Rapid detection of Mycobacterium ulcerans with isothermal recombinase polymerase amplification assay.

Background Access to an accurate diagnostic test for Buruli ulcer (BU) is a research priority according to the World Health Organization. Nucleic acid amplification of insertion sequence IS2404 by polymerase chain reaction (PCR) is the most sensitive and specific method to detect Mycobacterium ulcerans (M. ulcerans), the causative agent of BU. However, PCR is not always available in endemic communities in Africa due to its cost and technological sophistication. Isothermal DNA amplification systems such as the recombinase polymerase amplification (RPA) have emerged as a molecular diagnostic tool with similar accuracy to PCR but having the advantage of amplifying a template DNA at a constant lower temperature in a shorter time. The aim of this study was to develop RPA for the detection of M. ulcerans and evaluate its use in Buruli ulcer disease. Methodology and principal findings A specific fragment of IS2404 of M. ulcerans was amplified within 15 minutes at a constant 42°C using RPA method. The detection limit was 45 copies of IS2404 molecular DNA standard per reaction. The assay was highly specific as all 7 strains of M. ulcerans tested were detected, and no cross reactivity was observed to other mycobacteria or clinically relevant bacteria species. The clinical performance of the M. ulcerans (Mu-RPA) assay was evaluated using DNA extracted from fine needle aspirates or swabs taken from 67 patients in whom BU was suspected and 12 patients with clinically confirmed non-BU lesions. All results were compared to a highly sensitive real-time PCR. The clinical specificity of the Mu-RPA assay was 100% (95% CI, 84–100), whiles the sensitivity was 88% (95% CI, 77–95). Conclusion The Mu-RPA assay represents an alternative to PCR, especially in areas with limited infrastructure. Author summary Current diagnostic methods to detect M. ulcerans suffer from delayed time-to-results in most endemic countries by the prolonged period of time for the shipment and storage of samples to a distant, centralized laboratory. The M. ulcerans recombinase polymerase amplification assay (Mu-RPA) is a new, rapid diagnostic test developed for the detection of M. ulcerans infection, known commonly as Buruli ulcer, a chronic, debilitating, necrotizing disease of the skin and soft tissues. This assay is suitable for use on a portable detection device, with the potential to be used for quick diagnosis at the point of need, providing timely results to health workers at Buruli ulcer treatment clinics

The impact of a firm’s make, pseudoâ make, or buy strategy on product performance

The bulk of the product architecture and makeâ buy choice literature deals with product architecture changes from integral to modular form. This development is often associated with a firm’s tendency to change from a make to a buy strategy. However, a few studies investigate the change of product architecture in the reverse direction â from modular to integral form â and the subsequent change in the firm sourcing decision from a buy to a make strategy. These studies hold to the presumption that a firm following a make strategy will outperform firms following a buy strategy in dealing with integral product architectures. Based on the knowledgeâ based view, we argue for the viability of a sourcing strategy between the pure make and buy strategies â a pseudoâ make strategy. We also argue that as product architecture changes from a modular to integral form, firms adopting this pseudoâ make strategy are likely to show better product performance than firms following a pure make or buy strategy due to the relative knowledge advantages of the pseudoâ make strategy in dealing with the integral product architecture. We examine the impact of the make/pseudoâ make/buy strategies on product performance in the U.S. bicycle derailleur and freewheel market from 1980 to 1992 and provide theoretical and managerial implications of our results. Our findings highlight an important distinction between the pseudoâ make and makeâ buy strategies that has not previously been fully appreciated in the extant literature, and as a result increases our understanding of why some firms do not switch strategies from a buy to a make strategy when product architecture changes from modular to integral form as previously expected.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146818/1/joom289.pd

Approximation properties for dynamical W*-correspondences

Let $\mathbb{G}$ be a locally compact quantum group, and $A,B$ von Neumann algebras with an action by $\mathbb{G}$. We refer to these as $\mathbb{G}$-dynamical W$^*$-algebras. We make a study of $\mathbb{G}$-equivariant $A$-$B$-correspondences, that is, Hilbert spaces $\mathcal{H}$ with an $A$-$B$-bimodule structure by $*$-preserving normal maps, and equipped with a unitary representation of $\mathbb{G}$ which is equivariant with respect to the above bimodule structure. Such structures are a Hilbert space version of the theory of $\mathbb{G}$-equivariant Hilbert C$^*$-bimodules. We show that there is a well-defined Fell topology on equivariant correspondences, and use this to formulate approximation properties for them. Within this formalism, we then characterize amenability of the action of a locally compact group on a von Neumann algebra, using recent results due to Bearden and Crann. We further consider natural operations on equivariant correspondences such as taking opposites, composites and crossed products, and examine the continuity of these operations with respect to the Fell topology.Comment: 44 pages. Comments are welcome! Apart from small stylistic changes, we have added some results on non-strong equivariant amenability properties in Section 6, and have reorganized some of the material in Section 5.5. We have added a table at the end of Section 5 to summarize some of the result

TGFβ1 single-nucleotide polymorphism C-509T alters mucosal cell function in pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic Th2 antigen-driven disorder associated with tissue remodeling. Inflammation and remodeling lead to esophageal rigidity, strictures, and dysphagia. TGFβ1 drives esophageal remodeling including epithelial barrier dysfunction and subepithelial fibrosis. A functional SNP in the TGFβ1 gene that increases its transcription (C-509T) is associated with elevated numbers of esophageal TGFβ1-expressing cells. We utilized esophageal biopsies and fibroblasts from TT-genotype EoE children to understand if TGFβ1 influenced fibroblast and epithelial cell function in vivo. Genotype TT EoE esophageal fibroblasts had higher baseline TGFβ1, collagen1α1, periostin, and MMP2 (p < 0.05) gene expression and distinct contractile properties compared with CC genotype (n = 6 subjects per genotype). In vitro TGFβ1 exposure caused greater induction of target gene expression in genotype CC fibroblasts (p < 0.05). Esophageal biopsies from TT-genotype subjects had significantly less epithelial membrane-bound E-cadherin (p < 0.01) and wider cluster distribution at nanometer resolution. TGFβ1 treatment of stratified primary human esophageal epithelial cells and spheroids disrupted transepithelial resistance (p < 0.001) and E-cadherin localization (p < 0.0001). A TGFβ1-receptor-I inhibitor improved TGFβ1-mediated E-cadherin mislocalization. These data suggest that EoE severity can depend on genotypic differences that increase in vivo exposure to TGFβ1. TGFβ1 inhibition may be a useful therapy in subsets of EoE patients

Who’s afraid of response bias?

Response bias (or criterion) contamination is insidious in studies of consciousness: that observers report they do not see a stimulus may not mean they have absolutely no subjective experience; they may be giving such reports in relative terms in the context of other stimuli. Bias-free signal detection theoretic measures provide an excellent method for avoiding response bias confounds, and many researchers correctly adopt this approach. However, here we discuss how a fixation on avoiding criterion effects can also be misleading and detrimental to fruitful inquiry. In a recent paper, Balsdon and Azzopardi (Absolute and relative blindsight. Consciousness and Cognition 2015; 32:79–91.) claimed that contamination by response bias led to flawed findings in a previous report of “relative blindsight”. We argue that their criticisms are unfounded. They mistakenly assumed that others were trying (and failing) to apply their preferred methods to remove bias, when there was no such intention. They also dismissed meaningful findings because of their dependence on criterion, but such dismissal is problematic: many real effects necessarily depend on criterion. Unfortunately, these issues are technically tedious, and we discuss how they may have confused others to misapply psychophysical metrics and to draw questionable conclusions about the nature of TMS (transcranial magnetic stimulation)-induced blindsight. We conclude by discussing the conceptual importance of criterion effects in studies of conscious awareness: we need to treat them carefully, but not to avoid them without thinking

The interaction effect of relational norms and agent cooperativeness on opportunism in buyerâ supplier relationships

In this study, we examined the effect of relational norms and agent cooperativeness on opportunism in buyerâ supplier relationships. Drawing from the theoretical grounding of transaction cost economics, personality trait theory, and contingency theory, we proposed three distinct perspectives on opportunism mitigation in buyerâ supplier relationships: (1) organizationalist, (2) individualist, and (3) interactionist, where relational norms, agent cooperativeness, and the interaction between them, respectively, serve as the key predictors in these three perspectives. The results of replicated experiments indicated that relational norms and agent cooperativeness interact with each other in mitigating opportunism and that the interactionist perspective yielded the highest explained variance in opportunism. This suggests that the interactionist perspective, a multiâ level theoretical lens encompassing the dynamic interplay between organizationâ level and individualâ level factors, was a more complete model in explaining opportunism than either the organizationalist or individualist perspectives. The consensus which emerged from postâ experimental interviews of purchasing professionals is that agent personalities play an important role in buyerâ supplier relationships. Some purchasing professionals had observed that uncooperative agents or personnel turnover in the boundaryâ spanning functions can substantially undermine even established relational exchanges. These qualitative findings are in line with our theoretical arguments and experimental outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146947/1/joom398.pd

Cysteine proteinase-1 and cut protein isoform control dendritic innervation of two distinct sensory fields by a single neuron.

Dendrites often exhibit structural changes in response to local inputs. Although mechanisms that pattern and maintain dendritic arbors are becoming clearer, processes regulating regrowth, during context-dependent plasticity or after injury, remain poorly understood. We found that a class of Drosophila sensory neurons, through complete pruning and regeneration, can elaborate two distinct dendritic trees, innervating independent sensory fields. An expression screen identified Cysteine proteinase-1 (Cp1) as a critical regulator of this process. Unlike known ecdysone effectors, Cp1-mutant ddaC neurons pruned larval dendrites normally but failed to regrow adult dendrites. Cp1 expression was upregulated/concentrated in the nucleus during metamorphosis, controlling production of a truncated Cut homeodomain transcription factor. This truncated Cut, but not the full-length protein, allowed Cp1-mutant ddaC neurons to regenerate higher-order adult dendrites. These results identify a molecular pathway needed for dendrite regrowth after pruning, which allows the same neuron to innervate distinct sensory fields