respectively in the genome, along with 4,352 predicted protein sequences. Virulence factor (VF) analysis further revealed that V. vulnificus 1908-10 possess various virulence genes in classes of adherence, antiphagocytosis, chemotaxis and motility, iron uptake, quorum sensing, secretion system, and toxin. In the comparison of the presence/absence of virulence genes, V. vulnificus 1908-10 had fur, hlyU, luxS, ompU, pilA, pilF, rtxA, rtxC, and vvhA. Of the 30 V. vulnificus comparative strains, 80% of the C-genotype strains have all of these genes, whereas 40% of the E-genotype strains have all of them. In particular, pilA were identified in 80% of the C-type strains and 40% of the E-type strains, showing more difference than other genes. Therefore, V. vulnificus 1908-10 had similar VF characteristics to those of type C strains. Multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin of V. vulnificus 1908-10 contained 8 A-type repeats (GXXGXXXXXG), 25 B.1-type repeats (TXVGXGXX), 18 B2-type repeats (GGXGXDXXX), and 7 C-type repeats (GGXGXDXXX). The National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) showed that the RtxA protein of V. vulnificus 1908-10 had the effector domain in the order of cross-liking domain (ACD)-C58_PaToxP-like domain- α/β hydrolase-C58_PaToxP-like domain

Symmetry Control of Unconventional Spin–Orbit Torques in IrO\u3csub\u3e2\u3c/sub\u3e

Spin–orbit torques generated by a spin current are key to magnetic switching in spintronic applications. The polarization of the spin current dictates the direction of switching required for energy-efficient devices. Conventionally, the polarizations of these spin currents are restricted to be along a certain direction due to the symmetry of the material allowing only for efficient in-plane magnetic switching. Unconventional spin–orbit torques arising from novel spin current polarizations, however, have the potential to switch other magnetization orientations such as perpendicular magnetic anisotropy, which is desired for higher density spintronic-based memory devices. Here, it is demonstrated that low crystalline symmetry is not required for unconventional spin–orbit torques and can be generated in a nonmagnetic high symmetry material, iridium dioxide (IrO2), using epitaxial design. It is shown that by reducing the relative crystalline symmetry with respect to the growth direction large unconventional spin currents can be generated and hence spin–orbit torques. Furthermore, the spin polarizations detected in (001), (110), and (111) oriented IrO2 thin films are compared to show which crystal symmetries restrict unconventional spin transport. Understanding and tuning unconventional spin transport generation in high symmetry materials can provide a new route towards energy-efficient magnetic switching in spintronic devices

Traumatic Experiences and Mental Health of North Korean Refugees in South Korea

OBJECTIVE: This study was conducted at Hanawon-a government sponsored educational facility for the settlement of North Korean refugees during their initial phase in South Korea-in 2004 to explore their mental health status and traumatic experiences in North Korea and during their escape period. METHODS: A survey was conducted in November 2004 with 62 North Korean refugees at Hanawon, and the Trauma Checklist was used to measure their traumatic experiences. To measure their psychological-mental health status, the Personality Assessment Inventory was administered. RESULTS: In comparison with the traumatic experiences of the North Korean refugees found in the study conducted in 2001 at Hanawon using the same methods, the current study showed a relatively lower frequency of traumatic experiences among the participants. The Personality Assessment Inventory results revealed that the study participants scored higher than average South Koreans in all clinical scales. Particularly, their mania (62.51) and schizophrenia (61.75) scores were above 60, a clinically meaningful score. In the gender comparison, the males exhibited meaningfully higher levels of alcohol problem, non-support, and warmth scale scores. CONCLUSION: Compared to the 2001 study, the overall traumatic experiences among North Korean refugees participated in this study. But continous support is necessary for their successful adaptation to South Korean Society have declined. The North Korean refugees at Hanawon experienced difficulties maintaining their mental health and the men in particular requested more intensive care and support for this purpose.ope

Aptamer-functionalized nano-pattern based on carbon nanotube for sensitive, selective protein detection

We have developed a horizontally aligned carbon nanotube sensor that enables not only the specific detection of biomolecules with ultra-sensitivity, but also the quantitative characterization of binding affinity between biomolecules and/or interaction between a carbon nanotube and a biomolecule, for future applications in early diagnostics. In particular, we have fabricated horizontally aligned carbon nanotubes, which were functionalized with specific aptamers that are able to specifically bind to biomolecules (i.e. thrombin). Our detection system is based on scanning probe microscopy (SPM) imaging for horizontally aligned aptamer-conjugated carbon nanotubes (ACNTs) that specifically react with target biomolecules at an ultra-low concentration. It is shown that the binding affinity between thrombin molecule and ACNT can be quantitatively characterized using SPM imaging. It is also found that the smart carbon nanotube sensor coupled with SPM imaging permits us to achieve the high detection sensitivity even up to similar to 1 pM, which is much higher than that of other bioassay methods. Moreover, we have shown that our method enables a quantitative study on small molecule-mediated inhibition of specific biomolecular interactions. In addition, we have shown that our ACNT-based system allows for the quantitative study of the effect of chemical environment (e.g. pH and ion concentration) on the binding affinity. Our study sheds light on carbon nanotube sensor coupled with SPM imaging, which opens a new avenue to early diagnostics and drug screening with high sensitivity.close2

Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis

Background/AimsWe compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis.MethodsTwo hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated.ResultsThe mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4.ConclusionsThe results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis

Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein (RNP) electroporation

Background Genome editing has been considered as powerful tool in agricultural fields. However, genome editing progress in cattle has not been fast as in other mammal species, for some disadvantages including long gestational periods, single pregnancy, and high raising cost. Furthermore, technically demanding methods such as microinjection and somatic cell nuclear transfer (SCNT) are needed for gene editing in cattle. In this point of view, electroporation in embryos has been risen as an alternative. Results First, editing efficiency of our electroporation methods were tested for embryos. Presence of mutation on embryo was confirmed by T7E1 assay. With first combination, mutation rates for MSTN and PRNP were 57.6% ± 13.7% and 54.6% ± 13.5%, respectively. In case of MSTN/BLG, mutation rates were 83.9% ± 23.6% for MSTN, 84.5% ± 18.0% for BLG. Afterwards, the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing. Thirteen recipients were transferred for MSTN/PRNP, 4 calves were delivered, and one calf underwent an induction for double KO. Ten surrogates were given double-KO embryos for MSTN/BLG, and four of the six calves that were born had mutations in both genes. Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied. Finally, MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.This study was financially supported by the National Research Foundation of Korea (NRF-2021R1A5A1033157 for SRC program: 382 Comparative medicine Disease Research Center; NRF-2021R1F1A105195313), the Research Institute of Veterinary Science, the BK21 Four for Future Veterinary Medicine Leading Education and Research Center, and a Seoul National University (SNU) grant (#550e2020005