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Genomic best linear unbiased prediction (GBLUP) is the most widely used model for genome-wide predictions. Interestingly, it is also possible to perform genome-wide association studies (GWAS) based on GBLUP. Although the estimated marker effects in GBLUP are shrunken and the conventional test based on such effects has low power, it was observed that a modified test statistic can be produced and the result of test was identical to a standard GWAS model. Later, a mathematical proof was given for the special case that there is no fixed covariate in GBLUP. Since then, the new approach has been called "GWAS by GBLUP". Nevertheless, covariates such as environmental and subpopulation effects are very common in GBLUP. Thus, it is necessary to confirm the equivalence in the general case. Recently, the concept was generalized to GWAS for epistatic effects and the new approach was termed rapid epistatic mixed-model association analysis (REMMA) because it greatly improved the computational efficiency. However, the relationship between REMMA and the standard GWAS model has not been investigated. In this study, we first provided a general mathematical proof of the equivalence between "GWAS by GBLUP" and the standard GWAS model for additive effects. Then, we compared REMMA with the standard GWAS model for epistatic effects by a theoretical investigation and by empirical data analyses. We hypothesized that the similarity of the two models is influenced by the relative contribution of additive and epistatic effects to the phenotypic variance, which was verified by empirical and simulation studies. [ABSTRACT FROM AUTHOR]

Motivation: Brain imaging genetics studies the complex associations between genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). The neurodegenerative disorders usually exhibit the diversity and heterogeneity, originating from which different diagnostic groups might carry distinct imaging QTs, SNPs and their interactions. Sparse canonical correlation analysis (SCCA) is widely used to identify bimultivariate genotype–phenotype associations. However, most existing SCCA methods are unsupervised, leading to an inability to identify diagnosis-specific genotype–phenotype associations. Results: In this article, we propose a new joint multitask learning method, named MT–SCCALR, which absorbs the merits of both SCCA and logistic regression. MT–SCCALR learns genotype–phenotype associations of multiple tasks jointly, with each task focusing on identifying one diagnosis-specific genotype–phenotype pattern. Meanwhile, MT– SCCALR cannot only select relevant SNPs and imaging QTs for each diagnostic group alone, but also allows the selection of those shared by multiple diagnostic groups. We derive an efficient optimization algorithm whose convergence to a local optimum is guaranteed. Compared with two state-of-the-art methods, MT–SCCALR yields better or similar canonical correlation coefficients and classification performances. In addition, it owns much better discriminative canonical weight patterns of great interest than competitors. This demonstrates the power and capability of MTSCCAR in identifying diagnostically heterogeneous genotype–phenotype patterns, which would be helpful to understand the pathophysiology of brain disorders. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have gained central importance for the identification of candidate loci underlying complex traits. Single nucleotide polymorphism (SNP) markers are mostly used as genetic variants for the analysis of genotype-phenotype associations in populations, but closely linked SNPs that are grouped into haplotypes are also exploited. The benefit of haplotype-based GWAS approaches vs. SNP-based approaches is still under debate because SNPs in high linkage disequilibrium provide redundant information. To overcome some constraints of the commonly-used haplotype-based GWAS in which only consecutive SNPs are considered for haplotype construction, we propose a new method called functional haplotype-based GWAS (FH GWAS). FH GWAS is featured by combining SNPs into haplotypes based on the additive and epistatic effects among SNPs. Such haplotypes were termed functional haplotypes (FH). As shown by simulation studies, the FH GWAS approach clearly outperformed the SNP-based approach unless the minor allele frequency of the SNPs making up the haplotypes is low and the linkage disequilibrium between them is high. Applying FH GWAS for the trait flowering time in a large Arabidopsis thaliana population with whole-genome sequencing data revealed its potential empirically. FH GWAS identified all candidate regions which were detected in SNP-based and two other haplotype-based GWAS approaches. In addition, a novel region on chromosome 4 was solely detected by FH GWAS. Thus both the results of our simulation and empirical studies demonstrate that FH GWAS is a promising method and superior to the SNP-based approach even if almost complete genotype information is available. [ABSTRACT FROM AUTHOR]

In this paper, we consider the exponential stabilization for Timoshenko beam with different delays in the boundary control. Suppose that the controller outputs are of the form α1u1(t) + β1u1(t - τ1) + γ1u1 (t - τ2) and α2u2(t) + β2u2(t - τ1) + γ2u2(t - τ2), where u1(t) and u2(t) are the inputs of boundary controllers. [ABSTRACT FROM AUTHOR]

Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. [ABSTRACT FROM AUTHOR]

Plant non-specific lipid-transfer proteins (nsLTPs) are small, basic proteins present in abundance in higher plants. They are involved in key processes of plant cytology, such as the stablization of membranes, cell wall organization, and signal transduction. nsLTPs are also known to play important roles in resistance to biotic and abiotic stress, and in plant growth and development, such as sexual reproduction, seed development and germination. The structures of plant nsLTPs contain an eight-cysteine residue conserved motif, linked by four disulfide bonds, and an internal hydrophobic cavity, which comprises the lipid-binding site. This structure endows stability and increases the ability to bind and/or carry hydrophobic molecules. There is growing interest in nsLTPs, due to their critical roles, resulting in the need for a comprehensive review of their form and function. Relevant topics include: nsLTP structure and biochemical features, their classification, identification, and characterization across species, sub-cellular localization, lipid binding and transfer ability, expression profiling, functionality, and evolution. We present advances, as well as limitations and trends, relating to the different topics of the nsLTP gene family. This review collates a large body of research pertaining to the role of nsLTPs across the plant kingdom, which has been integrated as an in depth functional analysis of this group of proteins as a whole, and their activities across multiple biochemical pathways, based on a large number of reports. This review will enhance our understanding of nsLTP activity in planta, prompting further work and insights into the roles of this multifaceted protein family in plants. [ABSTRACT FROM AUTHOR]

Pathologists are expected to accurately diagnose increasingly smaller breast carcinomas. Correct classification (ie, lobular vs ductal or in situ vs invasive) directly affects subsequent management, especially when the focus is near a surgical margin or present in a needle core biopsy and is further challenging if the lesion is morphologically ambiguous. We assessed the diagnostic utility of a multiplex, trichromogen immunostain of 3 commonly employed antibodies (CK7, p63, and E-cadherin) developed in our laboratory to evaluate these small lesions. Of the 147 specimens containing minimal (defined as ≤3 mm in size) invasive carcinoma, 81 also contained in situ carcinoma. In each case, the Minimal Carcinoma Triple Stain was prepared with a parallel H&E-stained slide. Observations of staining characteristics in the focus of interest were recorded. The Minimal Carcinoma Triple Stain was diagnostically useful in all but 1 case. In a case of invasive lobular carcinoma in an excisional biopsy, the Minimal Carcinoma Triple Stain stained only the surrounding breast tissue (appropriately) and not the focus of interest. Also, a subset of 29 of 81 excisional biopsies had minimal invasive carcinoma located 2 mm or less from the inked surgical margin, in which in all cases the Minimal Carcinoma Triple Stain was fully interpretable despite morphologic distortion due to concomitant cautery artifact and tissue disruption in some cases. The Minimal Carcinoma Triple Stain offers an accurate and tissue-conserving method to diagnose small, morphologically problematic foci of breast carcinoma while ideally leaving more tissue for additional adjunctive studies. [ABSTRACT FROM AUTHOR]

1-Bromopropane (1-BP) was introduced as an alternative to ozone-depleting solvents. However, it was found to exhibit neurotoxicity, reproductive toxicity, and hepatotoxicity in rodents and neurotoxicity in human. However, the mechanisms underlying the toxicities of 1-BP remain elusive. The present study investigated the role of oxidative stress in 1-BP–induced hepatotoxicity using nuclear factor erythroid 2–related factor 2 (Nrf2)–null mice. Groups of 24 male Nrf2-null mice and 24 male wild-type (WT) C57BL/6J mice were each divided into three groups of eight and exposed to 1-BP at 0, 100, or 300 ppm for 8 h/day for 28 days by inhalation. Liver histopathology showed significantly larger area of necrosis in Nrf2-null mice relative to WT mice at the same exposure level. Nrf2-null mice also had greater malondialdehyde (MDA) levels, higher ratio of oxidized glutathione/reduced form of glutathione, and lower total glutathione content. The constitutive level and the increase in ratio per exposure level of glutathione S-transferase (GST) activity were lower in the liver of Nrf2-null mice than WT mice. Exposure to 1-BP at 300 ppm increased the messenger RNA levels of heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GcLm), glutamate-cysteine synthetase (GcLc), glutathione reductase, and NAD(P)H: quinone oxidoreductase 1 (NQO1) in WT mice but not in Nrf2-null mice except for GST Yc2. Nrf2-null mice were more susceptible to 1-BP–induced hepatotoxicity. That oxidative stress plays a role in 1-BP hepatotoxicity is deduced from the low expression levels and activities of antioxidant enzymes and high MDA levels in Nrf2-null mice. [ABSTRACT FROM PUBLISHER]

The linear reaction–diffusion problem – ε2Δu + bu = f is considered on the unit square with homogeneous Dirichlet boundary conditions. Here ε is a small positive parameter and the problem is in general singularly perturbed. The numerical solution of this problem is analysed on a Shishkin mesh that has N intervals in each coordinate direction, using the Galerkin finite-element method with bilinear trial functions. The accuracy of this method, measured in the associated energy norm, is shown to be O(N−2 + ε1/2N−1 ln N). It is proved that a two-scale sparse grid method achieves the same order of accuracy while reducing the number of degrees of freedom from O(N2) to O(N3/2). These results are then generalized to systems of reaction–diffusion equations. [ABSTRACT FROM PUBLISHER]

Possible promoter regions preceding 14 genes belonging to the proteolytic system of Streptococcus thermophilus KLDS 3.0503 were predicted by a promoter analysis softwarennpp. The 14 genes included an extracellular protease gene prtS, an oligopeptide ABC transport system gene amiA1, and 12 genes, respectively, encoding peptidases pepA, pepS, pepN, pepC, pepB, pepQ, pepV, pepT, pepM, pepXP, pepP, and pepO. These predicted promoter sequences were cloned and inserted into the upstream of a promoterless Escherichia coli gusA (β-glucuronidase) gene in a promoter probe vector pNZ273. The resulting vectors were, respectively, introduced into S. thermophilus KLDS 3.0503 and all 14 predicted promoter sequences were able to drive gusA expression, which indicated that these sequences were functional promoters. These promoters were able to interact with the S. thermophilus CodY homolog in an in vitro DNA binding assay but they did not contain a conserved CodY-box sequence identified in Lactococcus lactis. These results were useful for further studies on the regulation of protein metabolism in S. thermophilus. [ABSTRACT FROM AUTHOR]

Dechlorination of spiked 1,2,3,4-tetrachlorodibenzo- p-dioxin (1,2,3,4-TeCDD) was investigated in sediment microcosms from three polychlorinated dibenzo- p-dioxin and dibenzofuran (CDD/F)-contaminated sites: River Kymijoki, Finland; Gulf Island Pond, Maine; and Lake Roosevelt, Washington. Dechlorination was stimulated by addition of electron donor and halogenated priming compounds, and bioaugmentation by a mixed culture containing Dehalococcoides ethenogenes strain 195. Amendment with 1,2,3,4-tetrachlorobenzene (1,2,3,4-TeCB) promoted rapid dechlorination of 1,2,3,4-TeCDD to 2-monochlorodibenzo- p-dioxin (2MCDD) in Gulf Island Pond and River Kymijoki sediments, however, only slow dechlorination to 1,4-dichlorodibenzo- p-dioxin was observed in Lake Roosevelt sediments. The dechlorination pathway in 1,2,3,4-TeCB-amended microcosms proceeded mainly via 1,3-dichlorodibenzo- p-dioxin, with less production of 2,3-dichlorodibenzo- p-dioxin in comparison with other treatments. Microbial community analyses indicated that Dehalococcoides-like bacteria were enriched with 1,2,3,4-TeCB. Quantitative real-time PCR analysis of Dehalococcoides-specific 16S rRNA genes and the D. ethenogenes strain 195 dehalogenase gene, tceA, showed at least an order of magnitude higher gene copy numbers in the bioaugmented than in the nonbioaugmented microcosms. An active-dechlorinating population is present in the River Kymijoki and biostimulation may enhance both native Dehalococcoides spp. and the bioaugmented D. ethenogenes strain 195. [ABSTRACT FROM AUTHOR]

Mast cells have recently been found to be a major player in the host defence against bacterial infection through secretion of potent mediators. Identification of bacteria-induced mast cell mediators and intracellular signalling molecules involved during bacterial infection remains a major area of investigation. Recently we found an active interaction between mast cells and Pseudomonas aeruginosa bacteria. To further characterize specific genes in mast cells modulated by P. aeruginosa, we used a new approach for the study of mast cell–bacteria interaction; the suppression subtractive hybridization (SSH). SSH approach does not require a prerequisite knowledge of target genes and does not rely on the availability of the assay reagents for the specific genes. Using SSH, 94 clones were randomly selected from the subtracted cDNA library for differential screening leading to the identification of 14 P. aeruginosa–up-regulated transcripts. Sequence analysis revealed that expression of IL-1, IL-8 and CCL4 was increased by human mast cells after P. aeruginosa infection. Increased production of IL-1, IL-8 and CCL4 was confirmed at the protein levels. In addition, sequence analysis of the clones also suggests that ribosomal protein S3 and cytochrome b as well as additional 4 uncharacterized genes may potentially be involved in P. aeruginosa pathogenesis. Thus, SSH is an effective approach by identifying potential molecular targets for the study of mechanisms involved in P. aeruginosa and mast cell interaction. [ABSTRACT FROM AUTHOR]

The actions of pepsin and the admixture of pepsin and Monascus pilosus carboxypeptidase 1 (MpiCP-1) on the hydrolysis of soybean protein were studied. The results showed that the pepsin hydrolyzate of soybean protein was much more bitter and contained relatively smaller amounts of total free amino acids than the hydrolyzate obtained with the admixture of pepsin and MpiCP-1. In addition, hydrophilic and hydrophobic amino acids were present in almost equal proportions in the pepsin hydrolyzate, while mainly hydrophobic amino acids made up the hydrolyzate obtained with the admixture of pepsin and MpiCP-1. These results suggest that MpiCP-1 suppresses and reverses the development of the bitterness taste that results from the pepsin hydrolysis of soybean protein by releasing mainly hydrophobic amino acids from the C-termini of the bitter components. [ABSTRACT FROM AUTHOR]

2-D seismic modelling has notable dynamic information discrepancies with field data because of the implicit line-source assumption, whereas 3-D modelling suffers from a huge computational burden. The 2.5-D approach is able to overcome both of the aforementioned limitations. In general, the earth model is treated as an elastic material, but the real media is viscous. In this study, we develop an accurate and efficient frequency-domain finite-element method (FEM) formodelling 2.5-D viscoelasticwave propagation. To performthe 2.5-D approach, we assume that the 2-D viscoelastic media are based on the Kelvin-Voigt rheological model and a 3-D point source. The viscoelastic wave equation is temporally and spatially Fourier transformed into the frequency-wavenumber domain. Then, we systematically derive the weak form and its spatial discretization of 2.5-D viscoelastic wave equations in the frequency-wavenumber domain through the Galerkin weighted residual method for FEM. Fixing a frequency, the 2-D problem for each wavenumber is solved by FEM. Subsequently, a composite Simpson formula is adopted to estimate the inverse Fourier integration to obtain the 3-D wavefield. We implement the stiffness reduction method (SRM) to suppress artificial boundary reflections. The results show that this absorbing boundary condition is valid and efficient in the frequency- wavenumber domain. Finally, three numerical models, an unbounded homogeneous medium, a half-space layered medium and an undulating topography medium, are established. Numerical results validate the accuracy and stability of 2.5-D solutions and present the adaptability of finite-element method to complicated geographic conditions. The proposed 2.5-D modelling strategy has the potential to address modelling studies on wave propagation in real earth media in an accurate and efficient way. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs regulating gene expression in eukaryotes. They play important roles in regulating caste differentiation, behavior development, and immune defences in the honey bee, Apis mellifera (Linnaeus) (Hymenoptera: Apidae). In this study, we explored the effect of the neonicotinoid insecticide, thiamethoxam, on miRNA expression in this species using deep small RNA sequencing. The results showed that seven miRNAs were significantly differentially expressed (q-value <0.01 and log2(fold-change) >1) upon exposure to 10 ppb thiamethoxam over 10 d. Some candidate target genes were related to behavior, immunity, and neural function. Several miRNAs, including ame-miR-124, ame-miR-981, ame-miR-3791, and ame-miR-6038, were selected and further validated using real-time quantitative PCR analysis. The findings expand our understanding of the effects of neonicotinoid insecticides on honey bees at the molecular level. [ABSTRACT FROM AUTHOR]

: Objectives To investigate characteristics of nine carbapenem-non-susceptible (CP-NS) Escherichia coli isolates collected between 1999 and 2005 at a Taiwanese university hospital. : Methods Genetic relatedness was analysed by PFGE. β-Lactamases were characterized by PCR and isoelectric focusing. Outer membrane proteins and transcripts were investigated by SDS–PAGE and northern blotting. Cloning experiments were performed to investigate the role of membrane permeability in carbapenem non-susceptibility. : Results The nine CP-NS isolates were found to produce the CMY-2 AmpC enzyme (n = 8), the CTX-M-14-type extended-spectrum β-lactamase (ESBL) (n = 1), the SHV-12 ESBL (n = 1) and the IMP-8-type metallo-β-lactamase (n = 1) alone or in combination. All CP-NS isolates revealed a decrease in the transcription and protein expression of ompC, and susceptibility to carbapenems was restored in one isolate by introducing the cloned ompC gene. PFGE revealed genetic diversity among the nine isolates. All patients with the CP-NS isolates had been treated with carbapenems (six patients) and/or extended-spectrum cephalosporins (five patients) before isolation. : Conclusions Our study suggests that the decreased susceptibility to carbapenems in E. coli in the hospital might arise by the stepwise accumulations of multiple drug-resistance determinants in different clones. [ABSTRACT FROM AUTHOR]

: Objectives To investigate the role of a plasmid bearing the erm(B) gene on the prevalence of the macrolide, lincosamide and group B streptogramin (MLSB) phenotype of group A streptococci (GAS) and to characterize the plasmid and determine the clonal relation between the erythromycin-resistant isolates. : Methods Two hundred and five erythromycin-resistant GAS isolates were collected from 1990 to 2006. Colony hybridization, PCR, plasmid curing and PFGE techniques were used to analyse the mechanisms behind the phenotypes. : Results Among the 56 isolates with constitutive MLSB (cMLSB) resistance, 53 isolates harboured a plasmid, pA15, of 19 kb. erm(B) was on pA15 and it confered a cMLSB resistance phenotype. The prevalence rate of the pA15-containing isolates was 36.3% from 1993 to 1995, but the plasmid could not be detected from 2004 to 2006. To link the high-level resistance to pA15, clinical isolate A15 was selected and pA15 was cured by novobiocin. In the plasmid‐cured strain SW503, the erythromycin MIC decreased from 256 to 0.032 mg/L. By electroporation, pA15 was re-introduced into the plasmid-cured erythromycin-susceptible strain, and the high-level erythromycin resistance was restored. Plasmid pA15 was also transferred to group B streptococci and group C streptococci by electroporation. In all the pA15-containing isolates, emm1 type was present and pulse type J was predominant (48 of 54 isolates). : Conclusions The plasmid pA15 mediated cMLSB resistance in the mid-1990s, but pA15 was not detected in the clinical isolates from 2004 onwards, which correlates with the absence of cMLSB resistance in this region. [ABSTRACT FROM AUTHOR]

Objectives: The Minimal Carcinoma (MC) Triple Stain is a tri-chromogen multiplex immunostain (CK7, p63, and E-cadherin) helpful in classifying morphologically ambiguous and/or small carcinomas as either ductal or lobular and/or in situ or invasive. We compared the utility of this stain with two commercially available duplex/multiplex immunostains: Breast Triple Stain (BTS) (Clarient, Aliso Viejo, CA; CK5, p63, and CK8/18) and LC/DC Breast Cocktail (LCDC) (Biocare, Concord, CA; E-cadherin and p120).Methods: Ninety-seven mammary carcinomas stained with the MC Triple Stain, BTS, and LCDC were compared.Results: The MC Triple Stain, LCDC, and BTS were diagnostic in 90 (93%) of 97, 82 (85%) of 97, and 85 (88%) of 97 of cases, respectively. All stains showed decreased diagnostic utility due to variability in tissue integrity, quality of the staining, and/or ease of interpretation. In cases where all immunostains were interpretable, the MC Triple Stain yielded the most information.Conclusions: When technically sufficient, all three immunostains demonstrated relative strengths and weaknesses in their ability to provide diagnostic information with the highest consistency and ease of use. Many cases stained with LCDC were technically insufficient due to a suboptimal staining protocol provided by the company. Overall, the MC Triple Stain outperformed BTS and LCDC by more consistently providing more diagnostic information. The MC Triple Stain is a viable alternative to other multiplex immunostains in evaluating small foci of carcinoma, particularly when both the histologic type and extent of disease (in situ vs invasive) require clarification. [ABSTRACT FROM AUTHOR]

The use of usnic acid and usnic acid-containing products is associated with acute liver failure; however, mechanistic studies of hepatotoxicity caused by usnic acid are limited. In this study, we investigated and characterized the possible mechanisms, especially the role of autophagy in usnic acid's toxicity in human HepG2 cells. Usnic acid caused apoptosis as demonstrated by an increased caspase-3/7 activity and an increased subdiploid nucleus formation. Usnic acid-induced autophagy as demonstrated by the conversion of LC3B-I to LC3B-II, degradation of P62, and an increased number of puncta. Inhibition of autophagy by treating cells with autophagy inhibitors (3-methyladenine or chloroquine) or by small interfering RNA against Atg7 aggravated usnic acid-induced apoptosis and decreased cell viability, indicating that autophagy plays a protective role against usnic acid-induced toxicity. Moreover, usnic acid activated the MAPK signaling pathway. Usnic acid-elicited apoptosis was enhanced and autophagy was decreased when JNK was suppressed by a specific inhibitor. Additionally, inhibition of autophagy decreased the activity of JNK. Taken together, our results suggest that usnic acid perturbs various interrelated signaling pathways and that autophagy induction is a defensive mechanism against usnic acid-induced cytotoxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Eutopic endometria with endometriosis (EMs) differ dramatically from normal endometria, physiologically and biochemically, yet the pathogenesis of EMs remains unclear. Cofilin-1 (CFL1), a critical modulator of the actin cystoskeleton, is associated with tumour progression, cell motility, cell adhesion, cell invasion and angiogenesis. Although eutopic endometria with EMs exhibit many malignant-like behaviours and a higher expression of CFL1 than normal endometria, the effects of CFL1 on the pathogenesis of EMs are unknown. The aim of this study was to explore the role of CFL1 expression in proliferation, apoptosis, adhesion, invasion, angiogenesis and ultrastructure of endometrial cells. [ABSTRACT FROM AUTHOR]

As an effective means of multi-agent problem solving, autonomous individual programming and interaction that are essential need, are limited in their ability to accommodate the interests of others, and therefore, may unnecessarily constrain the solving ability and negotiability of an agent, particularly in a distributed cooperative environments founded on private and uncertain information. In this paper, a multi-agent group programming model is presented, where each agent executes local programming by evolutionary search. Based on co-evolution idea, agents resolve conflicts and revise their own search direction to optimize local and social objectives in an interactive process by means of clustering and group choice. Finally, the paper presents simulation results that illustrate the operational effectiveness of our agent group programming model. [ABSTRACT FROM PUBLISHER]

Maize (Zea mays) is a monoecious plant, in which inflorescence morphogenesis involves complicated molecular regulatory mechanisms. Although many related genes have been cloned, our understanding of the molecular mechanism underlying maize inflorescence development remains limited. Here, we identified a maize semi-dominant mutant Silky3 (Si3), which displays pleiotropic defects during inflorescence development, including loss of determinacy and identity in meristems and floral organs, as well as the sexual transformation of tassel florets. We cloned the si3 gene using a map-based approach. Functional analysis reveals that SI3 is a nuclear protein and may act as a transcriptional regulator. Transcriptome analysis reveals that the ectopic expression of si3 strongly represses multiple biological processes, especially the flower development pathways. RNA in situ hybridization similarly shows that the expression patterns of genes responsible for flower development are changed in the Si3 mutant. In addition, the homeostasis of jasmonic acid and gibberellic acid are altered in the Si3 young tassels, and application of exogenous jasmonic acid can rescue the sex reversal phenotype of Si3. The defects we characterized in various regulatory pathways can explain the complex phenotypes of Si3 mutant, and this study deepens our knowledge of maize inflorescence development. [ABSTRACT FROM AUTHOR]

The extrusion of toxins and substances at a cellular level is a vital life process in plants under abiotic stress. The multidrug and toxic compound extrusion (MATE) gene family plays a large role in the exportation of toxins and other substrates. We carried out a genome-wide analysis of MATE gene families in Gossypium raimondii and Gossypium arboreum and assessed their expression levels under salt, cadmium and drought stresses. We identified 70 and 68 MATE genes in G. raimondii and G. arboreum, respectively. The majority of the genes were predicted to be localized within the plasma membrane, with some distributed in other cell parts. Based on phylogenetic analysis, the genes were subdivided into three subfamilies, designated as M1, M2 and M3. Closely related members shared similar gene structures, and thus were highly conserved in nature and have mainly evolved through purifying selection. The genes were distributed in all chromosomes. Twenty-nine gene duplication events were detected, with segmental being the dominant type. GO annotation revealed a link to salt, drought and cadmium stresses. The genes exhibited differential expression, with GrMATE18, GrMATE34, GaMATE41 and GaMATE51 significantly upregulated under drought, salt and cadmium stress, and these could possibly be the candidate genes. Our results provide the first data on the genome-wide and functional characterization of MATE genes in diploid cotton, and are important for breeders of more stress-tolerant cotton genotypes. [ABSTRACT FROM AUTHOR]

The initiation of sexual development in the important edible and medicinal mushroom Flammulina velutipes is controlled by special genes at two different, independent, mating type (MAT) loci: HD and PR. We expanded our understanding of the F. velutipes mating type system by analyzing the MAT loci from a series of strains. The HD locus of F. velutipes houses homeodomain genes (Hd genes) on two separated locations: sublocus HD-a and HD-b. The HD-b subloci contained strain-specific Hd1/Hd2 gene pairs, and crosses between strains with different HD-b subloci indicated a role in mating. The function of the HD-a sublocus remained undecided. Many, but not all strains contained the same conserved Hd2 gene at the HD-a sublocus. The HD locus usually segregated as a whole, though we did detect one new HD locus with a HD-a sublocus from one parental strain, and a HD-b sublocus from the other. The PR locus of F. velutipes contained pheromone receptor (STE3) and pheromone precursor (Pp) genes at two locations, sublocus PR-a and PR-b. PR-a and PR-b both contained sets of strain-specific STE3 and Pp genes, indicating a role in mating. PR-a and PR-b cosegregated in our experiments. However, the identification of additional strains with identical PR-a, yet different PR-b subloci, demonstrated that PR subloci can recombine within the PR locus. In conclusion, at least three of the four MAT subloci seem to participate in mating, and new HD and PR loci can be generated through intralocus recombination in F. velutipes. [ABSTRACT FROM AUTHOR]

Plant height, which shows dynamic development and heterosis, is a major trait affecting plant architecture and has an indirect in uence on economic yield related to biological yield in cotton. In the present study, we carried out dynamic analysis for plant height and its heterosis by quantitative trait loci (QTL) mapping at multiple developmental stages using two recombinant inbred lines (RILs) and their backcross progeny. At the single-locus level, 47 QTL were identi ed at ve developmental stages in two hybrids. In backcross populations, QTL identi ed at an early stage mainly showed partial effects and QTL detected at a later stage mostly displayed overdominance effects. At the two-locus level, we found that main effect QTL played a more important role than epistatic QTL in the expression of heterosis in backcross populations. Therefore, this study implies that the genetic basis of plant height heterosis shows dynamic character and main effect QTL with dominance determines heterosis for plant height in Upland cotton. [ABSTRACT FROM AUTHOR]

Cotton fiber, a raw natural fiber material, is widely used in the textile industry. Understanding the genetic mechanism of fiber traits is helpful for fiber quality improvement. In the present study, the genetic basis of fiber quality traits was explored using two recombinant inbred lines (RILs) and corresponding backcross (BC) populations under multiple environments in Upland cotton based on marker analysis. In backcross populations, no significant correlation was observed between marker heterozygosity and fiber quality performance and it suggested that heterozygosity was not always necessarily advantageous for the high fiber quality. In two hybrids, 111 quantitative trait loci (QTL) for fiber quality were detected using composite interval mapping, in which 62 new stable QTL were simultaneously identified in more than one environment or population. QTL detected at the single-locus level mainly showed additive effect. In addition, a total of 286 digenic interactions (E-QTL) and their environmental interactions [QTL × environment interactions (QEs)] were detected for fiber quality traits by inclusive composite interval mapping. QE effects should be considered in molecular marker-assisted selection breeding. On average, the E-QTL explained a larger proportion of the phenotypic variation than the main-effect QTL did. It is concluded that the additive effect of single-locus and epistasis with few detectable main effects play an important role in controlling fiber quality traits in Upland cotton. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) production, essential for global food security, is threatened by the brown planthopper (BPH). The breeding of host-resistant crops is an economical and environmentally friendly strategy for pest control, but few resistance gene resources have thus far been cloned. An indica rice introgression line RBPH5, derived from wild rice Oryza rufipogon, has been identified with sustainable resistance to BPH, which is governed by recessive alleles at two loci. In this study, a map-based cloning approach was used to fine-map one resistance gene locus to a 24 kb region on the short arm of chromosome 6. Through genetic analysis and transgenic experiments, BPH29, a resistance gene containing a B3 DNA-binding domain, was cloned. The tissue specificity of BPH29 is restricted to vascular tissue, the location of BPH attack. In response to BPH infestation, RBPH54 activates the salicylic acid signalling pathway and suppresses the jasmonic acid/ethylene-dependent pathway, similar to plant defence responses to biotrophic pathogens. The cloning and characterization of BPH29 provides insights into molecular mechanisms of plant-insect interactions and should facilitate the breeding of rice host-resistant varieties. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells. Methods. The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined. Results. We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2–8 μmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD ( P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group ( P < 0.05). Conclusion. The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the in vivo antibacterial efficacy of nemonoxacin, a novel C8-methoxy non-fluorinated quinolone in murine systemic and local infection models. Methods The efficacy of nemonoxacin in systemic infections was evaluated in mouse peritonitis models using isolates of methicillin-susceptible Staphylococcus aureus (MSSA, n = 1), methicillin-resistant S. aureus (MRSA, n = 1), methicillin- and levofloxacin-resistant Staphylococcus capitis (levofloxacin-resistant MRSC, n = 1), penicillin-intermediate Streptococcus pneumoniae (PISP, n = 1), penicillin-resistant S. pneumoniae (PRSP, n = 2), Enterococcus faecalis (n = 2, including 1 vancomycin-resistant Enterococcus, VRE) and Escherichia coli (n = 3). The local infections included mouse pulmonary infections caused by PRSP (n = 1), Klebsiella pneumoniae (n = 1) and mouse ascending urinary tract infection caused by E. coli (n = 1). Results In the mouse systemic infection model, nemonoxacin demonstrated potent activity against MSSA (ED50 = 2.08 mg/kg), MRSA (ED50 = 2.59 mg/kg), levofloxacin-resistant MRSC (ED50 = 2.52 mg/kg), PISP (ED50 = 5.47 mg/kg), PRSP (ED50 = 3.68–5.28 mg/kg) and E. coli (ED50 = 3.13–5.28 mg/kg), and moderate activity towards E. faecalis infection (ED50 = 8.48–15.16 mg/kg). The therapeutic efficacy of nemonoxacin was significantly higher (P < 0.01) than that of levofloxacin in infections caused by Gram-positive isolates (MSSA, MRSA, levofloxacin-resistant MRSC, PISP, PRSP and E. faecalis), but less potent than that of levofloxacin against E. coli infection (P < 0.01). Nemonoxacin in vivo efficacy results with Gram-positive isolates (2- to 5-fold ED50 advantage over levofloxacin) are consistent with the MIC data (4- to 16-fold MIC advantage of nemonoxacin over levofloxacin). In the mouse pulmonary infection model, nemonoxacin showed potent activity towards PRSP (higher than levofloxacin) and K. pneumoniae (lower than levofloxacin) infections. In the mouse ascending urinary tract infection model, nemonoxacin exhibited potent activity against E. coli infection (lower than levofloxacin). Conclusions The results validated the potent efficacy of nemonoxacin in vivo. The higher efficacy of nemonoxacin than of levofloxacin towards infections caused by Gram-positive cocci (especially MRSA, levofloxacin-resistant MRSC, PRSP and VRE) warrants investigation of its clinical use. [ABSTRACT FROM PUBLISHER]

We consider the influence of magnetic fields on the model of neutrino-dominated accretion flows (NDAFs) for gamma-ray bursts (GRBs) via the assumption that the accretion rate of the disc is totally caused by the torque of the Lorentz force, i.e. the magnetic braking of large-scale magnetic fields and magnetic viscosity of small-scale magnetic fields. We calculate the structure, composition, luminosity of neutrino emission and the Poynting flux, and the rate of mass loss driven by neutrino heating or launched centrifugally by large-scale magnetic fields, based on the physical condition of the magnetized NDAFs. It is shown that the magnetized disc is favourable to interpret the diverse prompt emissions as well as the X-ray flares observed in the early afterglow of GRBs. [ABSTRACT FROM AUTHOR]

Plant roots show an impressive degree of plasticity in adapting their branching patterns to ever-changing growth conditions. An important mechanism underlying this adaptation ability is the interaction between hormonal and developmental signals. Here, we analyze the interaction of jasmonate with auxin to regulate lateral root (LR) formation through characterization of an Arabidopsis thaliana mutant, jasmonate-induced defective lateral root1 (idl1/asa1-1). We demonstrate that, whereas exogenous jasmonate promotes LR formation in wild-type plants, it represses LR formation in jdl1/ asa1-1. JDL1 encodes the auxin biosynthetic gene ANTHRANILATE SYNTHASE α1 (ASA1), which is required for jasmonate-induced auxin biosynthesis. Jasmonate elevates local auxin accumulation in the basal meristem of wild-type roots reduces local auxin accumulation in the basal meristem of mutant roots, suggesting that, in addition to activating ASA1- dependent auxin biosynthesis, jasmonate also affects auxin transport. Indeed, jasmonate modifies the expression of auxin transport genes in an ASA1-dependent manner. We further provide evidence showing that the action mechanism jasmonate to regulate LR formation through ASA1 differs from that of ethylene. Our results highlight the importance of ASA in jasmonate-induced auxin biosynthesis and reveal a role for jasmonate in the attenuation of auxin transport in the root the fine-tuning of local auxin distribution in the root basal meristem. [ABSTRACT FROM AUTHOR]

Here, we report our effort in generating an ORFeome collection for the Arabidopsis transcription factor (TF) genes. In total, ORFeome clones representing 1,282 Arabidopsis TF genes have been obtained in the Gateway high throughput cloning pENTR vector, including 411 genes whose annotation lack cDNA support. All the ORFeome inserts have also been mobilized into a yeast expression destination vector, with an estimated 85% rate of expressing the respective proteins. Sequence analysis of these clones revealed that 34 of them did not match with either the reported cDNAs or current predicted open-reading-frame sequences. Among those, novel alternative splicing of TF gene transcripts is responsible for the observed differences in at least five genes. However, those alternative splicing events do not appear to be differentially regulated among distinct Arabidopsis tissues examined. Lastly, expression of those TF genes in 17 distinct Arabidopsis organ types and the cultured cells was profiled using a 70-mer oligo microarray. [ABSTRACT FROM AUTHOR]