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Background: The abnormal proliferation and migration of airway smooth muscle (ASM) cells contributes to airway remodeling during asthma. MiR-19a has been demonstrated to promote cell proliferation and angiogenesis of several cancer types by regulating the PTEN/PI3K/AKT pathway. Our previous study has shown that High-mobility group box protein 1 (HMGB1) is involved in the pathogenesis of airway remodeling using a mouse model of chronic asthma. However, the effects of HMGB1 on proliferation and migration of ASM cells and its underlying mechanisms remain unknown. Methods: Human ASM cells were obtained by primary explant techniques. MiR-19a expression was evaluated using qRT-PCR. Cell proliferation and migration were evaluated by the CCK-8 and the transwell migration assays, respectively. Transfection studies of ASM cells were performed to identify the underlying mechanisms. Results: HMGB1 stimulated ASM cell proliferation and migration in a dose-dependent manner. The expression levels of miR-19a and the PTEN and AKT signaling proteins were also modulated by HMGB1. Functional studies indicated that overexpression of miR-19a enhanced the proliferation and migration of ASM cells, whereas inhibition of miR-19a decreased the proliferation and migration of ASM cells. Western blot analysis demonstrated that miR-19a negatively regulated PTEN expression and positively regulated p-AKT expression. MiR-19 only regulates the proliferation of HASM cells induced by HMGB1, but not PDGF, EGF, TGF-β1. Furthermore, we demonstrated that miR-19 contributed to the promoting effects of HMGB1 on ASM cells by targeting PTEN 3’-UTR. Conclusion: Our results demonstrated that HMGB1 induced proliferation and migration of ASM cells via the miR-19a /PTEN/AKT axis and provided direct evidence on the role of HMGB1 in ASM cells proliferation in vitro. The present study further indicated that miR-19a may be explored as a potential novel therapeutic target to reverse proliferation and migration of ASM cells. [ABSTRACT FROM AUTHOR]

Recent improvements in the speed and sensitivity of liquid chromatography-mass spectrometry systems have driven significant progress toward system-wide characterization of the proteome of many species. These efforts create large proteomic datasets that provide insight into biological processes and identify diagnostic proteins whose abundance changes significantly under different experimental conditions. Yet, these system-wide experiments are typically the starting point for hypothesis-driven, follow-up experiments to elucidate the extent of the phenomenon or the utility of the diagnostic marker, wherein many samples must be analyzed. Transitioning from a few discovery experiments to quantitative analyses on hundreds of samples requires significant resources both to develop sensitive and specific methods as well as analyze them in a high-throughput manner. To aid these efforts, we developed a workflow using data acquired from discovery proteomic experiments, retention time prediction, and standard-flow chromatography to rapidly develop targeted proteomic assays. We demonstrated this workflow by developing MRM assays to quantify proteins of multiple metabolic pathways from multiple microbes under different experimental conditions. With this workflow, one can also target peptides in scheduled/dynamic acquisition methods from a shotgun proteomic dataset downloaded from online repositories, validate with appropriate control samples or standard peptides, and begin analyzing hundreds of samples in only a few minutes. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are post-transcriptional regulatory RNAs that can modulate cell signaling and play key roles in cell state transitions. Epstein-Barr virus (EBV) expresses >40 viral miRNAs that manipulate both viral and cellular gene expression patterns and contribute to reprogramming of the host environment during infection. Here, we identified a subset of EBV miRNAs that desensitize cells to B cell receptor (BCR) stimuli, and attenuate the downstream activation of NF-kappaB or AP1-dependent transcription. Bioinformatics and pathway analysis of Ago PAR-CLIP datasets identified multiple EBV miRNA targets related to BCR signal transduction, including GRB2, SOS1, MALT1, RAC1, and INPP5D, which we validated in reporter assays. BCR signaling is critical for B cell activation, proliferation, and differentiation, and for EBV, is linked to reactivation. In functional assays, we demonstrate that EBV miR-BHRF1-2-5p contributes to the growth of latently infected B cells through GRB2 regulation. We further determined that activities of EBV miR-BHRF1-2-5p, EBV miR-BART2-5p, and a cellular miRNA, miR-17-5p, directly regulate virus reactivation triggered by BCR engagement. Our findings provide mechanistic insight into some of the key miRNA interactions impacting the proliferation of latently infected B cells and importantly, governing the latent to lytic switch. [ABSTRACT FROM AUTHOR]

We previously used whole-genome sequencing and Tn5 transposon mutagenesis to identify 16 critical genes involved in the halotolerance of Halomonas beimenensis, a species in the phylum Proteobacteria. In this present study, we sought to determine if orthologous genes in another phylum are also critical for halotolerance. Virgibacillus spp. are halotolerant species that can survive in high-saline environments. Some Virgibacillus species are used in different aspects of food processing, compatible solute synthesis, proteinase production, and wastewater treatment. However, genomic information on Virgibacillus chiguensis is incomplete. We assembled a draft V. chiguensis strain NTU-102 genome based on high-throughput next-generation sequencing (NGS) and used transcriptomic profiling to examine the high-saline response in V. chiguensis. The V. chiguensis draft genome is approximately 4.09 Mbp long and contains 4,166 genes. The expression profiles of bacteria grown in 5% and 20% NaCl conditions and the corresponding Gene Ontology (GO) and clusters of orthologous groups (COG) categories were also analyzed in this study. We compared the expression levels of these 16 orthologs of halotolerance-related genes in V. chiguensis and H. beimenensis. Interestingly, the expression of 7 of the 16 genes, including trkA2, smpB, nadA, mtnN2, rfbP, lon, and atpC, was consistent with that in H. beimenensis, suggesting that these genes have conserved functions in different phyla. The omics data were helpful in exploring the mechanism of saline adaptation in V. chiguensis, and our results indicate that these 7 orthologs may serve as biomarkers for future screening of halotolerant species in the future. [ABSTRACT FROM AUTHOR]

We present a lab-in-the-field experiment to demonstrate how individual behavior in the lab predicts their ability to identify phishing attempts. Using the business and finance staff members from a large public university in the U.S., we find that participants who are intolerant of risk, more curious, and less trusting commit significantly more errors when evaluating interfaces. We also replicate prior results on demographic correlates of phishing vulnerability, including age, gender, and education level. Our results suggest that behavioral characteristics such as intolerance of risk, curiosity, and trust can be used to predict individual ability to identify phishing interfaces. [ABSTRACT FROM AUTHOR]

A feature point based method is proposed for tracking multiple fish in 3D space. First, a simplified representation of the object is realized through construction of two feature point models based on its appearance characteristics. After feature points are classified into occluded and non-occluded types, matching and association are performed, respectively. Finally, the object's motion trajectory in 3D space is obtained through integrating multi-view tracking results. Experimental results show that the proposed method can simultaneously track 3D motion trajectories for up to 10 fish accurately and robustly. [ABSTRACT FROM AUTHOR]

Preharvest sprouting reduces the maize quality and causes a significant yield loss in maize production. vp-wl2 is a Mutator (Mu)-induced viviparous mutant in maize, causing white or pale yellow kernels, dramatically reduced carotenoid and ABA content, and a high level of zeta-carotene accumulation. Here, we reported the cloning of the vp-wl2 gene using a modified digestion-ligation-amplification method (DLA). The results showed that an insertion of Mu9 in the first intron of the zeta-carotene desaturase (ZDS) gene results in the vp-wl2 mutation. Previous studies have suggested that ZDS is likely the structural gene of the viviparous9 (vp9) locus. Therefore, we performed an allelic test using vp-wl2 and three vp9 mutants. The results showed that vp-wl2 is a novel allele of the vp9 locus. In addition, the sequences of ZDS gene were identified in these three vp9 alleles. The vp-wl2 mutant gene was subsequently introgressed into four maize inbred lines, and a viviparous phenotype was observed with yield losses from 7.69% to 13.33%. [ABSTRACT FROM AUTHOR]

Antibody therapy against antibiotics resistant Klebsiella pneumoniae infections represents a promising strategy, the success of which depends critically on the ability to identify appropriate antibody targets. Using a target-agnostic strategy, we recently discovered MrkA as a potential antibody target and vaccine antigen. Interestingly, the anti-MrkA monoclonal antibodies isolated through phage display and hybridoma platforms all recognize an overlapping epitope, which opens up important questions including whether monoclonal antibodies targeting different MrkA epitopes can be generated and if they possess different protective profiles. In this study we generated four anti-MrkA antibodies targeting different epitopes through phage library panning against recombinant MrkA protein. These anti-MrkA antibodies elicited strong in vitro and in vivo protections against a multi-drug resistant Klebsiella pneumoniae strain. Furthermore, mutational and epitope analysis suggest that the two cysteine residues may play essential roles in maintaining a MrkA structure that is highly compacted and exposes limited antibody binding/neutralizing epitopes. These results suggest the need for further in-depth understandings of the structure of MrkA, the role of MrkA in the pathogenesis of Klebsiella pneumoniae and the protective mechanism adopted by anti-MrkA antibodies to fully explore the potential of MrkA as an efficient therapeutic target and vaccine antigen. [ABSTRACT FROM AUTHOR]

Schisandra chinensis extracts (SEs) have traditionally been used as an oriental medicine for the treatment of various human diseases, however, their further application in the biocontrol of plant disease remains poorly understood. This study was conducted to develop eco-friendly botanical pesticides from extracts of S. chinensis and assess whether they could play a key role in plant disease defense. Concentrated active fractions (SE-I, SE-II, and SE-III) were obtained from S. chinensis via specific extraction and separation. Then, lignan-like substances, such as Schisanhenol B, were detected via High-Performance Liquid Chromatography-ElectroSpray Ionization-Mass Spectrometry (HPLC-ESI-MS) analyses of the active fractions. Moreover, the results from biological tests on colony growth inhibition and spore germination indicated that SE-I, SE-II, and SE-III could inhibit hyphal growth and spore generation of three important plant pathogenic fungi (Monilinia fructicola, Fusarium oxysporum, and Botryosphaeria dothidea). The study of the mechanisms of resistant fungi revealed that the oxidation resistance system, including reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), was activated. The expression of genes related to defense, such as pathogenesis-related protein (PR4), α-farnesene synthase (AFS), polyphenol oxidase (PPO), and phenylalanine ammonia lyase (PAL) were shown to be up-regulated after treatment with SEs, which suggested an increase in apple immunity and that fruits were induced to effectively defend against the infection of pathogenic fungi (B. dothidea). This study revealed that SEs and their lignans represent promising resources for the development of safe, effective, and multi-targeted agents against pathogenic fungi. [ABSTRACT FROM AUTHOR]

Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections. [ABSTRACT FROM AUTHOR]

Objective: LNK is an adapter protein negatively regulating the JAK/STAT cell signaling pathway. In this study, we observed the correlation between variation in LNK gene and the clinical type of myeloproliferative neoplasms (MPN). Methods: A total of 285 MPN cases were recruited, including essential thrombocythemia (ET) 154 cases, polycythemia vera (PV) 76 cases, primary myelofibrosis (PMF) 19 cases, and chronic myeloid leukemia (CML) 36 cases. Ninety-three healthy individuals were used as normal controls. V617F mutation in JAK2 was identified by allele-specific PCR method, RT-PCR was used for the detection of BCR/ABL1 fusion gene, and mutations and variations in coding exons and their flanking sequences of LNK gene were examined by PCR-sequencing. Results: Missense mutations of A300V, V402M, and R415H in LNK were found in 8 patients including ET (4 cases, all combined with JAK2-V617F mutation), PV (2 cases, one combined with JAK2-V617F mutation), PMF (one case, combined with JAK2-V617F mutation) and CML (one case, combined with BCR/ABL1 fusion gene). The genotype and allele frequencies of the three SNPs (rs3184504, rs111340708 and rs78894077) in LNK were significantly different between MPN patients and controls. For rs3184504 (T/C, in exon2), the T allele (p.262W) and TT genotype were frequently seen in ET, PV and PMF (P<0.01), and C allele (p.262R) and CC genotype were frequently seen in CML (P<0.01). For rs78894077 (T/C, in exon1), the T allele (p.242S) was frequently found in ET (P<0.05). For rs111340708 (TGGGGx5/TGGGGx4, in intron 5), the TGGGG x4 allele was infrequently found in ET, PMF and CML(P<0.01). Conclusion: Mutations in LNK could be found in some of MPN patients in the presence or absence of JAK2-V617F mutation. Several polymorphisms in LNK gene may affect the clinical type or the genetic predisposition of MPN. [ABSTRACT FROM AUTHOR]

Objectives: Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren’s syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS. Methods: BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA. Results: Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls. Conclusions: Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis. [ABSTRACT FROM AUTHOR]

To clarify the mechanisms of Nosema ceranae parasitism, we deep-sequenced both honey bee host and parasite mRNAs throughout a complete 6-day infection cycle. By time-series analysis, 1122 parasite genes were significantly differently expressed during the reproduction cycle, clustering into 4 expression patterns. We found reactive mitochondrial oxygen species modulator 1 of the host to be significantly down regulated during the entire infection period. Our data support the hypothesis that apoptosis of honey bee cells was suppressed during infection. We further analyzed genome-wide genetic diversity of this parasite by comparing samples collected from the same site in 2007 and 2013. The number of SNP positions per gene and the proportion of non-synonymous substitutions per gene were significantly reduced over this time period, suggesting purifying selection on the parasite genome and supporting the hypothesis that a subset of N. ceranae strains might be dominating infection. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the role of high-mobility group box-1 (HMGB1) in the seizure-induced P-glycoprotein (P-gp) overexpression and the underlying mechanism. Kainic acid (KA)-induced mouse seizure model was used for in vivo experiments. Male C57BL/6 mice were divided into four groups: normal saline control (NS) group, KA-induced epileptic seizure (EP) group, and EP group pretreated with HMGB1 (EP+HMGB1 group) or BoxA (HMGB1 antagonist, EP+BoxA group). Compared to the NS group, increased levels of HMGB1 and P-gp in the brain were observed in the EP group. Injection of HMGB1 before the induction of KA further increased the expression of P-gp while pre-treatment with BoxA abolished this up-regulation. Next, the regulatory role of HMGB1 and its potential involved signal pathways were investigated in mouse microvascular endothelial bEnd.3 cells in vitro. Cells were treated with HMGB1, HMGB1 plus lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) [toll-like receptor 4 (TLR4) antagonist], HMGB1 plus FPS-ZM1 [receptor for advanced glycation end products (RAGE) inhibitor], HMGB1 plus SN50 [nuclear factor-kappa B (NF-κB) inhibitor], or vehicle. Treatment with HMGB1 increased the expression levels of P-gp, TLR4, RAGE and the activation of NF-κB in bEnd.3 cells. These effects were inhibited by the pre-treatment with either LPS-RS or FPS-ZM1, and were abolished by the pre-treatment of SN50 or a combination treatment of both LPS-RS and FPS-ZM1. Luciferase reporter assays showed that exogenous expression of NF-κB p65 increased the promoter activity of multidrug resistance 1a (P-gp-encoding gene) in endothelial cells. These data indicate that HMGB1 contributes to the overexpression of P-gp in mouse epileptic brain tissues via activation of TLR4/RAGE receptors and the downstream transcription factor NF-κB in brain microvascular endothelial cells. [ABSTRACT FROM AUTHOR]

High throughput screenings of single chain Fv (scFv) antibody phage display libraries are currently done as soluble scFvs produced in E.coli. Due to endotoxin contaminations from bacterial cells these preparations cannot be reliably used in mammalian cell based assays. The monovalent nature and lack of Fc in soluble scFvs prevent functional assays that are dependent on target cross linking and/or Fc functions. A convenient approach is to convert scFvs into scFv.Fc fusion proteins and express them in mammalian cell lines for screening. This approach is low throughput and is only taken after primary screening of monovalent scFvs that are expressed in bacteria. There is no platform at present that combines the benefits of both bacterial and mammalian expression system for screening phage library output. We have, therefore, developed a novel dual expression vector, called pSplice, which can be used to express scFv.Fc fusion proteins both in E.coli and mammalian cell lines. The hallmark of the vector is an engineered intron which houses the bacterial promoter and signal peptide for expression and secretion of scFv.Fc in E.coli. When the vector is transfected into a mammalian cell line, the intron is efficiently spliced out resulting in a functional operon for expression and secretion of the scFv.Fc fusion protein into the culture medium. By applying basic knowledge of mammalian introns and splisosome, we designed this vector to enable screening of phage libraries in a product like format. Like IgG, the scFv.Fc fusion protein is bi-valent for the antigen and possesses Fc effector functions. Expression in E.coli maintains the speed of the bacterial expression platform and is used to triage clones based on binding and other assays that are not sensitive to endotoxin. Triaged clones are then expressed in a mammalian cell line without the need for any additional cloning steps. Conditioned media from the mammalian cell line containing the fusion proteins are then used for different types of cell based assays. Thus this system retains the speed of the current screening system for phage libraries and adds additional functionality to it. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a serious complication of systemic inflammatory response syndrome (SIRS), which has a high mortality rate. Previous studies showed that panaxadiol saponin (PDS) and Dexamethasone have similar anti-inflammatory properties and protect cardiopulmonary function in lipopolysaccharide (LPS)-induced septic shock rats. In the present study, we investigated whether PDS or Dexamethasone has a similar role in improving kidney function in LPS-induced AKI mice. Methods and Results: Mice subjected to LPS (10 mg/kg) treatment exhibited AKI demonstrated by markedly increased blood urea nitrogen and creatinine levels compared with controls (P<0.01). However, PDS and Dexamethasone induce similar reverse effects on renal function, such as reduced serum creatinine and blood urea nitrogen levels compared with the LPS group (P<0.05). PDS decreased the production and release of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by inhibiting the NF-κB signaling pathway, down-regulating inducible nitric oxide synthase protein expression levels and inhibiting oxidative stress. In most anti-AKI mechanisms, PDS and dexamethasone were similar, but PDS are better at inhibition of TNF production, promote SOD activity and inhibition of IKB phosphorylation. In addition, nuclear glucocorticoid receptor expression was markedly enhanced in PDS and Dexamethasone treatment groups. Further research is required to determine whether PDS can combine with the glucocorticoid receptor to enter the nucleus. Conclusion: This study demonstrated that PDS and dexamethasone have similar reverse amelioration for renal functions, and have potential application prospects in the treatment of sepsis-induced AKI. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the TNIP1 gene, which encodes the TNF-α–induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a TNIP1 specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance. Objective: To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood. Methods: 424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later. Results: Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight). Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001) in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001) in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index) at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglycerides at 10 years of age. Conclusions: Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis remains a major public health problem in China. The major endemic areas are located in the lake and marshland regions of southern China, particularly in areas along the middle and low reach of the Yangtze River. Spatial analytical techniques are often used in epidemiology to identify spatial clusters in disease regions. This study assesses the spatial distribution of schistosomiasis and explores high-risk regions in Hubei Province, China to provide guidance on schistosomiasis control in marshland regions. Methods: In this study, spatial autocorrelation methodologies, including global Moran’s I and local Getis–Ord statistics, were utilized to describe and map spatial clusters and areas where human Schistosoma japonicum infection is prevalent at the county level in Hubei province. In addition, linear logistic regression model was used to determine the characteristics of spatial autocorrelation with time. Results: The infection rates of S. japonicum decreased from 2009 to 2013. The global autocorrelation analysis results on the infection rate of S. japonicum for five years showed statistical significance (Moran’s I > 0, P < 0.01), which suggested that spatial clusters were present in the distribution of S. japonicum infection from 2009 to 2013. Local autocorrelation analysis results showed that the number of highly aggregated areas ranged from eight to eleven within the five-year analysis period. The highly aggregated areas were mainly distributed in eight counties. Conclusions: The spatial distribution of human S. japonicum infections did not exhibit a temporal change at the county level in Hubei Province. The risk factors that influence human S. japonicum transmission may not have changed after achieving the national criterion of infection control. The findings indicated that spatial–temporal surveillance of S. japonicum transmission plays a significant role on schistosomiasis control. Timely and integrated prevention should be continued, especially in the Yangtze River Basin of Jianghan Plain area. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and endometrial endometrioid adenocarcinoma (EEC) is the major histological type of endometrial cancer. There is a great need for better markers with high sensitivity and specificity to permit early diagnosis and proper management of EEC. The aim of our study is to identify a miRNA classifier within plasma as a noninvasive biomarker for EEC diagnosis. Methods: This study was a retrospective case-control analysis which contained two independent cohorts including 93 participants. First, we screened 375 miRNAs in 29 plasma samples. 9 of the miRNAs were selected to be evaluated their expression by quantitative reverse-transcriptase polymerase chain reaction. A stepwise logistic regression model was then used to establish a new classifier in the validation cohort. Area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy. Co-expression analysis was used to verify the independence of results. Results: miR-15b, -27a, and -223 were found to be differentially expressed in the EEC plasma between the two cohorts and had few connections with other miRNAs. The areas under the curve (AUC) were 0.768, 0.813, and 0.768 for miR-15b, -27a, and 223, respectively. miR-27a and CA125 can be combined as a potential non-invasive biomarker for detecting EEC, with the AUC of 0.894. Conclusion: Our study demonstrated three miRNAs, including miR-15b, -27a, and -233 have a good clinical value in EEC diagnosis. The classifier, including miR-27a and CA125, demonstrated a high accuracy in the diagnosis of EEC and might serve as a novel non-invasive biomarker in the future. [ABSTRACT FROM AUTHOR]

In Parkinson's disease (PD), neuronal cells undergo mitotic catastrophe and endoreduplication prior to cell death; however, the regulatory mechanisms remain to be defined. In this study, we investigated cell cycle regulation of DNA polymerase β (poly β) in rotenone-based dopaminergic cellular and animal models. Incubation with a low concentration (0.25 µM) of rotenone for 1.5 to 7 days resulted in a flattened cell body and decreased DNA replication during S phase, whereas a high concentration (2 µM) of rotenone exposure resulted in enlarged, multi-nucleated cells and converted the mitotic cycle into endoreduplication. Consistently, DNA poly β, which is mainly involved in DNA repair synthesis, was upregulated to a high level following exposure to 2 µM rotenone. The abrogation of DNA poly β by siRNA transfection or dideoxycytidine (DDC) treatment attenuated the rotenone-induced endoreduplication. The cell cycle was reactivated in cyclin D-expressing dopaminergic neurons from the substantia nigra (SN) of rats following stereotactic (ST) infusion of rotenone. Increased DNA poly β expression was observed in the substantia nigra pars compacta (SNc) and the substantia nigra pars reticulate (SNr) of rotenone-treated rats. Collectively, in the in vitro model of rotenone-induced mitotic catastrophe, the overexpression of DNA poly β promotes endoreduplication; in the in vivo model, the upregulation of DNA poly β and cell cycle reentry were also observed in the adult rat substantia nigra. Therefore, the cell cycle regulation of DNA poly β may be involved in the pathological processes of PD, which results in the induction of endoreduplication. [ABSTRACT FROM AUTHOR]

A crude extract of earthworms was used as an eco-friendly, environmentally benign, and easily accessible biocatalyst for various organic synthesis including the asymmetric direct aldol and Mannich reactions, Henry and Biginelli reactions, direct three-component aza-Diels-Alder reactions for the synthesis of isoquinuclidines, and domino reactions for the synthesis of coumarins. Most of these reactions have never before seen in nature, and moderate to good enantioselectivities in aldol and Mannich reactions were obtained with this earthworm catalyst. The products can be obtained in preparatively useful yields, and the procedure does not require any additional cofactors or special equipment. This work provides an example of a practical way to use sustainable catalysts from nature. [ABSTRACT FROM AUTHOR]

Israeli acute paralysis virus (IAPV) is a widespread RNA virus of honey bees that has been linked with colony losses. Here we describe the transmission, prevalence, and genetic traits of this virus, along with host transcriptional responses to infections. Further, we present RNAi-based strategies for limiting an important mechanism used by IAPV to subvert host defenses. Our study shows that IAPV is established as a persistent infection in honey bee populations, likely enabled by both horizontal and vertical transmission pathways. The phenotypic differences in pathology among different strains of IAPV found globally may be due to high levels of standing genetic variation. Microarray profiles of host responses to IAPV infection revealed that mitochondrial function is the most significantly affected biological process, suggesting that viral infection causes significant disturbance in energy-related host processes. The expression of genes involved in immune pathways in adult bees indicates that IAPV infection triggers active immune responses. The evidence that silencing an IAPV-encoded putative suppressor of RNAi reduces IAPV replication suggests a functional assignment for a particular genomic region of IAPV and closely related viruses from the Family Dicistroviridae, and indicates a novel therapeutic strategy for limiting multiple honey bee viruses simultaneously and reducing colony losses due to viral diseases. We believe that the knowledge and insights gained from this study will provide a new platform for continuing studies of the IAPV–host interactions and have positive implications for disease management that will lead to mitigation of escalating honey bee colony losses worldwide. [ABSTRACT FROM AUTHOR]

Bacterial endospores exhibit extreme resistance to most conditions that rapidly kill other life forms, remaining viable in this dormant state for centuries or longer. While the majority of Bacillus subtilis dormant spores germinate rapidly in response to nutrient germinants, a small subpopulation termed superdormant spores are resistant to germination, potentially evading antibiotic and/or decontamination strategies. In an effort to better understand the underlying mechanisms of superdormancy, membrane-associated proteins were isolated from populations of B. subtilis dormant, superdormant, and germinated spores, and the relative abundance of 11 germination-related proteins was determined using multiple-reaction-monitoring liquid chromatography-mass spectrometry assays. GerAC, GerKC, and GerD were significantly less abundant in the membrane fractions obtained from superdormant spores than those derived from dormant spores. The amounts of YpeB, GerD, PrkC, GerAC, and GerKC recovered in membrane fractions decreased significantly during germination. Lipoproteins, as a protein class, decreased during spore germination, while YpeB appeared to be specifically degraded. Some protein abundance differences between membrane fractions of dormant and superdormant spores resemble protein changes that take place during germination, suggesting that the superdormant spore isolation procedure may have resulted in early, non-committal germination-associated changes. In addition to low levels of germinant receptor proteins, a deficiency in the GerD lipoprotein may contribute to heterogeneity of spore germination rates. Understanding the reasons for superdormancy may allow for better spore decontamination procedures. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects and underlying mechanisms of early and late subconjunctival injection of bevacizumab on the inhibition of corneal neovascularization (NV). Methods: Corneal NV was induced by closed eye contact lens wear followed by a silk suture tarsorrhaphy in rabbits. Weekly subconjunctival injections of bevacizumab (5.0 mg) for 1 month were started immediately (early treatment group) or 1 month after induction of corneal NV with continuous induction (late treatment group). The severity of corneal NV was evaluated. Immunostaining was used to evaluate the intracorneal diffusion of bevacizumab, and the existence of pericytes and smooth muscle cells around the NV. The expression of AM-3K, an anti-macrophage antibody, vascular endothelial growth factor (VEGF) with its receptors (VEGFR1 and VEGFR2), and vascular endothelial apoptosis were also evaluated. Western blot analysis was performed to quantify the expression level of VEGF, VEGFR1 and VEGFR2 on corneal epithelium and stroma in different groups. Results: Early treatment with bevacizumab inhibited corneal NV more significantly than late treatment. Intracorneal diffusion of bevacizumab was not different among different groups. Immunostaining showed pericytes and smooth muscle cells around newly formed vessels as early as 2 weeks after induction. Immunostaining and Western blot analysis showed that VEGF, VEGFR1, and VEGFR2 on corneal stroma increased significantly in no treatment groups and late treatment groups, but not in early treatment group. Bevacizumab significantly inhibited macrophage infiltration in the early but not late treatment group. Sporadic vascular endothelial apoptosis was found at 4 weeks in the late but not early treatment group. Conclusions: Early but not late injection of bevacizumab inhibited corneal NV. Late injection of bevacizumab did not alter macrophage infiltration, and can't inhibit the expression of VEGF, VEGFR1, and VEGFR2 on corneal vessels. The inhibition of corneal NV in early treatment group does not occur via vascular endothelial apoptosis. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis remains a major public health problem in China. The major endemic foci are the lake and marshland regions of southern China, particularly the regions along the middle and lower reach of the Yangtze River in four provinces (Hubei, Hunan, Jiangxi, and Anhui). The purpose of our study is to assess the effect of a new integrated strategy emphasizing infection source control to curb schistosomiasis in marshland regions. Methods: In a longitudinal study, we implemented an integrated control strategy emphasizing infection source control in 16 villages from 2005 through 2012 in marshland regions of Hubei province. The interventions included removing cattle from snail-infested grasslands, providing farmers with mechanized farm equipment, improving sanitation by supplying tap water, building lavatories and latrines, praziquantel chemotherapy, controlling snails, and environmental modification. Results: Following the integrated control strategy designed to reduce the role of bovines and humans as sources of Schistosoma japonicum infection, the prevalence of human S. japonicum infection declined from 1.7% in 2005 to 0.4% in 2012 (P<0.001). Reductions were also observed in both sexes, across all age groups, and among high risk occupations. Moreover, the prevalence of bovine S. japonicum infection decreased from 11.7% in 2005 to 0.6% in 2012 (P<0.001). In addition, all the 16 villages achieved the national criteria of infection control in 2008. Conclusion: Our findings indicate that the integrated strategy was likely effective in controlling the transmission of S. japonicum in marshland regions in China. [ABSTRACT FROM AUTHOR]

The recessive opaque-2 mutant gene (o2) reduces α-zeins accumulation in maize endosperm, changes the amino acid composition of maize kernels, induces an opaque endosperm, and increases the lysine content of kernels. The quality protein maize (QPM) inbred line CA339 (o2o2) and an elite normal inbred line liao2345 (O2O2) were used to construct o2 near-isogenic lines (NILs) by marker-assisted selection (MAS) using the co-dominant SSR marker phi057. Two specific o2 NILs were constructed, named liao2345/o2-1 and liao2345/o2-2. However, the kernel phenotypes of the two o2 NILs were different from each other. liao2345/o2-1 had the wild-type vitreous endosperm, which is similar to its recurrent parent liao2345, while the endosperm of liao2345/o2-2 was opaque, identical to typical o2 mutant individuals. In comparison to their recurrent parent liao2345, the lysine concentration of liao2345/o2-1 was similar and the lysine concentration in liao2345/o2-2 was doubled. SDS-PAGE analysis indicated that liao2345/o2-1 had the same zeins ratio as liao2345, whereas the zeins concentration of liao2345/o2-2 was markedly lower. Sequence and transcript abundance analyses indicated that the CDS of two o2 NILs are derived from CA339, but they have different promoters. The O2 transcript of liao2345/o2-2 is largely inhibited because of an rbg transposable element inserted between the TATA box and initiator codon of liao2345/o2-2. We concluded that different crossing-over patterns during the process of o2 NIL construction resulted in the different kernel phenotypes of the two o2 NILs. We surmise that the reversion of liao2345/o2-1 to wild type was due to the recombination with the wild type liao2345 promoter during introgression and backcrossing. The o2 mutant gene of donor (CA339) is a null mutant because of low O2 expression. However, its CDS probably encodes a protein with normal function which can maintain the normal accumulation of zeins in maize endosperm. [ABSTRACT FROM AUTHOR]

Depletion of interstitial cells of Cajal (ICC) is certified in the stomach of diabetic patients. Though electroacupuncture (EA) at ST36 is an effective therapy to regulate gastric motility, the mechanisms of EA at ST36 on gastric emptying and networks of ICC remain to be elucidated. The aims of this study were to investigate the effects of EA on gastric emptying and on the alterations of ICC networks. Rats were randomized into the control, diabetic rats (DM), diabetic rats with sham EA (DM+SEA), diabetic rats with low frequency EA (DM+LEA) and diabetic rats with high frequency EA groups (DM+HEA). The expression of c-kit in each layer of gastric wall was assessed by western blotting. The proliferation of ICC was identified by immunolabeling of c-kit and Ki67 as the apoptosis of ICC was examined by TUNEL staining. The results were as follows: (1) Gastric emptying was severely delayed in the DM group, but accelerated in the LEA and HEA group, especially in the LEA group. (2) The expression of c-kit in each layer was reduced apparently in the DM group, but also up-regulated in the LEA and HEA group. (3) Plentiful proliferated ICC (c-kit+/Ki67+) forming bushy networks with c-kit+ cells were observed in the LEA and HEA group, while the apoptotic cells (c-kit+/TUNEL+) were hardly captured in the LEA and HEA group. Collectively, low and high frequency EA at ST36 rescue the damaged networks of ICC by inhibiting the apoptosis and enhancing the proliferation in the stomach of diabetic rats, resulting in an improved gastric emptying. [ABSTRACT FROM AUTHOR]

Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis. [ABSTRACT FROM AUTHOR]

Background: HIF-1α is a major regulator in tumor progression and metastasis which responds to hypoxia. Many studies have demonstrated that hypoxia-inducible factor1-α (HIF-1α) polymorphisms are significantly associated with cancer metastasis, but the results are inconsistent. We conducted a comprehensive meta-analysis to estimate the associations between HIF-1α C1772 T polymorphism and cancer metastasis. Methods: Comprehensive searches were conducted on PubMed and EMBASE database. Fifteen studies were included in the meta-analysis. We used the OR and 95%CI to assess the associations between HIF-1α C1772T polymorphism and cancer metastasis. Heterogeneity and publication bias were also assessed by Q test, I2, and funnel plot. Results: Totally, fifteen studies including 1239 cases with metastasis-positive (M+) and 2711 cases with metastasis-negative (M−) were performed in this meta-analysis. The results showed that HIF-1a C1772T polymorphism was associated with the increased risk of cancer metastasis (T allele vs. C allele, OR  = 1.36, 95% CI  = 1.12–1.64; TT+ TC vs. CC, OR  = 1.39, 95% CI  = 1.13–1.71; TT vs. TC+ CC, OR  = 1.93, 95% CI  = 0.86–4.36). In the subgroup analyses, the significant associations remained significant among Asians, Caucasians and other cancers in the dominant model. Publication bias was not observed in the analysis. Conclusions: Our results indicate that the HIF-1αC1772T polymorphism T allele may increase the risk of cancer metastasis, which might be a potential risk factor of cancer progress. [ABSTRACT FROM AUTHOR]

Background: Sensitive and specific detection of liver cirrhosis is an urgent need for optimal individualized management of disease activity. Substantial studies have identified circulation miRNAs as biomarkers for diverse diseases including chronic liver diseases. In this study, we investigated the plasma miRNA signature to serve as a potential diagnostic biomarker for silent liver cirrhosis. Methods: A genome-wide miRNA microarray was first performed in 80 plasma specimens. Six candidate miRNAs were selected and then trained in CHB-related cirrhosis and controls by qPCR. A classifier, miR-106b and miR-181b, was validated finally in two independent cohorts including CHB-related silent cirrhosis and controls, as well as non−CHB-related cirrhosis and controls as validation sets, respectively. Results: A profile of 2 miRNAs (miR-106b and miR-181b) was identified as liver cirrhosis biomarkers irrespective of etiology. The classifier constructed by the two miRNAs provided a high diagnostic accuracy for cirrhosis (AUC = 0.882 for CHB-related cirrhosis in the training set, 0.774 for CHB-related silent cirrhosis in one validation set, and 0.915 for non−CHB-related cirrhosis in another validation set). Conclusion: Our study demonstrated that the combined detection of miR-106b and miR-181b has a considerable clinical value to diagnose patients with liver cirrhosis, especially those at early stage. [ABSTRACT FROM AUTHOR]

Evaluation of food compounds by chemosensory cells is essential for animals to make appropriate feeding decisions. In the fruit fly Drosophila melanogaster, structurally diverse chemicals are detected by multimeric receptors composed of members of a large family of Gustatory receptor (Gr) proteins. Putative sugar and bitter receptors are expressed in distinct subsets of Gustatory Receptor Neurons (GRN) of taste sensilla, thereby assigning distinct taste qualities to sugars and bitter tasting compounds, respectively. Here we report a Ca2+ imaging method that allows association of ligand-mediated responses to a single GRN. We find that different sweet neurons exhibit distinct response profiles when stimulated with various sugars, and likewise, different bitter neurons exhibit distinct response profiles when stimulated with a set of bitter chemicals. These observations suggest that individual neurons within a taste modality are represented by distinct repertoires of sweet and bitter taste receptors, respectively. Furthermore, we employed this novel method to identify glucose as the primary ligand for the sugar receptor Gr61a, which is not only expressed in sweet sensing neurons of classical chemosensory sensilla, but also in two supersensitive neurons of atypical taste sensilla. Thus, single cell Ca2+ imaging can be employed as a powerful tool to identify ligands for orphan Gr proteins. [ABSTRACT FROM AUTHOR]

The lungs are highly susceptible to injury, including ischemia/reperfusion (I/R) injury. Pulmonary I/R injury can occur when correcting conditions such as primary pulmonary hypertension, and is also relatively common after lung transplantation or other cardiothoracic surgery. Methods to reduce pulmonary I/R injury are urgently needed to improve outcomes following procedures such as lung transplantation. Remote liver ischemic preconditioning (RLIPC) is an effective cardioprotective measure, reducing damage caused by subsequent cardiac I/R injury, but little is known about its potential role in pulmonary protection. Here, we analyzed the efficacy and mechanistic basis of RLIPC in a rat model of pulmonary I/R injury. RLIPC reduced lung I/R injury, lessening structural damage, inflammatory cytokine production and apoptosis. In addition, RLIPC preserved pulmonary function compared to controls following lung I/R injury. RLIPC stimulated phosphorylation of pulmonary STAT3, a component of the SAFE signaling pathway, but not phosphorylation of RISK pathway signaling proteins. Accordingly, STAT3 inhibition using AG490 eliminated the pulmonary protection afforded by RLIPC. Our data demonstrate for the first time that RLIPC protects against pulmonary I/R injury, via a signaling pathway requiring STAT3 phosphorylation. [ABSTRACT FROM AUTHOR]

The ability to predict what courses a student may enroll in the coming semester plays a pivotal role in the allocation of learning resources, which is a hot topic in the domain of educational data mining. In this study, we propose an innovative approach to characterize students’ cross-college course enrollments by leveraging a novel contextual graph. Specifically, different kinds of variables, such as students, courses, colleges and diplomas, as well as various types of variable relations, are utilized to depict the context of each variable, and then a representation learning algorithm node2vec is applied to extracting sophisticated graph-based features for the enrollment analysis. In this manner, the relations between any pair of variables can be measured quantitatively, which enables the variable type to transform from nominal to ratio. These graph-based features are examined by the random forest algorithm, and experiments on 24,663 students, 1,674 courses and 417,590 enrollment records demonstrate that the contextual graph can successfully improve analyzing the cross-college course enrollments, where three of the graph-based features have significantly stronger impacts on prediction accuracy than the others. Besides, the empirical results also indicate that the student’s course preference is the most important factor in predicting future course enrollments, which is consistent to the previous studies that acknowledge the course interest is a key point for course recommendations. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that caesarean section (CS) may increase the risk of asthma in children, but none of them could preclude potential confounding effects of underlying medical indications for CS. We aim to assess the association between CS itself (without medical indications) and risk of childhood asthma. Methods: We conducted a hospital-based case-control study on childhood asthma with 573 cases and 812 controls in Shanghai. Unconditional logistic regression models in SAS were employed to control for potential confounders. Results: Our study found that CS without medical indication was significantly associated with elevated asthma risk (adjusted OR = 1.58 [95% CI 1.17–2.13]). However, this risk was attenuated in children fed by exclusive breastfeeding in the first six months after birth (adjusted OR = 1.39 [95% CI 0.92–2.10]). In contrast, the risk was more prominent in children with non-exclusive breastfeeding or bottle feeding (adjusted OR = 1.91 [95% CI 1.22–2.99]). Conclusions: CS without medical indication was associated with an increased risk of childhood asthma. Exclusive breastfeeding in infancy may attenuate this risk. [ABSTRACT FROM AUTHOR]

The use of the Internet and social applications has many benefits for the elderly, but numerous investigations have shown that the elderly do not perceive online social networks as a friendly social environment. Therefore, TreeIt, a social application specifically designed for the elderly, was developed for this study. In the TreeIt application, seven mechanisms promoting social interaction were designed to allow older adults to use social networking sites (SNSs) to increase social connection, maintain the intensity of social connections and strengthen social experience. This study’s main objective was to investigate how user interface design affects older people’s intention and attitude related to using SNSs. Fourteen user interface evaluation heuristics proposed by Zhang et al. were adopted as the criteria to assess user interface usability and further grouped into three categories: system support, user interface design and navigation. The technology acceptance model was adopted to assess older people’s intention and attitude related to using SNSs. One hundred and one elderly persons were enrolled in this study as subjects, and the results showed that all of the hypotheses proposed in this study were valid: system support and perceived usefulness had a significant effect on behavioral intention; user interface design and perceived ease of use were positively correlated with perceived usefulness; and navigation exerted an influence on perceived ease of use. The results of this study are valuable for the future development of social applications for the elderly. [ABSTRACT FROM AUTHOR]

Carcass traits of beef cattle have been genetically improved to increase yield of high quality meat. Genome-wide association study (GWAS) is a powerful method to identify genetic variants associated with carcass traits. For the 770K genotyped SNPs from 1141 Chinese Simmental cattle, we used the compressed mixed linear model (CMLM) to perform a genome-wide association study for knuckle, biceps and shank of beef carcass traits. Seventeen significantly associated SNPs were found, which are located on BTA6, BTA14 and BTA15. Interestingly, one pleiotropic quantitative trait nucleotide (QTN), named BovineHD1400007259 (p < 10−8) within the well-known gene region PLAG1-CHCHD7 on BTA14, was found to govern variation of the knuckle, biceps and shank traits. The QTN accounted for 8.6% of phenotypic variance for biceps. In addition, 16 more SNPs distributed on BTA14 were detected as being associated with the carcass traits. [ABSTRACT FROM AUTHOR]

Obesity is a world-wide epidemic disease that correlates closely with type 2 diabetes and cardiovascular diseases. Obesity-induced chronic adipose tissue inflammation is now considered as a critical contributor to the above complications. Momordica charantia (bitter melon, BM) is a traditional Chinese food and well known for its function of reducing body weight gain and insulin resistance. However, it is unclear whether BM could alleviate adipose tissue inflammation caused by obesity. In this study, C57BL/6 mice were fed high fat diet (HFD) with or without BM for 12 weeks. BM-contained diets ameliorated HFD-induced obesity and insulin resistance. Histological and real-time PCR analysis demonstrated BM not only reduced macrophage infiltration into epididymal adipose tissues (EAT) and brown adipose tissues (BAT). Flow cytometry show that BM could modify the M1/M2 phenotype ratio of macrophages in EAT. Further study showed that BM lowered mast cell recruitments in EAT, and depressed pro-inflammatory cytokine monocyte chemotactic protein-1 (MCP-1) expression in EAT and BAT as well as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression in EAT. Finally, ELISA analysis showed BM-contained diets also normalized serum levels of the cytokines. In summary, in concert with ameliorated insulin resistance and fat deposition, BM reduced adipose tissue inflammation in diet-induced obese (DIO) mice. [ABSTRACT FROM AUTHOR]

Background:Previous observational studies have shown that insulin therapy may modify the risk of prostate cancer (PCa). However, these studies yielded controversial results. Thus, we performed this meta-analysis to determine whether insulin use was associated with PCa risk in patients with diabetes mellitus (DM). Method:A literature search was carried out in PubMed, EMBASE, and Cochrane Library Central database between January 1966 and January 2013. Fixed-effect and random-effect models were used to estimate pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were also performed. Result:A total of 11 (10 cohorts, and one case–control) studies published between 2007 and 2013 were included in the meta-analysis, representing data for 205,523 male subjects and 7,053 PCa cases. There were five studies investigating the influence of insulin and other glucose-lowering agents on the risk of PCa , and six studies investigating the influence of glargine and non-glargine insulin. Insulin use was not associated with PCa risk when compared with other glucose-lowering agents (RR=0.89, 95% CI, 0.72-1.09). Use of insulin glargine did not contribute to susceptibility to PCa as compared with use of non-glargine insulin (RR=1.26, 95% CI, 0.86-1.84). Sensitivity analysis confirmed the stability of present results, since no individual study affected the pooled result significantly. Conclusions:Our results suggest that, there may be no significant association between insulin use and risk of PCa as compared with other glucose-lowering agents in patients with DM, and there was no substantial evidence for increase risk of PCa among insulin glargine users as compared to non-glargine insulin users. Further studies are warranted to validate these conclusions. [ABSTRACT FROM AUTHOR]

In the past decade, community-associated (CA-) infections with methicillin-resistant Staphylococcus aureus (MRSA) have emerged throughout the world. Different CA-MRSA strains dominate in different geographical locations. Many CA-MRSA lineages contain genes coding for the Pantón-Valentine leukocidin. However, the role of this leukotoxin in CA-MRSA pathogenesis is still controversial. The genome sequences of two key PVL-positive CA-MRSA strains (USA300, USA400) have been reported, but we lack information on the more recently found PVL-negative CA-MRSA strains. One such strain is the PVL-negative ST72, the main cause of CA-MRSA infections in Korea. Here, we report the entire genome sequence of CA-MRSA ST72 and analyze its gene content with a focus on virulence factors. Our results show that this strain does not have considerable differences in virulence factor content compared to other CA-MRSA strains (USA300, USA400), indicating that other toxins do not substitute for the lack of PVL in ST72. This finding is in accordance with the notion that differential expression of widespread virulence determinants, rather than the acquisition of additional virulence factors on mobile genetic elements, such as PVL, is responsible for the increased virulence of CA- compared to hospital-associated MRSA. [ABSTRACT FROM AUTHOR]

The dynamical process of epidemic spreading has drawn much attention of the complex network community. In the network paradigm, diseases spread from one person to another through the social ties amongst the population. There are a variety of factors that govern the processes of disease spreading on the networks. A common but not negligible factor is people’s reaction to the outbreak of epidemics. Such reaction can be related information dissemination or self-protection. In this work, we explore the interactions between disease spreading and population response in terms of information diffusion and individuals’ alertness. We model the system by mapping multiplex networks into two-layer networks and incorporating individuals’ risk awareness, on the assumption that their response to the disease spreading depends on the size of the community they belong to. By comparing the final incidence of diseases in multiplex networks, we find that there is considerable mitigation of diseases spreading for full phase of spreading speed when individuals’ protection responses are introduced. Interestingly, the degree of community overlap between the two layers is found to be critical factor that affects the final incidence. We also analyze the consequences of the epidemic incidence in communities with different sizes and the impacts of community overlap between two layers. Specifically, as the diseases information makes individuals alert and take measures to prevent the diseases, the effective protection is more striking in small community. These phenomena can be explained by the multiplexity of the networked system and the competition between two spreading processes. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that maternal antibiotics exposure during pregnancy may increase the risk of childhood asthma, but the results were inconsistent. Furthermore, most studies did not examine periconception period as an exposure window. We aim to assess the associations between maternal exposure to specific antibiotics before and during pregnancy and the risk of asthma in early childhood. Methods: Data from the Collaborative Perinatal Project were used. Maternal exposure to antibiotics before and during pregnancy was recorded at each prenatal visit. A total of 39,907 singleton children were followed up to 7 years of age. Multilevel multiple logistic regression models were used to control for potential confounders and account for multiple pregnancies per woman. Results: Maternal use of penicillin or chloramphenicol was associated with an increased risk of asthma in the offspring (adjusted odds ratio = 1.21, 95% confidence interval 1.08–1.36 for penicillin; 1.72 [1.14–2.59] for chloramphenicol). The risk was significantly increased if penicillin or chloramphenicol was used in the 1st trimester (1.09 [1.04–1.13] for penicillin and 1.23 [1.01–1.51] for chloramphenicol). Conclusion: Maternal exposure to certain antibiotics is associated with childhood asthma by 7 years of age. Early pregnancy may be a sensitive window. [ABSTRACT FROM AUTHOR]

Cognitive impairments severely affect the quality of life of patients who undergo brain irradiation, and there are no effective preventive strategies. In this study, we examined the therapeutic potential of electroacupuncture (EA) administered immediately after brain irradiation in rats. We detected changes in cognitive function, neurogenesis, and synaptic density at different time points after irradiation, but found that EA could protect the blood-brain barrier (BBB), inhibit neuroinflammatory cytokine expression, upregulate angiogenic cytokine expression, and modulate the levels of neurotransmitter receptors and neuropeptides in the early phase. Moreover, EA protected spatial memory and recognition in the delayed phase. At the cellular/molecular level, the preventative effect of EA on cognitive dysfunction was not dependent on hippocampal neurogenesis; rather, it was related to synaptophysin expression. Our results suggest that EA applied immediately after brain irradiation can prevent cognitive impairments by protecting against the early changes induced by irradiation and may be a novel approach for preventing or ameliorating cognitive impairments in patients with brain tumors who require radiotherapy. [ABSTRACT FROM AUTHOR]

DNA methylation is thought to be involved in the etiology of neural tube defects (NTDs). However, the exact mechanism between DNA methylation and NTDs remains unclear. Herein, we investigated the change of methylation in mouse model of NTDs associated with folate dysmetabolism by use of ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS), liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS), microarray, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Real time quantitative PCR. Results showed that NTD neural tube tissues had lower concentrations of 5-methyltetrahydrofolate (5-MeTHF, P = 0.005), 5-formyltetrahydrofolate (5-FoTHF, P = 0.040), S-adenosylmethionine (SAM, P = 0.004) and higher concentrations of folic acid (P = 0.041), homocysteine (Hcy, P = 0.006) and S-adenosylhomocysteine (SAH, P = 0.045) compared to control. Methylation levels of genomic DNA decreased significantly in the embryonic neural tube tissue of NTD samples. 132 differentially methylated regions (35 low methylated regions and 97 high methylated regions) were selected by microarray. Two genes (Siah1b, Prkx) in Wnt signal pathway demonstrated lower methylated regions (peak) and higher expression in NTDs (P<0.05; P<0.05). Results suggest that DNA hypomethylation was one of the possible epigenetic variations correlated with the occurrence of NTDs induced by folate dysmetabolism and that Siah1b, Prkx in Wnt pathway may be candidate genes for NTDs. [ABSTRACT FROM AUTHOR]

Complex networks are everywhere, such as the power grid network, the airline network, the protein-protein interaction network, and the road network. The networks are ‘robust yet fragile’, which means that the networks are robust against random failures but fragile under malicious attacks. The cascading failures, system-wide disasters and intentional attacks on these networks are deserving of in-depth study. Researchers have proposed many solutions to improve the robustness of these networks. However whilst many solutions preserve the degree distribution of the networks, little attention is paid to the community structure of these networks. We argue that the community structure of a network is a defining characteristic of a network which identifies its functionality and thus should be preserved. In this paper, we discuss the relationship between robustness and the community structure. Then we propose a 3-step strategy to improve the robustness of a network, while retaining its community structure, and also its degree distribution. With extensive experimentation on representative real-world networks, we demonstrate that our method is effective and can greatly improve the robustness of networks, while preserving community structure and degree distribution. Finally, we give a description of a robust network, which is useful not only for improving robustness, but also for designing robust networks and integrating networks. [ABSTRACT FROM AUTHOR]

Recent years have witnessed the tremendous growth of the online social media. In China, Weibo, a Twitter-like service, has attracted more than 500 million users in less than five years. Connected by online social ties, different users might share similar affective states. We find that the correlation of anger among users is significantly higher than that of joy. While the correlation of sadness is surprisingly low. Moreover, there is a stronger sentiment correlation between a pair of users if they share more interactions. And users with larger number of friends possess more significant sentiment correlation with their neighborhoods. Our findings could provide insights for modeling sentiment influence and propagation in online social networks. [ABSTRACT FROM AUTHOR]

Due to its universality, swarm behavior in nature attracts much attention of scientists from many fields. Fish schools are examples of biological communities that demonstrate swarm behavior. The detection and tracking of fish in a school are of important significance for the quantitative research on swarm behavior. However, different from other biological communities, there are three problems in the detection and tracking of fish school, that is, variable appearances, complex motion and frequent occlusion. To solve these problems, we propose an effective method of fish detection and tracking. In this method, first, the fish head region is positioned through extremum detection and ellipse fitting; second, The Kalman filtering and feature matching are used to track the target in complex motion; finally, according to the feature information obtained by the detection and tracking, the tracking problems caused by frequent occlusion are processed through trajectory linking. We apply this method to track swimming fish school of different densities. The experimental results show that the proposed method is both accurate and reliable. [ABSTRACT FROM AUTHOR]

Background: In South China (Gejiu City, Yunnan Province), lung cancer incidence and associated mortality rate is the most prevalent and observed forms of cancer. Lung cancer in this area is called Gejiu squamous cell lung carcinoma (GSQCLC). Research has demonstrated that overexpression of miR-21 occurs in many cancers. However, the unique relationship between miR-21 and its target genes in GSQCLC has never been investigated. The molecular mechanism involved in GSQCLC must be compared to other non-small cell lung cancers in order to establish a relation and identify potential therapeutic targets. Methodology/Principal Findings: In the current study, we initially found overexpression of miR-21 occurring in non-small cell lung cancer (NSCLC) cell lines when compared to the immortalized lung epithelial cell line BEAS-2B. We also demonstrated that high expression of miR-21 could increase tumor cell proliferation, invasion, viability, and migration in GSQCLC cell line (YTMLC-90) and NSCLC cell line (NCI-H157). Additionally, our results revealed that miR-21 could suppress YTMLC-90 and NCI-H157 cell apoptosis through arresting cell-cycle at G2/M phase. Furthermore, we demonstrated that PTEN, RECK and Bcl-2 are common target genes of miR-21 in NSCLC. Finally, our studies showed that down-regulation of miR-21 could lead to a significant increase in PTEN and RECK and decrease in Bcl-2 at the mRNA and protein level in YTMLC-90 and NCI-H157 cell lines. However, we have not observed any remarkable difference in the levels of miR-21 and its targets in YTMLC-90 cells when compared with NCI-H157 cells. Conclusions/Significance: miR-21 simultaneously regulates multiple programs that enhance cell proliferation, apoptosis and tumor invasiveness by targeting PTEN, RECK and Bcl-2 in GSQCLC. Our results demonstrated that miR-21 may play a vital role in tumorigenesis and progression of lung squamous cell carcinoma and suppression of miR-21 may be a novel approach for the treatment of lung squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Macrosomia has been defined in various ways by obstetricians and researchers. The purpose of the present study was to search for a definition of macrosomia through an outcome-based approach. Methods: In a study of 30,831,694 singleton term live births and 38,053 stillbirths in the U.S. Linked Birth-Infant Death Cohort datasets (1995–2004), we compared the occurrence of stillbirth, neonatal death, and 5-min Apgar score less than four in subgroups of birthweight (4000–4099 g, 4100–4199 g, 4200–4299 g, 4300–4399 g, 4400–4499 g, 4500–4999 g vs. reference group 3500–4000 g) and birthweight percentile for gestational age (90th–94th percentile, 95th-96th, and ≥97th percentile, vs. reference group 75th–90th percentile). Results: There was no significant increase in adverse perinatal outcomes until birthweight exceeded the 97th percentile. Weight-specific odds ratios (ORs) elevated substantially to 2 when birthweight exceeded 4500 g in Whites. In Blacks and Hispanics, the aORs exceeded 2 for 5-min Apgar less than four when birthweight exceeded 4300 g. For vaginal deliveries, the aORs of perinatal morbidity and mortality were larger for most of the subgroups, but the patterns remained the same. Conclusions: A birthweight greater than 4500 g in Whites, or 4300 g in Blacks and Hispanics regardless of gestational age is the optimal threshold to define macrosomia. A birthweight greater than the 97th percentile for a given gestational age, irrespective of race is also reasonable to define macrosomia. The former may be more clinically useful and simpler to apply. [ABSTRACT FROM AUTHOR]