LOS oligosaccharide modification enhances dendritic cell responses to meningococcal native outer membrane vesicles expressing a non toxic lipid A.

Outer membrane vesicles (OMV) are released by many bacteria, and contain immunogenic antigens in addition to harmful inflammatory factors, like lipopolysaccharides. Chemically detoxified OMV have been used in vaccines against Neisseria meningitidis (Nm), however little is known about their interaction with antigen presenting cells. In this study, we investigated the interaction of Nm OMV with human dendritic cells (DC) to gain further understanding of their biological activity. We engineered a novel serogroup B Nm that is unencapsulated (siaD), expresses pentacylated lipid A (lpxL1), hence conferring reduced toxicity, and expresses an lgtB oligosaccharide structure designed to target OMV to DC via DC-SIGN. We show that the lgtB moiety is critical for internalization of NOMV by DC. Furthermore, the lgtB moiety significantly enhances DC maturation, IL-10 and IL-23 production in the presence of a pentacylated lipid A. Whilst different DC phenotypes were observed for each NOMV, this had little effect on Th1 and Th2 cell differentiation, however lgtB significantly increased Th17 cell expansion in the presence of pentacylated lipid A. We believe that lgtB/lpxL1 NOMV should be considered further as a vaccine vector, particularly considering the importance of lgtB in antigen uptake and further human studies on antigen specific responses should be considered

Cardiogenic shock in a patient with hypothyroid myopathy responsive only to thyroxin replacement: a case report

The effect of hypothyroidism on the cardiovascular system has been well documented. Cardiac dysfunction due to hypothyroidism manifests as both systolic and diastolic dysfunction of the heart leading to cardiac arrhythmia and congestive heart failure. Its presentation in the form of refractory hypotension is rare. We describe a 52 year old man on whom Hypothyroid Cardiomyopathy manifested as cardiogenic shock responsive only to thyroxin replacement

On the Importance of Countergradients for the Development of Retinotopy: Insights from a Generalised Gierer Model

During the development of the topographic map from vertebrate retina to superior colliculus (SC), EphA receptors are expressed in a gradient along the nasotemporal retinal axis. Their ligands, ephrin-As, are expressed in a gradient along the rostrocaudal axis of the SC. Countergradients of ephrin-As in the retina and EphAs in the SC are also expressed. Disruption of any of these gradients leads to mapping errors. Gierer's (1981) model, which uses well-matched pairs of gradients and countergradients to establish the mapping, can account for the formation of wild type maps, but not the double maps found in EphA knock-in experiments. I show that these maps can be explained by models, such as Gierer's (1983), which have gradients and no countergradients, together with a powerful compensatory mechanism that helps to distribute connections evenly over the target region. However, this type of model cannot explain mapping errors found when the countergradients are knocked out partially. I examine the relative importance of countergradients as against compensatory mechanisms by generalising Gierer's (1983) model so that the strength of compensation is adjustable. Either matching gradients and countergradients alone or poorly matching gradients and countergradients together with a strong compensatory mechanism are sufficient to establish an ordered mapping. With a weaker compensatory mechanism, gradients without countergradients lead to a poorer map, but the addition of countergradients improves the mapping. This model produces the double maps in simulated EphA knock-in experiments and a map consistent with the Math5 knock-out phenotype. Simulations of a set of phenotypes from the literature substantiate the finding that countergradients and compensation can be traded off against each other to give similar maps. I conclude that a successful model of retinotopy should contain countergradients and some form of compensation mechanism, but not in the strong form put forward by Gierer

Sprouty2 mediated tuning of signalling is essential for somite myogenesis

Background: Negative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development. Sprouty2 (Spry2) negatively regulates receptor tyrosine kinases (RTK) and FGF signalling and is important in differentiation, cell migration and proliferation. In vertebrate embryos, Spry2 is expressed in paraxial mesoderm and in forming somites. Expression is maintained in the myotome until late stages of somite differentiation. However, its role and mode of action during somite myogenesis is still unclear. Results: Here, we analysed chick Spry2 expression and showed that it overlaps with that of myogenic regulatory factors MyoD and Mgn. Targeted mis-expression of Spry2 led to inhibition of myogenesis, whilst its C-terminal domain led to an increased number of myogenic cells by stimulating cell proliferation. Conclusions: Spry2 is expressed in somite myotomes and its expression overlaps with myogenic regulatory factors. Overexpression and dominant-negative interference showed that Spry2 plays a crucial role in regulating chick myogenesis by fine tuning of FGF signaling through a negative feedback loop. We also propose that mir-23, mir-27 and mir-128 could be part of the negative feedback loop mechanism. Our analysis is the first to shed some light on in vivo Spry2 function during chick somite myogenesis

Organizational commitment, organization-based self-esteem, emotional exhaustion and turnover: A conservation of resources perspective

We examined the relationship of four commitment dimensions (affective, normative, continuance-perceived sacrifices and continuance-lack of alternatives) to emotional exhaustion over time under the lens of conservation of resources theory. Using data from 260 employees, Time 1 lack of alternatives and normative commitment contributed positively to Time 2 emotional exhaustion, controlling for Time 1 emotional exhaustion. Organization-based self-esteem (OBSE) moderated the relationship of lack of alternatives commitment to emotional exhaustion such that the relationship was stronger when OBSE was high. We further theorized that the resource drain engendered by emotional exhaustion would cause the latter to be positively related to turnover, controlling for commitment dimensions. Results supported this prediction. The implications of these findings for future research on commitment, emotional exhaustion and turnover are discussed

Universality of clone dynamics during tissue development.

The emergence of complex organs is driven by the coordinated proliferation, migration and differentiation of precursor cells. The fate behaviour of these cells is reflected in the time evolution their progeny, termed clones, which serve as a key experimental observable. In adult tissues, where cell dynamics is constrained by the condition of homeostasis, clonal tracing studies based on transgenic animal models have advanced our understanding of cell fate behaviour and its dysregulation in disease (1, 2). But what can be learned from clonal dynamics in development, where the spatial cohesiveness of clones is impaired by tissue deformations during tissue growth? Drawing on the results of clonal tracing studies, we show that, despite the complexity of organ development, clonal dynamics may converge to a critical state characterized by universal scaling behaviour of clone sizes. By mapping clonal dynamics onto a generalization of the classical theory of aerosols, we elucidate the origin and range of scaling behaviours and show how the identification of universal scaling dependences may allow lineage-specific information to be distilled from experiments. Our study shows the emergence of core concepts of statistical physics in an unexpected context, identifying cellular systems as a laboratory to study non-equilibrium statistical physics.Wellcome Trus

Dynamic 3D echocardiography in virtual reality

BACKGROUND: This pilot study was performed to evaluate whether virtual reality is applicable for three-dimensional echocardiography and if three-dimensional echocardiographic 'holograms' have the potential to become a clinically useful tool. METHODS: Three-dimensional echocardiographic data sets from 2 normal subjects and from 4 patients with a mitral valve pathological condition were included in the study. The three-dimensional data sets were acquired with the Philips Sonos 7500 echo-system and transferred to the BARCO (Barco N.V., Kortrijk, Belgium) I-space. Ten independent observers assessed the 6 three-dimensional data sets with and without mitral valve pathology. After 10 minutes' instruction in the I-Space, all of the observers could use the virtual pointer that is necessary to create cut planes in the hologram. RESULTS: The 10 independent observers correctly assessed the normal and pathological mitral valve in the holograms (analysis time approximately 10 minutes). CONCLUSION: this report shows that dynamic holographic imaging of three-dimensional echocardiographic data is feasible. However, the applicability and use-fullness of this technology in clinical practice is still limited

Evaluation of the Ez-HBT Helicobacter blood test to establish Helicobacter pylori eradication

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73012/1/j.1365-2036.2005.02655.x.pd

Prioritizing Land and Sea Conservation Investments to Protect Coral Reefs

Background: Coral reefs have exceptional biodiversity, support the livelihoods of millions of people, and are threatened by multiple human activities on land (e.g. farming) and in the sea (e.g. overfishing). Most conservation efforts occur at local scales and, when effective, can increase the resilience of coral reefs to global threats such as climate change (e.g. warming water and ocean acidification). Limited resources for conservation require that we efficiently prioritize where and how to best sustain coral reef ecosystems