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However, we found that mitochondrial function was impaired in patient-derived immortalized lymphocytes. CONCLUSION Our data revealed that m.14487T>C mutation is insufficient to cause mitochondrial deficiency; additional modifier genes may be involved in m.14487T>C-associated mitochondrial disease. Our results further demonstrated that a caution should be taken by solely use of m.14487T>C mutation for molecular diagnosis of mitochondrial disease. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.An efficient and refined method for the separation of six aconitine-type alkaloids from the alkaline prepared "Kusnezoff monkshood root" was extablished. It is the first study that two new lipo-alkaloids were successfully isolated from refined sample by pH-zone-refining counter-current chromatography rather than synthetic method. https://www.selleckchem.com/products/crcd2.html It was of interest that a great deal of lipo-alkaloids was produced in crude extract from the alkalization of "Kusnezoff monkshood root." A refined sample method was proposed to enrich two types of alkaloids by liquid-liquid extraction, i.e., lipo-alkaloids and monoester-diterpenoid alkaloids. The pH-zone-refining counter-current chromatography was performed with an optimized two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3545, v/v), where upper organic phase was added to 3 mmol/L triethylamine as a retainer and lower aqueous mobile phase was added to 3 mmol/L hydrochloric acid as an eluter. As a result, six aconitum alkaloids, including two lipo-alkaloids (8-lino-14-benzoylaconine, 8-pal-14-benzoylaconine), three monoester-diterpenoid alkaloids (14-benzoylmesaconine, 14-benzoylaconine, beyzoyldeoxyaconine) and one aconine alkaloid (neoline) were acquired from the plant at the same time. The anti-inflammatory activities of the two new lipo-alkaloids were compared to the six alkaloids in vitro, in cyclo-oxygen-ase-2 inhibition assays. The separation mechanism of six alkaloids by pH-zone-refining counter-current chromatography was illustrated. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVE Autoimmune responses to DNA topoisomerase-I (TOP1) are found in a subset of patients with scleroderma at high risk for interstitial lung disease (ILD) and mortality. https://www.selleckchem.com/products/crcd2.html Anti-TOP1 antibodies (ATA) are associated with specific HLA-DRB1 alleles, and the frequency of HLA-DR-restricted TOP1-specific CD4+ T cells is associated with the presence, severity, and progression of ILD. Although this strongly implicates the presentation of TOP1 peptides by HLA-DR in scleroderma pathogenesis, the processing and presentation of TOP1 has not been studied. METHODS We developed a natural antigen processing assay (NAPA) to identify putative CD4+ T cell epitopes of TOP1 presented by monocyte-derived dendritic cells (mo-DCs) from six ATA-positive patients with scleroderma. Mo-DCs were pulsed with TOP1 protein, HLA-DRpeptide complexes were isolated, and eluted peptides were analyzed by mass spectrometry. We then examined the ability of these naturally presented peptides to induce CD4+ T cell activation in 11 ATA-positive and 11 ATA-negative scleroderma patients. RESULTS We found that a common set of 10 TOP1 epitopes was presented by mo-DCs from scleroderma patients with diverse HLA-DR variants. Sequence analysis revealed shared peptide-binding motifs within the HLA-DRβ chains of ATA-positive patients and a subset of TOP1 epitopes with distinct sets of anchor residues capable of binding to multiple different HLA-DR variants. The NAPA-derived epitopes elicited robust CD4+ T cell responses in 73% (8/11) ATA-positive patients, and the number of epitopes recognized correlated with ILD severity (p=0.025). CONCLUSION These findings mechanistically implicate presentation of a convergent set of TOP1 epitopes in the development of scleroderma. This article is protected by copyright. All rights reserved.Metamaterial (MM) sensors and devices, usually consisting of artificially structured composite materials with engineered responses that are mainly determined by the unit structure rather than the bulk properties or composition, offer new functionalities not readily available in nature. A set of implantable and resorbable therapeutic MM devices at terahertz (THz) frequencies are designed and fabricated by patterning magnesium split ring resonators on drug-loaded silk protein substrates with controllable device degradation and drug release rates. To demonstrate proof-of-concept, a set of silk-based, antibiotics-loaded MM devices, which can serve as degradable antibacterial skin patches with capabilities to monitor drug-release in real time are fabricated. link2 The extent of drug release, which correlates with the degradation of the MM skin patch, can be monitored by analyzing the resonant responses in reflection during degradation using a portable THz camera. Animal experiments are performed to demonstrate the in vivo degradation process and the efficacy of the devices for antibacterial treatment. Thus, the implantable and resorbable therapeutic MM devices do not need to be retrieved once implanted, providing an appealing alternative for in-vivo sensing and in situ treatment applications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Physical examinations are recommended as part of a comprehensive evaluation for individuals with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder. These examinations should include assessment for morphological variants. Previous studies have shown an increase in morphological variants in individuals with NDDs, particularly ASD, and that these variants may be present in greater amounts in individuals with genetic alterations. https://www.selleckchem.com/products/crcd2.html Unfortunately, assessment for morphological variants can be subjective and time-consuming, and require a high degree of clinical expertise. Therefore, objective, automated methods of morphological assessment are desirable. This study compared the use of Face2Gene, an automated tool to explore facial morphological variants, to clinical consensus assessment, using a cohort of N = 290 twins enriched for NDDs (n = 135 with NDD diagnoses). Agreement between automated and clinical assessments were satisfactory to complete (78.3-100%). In our twin sample, individuals with NDDs did not have greater numbers of facial morphological variants when compared to those with typical development, nor when controlling for shared genetic and environmental factors within twin pairs. Common facial morphological variants in those with and without NDDs were similar and included thick upper lip vermilion, abnormality of the nasal tip, long face, and upslanted palpebral fissure. We conclude that although facial morphological variants can be assessed reliably in NDDs with automated tools like Face2Gene, clinical utility is limited when just exploring the facial region. Therefore, currently, automated assessments may best complement, rather than replace, in-person clinical assessments. link2 © 2020 The Authors. link3 American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.OBJECTIVE To provide reference data regarding frequency and safety of elective termination of pregnancy (ETOP) in women with autoimmune rheumatic diseases (ARD) followed in two referral databases. METHODS Two large databases, a referral ARD clinical practice (BVC) with a known interest in pregnancy and an observational study of SLE and antiphospholipid antibody-associated pregnancies (PROMISSE), were interrogated for histories of prior ETOP and complications related to incident ETOP. RESULTS Of women who had had prior pregnancies, 21.7% of 1,307 women in the BVC database and 25.3% of 297 patients in the PROMISSE database gave histories of 1 to 5 prior ETOPs; BVC patients reported no flare-up or hospitalizable complication due to ETOP. Of 674 incident pregnancies, termination for fetal or maternal reasons was recommended for 15 (2%); of these, 2 fetuses died before the procedure was carried out and one woman declined termination and though gravely ill successfully delivered. She died of cardiomyopathy three years later. CONCLUSION Many ARD patients undergo ETOP; few report complications. link2 In medically indicated ETOP there are no adverse signals of unusual complications or disease flare. This article is protected by copyright. All rights reserved.Molecular shape and pharmacological function are interconnected. link3 To capture shape, the fractal dimensionality concept was employed, providing a natural similarity measure for the virtual screening of de novo generated small molecules mimicking the structurally complex natural product (-)-englerin A. Two of the top-ranking designs were synthesized and tested for their ability to modulate transient receptor potential (TRP) cation channels which are cellular targets of (-)-englerin A. Intracellular calcium assays and electrophysiological whole-cell measurements of TRPC4 and TRPM8 channels revealed potent inhibitory effects of one of the computer-generated compounds. Four derivatives of this identified hit compound had comparable effects on TRPC4 and TRPM8. The results of this study corroborate the use of fractal dimensionality as an innovative shape-based molecular representation for molecular scaffold-hopping. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Extensive vaccination against Newcastle disease virus (NDV) induced more selective immune pressure from hosts that enhanced the evolutionary process of NDV. link3 Herein, we characterized 13 recently isolated NDV isolates from vaccinated chicken flocks during 2014-2017. Sequence analysis of F gene showed the presence of 112 RRQKRF117 velogenic cleavage motif in 11 isolates, whereas the other two isolates (Ck/ME3/Eg/16 and Ck/ME5/Eg/16) showed the monobasic motif 112 GGRQGRL117 . Interestingly, isolate Ck/ME5/Eg/16 showed 100% and 99.82% nucleotide identity with the LaSota F gene hypervariable region and full-length gene, respectively. On the other hand, isolate Ck/ME3/Eg/16 revealed natural recombination with strains NDV/Ck/Egypt/3/2006 and NDV/Teal/VRLCU/Egypt/2015 that indicates re-emergence of that old strain. Interestingly, all 13 isolates showed high intracerebral pathogenicity (ICPI) and mean death time (MDT) despite the presence of lentogenic motif in both Ck/ME5/Eg/16 and Ck/ME3/Eg/16 isolates. Comparative ights reserved.This review was conducted to synthesize and critically appraise the literature on knowledge, attitudes, understanding, perceptions, and expectations of mental health professionals (MHPs) and mental health professional (MHP) students' regarding recovery. A systematic search in Scopus, CINAHL, PsycINFO, Web of Science, Medline, and Embase as well as Google scholar and web-based repositories was conducted. The searches were conducted using a combination of key terms "mental health professionals", "students", 'knowledge', "understanding", "perception" "attitude", "expectation", "recovery". After screening and quality assessment, the review included 29 studies (18 quantitative, 8 qualitative, and 3 mixed-method studies) published in English, from January 2006 to June 2019, and was analysed systematically using a mixed-method synthesis. The findings revealed that there is increasing evidence (especially among MHPs) of knowledge, attitudes, understanding, perceptions, and expectations regarding recovery. However, there are disparities in how MHPs perceive and understand recovery.

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