The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

Efficient Incorporation of Clickable Unnatural Amino Acids Enables Rapid and Biocompatible Labeling of Proteins in Vitro and in Bacteria

Site-specific incorporation of unnatural amino acids (uAAs) bearing a bioorthogonal group has enabled the attachment – typically at a single site or at a few sites per protein – of chemical groups at precise locations for protein and biomaterial labeling, conjugation, and functionalization. Herein, we report the evolution of chromosomal Methanocaldococcus jannaschii tyrosyl-tRNA synthetase (aaRS) for the alkyne-bearing uAA, 4-propargyloxy-l -phenylalanine (pPR), with ∼30-fold increased production of green fluorescent protein containing three instances of pPR compared with a previously described M. jannaschii-derived aaRS for pPR, when expressed from a single chromosomal copy. We show that when expressed from multicopy plasmids, the evolved aaRSs enable the production – using a genomically recoded Escherichia coli and the non-recoded BL21 E. coli strain – of elastin-like polypeptides (ELPs) containing multiple pPR residues in high yields. We further show that the multisite incorporation of pPR in ELPs facilitates the rapid, robust, and nontoxic fluorescent labeling of these proteins in bacteria. The evolved variants described in this work can be used to produce a variety of protein and biomaterial conjugates and to create efficient minimal tags for protein labeling.     

Exploring critical attributes during air traffic congestion with a fuzzy DEMATEL–ANP technique: a case study in Ninoy Aquino International Airport

Railway Engineering Science - The constant growth of air travel in the Philippines has brought about significant consequences to air traffic congestion. Given limited resources, major airports seek...     

Safer asynchronous runtime monitoring using compensations

Asynchronous monitoring relieves the system from additional overheads induced through online runtime monitoring. The price paid with such monitoring approaches is that the system may proceed further despite having reached an anomalous state. Any actions performed by the system after the error occurring are undesirable, since for instance, an unchecked malicious user access may perform unauthorized actions. In this paper we investigate the use of compensations to enable the undoing of such undesired actions, thus enriching asynchronous monitoring with the ability to restore the system to the original state just after the anomaly had occurred. Furthermore, we show how adaptive synchronisation and desynchronisation of the monitor with the system can also be achieved and report on the use of the proposed approach on an industrial case study of a financial transaction handling system.     

Does carbon nanopowder threaten amphibian development?

Lethal and teratogenic potentials of carbon nanoparticles (CNPs) in their amorphous form were investigated by the standardized Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 96-h in vitro whole-embryo toxicity test based on the amphibian Xenopus laevis. Embryos were acutely exposed to 1, 10, 100 and 500 mg/L CNP suspensions and evaluated for lethality, malformations and growth inhibition. Larvae were processed for histological and ultrastructural analyses to detect the main affected organs, to look for specific lesions at the subcellular level and to image and track CNPs into tissues. Only the highest CNP suspension resulted in being embryolethal for X. laevis larvae, while malformed larva percentages significantly differed from controls starting from 100 mg/L. The stomach and gut were the preferential CNP accumulation sites, on the contrary, the digestive epithelium remained intact. The analyses showed the presence of isolated nanoparticles and/or aggregates in different secondary target organs. CNPs were found in circulating erythrocytes. The research confirms the good tolerance of X. laevis towards pure elemental carbon in its nanoparticulate amorphous form, but highlights the possibility of CNP transfer toward all body areas.     

Recent advances in infant cognition: Implications for long-chain polyunsaturated fatty acid supplementation studies

The assessment of cognitive function in early life has recently become an issue for consideration in long-chain polyunsaturated fatty acid (LC-PUFA) supplementation studies. This article reviews the various means by which such assessment has been done in past LC-PUFA supplementation studies and provides some background on recent advances in the measurement of infant cognition that may need to be considered when planning or designing future supplementation studies. These include (i) consideration of the specificity of LC-PUFA effects on cognition, (ii) inclusion of multiple tasks or levels of measurement as outcome measures, and (iii) a stronger emphasis on developmental processes in the design of such studies.     

Cross-linked soy protein as material for biodegradable films: Synthesis, characterization and biodegradation

The modification of soy protein isolate (SPI) with different amounts of a naturally occurring cross-linking agent (genipin, Gen) and glycerol used as plasticizer was carried out in this work. The films yielded were cast from heated and alkaline aqueous solution of SPI, glycerol and Gen and then dried in an oven. Total soluble matter, water vapor permeability and mechanical properties were improved by adding small amounts of Gen. These properties were not significantly affected (P ? 0.05) by additions exceeding 2.5% (w/w of SPI). The opacity and cross-linking degree were linearly increased with the addition of Gen, whereas the swelling ratios in water were decreased. All the films were submitted to degradation under indoor soil burial conditions and the weight loss of the films was measured at different times. This study revealed that the film biodegradation time can be controlled or modified from at least 14 to 33 days. The tests performed showed the potential of Gen to improve the SPI film properties, in which the possibility of employing such new films as biodegradable food packaging was raised.