Lamellar Structures of MUC2-Rich Mucin: A Potential Role in Governing the Barrier and Lubricating Functions of Intestinal Mucus

Mucus is a ubiquitous feature of mammalian wet epithelial surfaces, where it lubricates and forms a selective barrier that excludes a range of particulates, including pathogens, while hosting a diverse commensal microflora. The major polymeric component of mucus is mucin, a large glycoprotein formed by several MUC gene products, with MUC2 expression dominating intestinal mucus. A satisfactory answer to the question of how these molecules build a dynamic structure capable of playing such a complex role has yet to be found, as recent reports of distinct layers of chemically identical mucin in the colon and anomalously rapid transport of nanoparticles through mucus have emphasized. Here we use atomic force microscopy (AFM) to image a MUC2-rich mucus fraction isolated from pig jejunum. In the freshly isolated mucin fraction, we find direct evidence for trigonally linked structures, and their assembly into lamellar networks with a distribution of pore sizes from 20 to 200 nm. The networks are two-dimensional, with little interaction between lamellae. The existence of persistent cross-links between individual mucin polypeptides is consistent with a non-self-interacting lamellar model for intestinal mucus structure, rather than a physically entangled polymer network. We only observe collapsed entangled structures in purified mucin that has been stored in nonphysiological conditions

Values of travel time in Europe: Review and meta-analysis

This paper reports the most extensive meta-analysis of values of time yet conducted, covering 3109 monetary valuations assembled from 389 European studies conducted between 1963 and 2011. It aims to explain how valuations vary across studies, including over time and between countries. In addition to the customary coverage of in-vehicle time in review studies, this paper covers valuations of walk time, wait time, service headway, parking space search time, departure time switching, time in congested traffic, schedule delay early and late, mean lateness and the standard deviation of travel time. Valuations are found to vary with type of time, GDP, distance, journey purpose, mode, the monetary numeraire and a number of factors related to estimation. Model output values of time compare favourably with earnings data, replicate well official recommended values obtained from major national studies, and are transferable across countries. These implied monetary values serve as very useful benchmarks against which new evidence can be assessed and the meta-model provides parameters and values for countries and contexts where there is no other such evidence

Interaction between sodium chloride and texture in semi-hard Danish cheese as affected by brining time, dl -starter culture, chymosin type and cheese ripening

Reduced NaCl in semi-hard cheeses greatly affects textural and sensory properties. The interaction between cheese NaCl concentration and texture was affected by brining time (0–28 h), dl-starter cultures (C1, C2, and C3), chymosin type (bovine or camel), and ripening time (1–12 weeks). Cheese NaCl levels ranged from <0.15 to 1.90% (w/w). NaCl distribution changed during ripening; migration from cheese edge to core led to a more homogeneous NaCl distribution after 12 weeks. As ripening time increased, cheese firmness decreased. Cheeses with reduced NaCl were less firm and more compressible. Cheeses produced with C2 were significantly firmer than those produced with C1; cheeses produced with C3 had higher firmness and compressibility. In NaCl reduced cheese, use of camel chymosin as coagulant resulted in significantly higher firmness than that given using bovine chymosin. Overall, cheese NaCl content is reducible without significant textural impact using well-defined starter cultures and camel chymosin

Automating HAZOP studies using D-higraphs

In this paper, we present the use of D-higraphs to perform HAZOP studies. D-higraphs is a formalism that includes in a single model the functional as well as the structural (ontological) components of any given system. A tool to perform a semi-automatic guided HAZOP study on a process plant is presented. The diagnostic system uses an expert system to predict the behavior modeled using D-higraphs. This work is applied to the study of an industrial case and its results are compared with other similar approaches proposed in previous studies. The analysis shows that the proposed methodology fits its purpose enabling causal reasoning that explains causes and consequences derived from deviations, it also fills some of the gaps and drawbacks existing in previous reported HAZOP assistant tools

Changes in the site distribution of malignant melanoma in South East Scotland (1979–2002)

Scottish Melanoma Group (SMG) data on 2790 melanoma (MM) cases in South East Scotland over a 24-year time period were analysed in four periods each of 6 years duration grouped into frequently exposed, intermittently exposed, and always covered sites. Incidence increased significantly over time with females having a higher incidence rate than males. In both sexes, the proportion of cases seen on the posterior trunk and arm increased significantly (P<0.001), but declines were seen in the proportion of leg tumours in males (P=0.09) and of head tumours in females (P=0.011). Although the proportion of cases decreased for certain sites, the actual MM incidence increased at all sites. A significant increase in incidence occurred at usually and always covered sites (P<0.001 and P<0.001, respectively) in females and at usually covered sites in males (P<0.001)

Multi-omic detection of <i>Mycobacterium leprae</i> in archaeological human dental calculus

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record.publishedVersio

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects