Effects of zinc oxide filler on the curing and mechanical response of alkyd coatings

The mechanical properties of an alkyd resin filled with zinc oxide pigment were studied at different concentrations over a wide range of time scales using dynamic mechanical analysis, quartz crystal rheometry and nanoindentation. The motivation for this work stems from the interest in accessing the long-term properties of paint coatings by studying the mechanical properties of historic paints. In this foundational work, we compare three different modalities of mechanical measurements and systematically determine the effect of pigment filler loading on the measured properties. Quantitative agreement between the methods is obtained when the characteristic time scales of each of the methods is taken into account. While nanoindentation is the technique most readily applied to historic paint samples, the rheometric quartz crystal microbalance (rheo-QCM) is the best suited for obtaining mechanistic information from measurements of paint properties over time, provided that appropriate thin-film samples can be produced. In these studies we find that ZnO increases the rate of oxidation of the alkyd during the initial stages of cure by an amount that depends on the ZnO content

Molecular Mechanism of DNA Topoisomerase I-Dependent rDNA Silencing: Sir2p Recruitment at Ribosomal Genes

Saccharomyces cerevisiae sir2Δ or top1Δ mutants exhibit similar phenotypes involving ribosomal DNA, including (i) loss of transcriptional silencing, resulting in non-coding RNA hyperproduction from cryptic RNA polymerase II promoters; (ii) alterations in recombination; and (iii) a general increase in histone acetylation. Given the distinct enzymatic activities of Sir2 and Top1 proteins, a histone deacetylase and a DNA topoisomerase, respectively, we investigated whether genetic and/or physical interactions between the two proteins could explain the shared ribosomal RNA genes (rDNA) phenotypes. We employed an approach of complementing top1Δ cells with yeast, human, truncated, and chimeric yeast/human TOP1 constructs and of assessing the extent of non-coding RNA silencing and histone H4K16 deacetylation. Our findings demonstrate that residues 115–125 within the yeast Top1p N-terminal domain are required for the complementation of the top1Δ rDNA phenotypes. In chromatin immunoprecipitation and co-immunoprecipitation experiments, we further demonstrate the physical interaction between Top1p and Sir2p. Our genetic and biochemical studies support a model whereby Top1p recruits Sir2p to the rDNA and clarifies a structural role of DNA topoisomerase I in the epigenetic regulation of rDNA, independent of its known catalytic activity

Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, were functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterised. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism

SDSS 0956+5128: A Broad-line Quasar with Extreme Velocity Offsets

We report on the discovery of a Type 1 quasar, SDSS 0956+5128, with a surprising combination of extreme velocity offsets. SDSS 0956+5128 is a broad-lined quasar exhibiting emission lines at three substantially different redshifts: a systemic redshift of z ~ 0.714 based on narrow emission lines, a broad MgII emission line centered 1200 km/s bluer than the systemic velocity, at z ~ 0.707, and broad H\alpha and H\beta emission lines centered at z ~ 0.690. The Balmer line peaks are 4100 km/s bluer than the systemic redshift. There are no previously known objects with such an extreme difference between broad MgII and broad Balmer emission. The two most promising explanations are either an extreme disk emitter or a high-velocity black hole recoil. However, neither explanation appears able to explain all of the observed features of SDSS 0956+5128, so the object may provide a challenge to our general understanding of quasar physics.Comment: ApJ, accepte

Conversion of the Mycotoxin Patulin to the Less Toxic Desoxypatulinic Acid by the Biocontrol Yeast Rhodosporidium kratochvilovae Strain LS11

Se describe en este artículo el descubrimiento de la degradación de la micotoxina patulina por una levaduraThe infection of stored apples by the fungus Penicillium expansum causes the contamination of fruits and fruit-derived products with the mycotoxin patulin, which is a major issue in food safety. Fungal attack can be prevented by beneficial microorganisms, so-called biocontrol agents. Previous time-course thin layer chromatography analyses showed that the aerobic incubation of patulin with the biocontrol yeast Rhodosporidium kratochvilovae strain LS11 leads to the disappearance of the mycotoxin spot and the parallel emergence of two new spots, one of which disappears over time. In this work, we analyzed the biodegradation of patulin effected by LS11 through HPLC. The more stable of the two compounds was purified and characterized by nuclear magnetic resonance as desoxypatulinic acid, whose formation was also quantitated in patulin degradation experiments. After R. kratochvilovae LS11 had been incubated in the presence of 13C-labeled patulin, label was traced to desoxypatulinic acid, thus proving that this compound derives from the metabolization of patulin by the yeast. Desoxypatulinic acid was much less toxic than patulin to human lymphocytes and, in contrast to patulin, did not react in vitro with the thiol-bearing tripeptide glutathione. The lower toxicity of desoxypatulinic acid is proposed to be a consequence of the hydrolysis of the lactone ring and the loss of functional groups that react with thiol groups. The formation of desoxypatulinic acid from patulin represents a novel biodegradation pathway that is also a detoxification process

Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins

Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis

Enhancing the DVIL Chatbot through Linguistic Expertise

Treballs Finals de Grau de Lingüística. Facultat de Filologia. Universitat de Barcelona, Curs: 2022-2023, Tutora: Mariona Taulé[eng] This dissertation focuses on the development of DVIL chatbot integrated in the Data Visualisation in Linguistics (DVIL) platform, a resource that offers visualisation and analytical tools to enhance the analysis of toxicity in the NewsCom-TOX corpus. The chatbot facilitates natural language interaction with the interface by incorporating natural-language understanding techniques and machine learning algorithms to enable dialogue between the users and interface using queries, to carry out a comprehensive analysis of the corpus. The involvement of linguist has been fundamental in refining the chatbot's capabilities through the enhancement of natural language understanding (NLU) and improvement of responses provided by the chatbot. This work presents the current state of the DVIL chatbot and highlights its potential for facilitating analysis within the DVIL interface, while acknowledging ongoing efforts for future improvements. Keywords: chatbot, visualisation interface, natural-language understanding[spa] Este trabajo se centra en el desarrollo del chatbot DVIL integrado en la plataforma de Data Visualisation in Linguistics (DVIL), un recurso que ofrece herramientas de visualización y análisis para mejorar el análisis de toxicidad en el corpus NewsCom-TOX. El chatbot facilita la interacción en lenguaje natural con la interfaz, al incorporar técnicas de comprensión del lenguaje natural y algoritmos de aprendizaje automático para permitir el diálogo entre los usuarios y la interfaz mediante consultas, para llevar a cabo un análisis exhaustivo del corpus. La participación del lingüista ha sido fundamental para mejorar las capacidades del chatbot mediante la mejora de la comprensión del lenguaje natural y la mejora de las respuestas proporcionadas por el chatbot. Este trabajo presenta el estado actual del chatbot DVIL y resalta su potencial para facilitar el análisis dentro de la interfaz DVIL, al tiempo que identifica los esfuerzos en curso para futuras mejoras. Palabras clave: chatbot, interfaz de visualización, comprensión del lenguaje natural[cat] Aquest treball se centra en el desenvolupament del xatbot DVIL integrat en la plataforma de Data Visualisation in Linguistics (DVIL), un recurs que ofereix eines de visualització i anàlisi per millorar l'anàlisi de la toxicitat en el corpus NewsCom-TOX. El xatbot facilita la interacció en llenguatge natural amb la interfície. Incorpora tècniques de comprensió del llenguatge natural i algoritmes d'aprenentatge automàtic per permetre el diàleg entre els usuaris i la interfície mitjançant consultes, i per dur a terme una anàlisi exhaustiva del corpus. La participació del lingüista ha estat fonamental per afinar les capacitats del xatbot a través de la millora de la comprensió del llenguatge natural i de les respostes proporcionades pel xatbot. Aquest treball presenta l'estat actual del xatbot DVIL i destaca el seu potencial per facilitar l'anàlisi dins de la interfície DVIL, tot identificant els esforços en curs per a futures millores. Paraulas clau: xatbot, interfície de visualització, comprensió del llenguatge natura

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management.

Purpose Unexpected fetal abnormalities occur in 2-5% of pregnancies. While traditional cytogenetic and microarray approaches achieve diagnosis in around 40% of cases, lack of diagnosis in others impedes parental counseling, informed decision making, and pregnancy management. Postnatally exome sequencing yields high diagnostic rates, but relies on careful phenotyping to interpret genotype results. Here we used a multidisciplinary approach to explore the utility of rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as an exemplar. Methods Parents in pregnancies undergoing invasive testing because of sonographic fetal abnormalities, where multidisciplinary review considered skeletal dysplasia a likely etiology, were consented for exome trio sequencing (both parents and fetus). Variant interpretation focused on a virtual panel of 240 genes known to cause skeletal dysplasias. Results Definitive molecular diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings alone were of sufficient severity for parents to opt for termination. In others, molecular diagnosis informed accurate prediction of outcome, improved parental counseling, and enabled parents to terminate or continue the pregnancy with certainty. Conclusion Trio sequencing with expert multidisciplinary review for case selection and data interpretation yields timely, high diagnostic rates in fetuses presenting with unexpected skeletal abnormalities. This improves parental counseling and pregnancy management.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.30