The interaction between slip bands and grain boundaries in commercial-purity titanium was examined using cross-correlation-based electron backscatter diffraction. At a low strain level, three types ...of interactions were observed: blocked slip band with stress concentration; slip transfer; and blocked slip band with no stress concentration. The stress concentration induced by the blocked slip band was fitted with Eshelby’s theoretical model, from which a Hall–Petch coefficient was deduced. It was found that the Hall–Petch coefficient varies with the individual grain boundary. We investigated the geometric alignment between the slip band and various slip systems to the neighbouring grain. Stress concentration can be induced by the blocked slip band if the slip system is poorly aligned with 〈a〉 prismatic, pyramidal or basal slip systems in the neighbouring grain. Transfer of slip across the boundary occurs when there is good alignment on 〈a〉 prismatic or 〈a〉 pyramidal slip systems. Other stress-relieving mechanisms are possible when the best alignment is not with the slip system that has the lower critical resolved shear stress.
The evolution of dislocation storage in deformed copper was studied with cross-correlation-based high-resolution electron backscatter diffraction. Maps of 500μm×500μm areas with 0.5μm step size were ...collected and analysed for samples deformed in tension to 0%, 6%, 10%, 22.5% and 40% plastic strain. These maps cover ∼1500 grains each while also containing very good resolution of the geometrically necessary dislocation (GND) content. We find that the average GND density increases with imposed macroscopic strain in accord with Ashby’s theory of work hardening. The dislocation density distributions can be described well with a log-normal function. These data sets are very rich and provide ample data such that quantitative statistical analysis can also be performed to assess the impact of grain morphology and local crystallography on the storage of dislocations and resultant deformation patterning. Higher GND densities accumulate near grain boundaries and triple junctions as anticipated by Ashby’s theory, while lower densities are rather more spread through the material. At lower strains (⩽6%) the grain-averaged GND density was higher in smaller grains, showing a good correlation with the reciprocal of the grain size. When combined with a Taylor hardening model this last observation is consistent with the Hall–Petch grain size effect for the yield or flow stress.
The post-translational modification SUMOylation is a major regulator of protein function that plays an important role in a wide range of cellular processes. SUMOylation involves the covalent ...attachment of a member of the SUMO (small ubiquitin-like modifier) family of proteins to lysine residues in specific target proteins via an enzymatic cascade analogous to, but distinct from, the ubiquitination pathway. There are four SUMO paralogues and an increasing number of proteins are being identified as SUMO substrates. However, in many cases little is known about how SUMOylation of these targets is regulated. Compared with the ubiquitination pathway, relatively few components of the conjugation machinery have been described and the processes that specify individual SUMO paralogue conjugation to defined substrate proteins are an active area of research. In the present review, we briefly describe the SUMOylation pathway and present an overview of the recent findings that are beginning to identify some of the mechanisms that regulate protein SUMOylation.
Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually. Effective antituberculosis treatment monitoring is difficult as there are no existing ...biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance.
To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response.
Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis.
An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient.
Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response.
The recent Ebola epidemic in West Africa highlights how engaging with the sociocultural dimensions of epidemics is critical to mounting an effective outbreak response. Community engagement was ...pivotal to ending the epidemic and will be to post-Ebola recovery, health system strengthening and future epidemic preparedness and response. Extensive literatures in the social sciences have emphasized how simple notions of community, which project solidarity onto complex hierarchies and politics, can lead to ineffective policies and unintended consequences at the local level, including doing harm to vulnerable populations. This article reflects on the nature of community engagement during the Ebola epidemic and demonstrates a disjuncture between local realities and what is being imagined in post-Ebola reports about the lessons that need to be learned for the future. We argue that to achieve stated aims of building trust and strengthening outbreak response and health systems, public health institutions need to reorientate their conceptualization of ‘the community’ and develop ways of working which take complex social and political relationships into account.
This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.
The history of race in North America is still often conceived of in black and white terms. In this book, A. B. Wilkinson complicates that history by investigating how people of mixed African, ...European, and Native American heritage-commonly referred to as "Mulattoes," "Mustees," and "mixed bloods"-were integral to the construction of colonial racial ideologies. Thousands of mixed-heritage people appear in the records of English colonies, largely in the Chesapeake, Carolinas, and Caribbean, and this book provides a clear and compelling picture of their lives before the advent of the so-called one-drop rule. Wilkinson explores the ways mixed-heritage people viewed themselves and explains how they-along with their African and Indigenous American forebears-resisted the formation of a rigid racial order and fought for freedom in seventeenth- and eighteenth-century societies shaped by colonial labor and legal systems. As contemporary U.S. society continues to grapple with institutional racism rooted in a settler colonial past, this book illuminates the earliest ideas of racial mixture in British America well before the founding of the United States.
Summary Background We aimed to assess whether interferon-γ release assays (IGRAs) can predict the development of active tuberculosis and whether the predictive ability of these tests is better than ...that of the tuberculin skin test (TST). Methods Longitudinal studies of the predictive value for active tuberculosis of in-house or commercial IGRAs were identified through searches of PubMed, Embase, Biosis, and Web of Science and complementary manual searches up to June 30, 2011. Eligible studies included adults or children, with or without HIV, who were free of active tuberculosis at study baseline. We summarised incidence rates in forest plots and pooled data with random-effects models when appropriate. We calculated incidence rate ratios (IRR) for rates of disease progression in IGRA-positive versus IGRA-negative individuals. Findings 15 studies had a combined sample size of 26 680 participants. Incidence of tuberculosis during a median follow-up of 4 years (IQR 2–6), even in IGRA-positive individuals, was 4–48 cases per 1000 person-years. Seven studies with no possibility of incorporation bias and reporting baseline stratification on the basis of IGRA results showed a moderate association between positive results and subsequent tuberculosis (pooled unadjusted IRR 2·10, 95% CI 1·42–3·08). Compared with test-negative results, IGRA-positive and TST-positive results were much the same with regard to the risk of tuberculosis (pooled IRR in the five studies that used both was 2·11 95% CI 1·29–3·46 for IGRA vs 1·60 0·94–2·72 for TST at the 10 mm cutoff). However, the proportion of IGRA-positive individuals in seven of 11 studies that assessed both IGRAs and TST was generally lower than TST-positive individuals. Interpretation Neither IGRAs nor the TST have high accuracy for the prediction of active tuberculosis, although use of IGRAs in some populations might reduce the number of people considered for preventive treatment. Until more predictive biomarkers are identified, existing tests for latent tuberculosis infection should be chosen on the basis of relative specificity in different populations, logistics, cost, and patients' preferences rather than on predictive ability alone. Funding Special Programme for Research and Training in Tropical Diseases (WHO), Wellcome Trust, Canadian Institutes of Health Research, UK Medical Research Council, and the European and Developing Countries Clinical Trials Partnership.
New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the ...blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations.
To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases.
We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations.
An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls.
Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.
Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by ...muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons showed severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of parvalbumin-expressing neurons that predominantly mark proprioceptors was dependent on Piezo2 expression in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings was markedly reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors.
Uses data from all pathogenic Leptospira genomes to identify a partial region of the glmU gene as a suitable locus for the discrimination of the infecting species and serovars of New Zealand-endemic ...Leptospira. Explores the use of this locus as a molecular barcoding tool via the Oxford Nanopore Technology (ONT) sequencing platform MinION. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
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