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The salivary glands of hematophagous arthropods contain pharmacologically active molecules that interfere with host hemostasis and immune responses, favoring blood acquisition and pathogen transmission. Exploration of the salivary gland composition of the rat flea, Xenopsylla cheopis, revealed several abundant acid phosphatase-like proteins whose sequences lacked one or two of their presumed catalytic residues. In this study, we undertook a comprehensive characterization of the tree most abundant X. cheopis salivary acid phosphatase-like proteins. Our findings indicate that the three recombinant proteins lacked the anticipated catalytic activity and instead, displayed the ability to bind different biogenic amines and leukotrienes with high affinity. Moreover, X-ray crystallography data from the XcAP-1 complexed with serotonin revealed insights into their binding mechanisms. A structural and functional characterization of salivary acid phosphatase-like proteins derived from the flea Xenopsylla cheopis demonstrating their ability to bind host biogenic amines and leukotrienes, potentially favouring blood acquisition. [ABSTRACT FROM AUTHOR]

The hematophagy behavior has evolved independently several times within the Arthropoda phylum. Interestingly, the process of acquiring a blood meal in ticks is considerably distinct from that observed in other blood-feeding arthropods. Instead of taking seconds to minutes to complete a blood meal, an adult female Ixodes scapularis tick can remain attached to its host for numerous days. During this extended feeding period, the tick undergoes drastic morphological changes. It is well established that the tick midgut plays a pivotal role not only in blood meal digestion but also in pathogen acquisition and transmission. However, our understanding of the underlying molecular mechanisms involved in these events remains limited. To expedite tick research, we conducted a comprehensive longitudinal RNA-sequencing of the tick midgut before, during, and after feeding. By collecting ticks in different feeding stages (unfed, slow feeding, rapid feeding, and early post-detached), we obtained a comprehensive overview of the transcripts present in each stage and the dynamic transcriptional changes that occur between them. This provides valuable insights into tick physiology. Additionally, through unsupervised clustering, we identified transcripts with similar patterns and stage-specific sequences. These findings serve as a foundation for selecting targets in the development of anti-tick control strategies and facilitate a better understanding of how blood feeding and pathogen infection impact tick physiology. [ABSTRACT FROM AUTHOR]

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Recruitment of the GRIP domain golgins to the trans-Golgi network is mediated by Arl1, a member of the ARF/Arl small GTPase family, through interaction between their GRIP domains and Arl1-GTP. The crystal structure of Arl1-GTP in complex with the GRIP domain of golgin-245 shows that Arl1-GTP interacts with the GRIP domain predominantly in a hydrophobic manner, with the switch II region conferring the main recognition surface. The involvement of the switch and interswitch regions in the interaction between Arl1-GTP and GRIP accounts for the specificity of GRIP domain for Arl1-GTP. Mutations that abolished the Arl1-mediated Golgi localization of GRIP domain golgins have been mapped on the interface between Arl1-GTP and GRIP. Notably, the GRIP domain forms a homodimer in which each subunit interacts separately with one Arl1-GTP. Mutations disrupting the GRIP domain dimerization also abrogated its Golgi targeting, suggesting that the dimeric form of GRIP domain is a functional unit. [ABSTRACT FROM AUTHOR]

We constructed a peptide consisting of a staphylococcal AgrD1 pheromone fused to the channel-forming domain of colicin Ia and named it pheromonicin. This fusion peptide had bactericidal effects against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively), but not against Staphylococcus epidermidis or Streptococcus pneumoniae. Growth rates, vital staining and colony forming unit (CFU) counts showed that pheromonicin did not merely suppress growth but killed S. aureus cells. The specificity of pheromonicin was shown by the absence of bactericidal effects against an accessory gene regulator (agr) locus knockout of S. aureus, and a dose-dependent inhibition of the bactericidal effects of pheromonicin by competition with corresponding free AgrD pheromone. In vivo, all pheromonicin-treated mice survived administration of MRSA that was lethal to controls. No toxicity was detectable in human liver or renal cells in culture, or in livers, kidneys or spleens of pheromonicin-treated mice. The results suggest that these types of chimeric peptides may be of value as antibiotics against specific bacterial infections. [ABSTRACT FROM AUTHOR]

This paper presents the Hierarchical and Interactive Decision Refinement (HIDER) methodology for engineering design. This methodology hierarchically refines (or reduces) a large initial design space through a series of multiple-objective optimizations, until a fully specified design is obtained. This contrasts with the traditional approach to design optimization which involves picking a fully specified design from the space of possible designs and then iteratively modifying its specifications to maximize the performance. The HIDER methodology uses an adaptive modeling approach that combines machine learning and statistical techniques for developing fast empirical models with different levels of detail and evaluation speeds. These models are used for multiple-objective optimization at different stages of the design. The use of layered models enables HIDER methodology to be used at different stages of parametric design, including early stages when design specifications are not complete. This methodology also supports multiple perspectives in concurrent design because it provides means for transforming models from these different perspectives into a uniform representation, as well as facilitating decision-making with respect to multiple competing objectives. This paper presents the HIDER methodology with an example in the parametric design of a diesel engine. [ABSTRACT FROM AUTHOR]

This paper addresses the critical issues of knowledge acquisition in developing knowledge-based expert systems for engineering tasks. First, it reviews the role of knowledge acquisition and its current practice in expert system development. Then, a new approach based on three stages of knowledge refinement is suggested to improve the process of knowledge acquisition. This approach, called rule verification without rule construction, is proposed to allow knowledge engineers and domain experts to experience a more intimate and balanced role in developing intelligent systems. The communication tool developed for this concept is called knowledge map, which provides a systematic way of indexing and quantifying a piece of knowledge in the problem space by defining important attributes as the axes of the map. This approach is demonstrated by constructing a twodimensional map for a knowledge-based engineering design system, IDRILL, which we are currently developing. Future expansions of this knowledge acquisition technique are summarized as the conclusions of this paper. [ABSTRACT FROM AUTHOR]