Shigella applies molecular mimicry to subvert vinculin and invade host cells

Shigella flexneri, the causative agent of bacillary dysentery, injects invasin proteins through a type III secretion apparatus upon contacting the host cell, which triggers pathogen internalization. The invasin IpaA is essential for S. flexneri pathogenesis and binds to the cytoskeletal protein vinculin to facilitate host cell entry. We report that IpaA harbors two vinculin-binding sites (VBSs) within its C-terminal domain that bind to and activate vinculin in a mutually exclusive fashion. Only the highest affinity C-terminal IpaA VBS is necessary for efficient entry and cell–cell spread of S. flexneri, whereas the lower affinity VBS appears to contribute to vinculin recruitment at entry foci of the pathogen. Finally, the crystal structures of vinculin in complex with the VBSs of IpaA reveal the mechanism by which IpaA subverts vinculin's functions, where S. flexneri utilizes a remarkable level of molecular mimicry of the talin–vinculin interaction to activate vinculin. Mimicry of vinculin's interactions may therefore be a general mechanism applied by pathogens to infect the host cell

Objectives, design and main findings until 2020 from the Rotterdam Study

The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases.As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period

Weighted needle pinprick sensory thresholds: a simple test of sensory function in diabetic peripheral neuropathy

A simple device is described, consisting of 12 weighted 23 gauge disposable needles (0.2 to 5.2 g), for testing sensation in busy diabetic clinics. The pinprick sensory threshold (PPT) is the lightest weighted needle which consistently elicits a sharp sensation. The subjects were 48 healthy controls (hospital staff), 44 diabetic patients without neuropathic symptoms, and 35 diabetic patients with chronic painful neuropathy. In the controls, the mean PPT from the right hand and foot obtained on two test occasions a week apart did not differ significantly. In diabetic patients without symptomatic neuropathy, the mean PPT in the right hand and right foot were significantly higher than in the controls. The diabetic patients with painful neuropathy had clearly increased mean PPT in the right hand and foot compared with controls. Marstock thermal limen in diabetic patients with painful neuropathy correlated significantly with PPT determinations. PPT and thermal thresholds probably give comparable information on small fibre dysfunction in diabetic patients with symptomatic neuropathy. Compared with thermal threshold determinations however, the weighted needle apparatus is inexpensive, simple, and rapid to use

Growth, flesh adiposity and fatty acid composition of Atlantic salmon (Salmo salar) families with contrasting flesh adiposity: effects of replacement of dietary fish oil with vegetable oils

The present study compared the effects of diets formulated with reduced fishmeal (FM) content and either 100% fish oil (FO) or 100% of a vegetable oil (VO) blend in post-smolts of three family groups of Atlantic salmon. Two groups were selected as being either “Lean” or “Fat” based on estimated breeding values (EBV) for flesh adiposity of their parents derived from a breeding programme, while the third group (CAL) was a mix of non-pedigreed commercial families unrelated to the two groups above. The VO blend comprised rapeseed, palm and a new product, Camelina oil in a ratio of 5/3/2, and diets were fed to duplicate pens of each salmon group. After an ongrowing period of 55 weeks, to reach a mean weight of 3kg, the fish from all treatments were switched to a decontaminated FO for a further 24 weeks to follow restoration of long-chain n-3 polyunsaturated fatty acids (LC-PUFA) in the fish previously fed VO. Final weights were significantly affected by family group and there was also an interaction between diet and group with Fat and Lean FO fish being larger than the same fish fed VO. Specific growth rate (SGR) was highest in CAL fish (1.01), feed conversion ratio (FCR) was highest in the Lean fish but there were no significant effects on thermal growth coefficient (TGC). Condition Factor (CF) was lowest in CAL fish while the hepato-somatic index (HSI) was highest in Lean fish and viscero-somatic index (VSI) highest in Fat fish. Flesh and viscera lipid content was affected by both family group and diet with a significant interaction between the two. Flesh lipid in fish fed FO was in the order Fat > CAL > Lean although this order was Fat = Lean > CAL when fed VO. Flesh fatty acid compositions were affected mainly by diet although some minor fatty acids were also influenced by group. Fish fed VO had n-3 LC-PUFA reduced by ~65% compared to fish fed FO but this could be restored by a 16 week FO finishing diet phase. The differences observed in lipid and fatty acid deposition suggested that genetics affected lipid deposition and metabolism and that breeding programmes could select for fish that retained more n-3 LC-PUFA in their flesh, particularly when fed diets low in these fatty acids

The Woody Guthrie Centennial Bibliography

This bibliography updates two extensive works designed to include comprehensively all significant works by and about Woody Guthrie. Richard A. Reuss published A Woody Guthrie Bibliography, 1912–1967 in 1968 and Jeffrey N. Gatten\u27s article “Woody Guthrie: A Bibliographic Update, 1968–1986” appeared in 1988. With this current article, researchers need only utilize these three bibliographies to identify all English-language items of relevance related to, or written by, Guthrie

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements