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Background: Studies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence concerning the causal association of LTL with benign and malignant meningiomas or with the location of benign tumors. Methods: We used three LTL datasets from different sources, designated by name and sample size as LTL-78592, LTL-9190, and LTL-472174. The linkage disequilibrium score (LDSC) was used to explore the association between LTL and meningioma. We utilized two-sample bidirectional Mendelian randomization (TSMR) to evaluate whether LTL is causally related to meningioma risk. We adjusted for confounders by conducting multivariable Mendelian randomization (MVMR). Results: In the LTL-78592, longer LTL was significantly associated with increased risk of malignant [odds ratio (OR) = 5.14, p = 1.04 x 10-5], benign (OR = 4.81, p < 0.05), benign cerebral (OR = 5.36, p < 0.05), and benign unspecified meningioma (OR = 8.26, p < 0.05). The same results were obtained for the LTL- 9190. In the LTL-472174, longer LTL was significantly associated with increased risk of malignant (OR = 4.94, p < 0.05), benign (OR = 3.14, p < 0.05), and benign cerebral meningioma (OR = 3.59, p < 0.05). Similar results were obtained in the MVMR. In contrast, only benign cerebral meningioma displayed a possible association with longer LTL (OR = 1.01, p < 0.05). No heterogeneity or horizontal pleiotropy was detected. Conclusion: In brief, genetically predicted longer LTL may increase the risk of benign, malignant, and benign cerebral meningiomas, regardless of the LTL measure, in European populations. [ABSTRACT FROM AUTHOR]

Background: Spermatogenesis is a complex process that includes mitosis, meiosis, and spermiogenesis. During spermatogenesis, genetic factors play a vital role inthe formation of properly functioning sperm. GTPase-activating protein (SH3 domain)- binding protein 2 (G3BP2) is known to take part in immune responses, mRNA transport, and stress-granule assembly. However, its role in male fertility is unclear. Here, we generated a G3bp2 conditional knockout (cKO) mouse model to explore the function of G3BP2 in male fertility. Methods: Polymerase chain reaction (PCR) and western blotting (WB) were used to confirm testis-specific G3bp2 knockout. Hematoxylin-eosin (HE) staining to observe testicular morphology and epididymal structure. Computer-aided sperm analysis (CASA) to detect sperm concentration and motility. Terminal deoxynucleotidyl transferase-dUTP nick-end labeling (TUNEL) assay was used to detect apoptotic cells. Results: We found that cKO male mice are fertile with the normal morphology of the testis and sperm. Additionally, CASA of the semen from cKO mice showed that they all had a similar sperm concentration and motility. In addition, sperm from these mice exhibited a similar morphology. But the tunnel assay revealed increased apoptosis in their testes relative to the level in the wild type (WT). Conclusion: Together, our data demonstrate that G3BP2 is dispensable for spermatogenesis and male fertility in mice albeit with the increased germ-cell apoptosis. [ABSTRACT FROM AUTHOR]

In this study, barium calcium zirconate titanate nanoparticles and nanofibers (denoted as BZT-BCT NPs and BZT-BCT NFs, respectively) were prepared by the sol–gel method and electrospinning, respectively. Under different temperatures and frequencies, the dielectric spectra of polyvinylidene fluoride (PVDF), BZT-BCT NPs, and BZT-BCT NFs composites were measured. On the basis of the experimental data, the polarisation activation energies of the polymer matrix interfacial polarisation and the dipole turn polarisation were calculated, and the basic polarisation characteristic parameters of the polymer matrix materials and fillers were obtained. Moreover, the effects of the filling phase and filling ratio on the dielectric properties of the composites were studied through applying BZT-BCT NPs and BZT-BCT NFs as the filling phases of the PVDF matrix and PVDF matrix composites. Furthermore, the double-layer low-density polyethylene (LDPE)/PVDF composites as well as the LDPE/PVDF composites uniformly mixed at a volume fraction of 1:1 were prepared, and the interfacial polarisation behaviours of the two materials were studied by dielectric spectroscopy to establish an effective analytical method so as to characterize interfacial polarisation established. The experimental results revealed as follows: interfacial polarisation was a significant mechanism of the polarisation behaviour of the composite materials; the fillers with different shape factors had varying effects on the dielectric constant of composites; meanwhile, the dielectric constant of the composite conformed to the predictions of the effective medium theory model. [ABSTRACT FROM AUTHOR]

During 2012-2017, we collected throat swabs from dogs in China to characterize canine influenza virus (CIV) A(H3N2) isolates. A new antigenically and genetically distinct CIV H3N2 clade possessing mutations associated with mammalian adaptation emerged in 2016 and replaced previously circulating strains. This clade probably poses a risk for zoonotic infection. [ABSTRACT FROM AUTHOR]

In this study, an ordered SiO2 nanosphere array coated with vanadium dioxide (VO2) has been fabricated to enhance transmittance with the potential application as an energy-efficient coating in the field of smart windows. SiO2 arrays were formed using the methods of self-assembly, and VO2 thin films were prepared by rapid thermal annealing (RTA) of sputtered vanadium films. VO2@SiO2 arrays were characterized by scanning electron microscopy, X-ray diffraction, a four- point probe, and UV-vis-NIR spectrophotometry. Compared with the planar films, the films deposited on 300 nm diameter SiO2 nanospheres can offer approximately 18% enhancement of luminous transmission (Tlum) because the diameter is smaller than the given wavelength and the protuberance of the surface array behaves as a gradation of refractive index producing antireflection. The solar regulation efficiency was not much deteriorated. [ABSTRACT FROM AUTHOR]

In this study, an ordered SiO2 nanosphere array coated with vanadium dioxide (VO2) has been fabricated to enhance transmittance with the potential application as an energy-efficient coating in the field of smart windows. SiO2 arrays were formed using the methods of self-assembly, and VO2 thin films were prepared by rapid thermal annealing (RTA) of sputtered vanadium films. VO2@SiO2 arrays were characterized by scanning electron microscopy, X-ray diffraction, a fourpoint probe, and UV-vis-NIR spectrophotometry. Compared with the planar films, the films deposited on 300 nm diameter SiO2 nanospheres can offer approximately 18% enhancement of luminous transmission (Tlum) because the diameter is smaller than the given wavelength and the protuberance of the surface array behaves as a gradation of refractive index producing antireflection. The solar regulation efficiency was not much deteriorated. [ABSTRACT FROM AUTHOR]

Although traditional fault diagnosis methods can qualitatively identify the failure modes for power equipment, it is difficult to evaluate the failure probability quantitatively. In this paper, a failure probability calculation method for power equipment based on multi-characteristic parameters is proposed. After collecting the historical data of different fault characteristic parameters, the distribution functions and the cumulative distribution functions of each parameter, which are applied to dispersing the parameters and calculating the differential warning values, are calculated by using the two-parameter Weibull model. To calculate the membership functions of parameters for each failure mode, the Apriori algorithm is chosen to mine the association rules between parameters and failure modes. After that, the failure probability of each failure mode is obtained by integrating the membership functions of different parameters by a weighted method, and the important weight of each parameter is calculated by the differential warning values. According to the failure probability calculation result, the series model is established to estimate the failure probability of the equipment. Finally, an application example for two 220 kV transformers is presented to show the detailed process of the method. Compared with traditional fault diagnosis methods, the calculation results not only identify the failure modes correctly, but also reflect the failure probability changing trend of the equipment accurately. [ABSTRACT FROM AUTHOR]

First, a novel nonlinear Muskingum flood routing model with a variable exponent parameter and simultaneously considering the lateral flow along the river reach (named VEP-NLMM-L) was developed in this research. Then, an improved real-coded adaptive genetic algorithm (RAGA) with elite strategy was applied for precise parameter estimation of the proposed model. The problem was formulated as a mathematical optimization procedure to minimize the sum of the squared deviations (SSQ) between the observed and the estimated outflows. Finally, the VEP-NLMM-L was validated on three watersheds with different characteristics (Case 1 to 3). Comparisons of the optimal results for the three case studies by traditional Muskingum models and the VEP-NLMM-L show that the modified Muskingum model can produce the most accurate fit to outflow data. Application results in Case 3 also indicate that the VEP-NLMM-L may be suitable for solving river flood routing problems in both model calibration and prediction stages. [ABSTRACT FROM AUTHOR]

Background Melphalan resistance has been considered one of the major obstacles to improve outcomes in multiple myeloma (MM) therapy; unfortunately, the mechanistic details of this resistance remain unclear. Melphalan is a highly effective alkylating agent which causes many types of DNA lesions, including DNA base alkylation damage that is repaired by base excision repair (BER). We postulated that human apurinic/apyrimidinic endonuclease 1 (APE1), an essential BER enzyme, plays a vital role in acquired melphalan resistance. However, because APE1 is a multifunctional protein with redox activity and acetylation modification in addition to its major repair activity, the particular APE1 function that may play a more important role in melphalan resistance is unknown. Methods Two MM cell lines, RPMI-8226 and U266 were used to measure the difference in APE1 levels in melphalan-resistant and sensitive derivatives. APE1 functional mutants for DNA repair, redox and acetylation were employed to investigate the roles of individual APE1 activities in acquired melphalan resistance. Results Our results indicate that APE1 is overexpressed in both MM melphalan-resistant cells. Knocking down APE1 sensitizes the melphalan resistant MM cells to melphalan treatment. The exogenous expression of DNA repair mutant H309N and acetylation mutant K6R/K7R of APE1 failed to restore the melphalan resistance of the APE1 knockdown RPMI-8226 cells. The AP endonuclease activity and multidrug resistance protein 1 (MDR1) regulatory activity may play roles in the melphalan resistance of MM cells. Conclusions The present study has identified that the DNA repair functions and the acetylation modification of APE1 are involved in melphalan resistance of MM cells and has also shed light on future therapeutic strategies targeting specific APE1 functions by small molecule inhibitors. [ABSTRACT FROM AUTHOR]

Several viruses within the Coronaviridae family have been categorized as either emerging or re-emerging human pathogens, with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) being the most well known. The NIAID-sponsored Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org) supports bioinformatics workflows for a broad range of human virus pathogens and other related viruses, including the entire Coronaviridae family. ViPR provides access to sequence records, gene and protein annotations, immune epitopes, 3D structures, host factor data, and other data types through an intuitive web-based search interface. Records returned from these queries can then be subjected to web-based analyses including: multiple sequence alignment, phylogenetic inference, sequence variation determination, BLAST comparison, and metadata-driven comparative genomics statistical analysis. Additional tools exist to display multiple sequence alignments, view phylogenetic trees, visualize 3D protein structures, transfer existing reference genome annotations to new genomes, and store or share results from any search or analysis within personal private 'Workbench' spaces for future access. All of the data and integrated analysis and visualization tools in ViPR are made available without charge as a service to the Coronaviridae research community to facilitate the research and development of diagnostics, prophylactics, vaccines and therapeutics against these human pathogens [ABSTRACT FROM AUTHOR]

Lampreys are one of the most primitive vertebrates still living today. They attach themselves to the body surface of the host fish through their sucker-like mouths and suck blood of the host for days. Recent fossil evidence has indicated that morphology of lampreys in the late Devonian period, over 360 million years ago, already possessed the present day major characteristics, suggesting the evolutionary stability of a highly specialized parasitic feeding habit. Obviously, nociceptive responses and hemostasis of the host are two major barriers to long-term feeding of the parasitic lamprey. It has been found, to counteract hemostasis of the host, that paired buccal glands of lampreys secrete antihemostatic compounds to prevent blood of the host from coagulation. However, it is not known how lampreys make the host lose nociceptive responses. Here, we prepared components of the crude extract from the buccal glands of the lampreys ( Lampetra japonica). Then, we show that crude extract and one of its purified components reduce the firing frequency of neuronal action potentials probably through inhibiting the voltage-dependent Na+ channels. As the voltage-gated Na+ channels are highly conserved throughout evolution, we argue that the secretion of the lampreys could exert the similar effect on the Na+ channels of their host fish as well. Therefore, together with its antihemostatic effect, the secretion due to its inhibitory effect on neuronal excitability might provide a mechanism for the parasitic lampreys to keep their evolutionary stability. [ABSTRACT FROM AUTHOR]

The completion of the 5373,180-bp genome sequence of the marine psychrophilic bacterium Colwellia psychrerythraea 34H, a model for the study of life in permanently cold environments, reveals capabilities important to carbon and nutrient cycling, bioremediation, production of secondary metabolites, and cold- adapted enzymes. From a genomic perspective, cold adaptation is suggested in several broad categories involving changes to the cell membrane fluidity, uptake and synthesis of compounds conferring cryotolerance, and strategies to overcome temperature-dependent barriers to carbon uptake. Modeling of three-dimensional protein homology from bacteria representing a range of optimal growth temperatures suggests changes to proteome composition that may enhance enzyme effectiveness at low temperatures. Comparative genome analyses suggest that the psychrophilic lifestyle is most likely conferred not by a unique set of genes but by a collection of synergistic changes in overall genome content and amino acid composition. [ABSTRACT FROM AUTHOR]

We report the complete genome sequence of the model bacterial pathogen Pseudomonas syringae pathovar tomato DC3000 (DC3000), which is pathogenic on tomato and Arabidopsis thaliana. The DC3000 genome (6.5 megabases) contains a circular chromosome and two plasmids, which collectively encode 5,763 ORFs. We identified 298 established and putative virulence genes, including several clusters of genes encoding 31 confirmed and 19 predicted type III secretion system effector proteins. Many of the virulence genes were members of paralogous families and also were proximal to mobile elements, which collectively comprise 7% of the DC3000 genome. The bacterium possesses a large repertoire of transporters for the acquisition of nutrients, particularly sugars, as well as genes implicated in attachment to plant surfaces. Over 12% of the genes are dedicated to regulation, which may reflect the need for rapid adaptation to the diverse environments encountered during epiphytic growth and pathogenesis. Comparative analyses confirmed a high degree of similarity with two sequenced pseudomonads, Pseudomonas putida and Pseudomonas aeruginosa, yet revealed 1,159 genes unique to DC3000, of which 811 lack a known function. [ABSTRACT FROM AUTHOR]

An inverse design of electrostatic focusing field for electrostatic and magnetic imaging is investigated. Using the potential superimposition theorem of electrostatic field in multi-electrode system, a mathematical model has been developed and an optimization method has been introduced into computation for designing the electrostatic focusing field of the imaging system. [ABSTRACT FROM AUTHOR]

Sulphate transport in Neurospora crassa is achieved by two distinct sulphate permeases, I and II, encoded by the cys-13 and cys-14 genes, respectively. The synthesis of both sulphate permeases is subject to sulphur repression and requires the global positive-acting regulatory protein CYS3. CYS3, a bZIP DNA-binding protein, regulates cys-14 expression at the transcriptional level and binds in vitro specifically to three DNA-recognition sites, A, B, and C, in the cys-14 upstream region. In vivo functional analysis of the cys-14 promoter was carried out with 5 deletions and by deletions or mutations of CYS3 DNA-binding sites. The most distal CYS3-binding site, C, located 1.4 kb upstream of the transcriptional start site, is necessary and sufficient to mediate strong transcriptional activation by CYS3; moreover, site C was able to function equally well when it was located at variable distances upstream of the cys-14 gene. Site B, located 1 kb upstream, alone is able to support a moderate degree of cys-14 expression. Site A is not required and does not appear to play any functional role in cys-14 expression, even though it is in close proximity to the transcriptional start site. The presence of multiple copies of CYS3-binding elements A or B in the cys-14 promoter results in a parallel increase of regulated gene expression. When a transforming cys-14 gene becomes integrated at ectopic locations in the host genome, it can be expressed in an unregulated fashion, presumably by coming under the control of other promoter elements. Our results also suggested that at least one enzyme in the sulphate catabolic pathway requires a functional CYS3 protein for expression. [ABSTRACT FROM AUTHOR]