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In this study, we reported a patient who presents with multicentric reticulohistiocytosis (MRH)-like clinical feature, but the histology is not compatible with it. Like our patient, a couple of patients described previously also had the dilemma that they could not be classified appropriately into any current histiocytosis entity. Considering the clinical and pathological features together, all these patients had a similar clinical profile: xanthomatous rash, erosive arthritis and histopathological findings showing xanthomized histiocytes. Therefore, we propose a new disease entity - xanthomatous erosive arthritis (XEA), to accommodate these patients that cannot be classified appropriately into the current system.

Do ethnic enclaves assist or hinder immigrants’ economic performance? The empirical literature on this question is inconclusive. In this paper we extend the literature by constructing a dynamic variable from micro‐panel data to capture the effects of spatial networks of immigrants’ ethnic‐specific resources. We account for endogeneity of the network and other variables. Using the HILDA data set, and a suite of robustness checks, results show that immigrants’ earnings are positively associated with the concentration and resources of their country‐of‐birth group. The effect is prominent for immigrants born in non‐English‐speaking countries and for high‐skilled immigrants, highlighting positive ethnic network spill‐over effects for these groups. Moreover, accounting for the network variable provides a viable explanation for the divisions in previous international results on ethnic concentration.

The extensive phenotypic diversity within natural populations of Arabidopsis is associated with differences in gene expression. Transcript levels can be considered as inheritable quantitative traits, and used to map expression quantitative trait loci (eQTL) in genome-wide association studies (GWASs). In order to identify putative genetic determinants for variations in gene expression, we used publicly available genomic and transcript variation data from 665 Arabidopsis accessions and applied the single nucleotide polymorphism-set (Sequence) Kernel Association Test (SKAT) method for the identification of eQTL. Moreover, we used the penalized orthogonal-components regression (POCRE) method to increase the power of statistical tests. Then, gene annotations were used as test units to identify genes that are associated with natural variations in transcript accumulation, which correspond to candidate regulators, some of which may have a broad impact on gene expression. Besides increasing the chances to identify real associations, the analysis using POCRE and SKAT significantly reduced the computational cost required to analyze large datasets. As a proof of concept, we used this approach to identify eQTL that represent novel candidate regulators of immune responses. The versatility of this approach allows its application to any process that is subjected to natural variation among Arabidopsis accessions.

Single-nucleotide polymorphisms (SNPs) in protein-coding regions of genes which were previously reported to be associated with nonsyndromic cleft lip, with or without palate involvement (NSCL/P), were investigated. Twelve candidate loci [platelet-derived growth factor C (PDGFC), platelet-derived growth factor subunit A (PDGFA), platelet-derived growth factor receptor alpha (PDGFRA), glycine receptor alpha 2 (GLRA2), glycine receptor beta (GLRB), ATP binding cassette subfamily A member 4 (ABCA4), MAF bZIP transcription factor B (MAFB), interferon regulatory factor 6 (IRF6), CCDC26 long non-coding RNA (CCDC26), paired box 7 (PAX7), ventral anterior homeobox 1 (VAX1), and netrin 1 (NTN1)] covering 1.5 Mbp were sequenced in 136 NSCL/P patients and 54 healthy controls. Twenty-five genomic variants identified were further validated in another 400 NSCL/P and 200 controls. Two SNPs in IRF6 showed a protective effect against the development of NSCL/P (rs12405750, OR = 0.54, 95% CI: 0.41-0.69; and rs2235371, OR = 0.55, 95% CI: 0.43-0.71). The missense variant, rs2235371, alters the conserved amino acid valine to isoleucine at codon 274 (V274I). We observed that SNPs at IRF6 (rs2235371 and rs12405750) and GLRB (rs73856838 and rs72685584) show consistent interaction effects. The association between the missense SNP rs2235371 in gene IRF6 and NSCL/P suggests that this SNP may play an important role as a risk factor for NSCL/P in the Han Chinese populations. The marginal signal near 4q31 detected in previous genome-wide association studies might be caused by an interaction between the IRF6 and GLRB genes. This interaction needs to be further validated by experimentation in follow-up studies.

Wound healing is an inherent response resulting in the restoration of tissue integrity. It is a complex process involving cell migration, proliferation, differentiation, apoptosis, and the synthesis and remodeling of the extracellular matrix (ECM). The dermal tissue is an important component of skin that acts as a connecting link between the epidermis and hypodermis. The appearance of scars and contractures after autologous split-thickness skin transplantation or single epidermis diaphragm transplantation for full skin defects indicates that the dermal tissue plays an important role in skin regeneration. Theoretically, dermis cannot regenerate like the liver, bone and epidermis after being destroyed by burns or avulsion. Scarring is hard to avoid during the process of natural healing. However, if the dermis could be reconstructed perfectly, this would be a breakthrough in the methods used for wound healing. In this review, we summarize recent research about dermal regeneration and discuss the probability of advances in the field. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1208-1218, 2017.

The use of peripherally inserted central catheters (PICCs) provides important central venous accesses for clinical treatments, tests and monitoring. Compared with the traditional methods, intracardiac electrocardiogram (ECG)-guided method has the potential to guide more accurate tip positioning of PICCs. This study aimed to clinically evaluate the effectiveness of an intracardiac ECG to guide the tip positioning by monitoring characteristic P-wave changes. In this study, eligible patients enrolled September 2011 to May 2012 according to the inclusion and exclusion criteria received the catheterization monitored by intracardiac ECG. Then chest radiography was performed to check the catheter position. The results revealed that, with 117 eligible patients, all bar one patient who died (n = 116) completed the study, including 60 males and 56 females aged 51.2 ± 15.1 years. Most (n = 113, > 97%) had characteristic P-wave changes. The intracardiac ECG-guided positioning procedure achieved correct placement for 112 patients (96.56%), demonstrating 99.12% sensitivity and 100% specificity. In conclusion, the intracardiac ECG can be a promising technique to guide tip positioning of PICCs. However, since the sample size in this study is limited, more experience and further study during clinical practice are needed to demonstrate achievement of optimal catheterization outcomes.

Proper accumulation and function of miRNAs is essential for plant growth and development. While core components of the miRNA biogenesis pathway and miRNA-induced silencing complex have been well characterized, cellular regulators of miRNAs remain to be fully explored. Here we report that High Expression Of Osmotically Responsive Genes1 (HOS1) is a regulator of an important miRNA, mi168a/b, that targets the Argonaute1 (AGO1) gene in Arabidopsis. HOS1 functions as an ubiquitin E3 ligase to regulate plant cold-stress responses, associates with the nuclear pores to regulate mRNA export, and regulates the circadian clock and flowering time by binding to chromatin of the flowering regulator gene Flowering Locus C (FLC). In a genetic screen for enhancers of sic-1, we isolated a loss-of-function Arabidopsis mutant of HOS1 that is defective in miRNA biogenesis. Like other hos1 mutant alleles, the hos1-7 mutant flowered early and was smaller in stature than the wild-type. Dysfunction in HOS1 reduced the abundance of miR168a/b but not of other miRNAs. In hos1 mutants, pri-MIR168b and pre-MIR168b levels were decreased, and RNA polymerase II occupancy was reduced at the promoter of MIR168b but not that of MIR168a. Chromatin immunoprecipitation assays revealed that HOS1 protein is enriched at the chromatin of the MIR168b promoter. The reduced miR168a/b level in hos1 mutants results in an increase in the mRNA and protein levels of its target gene, AGO1. Our results reveal that HOS1 regulates miR168a/b and AGO1 levels in Arabidopsis by maintaining proper transcription of MIR168b.

Chronic subclinical inflammation represents a risk factor of type 2 diabetes and several diabetes complications, including neuropathy and atherosclerosis including macro-vasculopathy and micro-vasculopathy. However, the inflammatory response in the diabetic wound was shown to be remarkably hypocellular, unregulated and ineffective. Advanced glycation end products (AGEs) and one of its receptors, RAGE, were involved in inducing chronic immune imbalance in diabetic patients. Such interactions attracts immune cell into diffused glycated tissue and activates these cells to induce inflammatory damage, but disturbs the normal immune rhythm in diabetic wound. Traditional measurements of AGEs are high-performance liquid chromatography and immunohistochemistry staining, but their application faces the limitations including complexity, cost and lack of reproducibility. A new noninvasive method emerged in 2004, using skin autofluorescence as indicator for AGEs accumulation. It had been reported to be informative in evaluating the chronic risk of diabetic patients. Studies have indicated therapeutic potentials of anti-AGE recipes. These recipes can reduce AGE absorption/de novo formation, block AGE-RAGE interaction and arrest downstream signaling after RAGE activation.

MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells. In the present study, we investigated the roles and mechanisms of miR-200b in human breast cancer (BC). MiR-200b expression was carried out by qRT-PCR in human BC cell lines and clinical samples and the prognostic potential of miR-200b expression was further evaluated. In vitro, effects of miR-200b on BC cell proliferation, apoptosis and cell cycle distribution were tested by CCK-8 kit, flow cytometric analysis respectively. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-200b after the preliminary screening by employing open access software. We found that miR-200b was significantly down-regulated in both BC tissues and cell lines. The low expression of miR-200b was correlated with late TNM stage, negative oestrogen receptor and positive HER-2 status. Multivariate analysis showed that miR-200b expression was an independent prognostic predictor for BC patients. Integrated analysis identified Sp1 as a direct and functional target of miR-200b. Knockdown of Sp1 inhibited cell proliferation, induce apoptosis and act on cell cycle resembling that of miR-200b high expression. Our data demonstrates that miR-200b has potential to serve as prognostic biomarker and tumour suppressor for BC patients. As a direct and functional target of miR-200b, Sp1 and miR-200b both could be an exciting target for BC treatment strategy.

A novel dermal substitute of combining recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) with a porous heparinized collagen/chitosan scaffolds was developed, considering the inadequate angiogenesis during repair of full-thickness skin defects. The physicochemical properties of heparinized collagen/chitosan scaffolds were examined and in vitro release pattern of rhGM-CSF from scaffolds was measured by ELISA. Four groups of composite scaffolds (heparinized or unheparinized scaffolds loaded with or without rhGM-CSF) were fabricated for subcutaneous implantation in young adult male Sprague-Dawley (SD) rats. Tissue specimens were harvested at different time points after implantation for histopathological, immunohistochemical observation, and Western blotting analysis. The heparinized scaffolds (H1E) showed slower biodegradation and sustained release of rhGM-CSF in vitro, although no significantly different release pattern was observed between the H1E and unheparinized scaffolds (H0E). In vivo investigation revealed that the heparinized scaffolds loaded with rhGM-CSF (H1E/rhGM-CSF) had the best cellular adhesion and migration, new vessel formation, and highest expression of VEGF and TGF-β1, indicating promoted angiogenesis. This study demonstrated that composite dermal substitute of combining rhGM-CSF with a porous heparinized collagen/chitosan scaffolds could be a potential therapeutic agent for full-thickness skin defects because of its sustained delivery of rhGM-CSF. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.

During development all zebrafish males first develop a "juvenile ovary" that later degenerates and transforms into a testis. In this study, individuals undergoing gonadal transformation were identified from a vas::egfp transgenic line and used for gene expression analysis of anti-Müllerian hormone (amh), ovarian aromatase (cyp19a1a) and 11 beta-hydroxylase (cyp11b, also known as P450(11 beta)) by real-time polymerase chain reaction and in situ hybridization. In the "normal (i.e., nontransforming) juvenile ovary" cyp19a1a was expressed around the oocytes, but cyp11b and amh could not be detected. During gonadal transformation cyp19a1a was down-regulated and could not be detected anymore; in contrast amh was up-regulated and highly expressed at similar regions where cyp19a1a had been expressed earlier. Furthermore, the normalized transcript levels of cyp19a1a and amh showed a reciprocal picture, i.e., the higher was the level of amh, the lower was that of cyp19a1a. Expression of cyp11b was also up-regulated but later than amh, and its localization was not related to the position of degenerating oocytes. These data indicate that amh is a candidate gene down-regulating cyp19a1a, leading to "juvenile ovary-to-testis" transformation. Whereas, cyp11b or its product, 11-ketotestosterone, is unlikely to be the inducer of zebrafish gonad transformation, as proposed earlier for some protogynous hermaphroditic fish species.

Gonad differentiation in male zebrafish involves a transformation from a ‘juvenile ovary’ to testis. In our study, this phenomenon was analysed using a stable transgenic line (vas::egfp) created by Krovel & Olsen (Mechanisms of Development, 116: 141–150, 2002). Our data obtained by histological and immunohistochemical methods show that the onset of enhanced green fluorescent protein (EGFP) expression marks the conversion of the bipotential gonad into a ‘juvenile ovary’, and its subsequent decrease in the males indicates transformation into a testis. Furthermore, during the ‘juvenile ovary’ stage, a high level of variation was observed among individuals not only in the starting point and duration of EGFP expression but also in its intensity. The intensity of reporter expression in the males ranged from a high level of expression – similar to that observed in females – to invisible expression and correlated with the number of oocytes, the shape of ‘juvenile ovary’ and its lumen. Therefore, the authors conclude that although all males develop ‘juvenile ovaries’, they differ vastly in the extent of their commitment toward femaleness during this stage before testis differentiation. The differentiating zebrafish testis shows morphological features similar to those of the transforming gonad of protogynous hermaphrodites, and therefore, it could be a good model for the study of the process of female-to-male sex change in adult teleosts.