Emerging role of contact-mediated cell communication in tissue development and diseases

This is the final version. Available on open access from Springer via the DOI in this recordCells of multicellular organisms are in continuous conversation with the neighbouring cells. The sender cells signal the receiver cells to influence their behaviour in transport, metabolism, motility, division, and growth. How cells communicate with each other can be categorized by biochemical signalling processes, which can be characterised by the distance between the sender cell and the receiver cell. Existing classifications describe autocrine signals as those where the sender cell is identical to the receiver cell. Complementary to this scenario, paracrine signalling describes signalling between a sender cell and a different receiver cell. Finally, juxtacrine signalling describes the exchange of information between adjacent cells by direct cell contact, whereas endocrine signalling describes the exchange of information, e.g., by hormones between distant cells or even organs through the bloodstream. In the last two decades, however, an unexpected communication mechanism has been identified which uses cell protrusions to exchange chemical signals by direct contact over long distances. These signalling protrusions can deliver signals in both ways, from sender to receiver and vice versa. We are starting to understand the morphology and function of these signalling protrusions in many tissues and this accumulation of findings forces us to revise our view of contact-dependent cell communication. In this review, we will focus on the two main categories of signalling protrusions, cytonemes and tunnelling nanotubes. These signalling protrusions emerge as essential structural components of a vibrant communication network in the development and tissue homeostasis of any multicellular organism.BM and SS are funded by a LSI start-up grant awarded to SS

Subtle changes in the flavour and texture of a drink enhance expectations of satiety

Background: The consumption of liquid calories has been implicated in the development of obesity and weight gain. Energy-containing drinks are often reported to have a weak satiety value: one explanation for this is that because of their fluid texture they are not expected to have much nutritional value. It is important to consider what features of these drinks can be manipulated to enhance their expected satiety value. Two studies investigated the perception of subtle changes in a drink’s viscosity, and the extent to which thick texture and creamy flavour contribute to the generation of satiety expectations. Participants in the first study rated the sensory characteristics of 16 fruit yogurt drinks of increasing viscosity. In study two, a new set of participants evaluated eight versions of the fruit yogurt drink, which varied in thick texture, creamy flavour and energy content, for sensory and hedonic characteristics and satiety expectations. Results: In study one, participants were able to perceive small changes in drink viscosity that were strongly related to the actual viscosity of the drinks. In study two, the thick versions of the drink were expected to be more filling and have a greater expected satiety value, independent of the drink’s actual energy content. A creamy flavour enhanced the extent to which the drink was expected to be filling, but did not affect its expected satiety. Conclusions: These results indicate that subtle manipulations of texture and creamy flavour can increase expectations that a fruit yogurt drink will be filling and suppress hunger, irrespective of the drink’s energy content. A thicker texture enhanced expectations of satiety to a greater extent than a creamier flavour, and may be one way to improve the anticipated satiating value of energy-containing beverages

A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo

Extracellular matrix-modulated expression of human cell surface glycoproteins A42 and J143. Intrinsic and extrinsic signals determine antigenic phenotype.

Extracellular matrix (ECM)' plays an important regulatory role in cellular growth, migration, and differentiation (1-4). Pathologic processes such as tumor cell invasion and metastasis are also determined by cellular interactions with ECM (5, 6). Biochemical studies have identified collagens, fibronectin, laminin, proteoglycans, and several other proteins as major ECM components (1-3), and have shown that ECM composition varies between different normal and tumor tissues. The complexity and heterogeneity of ECM composition have hampered the molecular analysis of ECM-cell interactions . However, a range of phenotypic changes has been described for cultured cells after transfer from plastic surfaces to substrates coated with native ECM (7, 8) or with purified ECM components; ECM-induced phenotypic changes include enhanced substrate adhesiveness, cell spreading and migration, changes in cell morphology and proliferative activity, and expression of differentiated cellular functions (I-4). Some of these effects, e.g., increased substrate adhesion, may result directly from the binding of specialized cell surface structures to ECM molecules. Others are likely mediated by an active cellular response triggered by the interaction of ECM with cell surface receptors. Thus, ECM-derived signals (9) may activate a cascade of molecular changes within the cell and on the cell surface that account for the pleiotropic effects observed with ECM

Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target

Background: The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Relatively little is known, however, about the role of miRNAs in inflammatory and immunologically-driven disorders. In a mouse model, we have previously shown that miRNAs are potentially important therapeutic targets in allergic asthma, because inhibition of miR-126, one of a small subset of miRNAs upregulated in the airway wall, effectively suppressed Th2-driven airway inflammation and other features of asthma. In the present study, we extended investigation of the therapeutic potential of miRNA inhibition to our well-established model of chronic asthma. Methods: Female BALB/c mice were systemically sensitised with ovalbumin (OVA) and chronically challenged with low mass concentrations of aerosolised OVA for up to 6 weeks. Airway tissue was obtained by blunt dissection and RNA was isolated for miRNA profiling. On the basis of the results obtained, animals were subsequently treated with either an antagomir to miR-126 (ant-miR-126) or a scrambled control antagomir once weekly during the 6 weeks of chronic challenge, and the effects on airway inflammation and remodelling were assessed using established morphometric techniques. Results: Compared to naïve mice, there was selective upregulation of a modest number of miRNAs, notably miR-126, in the airway wall tissue of chronically challenged animals. The relative increase was maximal after 2 weeks of inhalational challenge and subsequently declined to baseline levels. Compared to treatment with the scrambled control, ant-miR-126 significantly reduced recruitment of intraepithelial eosinophils, but had no effect on the chronic inflammatory response, or on changes of airway remodelling. Conclusions: In this model of chronic asthma, there was an initial increase in expression of a small number of miRNAs in the airway wall, notably miR-126. However, this later declined to baseline levels, suggesting that sustained changes in miRNA may not be essential for perpetuation of chronic asthma. Moreover, inhibition of miR-126 by administration of an antagomir suppressed eosinophil recruitment into the airways but had no effect on chronic inflammation in the airway wall, or on changes of remodelling, suggesting that multiple miRNAs are likely to regulate the development of these lesions

Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation

This is the final version of the article. Available from American Society for Biochemistry and Molecular Biology via the DOI in this record.Convergent extension movements during vertebrate gastrulation require a balanced activity of non-canonical Wnt signaling pathways, but the factors regulating this interplay on the molecular level are poorly characterized. Here we show that sFRP2, a member of the secreted frizzled-related protein (sFRP) family, is required for morphogenesis and papc expression during Xenopus gastrulation. We further provide evidence that sFRP2 redirects non-canonical Wnt signaling from Frizzled 7 (Fz7) to the receptor tyrosine kinase-like orphan receptor 2 (Ror2). During this process, sFRP2 promotes Ror2 signal transduction by stabilizing Wnt5a-Ror2 complexes at the membrane, whereas it inhibits Fz7 signaling, probably by blocking Fz7 receptor endocytosis. The cysteine-rich domain of sFRP2 is sufficient for Ror2 activation, and related sFRPs can substitute for this function. Notably, direct interaction of the two receptors via their cysteine-rich domains also promotes Ror2-mediated papc expression but inhibits Fz7 signaling. We propose that sFRPs can act as a molecular switch, channeling the signal input for different non-canonical Wnt pathways during vertebrate gastrulation

Ferroelectricity in the xAg2Nb4O11–(1−x)Na2Nb4O11 solid solution

Compositions in the (AgxNa1-x)2Nb4O11 solid solution have been prepared by a conventional solid state method. Composites containing Ag2Nb4O11 have been shown to be ferroelectric and the Curie temperature shown to decrease from 149 °C at x = 1 to 62 °C at x = 0.7. Roomtemperature compositions with x ≤ 0.7 are monoclinic, while those with x ≥ 0.8 are rhombohedral with structures consistent with the relevant end-members. At x = 0.75, the structure was mainly rhombohedral but with coexistence of the monoclinic structure, indicating the proximity of a phase boundary

Manual of Infant Lung Function Tests

This manual provides a step-by-step guide to assessments of infant lung function using the CareFusion MasterScreen™ BabyBody Plethysmograph. The authors have included a section to cover essential background information and developmental changes in respiratory physiology during the first years of life which affect both the measurement and the interpretation of lung function results in infants and young children. A detailed section on data interpretation and management and a recommended reading list have also been included. The main aims of the manual are to provide: • Background information on developmental physiology and insight into the special considerations to bear in mind when assessing infants; • A step-by-step guide to new/current users of ILFT equipment to ensure the assessments of infant lung function tests are performed as accurately as possible • Guidance on data analysis and interpretation. The manual is aimed at all paediatricians, respiratory physiologists and researchers who are interested in the field, and have purchased the CareFusion MasterScreen BabyBody device for use in their lung function laboratory (or are intending to do so)