25 research outputs found

    Structural basis for the role of Serine-Rich Repeat Proteins from Lactobacillus reuteri in gut microbe-host interactions

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    Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP100-23) that was vital for L. reuteri biofilm formation in mice. SRRPs have emerged as an important group of surface proteins on many pathogens but no structural information is available in commensal bacteria. Here we report the 2.00 Å and 1.92 Å crystal structures of the binding regions (BRs) of SRRP100-23 and SRRP53608 from L. reuteri ATCC 53608, revealing a unique “β-solenoid” fold in this important adhesin family. BRSRRP53608 boundto host epithelial cells and DNA at neutral pH and recognised polygalacturonic acid (PGA), rhamnogalacturonan I or chondroitin sulfate A at acidic pH. Mutagenesis confirmed the role of the BR putative binding site in the interaction of BRSRRP53608 with PGA. Long molecular dynamics simulations showed that SRRP53608 undergoes a pH-dependent conformational change. Together, these findings shed new mechanistic insights into the role of SRRPs in host-microbe interactions and open new avenues of research into the use of biofilm-forming probiotics against clinically important pathogens

    Charting Past, Present, and Future Research in the Semantic Web and Interoperability

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    Huge advances in peer-to-peer systems and attempts to develop the semantic web have revealed a critical issue in information systems across multiple domains: the absence of semantic interoperability. Today, businesses operating in a digital environment require increased supply-chain automation, interoperability, and data governance. While research on the semantic web and interoperability has recently received much attention, a dearth of studies investigates the relationship between these two concepts in depth. To address this knowledge gap, the objective of this study is to conduct a review and bibliometric analysis of 3511 Scopus-registered papers on the semantic web and interoperability published over the past two decades. In addition, the publications were analyzed using a variety of bibliometric indicators, such as publication year, journal, authors, countries, and institutions. Keyword co-occurrence and co-citation networks were utilized to identify the primary research hotspots and group the relevant literature. The findings of the review and bibliometric analysis indicate the dominance of conference papers as a means of disseminating knowledge and the substantial contribution of developed nations to the semantic web field. In addition, the keyword co-occurrence network analysis reveals a significant emphasis on semantic web languages, sensors and computing, graphs and models, and linking and integration techniques. Based on the co-citation clustering, the Internet of Things, semantic web services, ontology mapping, building information modeling, bioinformatics, education and e-learning, and semantic web languages were identified as the primary themes contributing to the flow of knowledge and the growth of the semantic web and interoperability field. Overall, this review substantially contributes to the literature and increases scholars’ and practitioners’ awareness of the current knowledge composition and future research directions of the semantic web field. View Full-Tex

    Robust neuronal symmetry breaking by Ras-triggered local positive feedback

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    Neuronal polarity is initiated by a symmetry-breaking event whereby one out of multiple minor neurites undergoes rapid outgrowth and becomes the axon [1]. Axon formation is regulated by phosphatidylinositol 3-kinase (PI3K)-related signaling elements [2-10] that drive local actin [11] and microtubule reorganization [3, 12], but the upstream signaling circuit that causes symmetry breaking and guarantees the formation of a single axon is not known. Here, we use live FRET imaging in hippocampal neurons and show that the activity of the small GTPase HRas, an upstream regulator of PI3K, markedly increases in the nascent axonal growth cone upon symmetry breaking. This local increase in HRas activity results from a positive feedback loop between HRas and PI3K, locally reinforced by vesicular transport of HRas to the axonal growth cone. Recruitment of HRas to the axonal growth cone is paralleled by a decrease in HRas concentration in the remaining neurites, suggesting that competition for a limited pool of HRas guarantees that only one axon forms. Mathematical modeling demonstrates that local positive feedback between HRas and PI3K, coupled to recruitment of a limited pool of HRas, generates robust symmetry breaking and formation of a single axon in the absence of extrinsic spatial cues

    Genome Degradation in Brucella ovis Corresponds with Narrowing of Its Host Range and Tissue Tropism

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    Brucella ovis is a veterinary pathogen associated with epididymitis in sheep. Despite its genetic similarity to the zoonotic pathogens B. abortus, B. melitensis and B. suis, B. ovis does not cause zoonotic disease. Genomic analysis of the type strain ATCC25840 revealed a high percentage of pseudogenes and increased numbers of transposable elements compared to the zoonotic Brucella species, suggesting that genome degradation has occurred concomitant with narrowing of the host range of B. ovis. The absence of genomic island 2, encoding functions required for lipopolysaccharide biosynthesis, as well as inactivation of genes encoding urease, nutrient uptake and utilization, and outer membrane proteins may be factors contributing to the avirulence of B. ovis for humans. A 26.5 kb region of B. ovis ATCC25840 Chromosome II was absent from all the sequenced human pathogenic Brucella genomes, but was present in all of 17 B. ovis isolates tested and in three B. ceti isolates, suggesting that this DNA region may be of use for differentiating B. ovis from other Brucella spp. This is the first genomic analysis of a non-zoonotic Brucella species. The results suggest that inactivation of genes involved in nutrient acquisition and utilization, cell envelope structure and urease may have played a role in narrowing of the tissue tropism and host range of B. ovis

    Analytics-based decision-making for service systems: A qualitative study and agenda for future research

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    While the use of big data tends to add value for business throughout the entire value chain, the integration of big data analytics (BDA) to the decision-making process remains a challenge. This study, based on a systematic literature review, thematic analysis and qualitative interview findings, proposes a set of six-steps to establish both rigor and relevance in the process of analytics-driven decision-making. Our findings illuminate the key steps in this decision process including problem definition, review of past findings, model development, data collection, data analysis as well as actions on insights in the context of service systems. Although findings have been discussed in a sequence of steps, the study identifies them as interdependent and iterative. The proposed six-step analytics-driven decision-making process, practical evidence from service systems, and future research agenda, provide altogether the foundation for future scholarly research and can serve as a step-wise guide for industry practitioners

    Institutions in the Agricultural Sector of Jamaica (a catalogue)

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    286 páginas pdf. Series Miscellaneous Publication no. 359.This catalogue is presented with an admission of incompleteness and a hope for better edition to follow it soon. It is far from a complete listing by way of comprehensiveness both of coverage as well as of individual entries. In other words it can have more entries and its entries could be more complete. What has been attempted here in this provisional edition is an identification of units as a basic first step so that it will stimulate interest and pave the way for a better version in which some of these inadequacies could be made good.The Reasons for deciding to issue this version as it is, need to be stated and it is best done through setting out the sequence of events that led to its compilation. Este catálogo se presenta con una admisión de incompletitud y la esperanza de una mejor edición para seguirlo pronto. Está lejos de ser una lista completa en términos de exhaustividad tanto de la cobertura como de las entradas individuales. En otras palabras, puede tener más entradas y sus entradas podrían ser más completas. Lo que se ha intentado aquí en esta edición provisional es una identificación de unidades como un primer paso básico para estimular el interés y allanar el camino para una mejor versión en la que se puedan subsanar algunas de estas deficiencias. Las razones para decidir publicar esta versión tal como está, deben indicarse y es mejor hacerlo estableciendo la secuencia de eventos que llevaron a su compilación

    Optimal experimental design for parameter estimation of a cell signaling model.

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    Differential equation models that describe the dynamic changes of biochemical signaling states are important tools to understand cellular behavior. An essential task in building such representations is to infer the affinities, rate constants, and other parameters of a model from actual measurement data. However, intuitive measurement protocols often fail to generate data that restrict the range of possible parameter values. Here we utilized a numerical method to iteratively design optimal live-cell fluorescence microscopy experiments in order to reveal pharmacological and kinetic parameters of a phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) second messenger signaling process that is deregulated in many tumors. The experimental approach included the activation of endogenous phosphoinositide 3-kinase (PI3K) by chemically induced recruitment of a regulatory peptide, reversible inhibition of PI3K using a kinase inhibitor, and monitoring of the PI3K-mediated production of PIP(3) lipids using the pleckstrin homology (PH) domain of Akt. We found that an intuitively planned and established experimental protocol did not yield data from which relevant parameters could be inferred. Starting from a set of poorly defined model parameters derived from the intuitively planned experiment, we calculated concentration-time profiles for both the inducing and the inhibitory compound that would minimize the predicted uncertainty of parameter estimates. Two cycles of optimization and experimentation were sufficient to narrowly confine the model parameters, with the mean variance of estimates dropping more than sixty-fold. Thus, optimal experimental design proved to be a powerful strategy to minimize the number of experiments needed to infer biological parameters from a cell signaling assay

    Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons.

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    In the vertebrate central nervous system, exploratory filopodia transiently form on dendritic branches to sample the neuronal environment and initiate new trans-neuronal contacts. While much is known about the molecules that control filopodia extension and subsequent maturation into functional synapses, the mechanisms that regulate initiation of these dynamic, actin-rich structures have remained elusive. Here, we find that filopodia initiation is suppressed by recruitment of ArhGAP44 to actin-patches that seed filopodia. Recruitment is mediated by binding of a membrane curvature-sensing ArhGAP44 N-BAR domain to plasma membrane sections that were deformed inward by acto-myosin mediated contractile forces. A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis, thus reducing actin polymerization required for filopodia formation. Additionally, ArhGAP44 expression increases during neuronal development, concurrent with a decrease in the rate of filopodia formation. Together, our data reveals a local auto-regulatory mechanism that limits initiation of filopodia via protein recruitment to nanoscale membrane deformations
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