Foot-and-mouth disease (FMD) is one of most contagious animal diseases. It affects millions of cloven-hoofed animals and causes huge economic losses in many countries of the world. There are seven serotypes of which three (O, A and Asia 1) are endemic in China. Efficient control of FMD in China is crucial for the prevention and control of FMD in Asia and throughout the world. For the control of FMD, a powerful veterinary administration, a well-trained veterinary staff, a system of rapid and accurate diagnostic procedures and, in many countries, compulsory vaccination of susceptible animals are indispensable. This article strives to outline the Chinese animal disease control and prevention system, in particular for FMD, with the emphasis on diagnostic procedures applied in Chinese laboratories. In addition, new technologies for FMD diagnosis, which are currently in the phase of development or in the process of validation in Chinese laboratories, are described, such as lateral flow devices (LFD), Mab-based ELISAs, reverse transcription loop-mediated isothermal amplification (RT-LAMP) and gold nanopariticle immuno-PCR (GNP-IPCR).

Background

Conventional ways of making bio-electrodes are generally complicated, expensive and unconformable. Here we describe for the first time the method of applying Ga-based liquid metal ink as drawable electrocardiogram (ECG) electrodes. Such material owns unique merits in both liquid phase conformability and high electrical conductivity, which provides flexible ways for making electrical circuits on skin surface and a prospective substitution of conventional rigid printed circuit boards (PCBs).

Methods

Fundamental measurements of impedance and polarization voltage of the liquid metal ink were carried out to evaluate its basic electrical properties. Conceptual experiments were performed to draw the alloy as bio-electrodes to acquire ECG signals from both rabbit and human via a wireless module developed on the mobile phone. Further, a typical electrical circuit was drawn in the palm with the ink to demonstrate its potential of implementing more sophisticated skin circuits.

Results

With an oxide concentration of 0.34%, the resistivity of the liquid metal ink was measured as 44.1 µΩ·cm with quite low reactance in the form of straight line. Its peak polarization voltage with the physiological saline was detected as −0.73 V. The quality of ECG wave detected from the liquid metal electrodes was found as good as that of conventional electrodes, from both rabbit and human experiments. In addition, the circuit drawn with the liquid metal ink in the palm also runs efficiently. When the loop was switched on, all the light emitting diodes (LEDs) were lit and emitted colorful lights.

Conclusions

The liquid metal ink promises unique printable electrical properties as both bio-electrodes and electrical wires. The implemented ECG measurement on biological surface and the successfully run skin circuit demonstrated the conformability and attachment of the liquid metal. The present method is expected to innovate future physiological measurement and biological circuit manufacturing technique in a large extent.

Mammalian cells consume and metabolize various substrates from their surroundings for energy generation and biomass synthesis. Glucose and glutamine, in particular, are the primary carbon sources for proliferating cancer cells. While this combination of substrates generates static labeling patterns for use in 13C metabolic flux analysis (MFA), the inability of single tracers to effectively label all pathways poses an obstacle for comprehensive flux determination within a given experiment. To address this issue we applied a genetic algorithm to optimize mixtures of 13C-labeled glucose and glutamine for use in MFA. We identified tracer combinations that minimized confidence intervals in an experimentally determined flux network describing central carbon metabolism in tumor cells. Additional simulations were used to determine the robustness of the [1,2-13C2]glucose/[U-13C5]glutamine tracer combination with respect to perturbations in the network. Finally, we experimentally validated the improved performance of this tracer set relative to glucose tracers alone in a cancer cell line. This versatile method allows researchers to determine the optimal tracer combination to use for a specific metabolic network, and our findings applied to cancer cells significantly enhance the ability of MFA experiments to precisely quantify fluxes in higher organisms.

Motivation: The folding free energy is an important characteristic of proteins stability and is directly related to protein's wild-type function. The changes of protein's stability due to naturally occurring mutations, missense mutations, are typically causing diseases. Single point mutations made in vitro are frequently used to assess the contribution of given amino acid to the stability of the protein. In both cases, it is desirable to predict the change of the folding free energy upon single point mutations in order to either provide insights of the molecular mechanism of the change or to design new experimental studies.

Results: We report an approach that predicts the free energy change upon single point mutation by utilizing the 3D structure of the wild-type protein. It is based on variation of the molecular mechanics Generalized Born (MMGB) method, scaled with optimized parameters (sMMGB) and utilizing specific model of unfolded state. The corresponding mutations are built in silico and the predictions are tested against large dataset of 1109 mutations with experimentally measured changes of the folding free energy. Benchmarking resulted in root mean square deviation = 1.78 kcal/mol and slope of the linear regression fit between the experimental data and the calculations was 1.04. The sMMGB is compared with other leading methods of predicting folding free energy changes upon single mutations and results discussed with respect to various parameters.

Availability: All the pdb files we used in this article can be downloaded from http://compbio.clemson.edu/downloadDir/mentaldisorders/sMMGB_pdb.rar

Contact: ealexov@clemson.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

A widespread porcine epidemic diarrhea virus (PEDV) occurred in southern China during 2010 to 2012. A virulent field PEDV strain, GD-B, was isolated from a sucking piglet suffering from severe diarrhea in Guangdong, China. We sequenced and analyzed the complete genome of strain GD-B, which will promote a better understanding of the molecular epidemiology and genetic diversity of PEDV field isolates in southern China.

The cry1Ac gene of Bacillus thuringiensis subsp. kurstaki HD-73 (B. thuringiensis HD-73) is a typical example of a sporulation-dependent crystal gene and is controlled by sigma E and sigma K during sporulation. To monitor the production and accumulation of Cry1Ac at the cellular level, we developed a green fluorescent protein-based reporter system. The production of Cry1Ac was monitored in spo0A, sigE, and sigK mutants, and these mutants were able to express the Cry1Ac-green fluorescent protein fusion protein. In nonsporulating B. thuringiensis HD-73 cells, low-level expression of cry1Ac was also observed. Reverse transcription-PCR and Western blotting results confirmed that the cry1Ac promoter has low activity in nonsporulating B. thuringiensis cells. A beta-galactosidase assay demonstrated that the transcription of the cry1Ac gene during exponential and transition phases is positively regulated by Spo0A. Additional bioassay results indicated that spo0A and sigE mutants containing the cry1Ac-gfp fusion exhibited insecticidal activity against Plutella xylostella larvae.

Since early 2010, outbreaks of porcine epidemic diarrhea (PED) have been observed frequently in immunized swine herds in southern China. The suckling piglets are particularly susceptible to porcine epidemic diarrhea virus (PEDV), with a high mortality rate (90%). Recently, a virulent PEDV strain, GD-A, was isolated from an immunized-swine breeding farm in Guangdong, China. This report describes the complete genome sequence of GD-A, and the data will provide important insights into the variation of PEDV field isolates in southern China.

Knowledge of mineral localization within rice grains is important for understanding the role of different elements in seed development, as well as for facilitating biofortification of seed micronutrients in order to enhance seeds’ values in human diets. In this study, the concentrations of minerals in whole rice grains, hulls, brown rice, bran and polished rice were quantified by inductively coupled plasma mass spectroscopy. The in vivo mineral distribution patterns in rice grains and shifts in those distribution patterns during progressive stages of germination were analyzed by synchrotron X-ray microfluorescence. The results showed that half of the total Zn, two thirds of the total Fe, and most of the total K, Ca and Mn were removed by the milling process if the hull and bran were thoroughly polished. Concentrations of all elements were high in the embryo regions even though the local distributions within the embryo varied between elements. Mobilization of the minerals from specific seed locations during germination was also element-specific. High mobilization of K and Ca from grains to growing roots and leaf primordia was observed; the flux of Zn to these expanding tissues was somewhat less than that of K and Ca; the mobilization of Mn or Fe was relatively low, at least during the first few days of germination.

The asymmetric unit of the title compound, C17H24O2, contains two independent mol­ecules with different conformations. The least-squares plane through the cyclohexane ring makes dihedral angles of 52.9 (5) and 81.4 (4)° with the benzene ring in the two molecules. The cyclo­hexane ring adopts a chair conformation in both mol­ecules. In the crystal, weak C—H⋯O hydrogen bonds link mol­ecules related by translation in [100] into two crystallographically independent chains.

Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P = 0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P = 0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P = 0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P = 0.046) and increased waist/hip (W/H) ratio (TT/CC: P = 0.013; TT/TC: P = 0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P = 0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D.

Background

MicroRNAs (miRNAs) are a type of non-coding small RNA ~22 nucleotides in length that regulate the expression of protein coding genes at the post-transcriptional level. Glycolytic and oxidative myofibers, the two main types of skeletal muscles, play important roles in metabolic health as well as in meat quality and production in the pig industry. Previous expression profile studies of different skeletal muscle types have focused on these aspects of mRNA and proteins; nonetheless, an explanation of the miRNA transcriptome differences between these two distinct muscles types is long overdue.

Results

Herein, we present a comprehensive analysis of miRNA expression profiling between the porcine longissimus doris muscle (LDM) and psoas major muscle (PMM) using a deep sequencing approach. We generated a total of 16.62 M (LDM) and 18.46 M (PMM) counts, which produced 15.22 M and 17.52 M mappable sequences, respectively, and identified 114 conserved miRNAs and 89 novel miRNA*s. Of 668 unique miRNAs, 349 (52.25%) were co-expressed, of which 173 showed significant differences (P < 0.01) between the two muscle types. Muscle-specific miR-1-3p showed high expression levels in both libraries (LDM, 32.01%; PMM, 20.15%), and miRNAs that potentially affect metabolic pathways (such as the miR-133 and -23) showed significant differences between the two libraries, indicating that the two skeletal muscle types shared mainly muscle-specific miRNAs but expressed at distinct levels according to their metabolic needs. In addition, an analysis of the Gene Ontology (GO) terms and KEGG pathway associated with the predicted target genes of the differentially expressed miRNAs revealed that the target protein coding genes of highly expressed miRNAs are mainly involved in skeletal muscle structural development, regeneration, cell cycle progression, and the regulation of cell motility.

Conclusion

Our study indicates that miRNAs play essential roles in the phenotypic variations observed in different muscle fiber types.

AIM: To estimate hepatitis B virus (HBV) infection testing rate in cancer patients before chemotherapy with a focus on HBV reactivation.

METHODS: A retrospective study was conducted from January 1, 2009 to June 30, 2010. Inclusion required that patients be naïve to cancer chemotherapy but have indications for it. Patients who did not receive chemotherapy for any reason were excluded. Important clinical information, such as the levels of HBV DNA and serological markers were collected. HBV reactivation was defined as an increase in serum HBV DNA to > 1 log higher than that of the pre-exacerbation baseline, or serum HBV DNA conversion from negative to positive. HBV DNA levels > 1000 copies/mL were defined as HBV DNA positive. The χ2 or Fisher’s exact test was used for analysis of categorized data. Multiple logistic regression analysis was used to estimate the odd ratio and 95%CI of the HBV screening rate.

RESULTS: Of 6646 patients, 5616 (84.5%) received chemotherapy. Only 17.1% of the cancer patients received pre-chemotherapy HBV testing (43.2% for hematological malignancies and 14.9% for solid tumors). Patients who had received rituximab therapy, had elevated aminotransferase levels, or had hematological malignancies were more likely to receive HBV testing. The prevalence of hepatitis B surface antigen (HBsAg) positivity was 13.4%. HBV reactivation (appearance of HBV DNA or an increase in HBV DNA levels by 1 log10) was observed in 33.1% (53/160) of the patients after chemotherapy. Among patients without prophylactic antiviral therapy, the reactivation rate was 43.9% (43/98) in the solid tumor group. Two reactivation cases occurred in patients who were HBsAg negative, but positive for hepatitis B core antibody. HBV reactivation was more likely to occur in patients with lymphoma, high levels of HBV DNA, or hepatitis B e antigen, and in men.

CONCLUSION: Less than 20% of patients received HBV testing before chemotherapy. HBV reactivation would have occurred in about 50% of infected patients with solid tumors without antiviral prophylaxis.

Background

Serum preptin levels among subjects with different bone mineral densities (BMD) were measured and investigated to determine the correlation between BMD and bone-metabolic markers.

Methods

Approximately 52 elderly male patients with osteoporosis, 50 elderly men with osteopaenia, and 31 age-matched normal bone mass controls participated in the study. The serum preptin levels and bone metabolic markers were measured by enzyme-linked immunosorbent assay. The relationships between preptin levels, BMD, and metabolic parameters were also assessed.

Results

The serum preptin level was the lowest in the osteoporosis group and positively correlated with BMD. All the bone formation markers in the osteoporosis and osteopaenia groups were significantly reduced compared with those in the normal group. Serum preptin level was positively correlated with all the bone formation markers, whereas no correlation was observed with the bone resorption marker TRACP-5b.

Conclusions

Serum preptin levels are decreased in osteoporosis and osteopaenia patients and positively correlated with BMD. Therefore, preptin is involved in the pathogenesis of osteoporosis, probably through bone formation rather than bone resorption.

There is increasing evidence that Special AT-rich sequence-binding protein 1 (SATB1) is aberrantly expressed in several cancers and is correlated with clinicopathologic parameters in these tumors. In this study, we showed over-expression of SATB1 in 80 cases of colorectal cancer and in 3 colorectal cancer cell lines and found expression levels were strongly associated with tumor differentiation and stage. Expression levels of SATB1 protein were higher in poorly-differentiated as compared with well-differentiated cell lines, and both quantity and distribution patterns of SATB1 were associated with tumor differentiation and pTNM stage. Strikingly, we further investigated the effect of down regulation of SATB1 expression on malignant phenotypic features in colorectal cancer cells in vitro, and showed that SABT1 down-regulation negatively affected growth potential, anchorage-independent colony formation and cancer cell invasion, and resulted in increased apoptosis. SATB1 expression was positively associated with the expression of various biological and genetic markers, including Cyclin D1, MMP-2, NF-κB, and PCNA, and was associated with loss of APC and BRAFV600E. These findings suggest that SATB1 is involved in the carcinogenesis, development and progression of colorectal cancer.

Purpose

3,3′-Diindolylmethane (DIM) is a natural component of cruciferous plants. It has strong antioxidant and anti-angiogenic effects and promotes the apoptosis of a variety of tumor cells. However, little is known about the critical role of DIM on cardiac hypertrophy. In the present study, we investigated the effects of DIM on cardiac hypertrophy.

Methods

Multiple molecular techniques such as Western blot analysis, real-time PCR to determine RNA expression levels of hypertrophic, fibrotic and oxidative stress markers, and histological analysis including H&E for histopathology, PSR for collagen deposition, WGA for myocyte cross-sectional area, and immunohistochemical staining for protein expression were used.

Results

In pre-treatment and reverse experiments, C57/BL6 mouse chow containing 0.05% DIM (dose 100 mg/kg/d DIM) was administered one week prior to surgery or one week after surgery, respectively, and continued for 8 weeks after surgery. In both experiments, DIM reduced to cardiac hypertrophy and fibrosis induced by aortic banding through the activation of 5′-adenosine monophosphate-activated protein kinase-α2 (AMPKα2) and inhibition of mammalian target of the rapamycin (mTOR) signaling pathway. Furthermore, DIM protected against cardiac oxidative stress by regulating expression of estrogen-related receptor-alpha (ERRα) and NRF2 etc. The cardioprotective effects of DIM were ablated in mice lacking functional AMPKα2.

Conclusion

DIM significantly improves left ventricular function via the activation of AMPKα2 in a murine model of cardiac hypertrophy.

Mast cells are critical effectors in the development of allergic diseases and in many immunoglobulin E–mediated immune responses. These cells exert their physiological and pathological activities by releasing granules containing histamine, cytokines, chemokines, and proteases, including mast cell-specific chymase and tryptase. Like macrophages and T lymphocytes, mast cells are inflammatory cells, and they participate in the pathogenesis of inflammatory diseases such as cardiovascular complications and metabolic disorders. Recent observations suggested that mast cells are involved in insulin resistance and type 2 diabetes. Data from animal models proved the direct participation of mast cells in diet-induced obesity and diabetes. Although the mechanisms by which mast cells participate in these metabolic diseases are not fully understood, established mast cell pathobiology in cardiovascular diseases and effective mast cell inhibitor medications used in pre-formed obesity and diabetes in experimental models offer hope to patients with these common chronic inflammatory diseases.

Objectives

Cathepsin K (CatK) is one of the most potent mammalian elastases. We have previously shown increased expression of CatK in human abdominal aortic aneurysm (AAA) lesions. Whether this protease participates directly in AAA formation, however, remains unknown.

Methods and Results

Mouse experimental AAA was induced with aortic perfusion of a porcine pancreatic elastase. Using this experimental model, we demonstrated that absence of CatK prevented AAA formation in mice 14 days post-perfusion. CatK deficiency significantly reduced lesion CD4+ T-cellcontent, total lesion and medial cell proliferation and apoptosis, medial smooth-muscle cell (SMC) loss, elastinolytic CatL and CatS expression, and elastin fragmentation, but did not affect AAA lesion Mac-3+ macrophage accumulation or CD31+ microvessel numbers. In vitro studies revealed that CatK contributed importantly to CD4+ T-cell proliferation, SMC apoptosis, and other cysteinyl cathepsin and matrix metalloproteinase expression and activities in SMC and endothelial cells, but played negligible roles in microvessel growth and monocyte migration. AAA lesions from CatK-deficient mice showed reduced elastinolytic cathepsin activities compared with those from wild-type control mice.

Conclusion

This study demonstrates that CatK plays an essential role in AAA formation by promoting T-cell proliferation, vascular SMC apoptosis, and elastin degradation, and by affecting vascular cell protease expression and activities.

AIM: To investigate the feasibility and the effectiveness of ileoileostomy in the region adjacent to the ileocecal valve, which can retain the ileocecal valve in infants.

METHODS: This is a retrospective review of 48 patients who underwent ileoileostomy in the region adjacent to the ileocecal valve (group 1) and 34 patients who underwent ileocecal resections and ileotransversanastomosis (group 2). Patients were monitored for the time to flatus, resumption of eating, length of hospital stay after surgery, serum total bile acid, vitamin B12 and postoperative complications.

RESULTS: The time to flatus, time until resumption of eating and post-operative length of hospital stay showed no statistically significant differences between the two groups. Serum total bile acid and vitamin B12 were not significantly different between the two groups at post-operative day 1 and day 3, but were significantly decreased at 1 wk after operation in group 2. None of the patients died or suffered from stomal leak in these two groups. However, the incidence of diarrhea, intestinal infection, disturbance of acid-base balance and water-electrolytes in group 1 was lower than in group 2.

CONCLUSION: Ileoileostomy in the region adjacent to the ileocecal valve is safe and results in fewer complications than ileotransversanastomosis in infants.

Background

Histone modification plays an important role in cell differentiation and tissue development. A recent study has shown that the dimethylation of lysine 4 residue on histone 3 (H3K4me2) marks the gene body area of tissue specific genes in the human CD4+ T cells and neural cells. However, little is known of the H3k4me2 distribution dynamics through the cell differentiation and tissue development.

Results

We applied several clustering methods including K-means, hierarchical and principle component analysis on H3K4me2 ChIP-seq data from embryonic stem cell, neural progenitor cell and whole brain of mouse, trying to identify genes with the H3K4me2 binding on the gene body region in different cell development stage and study their redistribution in different tissue development stages.

A cluster of 356 genes with heavy H3K4me2 labeling in the gene body region was identified in the mouse whole brain tissue using K-means clustering. They are highly enriched with neural system related functions and pathways, and are involved in several central neural system diseases. The distribution of H3K4me2 on neural function related genes follows three distinctive patterns: a group of genes contain constant heavy H3K4me2 marks in the gene body from embryonic stem cell stage through neural progenitor stage to matured brain tissue stage; another group of gene have little H3K4me2 marks until cells mature into brain cells; the majority of the genes acquired H3K4me2 marks in the neural progenitor cell stage, and gain heavy labeling in the matured brain cell stage. Gene ontology enrichment analysis also revealed corresponding gene ontology terms that fit in the scenario of each cell developmental stages.

Conclusions

We investigated the process of the H3K4me2 mark redistribution during tissue specificity development for mouse brain tissue. Our analysis confirmed the previous report that heavy labeling of H3K4me2 in the downstream of TSS marks tissue specific genes. These genes show remarkable enrichment in central neural system related diseases. Furthermore, we have shown that H3K4me2 labeling can be acquired as early as the embryonic stem cell stage, and its distribution is dynamic and progressive throughout cell differentiation and tissue development.

Previous studies have indicated two main domestic pig dispersal routes in East Asia: one is from the Mekong region, through the upstream region of the Yangtze River (URYZ) to the middle and upstream regions of the Yellow River, the other is from the middle and downstream regions of the Yangtze River to the downstream region of the Yellow River, and then to northeast China. The URYZ was regarded as a passageway of the former dispersal route; however, this assumption remains to be further investigated. We therefore analyzed the hypervariable segements of mitochondrial DNA from 513 individual pigs mainly from Sichuan and the Tibet highlands and 1,394 publicly available sequences from domestic pigs and wild boars across Asia. From the phylogenetic tree, most of the samples fell into a mixed group that was difficult to distinguish by breed or geography. The total network analysis showed that the URYZ pigs possessed a dominant position in haplogroup A and domestic pigs shared the same core haplotype with the local wild boars, suggesting that pigs in group A were most likely derived from the URYZ pool. In addition, a region-wise network analysis determined that URYZ contains 42 haplotypes of which 22 are unique indicating the high diversity in this region. In conclusion, our findings confirmed that pigs from the URYZ were domesticated in situ.

This study aims to retrospectively analyze the clinical characteristics, treatments, and prognosis of aggressive peripheral T cell lymphoma (PTCL) patients with a lymphoma-associated hemophagocytosis syndrome (LAHS). We compared the clinical features and the overall survival (OS) rates of 159 PTCL patients with and without LAHS as well as the treatment outcomes of these patients with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or intensive chemotherapy regimens. We observed that in 23 % (36/159) patients PTCL was associated with LAHS. Different subtypes of PTCL in LAHS patients were diagnosed and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) was the main subtype (78 %). The median survival rates of the LAHS and non-LAHS groups were 3 and 16 months, respectively. The elevated rates of serum β2-microglobulin, ferritin, fasting triglycerides, and hypofibrinogen levels were higher in the LAHS group, so were bone marrow involvement, liver dysfunction, hepatosplenomegaly, and B symptoms. Three patients who were treated with a plasma exchange had a longer survival time. There was no statistically significant difference in the OS rates between the intensive chemotherapy and CHOP regimen groups (P > 0.05). PTCL patients with LAHS had a poorer prognosis. Awareness of the clinical symptoms and laboratory findings are crucial in order to diagnose LAHS in an early stage and repeated biopsies of multiple bone marrows from different locations in those patients without enlargement of superficial lymph nodes are necessary to improve the diagnosis. Intensive chemotherapy due to its severe toxicity was not obviously advantageous for the OS rate compared to the CHOP regimen.

Background

The abalone Haliotis diversicolor is a good model for study of the settlement and metamorphosis, which are widespread marine ecological phenomena. However, information on the global gene backgrounds and gene expression profiles for the early development of abalones is lacking.

Methodology/Principal Findings

In this study, eight non-normalized and multiplex barcode-labeled transcriptomes were sequenced using a 454 GS system to cover the early developmental stages of the abalone H. diversicolor. The assembly generated 35,415 unigenes, of which 7,566 were assigned GO terms. A global gene expression profile containing 636 scaffolds/contigs was constructed and was proven reliable using qPCR evaluation. It indicated that there may be existing dramatic phase transitions. Bioprocesses were proposed, including the ‘lock system’ in mature eggs, the collagen shells of the trochophore larvae and the development of chambered extracellular matrix (ECM) structures within the earliest postlarvae.

Conclusion

This study globally details the first 454 sequencing data for larval stages of H. diversicolor. A basic analysis of the larval transcriptomes and cluster of the gene expression profile indicates that each stage possesses a batch of specific genes that are indispensable during embryonic development, especially during the two-cell, trochophore and early postlarval stages. These data will provide a fundamental resource for future physiological works on abalones, revealing the mechanisms of settlement and metamorphosis at the molecular level.

BACKGROUND

Sodium channel α-subunits in ventricular myocytes (VMs) segregate either to the intercalated disc, or to lateral membranes, where they associate with region-specific molecules.

OBJECTIVE

To determine the functional properties of sodium channels as a function of their location in the cell.

METHODS

Local sodium currents were recorded from adult rodent VMs and Purkinje cells using the cell-attached macropatch configuration. Electrodes were placed either in the cell midsection (M), or cell end (area originally occupied by the intercalated disc; ID). Channels were identified as TTX-sensitive (TTX-S) or TTX-resistant (TTX-R) by application of 100 nM TTX.

RESULTS

Average peak-current amplitude was larger in ID than M, and largest at site of contact between attached cells. TTX-S channels were found only in M region of VMs, and not in Purkinje myocytes. TTX-R channels were found in M and ID, but their biophysical properties differed depending on recording location. Sodium current in rat VMs was upregulated by TNF-α. The magnitude of current increase was largest in M, but this difference was abolished by 100 nM TTX.

CONCLUSIONS

Our data suggest that: a) a large fraction of TTX-R (likely Nav1.5) channels in the M region of VMs are inactivated at normal resting potential, leaving most of the burden of excitation to TTX-R channels in the ID; b) cell-cell adhesion increases functional channel density at ID. c) TTX-S (likely non-Nav1.5) channels make a minimal contribution to sodium current under control conditions, but represent a functional reserve that can be upregulated by exogenous factors.

Objective

The study aims to examine the threshold in disease activity associated with switching biologic treatment regimens in RA patients in real-world clinical practice.

Methods

Using data from a prospective observational North American cohort of RA patients through 12/30/2009, patients who initiated a new anti-TNF agent with ≥ 6 months of follow-up were identified. Patients were classified as switchers or maintainers depending on whether they continued their anti-TNF treatment or switched (including discontinuation) within 12 months. Level of disease activity measured by CDAI and DAS28 at time of switch (corresponding follow-up visit for maintainers) was examined and random effect multivariable logistic regression was used to adjust for covariates.

Results

Mean age and RA duration among 1,549 eligible patients were 56.1 and 9.6 years, 80% were women, 62% were initiating their 1st biologic and 30% 2nd. At time of switch, the median DAS28 and CDAI were 3.1 and 8.4 among maintainers, and 4.0 and 15.2 among switchers. Maintainers also experienced a greater amount of reduction in disease activity compared with switchers (CDAI: −7.7 vs. −2.3; DAS28: −1.1 vs. −0.3). The threshold to switch decreased over calendar time, with the greatest amount of reduction observed among patients with moderate disease activity.

Conclusion

On average, physicians and patients were willing to continue biologic treatment for patients who are at or near low disease activity. The threshold to switch decreased over time, especially among partial responders.

Abstract

Crude water-soluble Chinese truffle Tuber indicum polysaccharide (TIP) was extracted from the fruiting bodies with water and then successively purified by DEAE–cellulose 52 and Sephadex G-100 column chromatography, yielding two major polysaccharide fractions: TIP1-1 and TIP2-1. High-performance gel permeation chromatography analysis showed that the average molecular sizes of TIP1-1 and TIP2-1 were approximately 1.75×104 Da and 5.73×103 Da, respectively. Monosaccharide component analysis by gas chromatography indicated that TIP1-1 was composed of mannose, glucose, galactose, and rhamannose in the respective molar ratio of 3.93:1.24:0.75:1.26 and that TIP2-1 contained mannose, glucose, and arabinose in the respective molar ratio of 5.27:1.44:0.43. The antioxidant activity analyses revealed that TIP1-1 and TIP2-1 possessed considerable antioxidant activity. Compared with TIP1-1, which has a higher molecular weight and contains no uronic acid, TIP2-1 exhibited a protective effect on PC12 cells injured by H2O2 and a higher scavenging activity against free radicals. The relative effects of the lower molecular size, the presence of uronic acid, and the antioxidant activity of TIP2-1 appear to be significant. Accordingly, the Chinese truffle T. indicum might serve as an effective antioxidative healthcare food and source of natural antioxidants.