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Plants belonging to family Paeoniaceae are not only economically important ornamental plants but also medicinal plants used as an important source of traditional Chinese medicine. Owing to the complex network evolution and polyploidy evolution of this family, its systematics and taxonomy are controversial and require a detailed investigation. In this study, three complete chloroplast genomes of sect. Paeonia, one of the sections of Paeonia, were sequenced and then analysed together with 16 other published chloroplast genomes of Paeoniaceae species. The total lengths of the chloroplast genomes of these species were 152,153–154,405 bp. A total of 82–87 protein-coding genes, 31–40 tRNA genes and 8 rRNA genes were annotated. Bioinformatics analysis revealed 61–74 simple sequence repeats (SSRs) in the chloroplast genomes, most of which have A/T base preference. Codon usage analysis showed that A/U-ending codons were more positive than C/G-ending codons, and a slight bias in codon usage was observed in these species. A comparative analysis of these 19 species of Paeoniaceae was then conducted. Fourteen highly variable regions were selected for species relationship study. Phylogenetic analysis revealed that the species of sect. Paeonia gathered in one branch and then divided into different small branches. P. lactiflora, P. anomala, P. anomala subsp. veitchii and P. mairei clustered together. P. intermedia was related to P. obovata and P. obovata subsp. willmottiae. P. emodi was the sister to all other species in the sect. Paeonia. [ABSTRACT FROM AUTHOR]

The protein phosphatase 2C (PP2C) gene family, which is known to participate in cellular processes, is one of the most conserved plant-specific gene families that regulate signal transduction in eukaryotic organisms. However, the PP2C gene family of Glycyrrhiza uralensis Fisch. has not yet been systematically characterized. In this study, 76 PP2C genes of G. uralensis (GuPP2Cs) were identified. Phylogenetic analysis divided these GuPP2Cs into 12 subfamilies. The gene structure and protein motifs of the GuPP2Cs were then analysed. The analysis of the transcriptomic data of the GuPP2Cs revealed that nine genes were highly sensitive to abscisic acid (ABA) stress and might respond to ABA treatment. These nine genes were validated via quantitative real-time polymerase chain reaction. This study provides a foundation for future studies on the functional PP2C genes of G. uralensis and the improvement of the cultivation and quality of G. uralensis. [ABSTRACT FROM AUTHOR]

In this paper, the authors introduce a definition of the Schwarzian derivative of any locally univalent harmonic mapping defined on a simply connected domain in the complex plane. Using the new definition, the authors prove that any harmonic mapping f which maps the unit disk onto a convex domain has Schwarzian norm ∥Sf∥ ≤ 6. Furthermore, any locally univalent harmonic mapping f which maps the unit disk onto an arbitrary regular n-gon has Schwarzian norm ‖ S f ‖ < 8 3 . [ABSTRACT FROM AUTHOR]

Arctium lappa, commonly called burdock, has a long medicinal and edible history. It has recently gained increasing attention because of its economic value. In this study, we obtained the complete chloroplast genome of A. lappa by Illumina Hiseq. The complete chloroplast genome of A. lappa is a typical circular structure with 152 708 bp in length. The GC content in the whole chloroplast genome of A. lappa is 37.7%. A total of 37 tRNA genes, 8 rRNA genes, and 87 protein-coding genes were successfully annotated. And the chloroplast genome contains 113 unique genes, 19 of which are duplicated in the inverted repeat. The distribution of 39 simple sequence repeats was analysed, and most of them are in the large single-copy (LSC) sequence. An inversion comprising 16 genes was found in the LSC region, which is 26 283 bp long. We performed multiple sequence alignments using 72 common protein-coding genes of 29 species and constructed a Maximum Parsimony (MP) tree. The MP phylogenetic result shows that A. lappa grouped together with Carthamus tinctorius, Centaurea diffusa, and Saussurea involucrata. The chloroplast genome of A. lappa is a valuable resource for further studies in Asteraceae. [ABSTRACT FROM AUTHOR]

An outcome of the intricate K+ regulation in the cochlear duct is the endocochlear potential (EP), ∼80 mV, the "battery" that runs hair-cell transduction; however, the detailed molecular mechanisms for the generation of the EP remain unclear. We provide strong evidence indicating that the intermediate cells (ICs) of the stria vascularis (StV) express outward K+ current that rectifies inwardly at positive potentials. The channel belongs to the ether-a-go-go-related gene (erg) family of K+ channels. We cloned an ERG1a channel in the mouse inner ear (MERG1a). The cellular distribution of MERG1a in the cochlea displayed the highest levels of immunoreactivity in the ICs and modest reactivity in the marginal cells as well as in several extrastrial cells (e.g., hair cells). Functional expression of the StV-specific MERG1a channel reveals a current that activates at relatively negative potentials (approximately -50 mV) and shows rapid inactivation reflected as inward rectification at depolarized potentials. The current was sensitive to the methanesulfonanilide drug E-4031 (IC50, ∼165 nM) and the recombinant peptide rBeKm-1 (IC50, ∼16 nM), and the single-channel conductance in symmetrical K+ was ∼14 pS. The site of expression of MERG1a and its functional phenotype (e.g., modulation of the current by external K+) make it one of the most likely candidates for establishing the high throughput of K+ ions across ICs to generate EP. In addition, the property of the channel that produces marked K+ extrusion in increased external K+ may be important in shaping the dynamics of K+ cycling in the inner ear. [ABSTRACT FROM AUTHOR]

Functional interactions between ligand-gated, voltage-, and Ca(2+)-activated ion channels are essential to the properties of excitable cells and thus to the working of the nervous system. The outer hair cells in the mammalian cochlea receive efferent inputs from the brain stem through cholinergic nerve fibers that form synapses at their base. The acetylcholine released from these efferent fibers activates fast inhibitory postsynaptic currents mediated, to some extent, by small-conductance Ca(2+)-activated K+ channels (SK) that had not been cloned. Here we report the cloning, characterization, and expression of a complete SK2 cDNA from the mouse cochlea. The cDNAs of the mouse cochlea alpha9 and alpha10 acetylcholine receptors were also obtained, sequenced, and coexpressed with the SK2 channels. Human cultured cell lines transfected with SK2 yielded Ca(2+)-sensitive K+ current that was blocked by dequalinium chloride and apamin, known blockers of SK channels. Xenopus oocytes injected with SK2 in vitro transcribed RNA, under conditions where only outward K+ currents could be recorded, expressed an outward current that was sensitive to EGTA, dequalinium chloride, and apamin. In HEK-293 cells cotransfected with cochlear SK2 plus alpha9/alpha10 receptors, acetylcholine induced an inward current followed by a robust outward current. The results indicate that SK2 and the alpha9/alpha10 acetylcholine receptors are sufficient to partly recapitulate the native hair cell efferent synaptic response. [ABSTRACT FROM AUTHOR]

Macrosolen plants are parasitic shrubs, several of which are important medicinal plants, that are used as folk medicine in some provinces of China. However, reports on Macrosolen are limited. In this study, the complete chloroplast genome sequences of Macrosolen cochinchinensis, Macrosolen tricolor and Macrosolen bibracteolatus are reported. The chloroplast genomes were sequenced by Illumina HiSeq X. The length of the chloroplast genomes ranged from 129,570 bp (M. cochinchinensis) to 126,621 bp (M. tricolor), with a total of 113 genes, including 35 tRNA, eight rRNA, 68 protein-coding genes, and two pseudogenes (ycf1 and rpl2). The simple sequence repeats are mainly comprised of A/T mononucleotide repeats. Comparative genome analyses of the three species detected the most divergent regions in the non-coding spacers. Phylogenetic analyses using maximum parsimony and maximum likelihood strongly supported the idea that Loranthaceae and Viscaceae are monophyletic clades. The data obtained in this study are beneficial for further investigations of Macrosolen in respect to evolution and molecular identification. [ABSTRACT FROM AUTHOR]

Ephedrae Herba and Ephedrae Radix et Rhizoma (Mahuang) have been used as Chinese herbal medicines. Ephedra plants mainly live in deserts and have good governance of desertification. Despite their important medicinal and environmental protection value, dietary supplements containing ephedrine from Ephedra species may threaten the health of people. Morphological resemblance amongst species causes difficulty in identifying the original species of Ephedra herbs. Chloroplast (CP) genome shows good prospects in identification and phylogenetic analysis. This study introduced the structures of the CP genomes of three Ephedra species and analysed their phylogenetic relationships. Three complete CP genomes of Ephedra showed four-part annular structures, namely, two single-copy regions and two inverted repeat regions. The entire CP genomes of three Ephedra species in terms of size were 109,550 bp (E. sinica), 109,667 bp (E. intermedia), and 109,558 bp (E. equisetina). Each CP genome of the three Ephedra species encoded 118 genes, including 73 protein-coding genes, 37 tRNA genes and 8 ribosomal RNA genes. Eleven high-variation regions were screened through mVISTA to be potential specific DNA barcodes for identifying Ephedra species. Maximum likelihood and maximum parsimony trees showed that CP genomes could be used to identify Ephedra species. The Ephedra species had a close phylogenetic relationship with Gnetum species and Welwitschia mirabilis. This research provided valuable information for the identification and phylogenetic analysis of gymnosperms and drug safety of Ephedra. [ABSTRACT FROM AUTHOR]

After solutionizing and aging at 980°C for various durations, the compressive deformation behaviour and mechanisms of the directionally solidified nickel-based superalloy CM247LC are investigated at room temperature. Experimental results show that the yield strength decreases gradually from 991 ± 1.2–672 ± 7.5 MPa with increasing the γ′ precipitate size from 145 ± 2–604 ± 19 nm. Transmission electron microscope observations on the slightly deformed specimens reveal that, in contrast to previous researches, plastic deformation of all the specimens is controlled by strongly coupled dislocations cutting through γ′ precipitates. Based on these experimental results, the relationship between the yield strength and precipitate size is discussed. [ABSTRACT FROM AUTHOR]

Summary: The biosynthetic gene cluster for the enediyne antitumor antibiotic neocarzinostatin (NCS) was localized to 130 kb continuous DNA from Streptomyces carzinostaticus ATCC15944 and confirmed by gene inactivation. DNA sequence analysis of 92 kb of the cloned region revealed 68 open reading frames (ORFs), 47 of which were determined to constitute the NCS cluster. Sequence analysis of the genes within the NCS cluster suggested dNDP-D-mannose as a precursor for the deoxy aminosugar, revealed two distinct type I polyketide synthases (PKSs), and supported a convergent model for NCS chromophore biosynthesis from the deoxy aminosugar, naphthoic acid, and enediyne core building blocks. These findings shed light into deoxysugar biosynthesis, further support the iterative type I PKS paradigm for enediyne core biosynthesis, and unveil a mechanism for microbial polycyclic aromatic polyketide biosynthesis by an iterative type I PKS. [Copyright &y& Elsevier]

Amomum villosum is an important medicinal and edible plant with several pharmacologically active volatile oils. However, identifying A. villosum from A. villosum var. xanthioides and A. longiligulare which exhibit similar morphological characteristics to A. villosum, is difficult. The main goal of this study, therefore, is to mine genetic resources and improve molecular methods that could be used to distinguish these species. A total of eight complete chloroplasts (cp) genomes of these Amomum species which were collected from the main producing areas in China were determined to be 163,608–164,069 bp in size. All genomes displayed a typical quadripartite structure with a pair of inverted repeat (IR) regions (29,820–29,959 bp) that separated a large single copy (LSC) region (88,680–88,857 bp) from a small single copy (SSC) region (15,288–15,369 bp). Each genome encodes 113 different genes with 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. More than 150 SSRs were identified in the entire cp genomes of these three species. The Sanger sequencing results based on 32 Amomum samples indicated that five highly divergent regions screened from cp genomes could not be used to distinguish Amomum species. Phylogenetic analysis showed that the cp genomes could not only accurately identify Amomum species, but also provide a solid foundation for the establishment of phylogenetic relationships of Amomum species. The availability of cp genome resources and the comparative analysis is beneficial for species authentication and phylogenetic analysis in Amomum. [ABSTRACT FROM AUTHOR]

WC-Co hardmetals are widely used in wear-resistant parts, cutting tools, molds, and mining parts, owing to the combination of high hardness and high toughness. WC-Co hardmetal parts are usually produced by casting and powder metallurgy, which cannot manufacture parts with complex geometries and often require post-processing such as machining. Additive manufacturing (AM) technologies are able to fabricate parts with high geometric complexity and reduce post-processing. Therefore, additive manufacturing of WC-Co hardmetals has been widely studied in recent years. In this article, the current status of additive manufacturing of WC-Co hardmetals is reviewed. The advantages and disadvantages of different AM processes used for producing WC-Co parts, including selective laser melting (SLM), selective electron beam melting (SEBM), binder jet additive manufacturing (BJAM), 3D gel-printing (3DGP), and fused filament fabrication (FFF) are discussed. The studies on microstructures, defects, and mechanical properties of WC-Co parts manufactured by different AM processes are reviewed. Finally, the remaining challenges in additive manufacturing of WC-Co hardmetals are pointed out and suggestions on future research are discussed. [ABSTRACT FROM AUTHOR]

The present study aimed to observe the identification of biomarkers of silicosis based on the differentially expressed serum proteins between normal healthy individuals and patients with silicosis fibrosis. A total number of 20 patients with clinically diagnosed silicosis were screened, which were designated as the foundation treatment group. In addition, 20 age-matched healthy patients attending a check-up at the physical examination department were selected. Serum samples were obtained and a combined protein chip with surface-enhanced laser desorption ionization flight mass spectrometry was applied to perform serum analysis. Data preprocessing, screening differences in peak, hierarchical cluster analysis, Principal Component Analysis, construction of a decision tree model, and prediction based on the differences between peaks corresponding to proteins were performed to analyze the data. The results revealed differences in the proteins in serum between the normal group and the group prior to foundation treatment prediction. The corresponding names of the protein peak, predicted protein, and gene name were as follows: M1948_00, complement c3 frag, C3; M2017_02, amyloid-βa4 protein, APP; and M2879_56, hepcidin, HAMP. Differentially expressed serum proteins in the normal group and the basis treatment group were predicted, including M2017_02, amyloid-βa4 protein, APP; M2879_56, hepcidin, HAMP; and M3224_97, fibrinogen-α chain frags, FGA. The differentially expressed serum proteins in the group prior to basis treatment and the group following basis treatment were predicted, including M2001_69, amyloid-βa4 protein, APP; M2017_02, amyloid-βa4 protein, APP, M4144_81, plasma protease c1 inhibitor frag, and SERPING1. In conclusion, there were differences in the proteins in serum between the patients with silicosis fibrosis and healthy individuals. [ABSTRACT FROM AUTHOR]

• (1)Naive CD8+ T cells were negatively correlated with clinical and pathological parameters of RA. • (2)CD8+ CD28- T cells and CD8+ CD27- T cells were both positively correlated with clinical inflammatory parameters of RA. • (3)TCRγδ + CD8+ T cells and Activated CD8+ T cells may involve in lipid metabolism and lung fibrosis of RA. • (4)These CD8+ T cell subsets may be new biomakers and targets for RA disease evaluation, therapeutic target-selecting, curative effects and prognoses assessment. CD8+ T cells are plentiful in rheumatoid arthritis (RA) and have a important role in it's pathogenesis. Many subsets have been identified in CD8+ T cells, however, the relationship between CD8+ T subpopulations and disease activity of RA is poorly defined. Here we detected different CD8+ T cell subsets in peripheral blood and examined their relationships with clinical features and serological parameters in RA. CD8+ T cell phenotypes and percentages in peripheral blood were determined by flow cytometry in 39 patients with RA. The clinical characteristics and serological parameters of RA patients were collected and DAS28-ESR was measured as indicator of disease activity. Linear regression was performed to assess the correlation of CD8+ T cell subsets with RA clinical variables. Naive CD8+ T cells were significantly and negatively correlated with RA disease activity indicator DAS28-ESR(r2 = 0.1027, p = 0.0468), erythrocyte sedimentation rate (ESR)(r2 = 0.1891, p = 0.0057), clinical disease activity index(CDAI)(r2 = 0.1474, p = 0.0158), simplified disease activity index(SDAI)(r2 = 0.1465, p = 0.0255), and duration(r2 = 0.1247, p = 0.0274). And the percent of naive CD8+ T cells were obviously decreased in RA with high disease activity when compared with RA in low disease activity(p < 0.01). In addition, Our results indicated significant positive correlations between CD8+ CD28- T cells and DAS28-ESR(r2 = 0.1881, p = 0.0058), ESR(r2 = 0.2279, p = 0.0021), c reaction protein (CRP)(r2 = 0.2203, p = 0.0051), CDAI (r2 = 0.1778, p = 0.0075), SDAI (r2 = 0.2618, p = 0.0020), rheumatoid factor(RF)(r2 = 0.1823, p = 0.0067), age(r2 = 0.1968, p = 0.0047), as well as similar positive correlations between CD8+ CD27- T cells and DAS28-ESR(r2 = 0.1661, p = 0.01), ESR(r2 = 0.1586, p = 0.012), CRP(r2 = 0.1778, p = 0.013), CDAI (r2 = 0.1622, p = 0.0110), SDAI(r2 = 0.2316, p = 0.0040), RF(r2 = 0.2097, p = 0.0034), age(r2 = 0.1932, p = 0.0051). Furthermore, interesting results showed observable positive correlations between activated CD8+ T cells and total cholesterol(TC)(r2 = 0.2757, p = 0.0007), triglyceride(TG)(r2 = 0.2886, p = 0.0005), low density lipoprotein(LDL-C)(r2 = 0.09643, p = 0.0264) and Krebs yon denlungen-6(KL-6)(r2 = 0.4171, p = 0.0002). And TCRγδ + CD8+ T cells were also found positively related with total cholesterol(TC)(r2 = 0.5015, p < 0.0001), triglyceride(TG)(r2 = 0.2031, p = 0.0045), and KL-6(r2 = 0.2122, p = 0.0136). Our results suggest that naive CD8+ T cells, CD8+ CD28- T cells, and CD8+ CD27- T cells are obviously correlated with inflammation and disease activity of RA. While activated CD8+ T cells and TCRγδ + CD8+ T cells may involve in lipid metabolism and lung fibrosis of RA. These CD8+ T cell subsets may be new biomarkers and targets for RA disease evaluation, therapeutic target-selecting, curative effects and prognoses assessment. [ABSTRACT FROM AUTHOR]

Objective. To observe the curative effect of VAWI on Xinjiang Uygur patients with silicosis fibrosis. Methods. After we diagnosed the 40 patients with the first phase of silicosis, we randomly divided them into two groups: the basic treatment group (group A, n=20) and the VAWI group (group B, n=20). At the same time, we selected the age-matched healthy patients (n=20). We applied the combined protein chip with SELDI-TOF-MS to carry out the serum analysis. The data were analyzed throughout data preprocessing, difference in PEAK screening, hierarchical cluster analysis, and Principal Component Analysis (PCA). We built decision tree model and predict the difference between the PEAK corresponding proteins. Results. The proteins peaks corresponding to name, predicted protein, and gene name were as follows: M2001_69, amyloid beta a4 protein, APP, and M2017_02, amyloid beta a4 protein, APP. The different expression of proteins in patients with silicosis was found before and after with VAWI treatment. The predicted proteins were as follows: M1982_50, amyloid beta a4 protein, APP; M3164_50, fibrinogen alpha chain frag, FGA; M3379_28, fibrinogen alpha chain frag, FGA; and so on. Conclusion. VAWI presented curative effect on patients with silicosis fibrosis via the alternation of proteins expression in serum. [ABSTRACT FROM AUTHOR]

Purpose: Abnormal expression of miRNAs is closely related to a variety of human cancers. The purpose of this study is to identify new tumor suppressor miRNA and elucidate its physiological function and mechanism in renal cell carcinoma (RCC). Methods: The expression of miR-145 in 45 RCC and adjacent normal tissues was performed by quantitative RT-PCR. Cell proliferation, migration, invasion, apoptosis and cycle assays were carried out for functional analysis after miR-145 transfection. Two target genes of miR-145 were identified by luciferase reporter assay. The altered expression of 84 epithelial to mesenchymal transition (EMT)-related genes after miR-145 transfection was detected by RT Profiler EMT PCR array. Results: The expression of miR-145 was downregulated in RCC compared to their normal adjacent tissues. Restoring miR-145 expression in RCC cell lines dramatically suppressed cell proliferation, migration and invasion, and induced cell apoptosis and G2-phase arrest. We further validated those miR-145 targets two oncogenes, ANGPT2 and NEDD9 in RCC. In addition, miR-145 was found to regulate numerous genes involved in the EMT. Conclusions: These findings demonstrate that miR-145 functions as tumor suppressor in RCC, suggesting that miR-145 may be a potential therapeutic target for RCC. [ABSTRACT FROM AUTHOR]

Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues. [ABSTRACT FROM AUTHOR]

Objective: To study the expression patterns of long noncoding ribonucleic acid (RNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the cell proliferation inhibition, apoptosis, and motility changes induced by silencing MALAT1 in urothelial carcinoma of the bladder. Materials and Methods: The expression levels of MALAT1 were determined using real-time quantitative polymerase chain reaction in cancerous tissues and paired normal tissues in a total of 36 patients with urothelial carcinoma of the bladder. Expression differences were analyzed according to the grade and stage. Bladder urothelial carcinoma T24 and 5637 cells were transfected with MALAT1 small interfering RNA or negative control small interfering RNA. The cell proliferation changes of the transfected bladder urothelial carcinoma cells were determined using the MTT assay. Apoptosis caused by silencing MALAT1 was evaluated using the flow cytometry assay and enzyme-linked immunosorbent assay. The motility changes induced by silencing MALAT1 were measured using the wound healing assay. Results: MALAT1 was upregulated in bladder urothelial carcinoma compared with matched normal urothelium (P = .008). The MALAT1 expression levels were greater in high-grade carcinomas than in low-grade carcinoma (P = .001). The MALAT1 expression levels were greater in invasive carcinoma than in noninvasive carcinoma (P = .018). Cell proliferation inhibition, increased apoptosis, and decreased motility were observed in MALAT1 small interfering RNA-transfected bladder urothelial carcinoma T24 and 5637 cells. Conclusion: MALAT1 plays an oncogenic role in urothelial carcinoma of the bladder. Silencing MALAT1 is a potential novel therapeutic approach for this cancer. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in the KCNQ4 channel cause DFNA2, a subtype of autosomal dominant non-syndromic deafness that is characterized by progressive sensorineural hearing loss. Previous studies have demonstrated that the majority of the pathogenic KCNQ4 mutations lead to trafficking deficiency and loss of KCNQ4 currents. Over the last two decades, various strategies have been developed to rescue trafficking deficiency of pathogenic mutants; the most exciting advances have been made by manipulating activities of molecular chaperones involved in the biogenesis and quality control of the target protein. However, such strategies have not been established for KCNQ4 mutants and little is known about the molecular chaperones governing the KCNQ4 biogenesis. To identify KCNQ4-associated molecular chaperones, a proteomic approach was used in this study. As a result, two major molecular chaperones, HSP70 and HSP90, were identified and then confirmed by reciprocal co-immunoprecipitation assays, suggesting that the HSP90 chaperone pathway might be involved in the KCNQ4 biogenesis. Manipulating chaperone expression further revealed that two different isoforms of HSP90, the inducible HSP90α and the constitutive HSP90β, had opposite effects on the cellular level of the KCNQ4 channel; that HSP40, HSP70, and HOP, three key components of the HSP90 chaperone pathway, were crucial in facilitating KCNQ4 biogenesis. In contrast, CHIP, a major E3 ubiquitin ligase, had an opposite effect. Collectively, our data suggest that HSP90α and HSP90β play key roles in controlling KCNQ4 homeostasis via the HSP40-HSP70-HOP-HSP90 chaperone pathway and the ubiquitin-proteasome pathway. Most importantly, we found that over-expression of HSP90β significantly improved cell surface expression of the trafficking-deficient, pathogenic KCNQ4 mutants L274H and W276S. KCNQ4 surface expression was restored by HSP90β in cells mimicking heterozygous conditions of the DFNA2 patients, even though it was not sufficient to rescue the function of KCNQ4 channels. [ABSTRACT FROM AUTHOR]

Background: Acute appendicitis (AA) is usually associated with a systemic inflammatory response that often leads to activation of coagulation. However, limited data about coagulation changes in AA are available. Methods: Results of preoperative coagulation testing in 702 patients with confirmed AA and 697 patients undergoing minor elective surgery (control) during the same period were analyzed retrospectively. Coagulation activity of factors VII, IX (FVII:C, FIX:C) and the concentration of plasma endotoxin from 40 patients with AA and 15 control subjects were measured. Results: Compared with control subjects, prothrombin time (PT), fibrinogen (Fib) and endotoxin increased (all p<0.01), FVII:C decreased (p<0.05), and thrombin time shortened (p<0.01) significantly in patients with AA, which showed trends with increasing severity of disease. Areas under the receiver operating characteristic curve of Fib for discriminating complicated appendicitis or acute perforated appendicitis from enrolled patients were larger than those for leukocyte parameters. The concentration of endotoxin correlated negatively with FVII:C (r=−0.860, p<0.001), positively with PT (0.713, <0.001), and FVII:C negatively with PT (−0.729, <0.001) in individuals that were evaluated. The change in activated partial thromboplastin time and difference in FIX:C among patients with various pathological types of appendicitis were not significant. Conclusions: Endotoxin-induced activation of the extrinsic coagulation pathway was present in patients with AA. Fib may be useful as a potential indicator for excluding complicated appendicitis. [ABSTRACT FROM AUTHOR]

A systematic review of the Chinese literature was conducted from 1956 to 2005. The survey included both online and manual searching, as well as expert discussions aimed at providing insight into factors affecting benzene exposure levels in paint/coatings industries. Data extracted from 204 papers included: (1) year of occurrence, (2) type of paint/coatings products, (3) type of industries where the products were used or produced, (4) job titles and work activities, (5) type of literature searched, (6) working conditions whenever data were available, and (7) exposure levels. Most benzene measurements were short-term samples for comparison with the Chinese maximum allowable concentration standard. The accuracy and precision of the sampling and analytical methods were not reported. The distribution of benzene concentrations was tested and found to fit neither normal nor lognormal distributions. Analysis of variance (comparison for more than two groups) and t-test (comparison for two groups) were conducted on Blom-transformed benzene concentration data. The overall median benzene exposure levels were 215, 82, 31, and 6 mg/m3 during the periods 1956-1978, 1979-1989, 1990-2001, and 2002-2005, respectively. Mean benzene exposure was significantly lower for paint manufacturing than paint spraying. No significant difference was found among paint types and benzene exposure for paint application. Benzene exposure was significantly higher in workplaces judged to have poor ventilation. No significant differences were found in benzene exposure as a function of industry type. Even though substantially lower when compared with levels in the past, recent benzene exposure measurements suggested that many facilities in the paint/coatings industries in China still have benzene concentrations that are above the current China occupational exposure limit for benzene (6 mg/m3 as a time-weighted average). Benzene concentrations from the present exercise, while not directly supporting quantitative retrospective exposure estimating, provide insight on relative benzene exposure for painting tasks in the reported industries over time. [Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Occupational and Environmental Hygiene for the following free supplemental resource: tables detailing benzene concentration for different types of painting and other tasks in Chinese industry.] [ABSTRACT FROM AUTHOR]

Inherited long QT syndrome is most frequently associated with mutations in KCNQ1, which encodes the primary subunit of a potassium channel. Patients with mutations in KCNQ1 may show only the cardiac defect (Romano-Ward syndrome or RWS) or may also have severe deafness (Jervell and Lange-Nielsen syndrome or JLNS). Targeted disruption of mouse Kcnq1 models JLNS in that mice are deaf and show abnormal ECGs. However, the phenotype is broader than that seen in patients. Most dramatically, the inner ear defects result in a severe hyperactivity/circling behavior, which may influence cardiac function. To understand the etiology of the cardiac phenotype in these mice and to generate a potentially more useful model system, we generated new mouse lines by introducing point mutations associated with RWS. The A340E line phenocopies RWS: the repolarization phenotype is inherited in a dominant manner and is observed independent of any inner ear defect. The T311I line phenocopies JLNS, with deafness associated with inner hair cell malfunction. [Copyright &y& Elsevier]