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Investigated in this paper is the (2 + 1)-dimensional coupled nonlinear Schrödinger system, which describes the propagation of the optical soliton through the Kerr nonlinear fiber in which each component diffracts in two transverse dimensions. By virtue of the Kadomtsev-Petviashvili hierarchy reduction, we obtain the bright, dark and mixed vector soliton solutions in terms of the Gramian. We investigate the vector solitons graphically: (1) Bright-dark one solitons with one of the components being gray or black are shown. Bouncing, beating, oscillating and breathing effects which appear during the interactions between the bright-dark two solitons are discussed, and those interactions are shape-preserving; (2) Degenerate and non-degenerate dark-dark one solitons are presented. Interaction of the dark-dark two solitons is discussed and the two solitons keep their amplitudes and velocities invariant except for some phase shifts during the interaction; (3) Bound-state and complexes of the bright-bright solitons are presented. [ABSTRACT FROM AUTHOR]

The spectroscopic characteristics of Er-doped lead silicate glasses were investigated with respect to the effects of glass modifiers (Li+, Na+, K+, Mg2+, Ca2+, Sr2+, and Ba2+)with various optical basicities. Using the absorption spectra of the glasses, the Judd--Ofelt parameters of the glasses were calculated and examined, with an emphasis on the glass emission intensity ratio at 1572 nm. The spectra of the samples at low temperatures were examined, and the Stark splitting of Er3+ was investigated. The McCumber method was used to determine the emission cross sections of glasses. The SPM glass exhibited high values of full width at half maximum (51.24 nm) and the emission cross section at 1572 nm (1.908 x 10-21 cm²), with potential applications for guiding component design of 1.5-μm fiber lasers and amplifiers. [ABSTRACT FROM AUTHOR]

Lipocalin‐2 is a functional biomarker for acute and chronic kidney diseases, heart failure and obesity‐related medical complications. It is rapidly induced in epithelial cells under stress conditions, but constitutively produced from pre‐adipocytes and mature adipocytes. Measuring the lipocalin‐2 levels represents an effective approach for risk prediction, patient stratification and disease management. Nevertheless, due to ligand‐binding, post‐translational modification and protein‐protein interaction, lipocalin‐2 exists as multiple variants that elicit different pathophysiological functions. To characterize the specific structure‐functional relationships of lipocalin‐2 variants is critical for the development of biomarker assays with sufficient precision and reliability. Moreover, identifying the pathological forms of lipocalin‐2 will provide new therapeutic targets and treatment approaches for obesity‐related complications. [ABSTRACT FROM AUTHOR]

In some forms of gait analysis, it is important to be able to capture when the heel strikes occur. In addition, in terms of video analysis of gait, it is important to be able to localise the heel where it strikes on the floor. In this study, a new motion descriptor, acceleration flow, is introduced for detecting heel strikes. The key frame of heel strike can be determined by the quantity of acceleration flow within the region of interest, and positions of the strike can be found from the centre of rotation caused by radial acceleration. Our approach has been tested on a number of databases which were recorded indoors and outdoors with multiple views and walking directions for evaluating the detection rate under various environments. Experiments show the ability of our approach for both temporal detection and spatial positioning. The immunity of this new approach to three anticipated types of noises in real CCTV footage is also evaluated in our experiments. The authors acceleration flow detector is shown to be less sensitive to Gaussian white noise, whilst being effective with images of low-resolution and with incomplete body position information when compared with other techniques. [ABSTRACT FROM AUTHOR]

A methodology based on the support vector machine (SVM) combined with a hybrid kernel function (HKF) for accurately modeling the resonant frequencies of the compact microstrip antenna (MSA) is presented and dedicated to reduce the number of samples and simplify the structure when predicting the resonant frequency of the compact MSA by artificial neural network. The parameters of the SVMs and weight coefficients of the HKF are optimized by means of particle swarm optimization algorithm. In addition, two different kernel functions (KFs), namely polynomial KF (a kind of global KF) and Cauchy KF (a kind of local KF), are employed to overcome the disadvantages of traditional KF. The proposed method is validated by the UCI database. The evaluation results show that the HKF can improve the learning ability and generalization ability of the SVM. Furthermore, the resonant frequencies of a planar inverted F-shaped antenna and an L-shaped MSA are modeled by the proposed method. Predictive results with high accuracy demonstrate that the particle swarm optimization-based SVM with the HKF can improve the prediction accuracy for a small dataset. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle (VSM) expresses calcium/calmodulin-dependent protein kinase II (CaMKII)-δ and -β isoforms. CaMKIIδ promotes VSM proliferation and vascular remodeling. We tested CaMKIIβ function in vascular remodeling after injury. CaMKIIβ protein decreased 90% 14 d after balloon injury in rat carotid artery. Intraluminal transduction of adenovirus encoding CaMKIIβC rescued expression to 35% of uninjured controls, inhibited neointima formation (>70%), inhibited VSM proliferation (>60%), and increased expression of the cell-cycle inhibitor p21 (>2-fold). Comparable doses of CaMKIIδ2 adenovirus had no effect. Similar dynamics in CaMKIIβ mRNA and protein expression were observed in ligated mouse carotid arteries, correlating closely with expression of VSM differentiation markers. Targeted deletion of CaMKIIβ in smooth muscle resulted in a 20-fold increase in neointimal area, with a 3-fold increase in the cell proliferation index, no change in apoptosis, and a 60% decrease in p21 expression. In cultured VSM, CaMKIIβ overexpression induced p53 mRNA (1.7 fold) and protein (1.8-fold) expression; induced the p53 target gene p21 (3-fold); decreased VSM cell proliferation (>50%); and had no effect on expression of apoptosis markers. We conclude that regulated CaMKII isoform composition is an important determinant of the injury-induced vasculoproliferative response and that CaMKIIβ and -δ isoforms have nonequivalent, opposing functions. [ABSTRACT FROM AUTHOR]

Despite the abundance of iron in nature, it is the third most limiting nutrient for plants due to its minimal solubility in most soils. While certain soil microbes produce chelating agents that enhance the solubility of iron, the effectiveness of such siderophores in the assimilation of iron by plants is debated. With an increasing understanding that select soil microbes play a signaling role in activating growth and stress responses in plants, the question arises as to whether such symbionts regulate iron assimilation. Here we report a previously unidentified mechanism in which the growth-promoting bacterium Bacillus subtilis GB03 activates the plant’s own iron acquisition machinery to increase assimilation of metal ions in Arabidopsis. Mechanistic studies reveal that GB03 transcriptionally up-regulates the Fe-deficiency-induced transcription factor 1 ( FIT1), which is necessary for GB03-induction of ferric reductase FRO2 and the iron transporter IRT1. In addition, GB03 causes acidification of the rhizosphere by enhancing root proton release and by direct bacterial acidification, thereby facilitating iron mobility. As a result, GB03-exposed plants have elevated endogenous iron levels as well as increased photosynthetic capacity compared with water-treated controls. In contrast, loss-of-function fit1-2 mutants are compromised in terms of enhanced iron assimilation and photosynthetic efficiency triggered by GB03. In all studies reported herein, a physical partition separating roots from bacterial media precludes non-volatile microbial siderophores from contributing to GB03-stimulated iron acquisition. These results demonstrate the potential of microbes to control iron acquisition in plants and emphasize the sophisticated integration of microbial signaling in photosynthetic regulation. [ABSTRACT FROM AUTHOR]

Summary Insect and vertebrate eyes differ in their formation, cellular composition, neural connectivity, and visual function. Despite this diversity, Drosophila atonal and its vertebrate Ortholog in the eye, Ath5 , each regulate determination of the first retinal neuron class—R8 photo-receptors and retinal ganglion cells (RGCs)—in their respective organisms. We have performed a cross-species functional comparison of these genes. In ato [sup 1 ] mutant Drosophila , ectopic Xenopus Ath5 (Xath5 ) rescues photoreceptor cell development comparably with atonal . In contrast, mouse Ath5 (Math5 ) induces formation of very few ommatidia, and most of these lack R8 cells. In the developing frog eye, ectopic atonal , like Xath5 , promotes the differentiation RGCs. Despite strong conservation of atonal , Xath5 , and Math5 structure and shared function, other factors must contribute to the species specificity of retinal neuron determination. These observations suggest that the atonal family may occupy a position in a gene hierarchy where differences in gene regulation or function can be correlated with evolutionary diversity of eye development. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the effects of melatonin on ischemia-induced neuronal DNA strand breaks and its possible mechanisms in a transient middle cerebral artery (MCA) occlusion model. Information on the in situ detection of DNA strand breaks; Discussion on transient MCA occlusion; Assessment of histopathologic outcome; Double staining and confocal laser scanning microscopic analysis.

The title compound, C19H18F2IO6P, prepared as a potential antiviral and anticancer agent from 3-methylsalicylchlorophosphane and 1-(2,4-difluoro-5-iodophenyl)-2-deoxy-β-D-ribofuranose, is one of a 1:1 mixture of two diastereomers. The diastereomers differ in their configuration, S or R, at the asymmetric phosphorus center. X-Ray crystallographic analysis of the title compound has determined the absolute configuration at the asymmetric P center to be S. [ABSTRACT FROM AUTHOR]

Background: This study sought to analyse the impact of elderly age on long-term prognosis of superficial spreading melanoma (SSM) after surgery. Methods: A population-based cohort of patients undergoing resection for SSM from 2004 to 2015 was collected, using data from National Cancer Institute‘ Surveillance, Epidemiology, and End Results (SEER)* Stat software. Patients were divided into the non-elderly group (≤70 years) and elderly group (>70 years). Baseline characteristics and long-term survivals were compared between the two groups. A 1:1 propensity score matching (PSM) was used to reduce the risk of bias. The impact of the elderly age on overall survival (OS) and cause-specific mortality (CSM) was estimated by Cox-regression and competing-risk regression models. Results: Among 12 536 patients with SSM after resection included into the cohort, 8664 patients were ≤70 years, and 3872 were >70 years. Patients in the elderly group had higher incidences of multiple tumours, worse tumour stage and infiltration degree, lymphatic metastasis, and larger size of primary lesions. Using PSM, 3581 pairs of patients were created. On matched analysis, the elderly group was associated with worse OS and CSM. On multivariable Cox-regression and competing-risk regression analyses, elderly age was identified as an independent risk factor of OS and CSM after adjusting for other prognostic variables. Conclusions: The elderly age of patients was independently associated with worse OS and CSM after resection of SSM when baseline and tumour characteristics were balanced. Adjuvant therapy and individualized strategy on follow-up should be made for elderly patients after resection of SSM. [ABSTRACT FROM AUTHOR]

The effects of elevated CO2 (eCO2) on the relative uptake of inorganic and organic nitrogen (N) are unclear. The uptake of different N sources by pak choi (Brassica chinensis L.) seedlings supplied with a mixture of nitrate, glycine and ammonium was studied using 15N‐labelling under ambient CO2 (aCO2) (350 ppm) or eCO2 (650 ppm) conditions. 15N‐labelled short‐term uptake and 15N‐gas chromatography mass spectrometry (GC–MS) were applied to measure the effects of eCO2 on glycine uptake and metabolism. Elevated CO2 increased the shoot biomass by 36% over 15 days, but had little effect on root growth. Over the same period, the N concentrations of shoots and roots were decreased by 30 and 2%, respectively. Elevated CO2 enhanced the uptake and N contribution of glycine, which accounted for 38–44% and 21–40% of total N uptake in roots and shoots, respectively, while the uptake of nitrate and ammonium was reduced. The increased glycine uptake resulted from the enhanced active uptake and enhanced metabolism in the roots. We conclude that eCO2 may increase the uptake and contribution of organic N forms to total plant N nutrition. Our findings provide new insights into plant N regulation under eCO2 conditions. [ABSTRACT FROM AUTHOR]

Traditional offline cable diagnosis methods need power outages during detection, affecting power supply reliability. Here, a hierarchical diagnosis method of cable aged segment based on transfer function is proposed. Firstly, the calculation model of cable transfer function with the aged segment is established; on this basis, the correlation between transfer function and cable aging is analysed. Then, a structure with combined sparse autoencoder and convolutional neural network is trained to estimate the aging location, and a hierarchical diagnosis model of distribution cable based on transfer function is proposed. The sensitivity and accuracy of aged segment detection are improved after hierarchical diagnosis. Finally, the simulation results show that the method proposed in this paper can effectively realize the online identification and location of the cable aged segment. The proposed method makes use of the advantage that the cable transfer function can be obtained online. Compared with the existing methods, this method does not need power outages in the diagnosis process, and the aged segment can be located without a lot of additional equipment. [ABSTRACT FROM AUTHOR]

As a conserved microRNA (miRNA) family in plants, miR408 is known to be involved in different abiotic stress responses, including drought. Interestingly, some studies indicated a species- and/or cultivar-specific drought-responsive characteristic of miR408 in plant drought stress. Moreover, the functions of miR408 in perennial grass species are unknown. In this study, we investigated the role of miR408 in perennial ryegrass (Lolium perenne L.) by withholding water for 10 days for both wild type and transgenic plants with heterologous expression of rice (Oryza sativa L.) miR408 gene, Os-miR408. The results showed that transgenic perennial ryegrass plants displayed morphological changes under normal growth conditions, such as curl leaves and sunken stomata, which could be related to decreased leaf water loss. Moreover, transgenic perennial ryegrass exhibited improved drought tolerance, as demonstrated by maintaining higher leaf relative water content (RWC), lower electrolyte leakage (EL), and less lipid peroxidation compared to WT plants under drought stress. Furthermore, the transgenic plants showed higher antioxidative capacity under drought. These results showed that the improved drought tolerance in Os-miR408 transgenic plants could be due to leaf morphological changes favoring the maintenance of water status and to increased antioxidative capacity protecting against the reactive oxygen species damages under stress. These findings implied that miR408 could serve as a potential target for genetic manipulations to engineer perennial grass plants for improved water stress tolerance. [ABSTRACT FROM AUTHOR]

The aFGF (acidic fibroblast growth factor) plays an important role in morphogenesis, angiogenesis and wound healing and is therefore of potential medical interest. A DNA fragment encoding haFGF (human aFGF) has been cloned into the PVX (potato virus X)-based binary vector (pgR107) and transiently expressed in Nicotiana benthamiana (a wild Australian tobacco) by agroinfection. Approx. 1 week after agroinfection, the recombinant haFGF accumulated in the agroinfected plants reached up to 1% of the total soluble protein. haFGF was then purified on heparin–Sepharose CL-6B. The purified haFGF could stimulate the growth of NIH 3T3 cells, suggesting that the recombinant haFGF expressed via PVX viral vector in N. benthamiana was active biologically. [ABSTRACT FROM AUTHOR]

Commercial formulations of hexachlorocyclohexane (HCH) consist of a mixture of four isomers, α, β, γ and δ. All these four isomers are toxic and recalcitrant pollutants. Sphingobium (formerly Sphingomonas) sp. strain BHC-A is able to degrade all four HCH isomers. Eight lin genes responsible for the degradation of γ-HCH in BHC-A were cloned and analysed for their role in the degradation of δ-HCH, and the initial conversion steps in δ-HCH catabolism by LinA and LinB in BHC-A were found. LinA dehydrochlorinated δ-HCH to produce 1,3,4,6-tetrachloro-1,4-cyclohexadiene (1,4-TCDN) via δ-pentachlorocyclohexene (δ-PCCH). Subsequently, both 1,4-TCDN and δ-PCCH are catalysed by LinB via two successive rounds of hydrolytic dechlorinations to form 2,5-dichloro-2,5-cyclohexadiene-1,4-diol (2,5-DDOL) and 2,3,5-trichloro-5-cyclohexene-1,4-diol (2,3,5-TCDL) respectively. LinB could also catalyse the hydrolytic dechlorination of δ-HCH to 2,3,5,6-tetrachloro-1,4-cyclohexanediol (TDOL) via 2,3,4,5,6-pentachlorocyclohexanol (PCHL). [ABSTRACT FROM AUTHOR]

In the present study, we investigated the effect of melatonin on the outward delayed rectifier potassium currents ( IK) in CA1 pyramidal neurons of rat hippocampal slices using patch-clamp technique in whole-cell configuration. In a concentration-dependent manner, melatonin caused a reduction of IK with a half-maximal inhibitory concentration (IC50) of 3.75 m m. The inhibitory effect had rapid onset and was readily reversible. Melatonin shifted steady-state inactivation of IK in hyperpolarizing direction but did not alter its steady-state activation. Neither luzindole, an MT1/MT2 receptor antagonist, nor prazosin, an MT3 receptor antagonist, blocked melatonin-induced current reduction. The results indicate that melatonin-induced IK inhibition was not via activation of its own membrane receptors. 5-Hydroxytryptamine (5-HT), a melatonin precursor and an agonist of serotonin receptors, when it was given in pipette internal solution but not bath solution, produced a similar inhibitory effect to that of melatonin. Moreover, indole, a major component of melatonin, reversibly and dose dependently inhibited IK with an IC50 of 3.44 m m. Present results suggest that melatonin inhibits IK in hippocampal CA1 pyramidal neurons probably through its interaction with the intracellular indole-related domains of potassium channels. [ABSTRACT FROM AUTHOR]

The dose-range pharmacokinetics of l-(2-deoxy-β-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (5-IDFPdR), a C-aryl nucleoside mimic of IUdR, were studied in male Sprague-Dawley rats following single intravenous (i.v.) and oral doses. After i.v. administration, the blood clearance decreased from ~32 ml/min/kg at a dose of 15 mg/kg, to ~19 ml/min/kg when dosed at 54 mg/kg, and the elimination half-life increased from 8.4 min to 21.5 min, for the respective doses. While the dose-normalized area under the concentration-time curve (AUCnorm) remained practically unchanged (0.132 kg min ml-1) upon increasing the i.v. dose from 5 to 15 mg/kg, it increased by about 44% (~0.19 kg min ml-1) when the i.v. dose was increased from 15 to 54 mg/kg. Similarly, there was a dose-dependent increase in AUCnorm with increasing oral doses: AUCnorm increased by 49% as the oral dose increased from 20 to 40 mg/kg, and further by 55% as the oral dose was increased from 40 mg/kg to 54 mg/kg. For the respective oral doses, the elimination half-life increased from 24.5 min to 176 min, while blood clearance was reduced from ~37 ml/min/kg to ~17 ml/min/kg. The urinary recoveries of unchanged 5-IDFPdR and its glucuronides (as percent of the dose) were somewhat increased at higher doses. This increase was more pronounced following the highest oral dose. The total biliary recovery of 5-IDFPdR (as percent of the dose) was, however, decreased with increasing doses. The overall kinetic profile of 5-IDFPdR based on these data is suggestive of dose-dependent pharmacokinetics. Decreased elimination of 5-IDFPdR with increasing dose, as supported by longer elimination half-lives at higher doses, is one likely mechanism contributing to the dose-dependent behaviour of this compound. Saturable non-renal metabolism might explain the reduced total body clearance of 5-IDFPdR at higher doses, despite the unchanged or increased urinary clearance. For drugs exhibiting nonlinear kinetics, the dosage regimens may need to be carefully designed to avoid potential unpredictable toxicity and/or lack of pharmacological response associated with the disproportional changes in steady state drug concentrations on changing dose. Manifestation in the rat of nonlinear kinetics at doses of 5-IDFPdR, which may be of therapeutic relevance, warrants extended dose-range evaluations of this compound in future preclinical and clinical studies, to establish safe and efficacious dosage regimens. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. However, its pathogenetic mechanism is still poorly understood. An increasing number of studies have evidenced the important role of long noncoding RNAs (lncRNAs) in AD. The aim of the current study was to investigate the effect and molecular mechanism of the lncRNA X‐inactive specific transcript (XIST) in AD. Bilateral common carotid artery occlusion (2VO) was used to induce an AD model in mice. Hydrogen peroxide (H2O2) was used to induce an AD model in N2a cells. The lncRNA XIST, miR‐124, and BACE1 messenger RNA expression levels were detected by a real‐time polymerase chain reaction. The BACE1 protein expression level was detected by western blot and immunofluorescence assay. The Aβ1–42 expression level was detected using an enzyme‐linked immunosorbent assay kit. The expression level of lncRNA XIST was significantly upregulated in AD models, both in vivo and in vitro. Silencing of lncRNA XIST negatively regulated miR‐124 and positively regulated BACE1 expression in N2a cells, which is attenuated by cotransfection of anti‐miR‐124 oligodeoxyribonucleotide (AMO‐124). Silencing of lncRNA XIST reversed the effect of H2O2 on miR‐124, BACE1, and Aβ1–42 expression in N2a cells, which was reversed by cotransfection of AMO‐124. Silencing of lncRNA XIST attenuated AD‐related BACE1 alteration through miR‐124. LncRNA XIST may be a new potential target for the treatment of AD. [ABSTRACT FROM AUTHOR]

Evidence has shown that long noncoding RNAs (lncRNAs) in the competing endogenous RNA (ceRNA) network are involved in various diseases. However, there is a lack of studies of the ceRNA network in diabetic nephropathy (DN). In this study, we investigated the effect of lncRNAs on mesangial cell (MC) proliferation in DN-related ceRNA networks. Differences in lncRNA and mRNA expression between DN and normal mouse kidney tissues were detected with RNA-seq, and DN-related lncRNA/mRNA/microRNA (miRNA) ceRNA networks were constructed by R3.4.3. Computational analysis was performed, and expression and interactions between the topological RNAs were detected by bioinformatics methods, real-time quantitative PCR (qPCR), and luciferase assay. Cell proliferation ability was measured by 5-ethynyl-2'-deoxyuridine (EdU) in MCs cultured under high- or low-glucose conditions. Moreover, the effect of the topological key lncRNA histocompatibility 2 K region locus 2 (H2k2) H2k2 on MC proliferation via the miRNA (miR)-449a/b/triplet motif 11 (Trim11)/Mek signaling pathway was examined by EdU, flow cytometry analysis, and Western blot. In total, 153 lncRNAs, 428 mRNAs, and 2242 interactions were included in the constructed DN-related ceRNA network. There were 15 RNAs in the top 5% of degree and betweenness. The expression of lncRNA H2k2 and mRNA Trim11 in MCs was increased in DN, which is consistent with the results of RNA-seq and real-time qPCR invivo and in vitro. miR-449a and miR-449b, which were down-regulated in MCs cultured with high glucose, were selected for further analysis. The results of real-time qPCR and luciferase assay revealed the lncRNA H2k2-miR-449a/b-Trim11 interaction in MCs. In addition, the data showed that H2k2 regulates MC proliferation via the miR-449ab/Trim11/Mek signaling pathway. Taken together, these results provide new insight into the association between the topological key lncRNA H2k2 in the DN-related ceRNA network and the miR-449a/b/Trim11/Mek signaling pathway during MC proliferation in DN. [ABSTRACT FROM AUTHOR]

Abstract: Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T‐cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy. Furthermore, this work is further to understand the complex interactions between the immune surveillance and develop resistance in tumor cells. As expected, if the promise of these developments is fulfilled, it could develop the effective therapeutic strategies and novel combinations to overcome immune resistance and enhance effector responses, which guide clinicians toward a more “personalized” treatment for advanced CRC patients. [ABSTRACT FROM AUTHOR]

Peroxisomes are a major cellular compartment of eukaryotic cells, and are involved in a variety of metabolic functions and pathways according to species, cell type and environmental conditions. Their biogenesis relies on conserved genes known as PEX genes that encode peroxin proteins. Peroxisomal membrane proteins and peroxisomal matrix proteins are generated in the cytosol and are subsequently imported into the peroxisome post‐translationally. Matrix proteins containing a peroxisomal targeting signal type 1 (PTS1) are recognized by the cycling receptor Pex5p and transported to the peroxisomal lumen. Pex5p docking, release of the cargo into the lumen and recycling involve a number of peroxins, but a key player is the Pex4p–Pex22p complex described in this manuscript. Pex4p from the yeast Saccharomyces cerevisiae is a ubiquitin‐conjugating enzyme that is anchored on the cytosolic side of the peroxisomal membrane through its binding partner Pex22p, which acts as both a docking site and a co‐activator of Pex4p. As Pex5p undergoes recycling and release, the Pex4p–Pex22p complex is essential for monoubiquitination at the conserved cysteine residue of Pex5p. The absence of Pex4p–Pex22p inhibits Pex5p recycling and hence PTS1 protein import. This article reports the crystallization of Pex4p and of the Pex4p–Pex22p complex from the yeast Hansenula polymorpha, and data collection from their crystals to 2.0 and 2.85 Å resolution, respectively. The resulting structures are likely to provide important insights to understand the molecular mechanism of the Pex4p–Pex22p complex and its role in peroxisome biogenesis. [ABSTRACT FROM AUTHOR]

Our previous studies have found that Growth factor receptor-bound protein 2-associated binding protein 2 (Gab2)--a docking protein--governs the development of fatty liver disease. Here, we further demonstrate that Gab2 mediates hepatocarcinogenesis. Compared with a faint expression in para-carcinoma tissue, Gab2 was highly expressed in ~60-70% of human hepatocellular carcinoma (HCC) specimens. Deletion of Gab2 dramatically suppressed diethylnitrosamine-induced HCC in mice. The oncogenic effects of Gab2 in HepG2 cells were promoted by Gab2 overexpression but were rescued by Gab2 knockdown. Furthermore, Gab2 knockout in HepG2 cells restrained cell proliferation, migration and tumor growth in nude mice. Signaling pathway analysis with protein kinase inhibitors demonstrated that oncogenic regulation by Gab2 in hepatic cells involved multiple signaling molecules, including ERK, Akt, and Janus kinases (Jaks), especially those that mediate inflammatory signaling. IL-6 signaling was increased by Gab2 overexpression and impaired by Gab2 deletion via regulation of Jak2 and signal transducer and activator of transcription 3 phosphorylation and the expression of downstream genes, such as Bcl-2 (B-cell lymphoma 2), c-Myc, MMP7 (matrix metalloproteinase-7), and cyclin D1 in vitro and in vivo. These data indicate that Gab2 mediates the pathologic progression of HCC by integrating multiple signaling pathways and suggest that Gab2 might be a powerful therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Transcriptional activation by transcription factors is coupled with histone acetylation and chromatin remodeling. However, the relationship between TGF-β1-induced gene transcription by Krüppel-like factor (KLF)-4 and histone acetylation remains unknown. In our study, KLF4 overexpression or knockdown, respectively increased or decreased H3 acetylation and p300 occupancy, which is concentrated in the region containing TGF-β1 control elements (TCEs) of the genes by TGF-β1 regulation during vascular smooth muscle cell (VSMC) differentiation. Coimmunoprecipitation and glutathione S-transferase pull-down assays showed that phosphatase and tensin homolog (PTEN) formed a complex with KLF4 to inhibit the phosphorylation of the latter in basal conditions. After TGF-β1 signaling activation, PTEN was phosphorylated by p38 MAPK or PI3K/Akt signaling, phosphorylated PTEN lost its ability to dephosphorylate KLF4, and the cofactors interacting with KLF4 switched from PTEN to p300. Then, KLF4-p300 complexes were recruited to KLF4-binding sites of the gene promoter of VSMCs, to acetylate histone H3 and activate transcription. In addition, phosphorylated KLF4 enhanced p300 histone acetyltransferase (HAT) activity via the p38 MAPK pathway, which may be responsible for H3 acetylation. Taken together, the results of our study reveal a novel mechanism whereby KLF4 mediates the link between TGF-β1-induced gene transcription activation and H3 acetylation during VSMC differentiation. [ABSTRACT FROM AUTHOR]

Small 21- to 24-nucleotide (nt) ribonucleic acids (RNAs), notably the microRNA (miRNA), are emerging as a posttranscriptional regulation mechanism. Salt stress is one of the primary abiotic stresses that cause the crop losses worldwide. In saline lands, root growth and function of plant are determined by the action of environmental salt stress through specific genes that adapt root development to the restrictive condition. To elucidate the role of miRNAs in salt stress regulation in Medicago, we used a high-throughput sequencing approach to analyze four small RNA libraries from roots of Zhongmu-1 (Medicago sativa) and Jemalong A17 (Medicago truncatula), which were treated with 300 mM NaCl for 0 and 8 h. Each library generated about 20 million short sequences and contained predominantly small RNAs of 24-nt length, followed by 21-nt and 22-nt small RNAs. Using sequence analysis, we identified 385 conserved miRNAs from 96 families, along with 68 novel candidate miRNAs. Of all the 68 predicted novel miRNAs, 15 miRNAs were identified to have miRNA*. Statistical analysis on abundance of sequencing read revealed specific miRNA showing contrasting expression patterns between M. sativa and M. truncatula roots, as well as between roots treated for 0 and 8 h. The expression of 10 conserved and novel miRNAs was also quantified by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The miRNA precursor and target genes were predicted by bioinformatics analysis. We concluded that the salt stress related conserved and novel miRNAs may have a large variety of target mRNAs, some of which might play key roles in salt stress regulation of Medicago. [ABSTRACT FROM AUTHOR]

Quantitative prediction of deep orebody based on 3D visualization technology is of great significance in mineral exploration. Based on the 2D traditional quantitative predicting method, the geoanomaly theory and the mineral exploration model idea, we constructed 3D models of the topography, strata, structure, magmatite and prospecting engineering of the study area using the commercial 3D modeling software Micromine, delineated eight prospective areas and estimated the gold resources amount with methods of Abundance Estimation and Volume Estimation. Then, we compared and counted the known ore blocks and the predicted blocks, which quantitatively explains this prediction's validity. The results show that Xiaoqinling gold belt in Tongguan has convincing potential for gold development and utilization and the prediction method based on 3D visualization technology proves to be effective. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. [ABSTRACT FROM PUBLISHER]

Background and Aim: Perineural invasion (PNI) is one of the most common routes of invasion in pancreatic cancer and the exact mechanism is still not clear. The aim of the present study was to investigate the effect of nerve growth factor (NGF) and tyrosine kinase receptor A (TrkA) on PNI and to clarify the possible mechanism of PNI in pancreatic cancer. Methods: Expressions of NGF/TrkA were examined in 51 human primary pancreatic cancer using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). The molecular findings were correlated with PNI, clinicopathological parameters and expression of Ki-67. Results: Immunohistochemical analysis indicated that the presence and kind of PNI are prognostic parameters ( P = 0.002,, P = 0.004). Tumors with high NGF expression exhibited more frequent presence of PNI ( P = 0.033). NGF expression was significantly correlated with metastasis of lymph nodes and involvement of surgical margins ( P = 0.006, 0.015). TrkA expression was significantly correlated with degree of PNI ( P = 0.017). Negative correlations were found between expression of NGF/TrkA and Ki-67. As shown by RT-PCR, mRNA levels of NGF/TrkA with PNI were significantly higher than that without PNI. Conclusions: In pancreatic cancer, overexpression of NGF may contribute to PNI by prompting the hyperplasia of nerves, restraining the apoptosis of tumor cells and specifically combining NGF and TrkA. [ABSTRACT FROM AUTHOR]

Aim: To compare the clinical features of hepatitis B e antigen (HBeAg)-negative and HBeAg-positive cirrhosis, and to define the survival and prognostic indicators of Chinese HBeAg-negative hepatitis B virus (HBV)-related cirrhosis. Methods: Two hundred and seventeen patients with chronic hepatitis B cirrhosis were studied. Survival was calculated using the Kaplan–Meier method. Proportional hazards Cox regression procedure was used to identify independent predictors of survival. The relationship between HBV-DNA viral load and prognosis was also investigated. Results: The mean follow-up time was 35 months (3–47 months). HBeAg-negative liver cirrhosis patients comprised the greatest number of cirrhosis patients. Median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, median total leukocytes (WBC), hemoglobin (Hb), platelet (Plt) and HBV-DNA levels and the proportion of HBV-DNA > 105 copies/mL were lower in HBeAg-negative patients. There were fewer complications in patients treated with lamivudine than in other patients. Survival rates were significantly reduced in patients with HBeAg-negative cirrhosis ( P = 0.0024). The baseline Child–Pugh scores and more than one decompensation during follow up were independent variables correlated with survival of HBeAg-negative liver cirrhosis patients ( P = 0.006 and P = 0.001, respectively). The HBV-DNA viral load did not correlate with any complications or mortality rates of HBeAg-negative patients. Conclusions: The clinical features of HBeAg-negative and -positive liver cirrhosis differ. Survival was significantly reduced for Chinese patients with HBeAg-negative than -positive cirrhosis. Factors contributing to the prognosis were baseline Child–Pugh scores and the presence of more than one decompensation during follow up. [ABSTRACT FROM AUTHOR]

Interleukin 6 (IL-6) influences the growth and survival of multiple myeloma (MM) cells via the activation of multiple signalling cascades. Although sphingosine kinase (SPHK) signalling is known to play important roles in the regulation of cell proliferation and apoptosis, the role of SPHK activation in IL-6 signalling and in the pathology of MM remains unclear. This study found that IL-6 activated SPHK in MM cells, which mediates the suppressive effects of IL-6 on MM cell apoptosis. Both MM cell lines and primary MM cells constitutively expressed SPHK, and treatment of MM cells with IL-6 resulted in activation of SPHK in a concentration-dependent manner. Specific inhibitors of the phosphatidylinositol-3 kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways blocked the IL-6-induced activation of SPHK. It was further demonstrated that IL-6-induced activation of SPHK inhibited dexamethasone-induced apoptosis of MM cells. IL-6 stimulation or retroviral-mediated overexpression of SPHK1 in MM cells resulted in increased intracellular SPHK activity and upregulation of myeloid cell leukaemia-1 (Mcl-1), leading to increased cell proliferation and survival. Conversely, inhibition of SPHK1 by small interfering RNA reduced IL-6-induced upregulation of Mcl-1 and blocked the suppressive effect of IL-6 on MM cell apoptosis. Taken together, these results delineate a key role for SPHK activation in IL-6-induced proliferation and survival of MM cells, and suggest that SPHK may be a potential new therapeutic target in MM. [ABSTRACT FROM AUTHOR]

The effects of melatonin on the mitochondrial DNA (mtDNA) damage induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine ion (MPP+) were investigated both in vivo and in vitro. MPTP (24 mg/kg, s.c.) induced a rapid increase in the immunoreactivity of 8-hydroxyguanine (8-oxoG), a common biomarker of DNA oxidative damage, in the cytoplasm of neurons in the Substantia Nigra Compact of mouse brain. Melatonin preinjection (7.5, 15 or 30 mg/kg, i.p.) dose-dependently prevented MPTP-induced DNA oxidative damage. In SH-SY5Y cells, MPP+ (1 m m) increased the immunoreactivity of 8-oxoG in the mitochondria at 1 hr and in the nucleus at 3 hr after treatment. Melatonin (200 μ m) preincubation significantly attenuated MPP+-induced mtDNA oxidative damage. Furthermore, MPP+ time-dependently increased the accumulation of mitochondrial oxygen free radicals (mtOFR) from 1 to 24 hr and gradually decreased the mitochondrial membrane potential (Ψ m) from 18 to 36 hr after incubation. At 72 hr after incubation, MPP+ caused cell death in 49% of the control. However, melatonin prevented MPP+-induced mtOFR generation and Ψ m collapse, and later cell death. The present results suggest that cytoprotection of melatonin against MPTP/MPP+-induced cell death may be associated with the attenuation of mtDNA oxidative damage via inhibition of mtOFR generation and the prevention of Ψ m collapse. [ABSTRACT FROM AUTHOR]

Herein we report on a simple, low cost, and feasible route for the construction of PbZr0.4Ti0.6O3 (PZT)- or Ba0.9Sr0.1TiO3 (BST)-based optical microcavities using a single chemical solution containing polymer polyvinylpyrrolidone. The obtained multilayer systems not only exhibit good ferroelectric performance, but also display well-defined resonant modes with a quality factor of no <66. Compared with PZT microcavities, the optical properties of the BST microcavities appear to be superior. [ABSTRACT FROM AUTHOR]

Quasiperiodic Ba0.9Sr0.1TiO3 (BST) multilayers have been fabricated on SrTiO3 substrates by using chemical solutions containing polyethylene glycol (PEG), and effect of PEG content on optical properties of the BST multilayers have been investigated. Each multilayer with a single perovskite phase displays a layered structure consisting of dense and porous BST layers. It is found that the central wavelength of the reflection-band for BST multilayers shifts to longer wavelength with increasing the PEG concentration within a given polymer amount range. With the same numbers of period and processing condition, the BST multilayers derived from chemical solutions containing PEG additives with a relative molar amount of 0.5, exhibit the highest optical reflectivities. [ABSTRACT FROM AUTHOR]