Molecular clutch drives cell response to surface viscosity

Cell response to matrix rigidity has been explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. Here the molecular clutch model is extended to account for cell interactions with purely viscous surfaces (i.e., without an elastic component). Supported lipid bilayers present an idealized and controllable system through which to study this concept. Using lipids of different diffusion coefficients, the mobility (i.e., surface viscosity) of the presented ligands (in this case RGD) was altered by an order of magnitude. Cell size and cytoskeletal organization were proportional to viscosity. Furthermore, there was a higher number of focal adhesions and a higher phosphorylation of FAK on less-mobile (more-viscous) surfaces. Actin retrograde flow, an indicator of the force exerted on surfaces, was also seen to be faster on more mobile surfaces. This has consequential effects on downstream molecules; the mechanosensitive YAP protein localized to the nucleus more on less-mobile (more-viscous) surfaces and differentiation of myoblast cells was enhanced on higher viscosity. This behavior was explained within the framework of the molecular clutch model, with lower viscosity leading to a low force loading rate, preventing the exposure of mechanosensitive proteins, and with a higher viscosity causing a higher force loading rate exposing these sites, activating downstream pathways. Consequently, the understanding of how viscosity (regardless of matrix stiffness) influences cell response adds a further tool to engineer materials that control cell behavior

geo climatic applicability of direct evaporative cooling in italy

This chapter focuses on the climatic applicability of passive direct (downdraught) evaporative cooling (PDEC) techniques in the provincial capital cities of Italy. First, a PDEC potentiality map was produced using a previously developed method based on three variables: wet bulb depression, summer comfort air temperature threshold (25 °C) and cooling degree hours (CDHs). Second, an applicability map was produced by comparing the PDEC potentiality map to the local cooling energy demand. Third, a new method is presented including a calculation of the residual local cooling energy demand, i.e. residual CDH, related to air treatment by direct evaporative cooling. These residual CDH values were calculated considering different step-wise increasing outlet temperatures (WBT; WBT + 1 °C; …; WBT + 5 °C) as a function of the covered amount of wet bulb depression. Finally, three cities chosen as being representative of their respective Italian climatic macro-zones were selected in order to assess in greater detail the yearly variation of CDH aimed at supporting specific design strategies for ventilative passive cooling solutions

Influence of two breakfast meals differing in glycemic load on satiety, hunger, and energy intake in preschool children

<p>Abstract</p> <p>Background</p> <p>Glycemic load (GL) is the product of glycemic index of a food and amount of available carbohydrate in that food divided by 100. GL represents quality and quantity of dietary carbohydrate. Little is known about the role of GL in hunger, satiety, and food intake in preschool children. The aim of this study was to investigate the effect of two breakfast meals differing in GL on hunger, satiety, and subsequent food intake at lunch in preschool children aged 4-6 y.</p> <p>Methods</p> <p>Twenty three subjects consumed low-GL (LGL) and high-GL (HGL) breakfast meals according to a randomized crossover design followed by an <it>ad libitum </it>lunch 4 h after consumption of breakfast. Children were asked to consume meals until they are full. Each treatment was repeated twice in non-consecutive days and data were averaged.</p> <p>Results</p> <p>Children in LGL group consumed significantly lower amounts of GL, total carbohydrate, energy, energy density, and dietary fiber and higher amounts of protein and fat at the breakfast compared to those in HGL group. Prior to lunch, children were hungrier in the HGL intervention group compared to the LGL intervention group (<it>P </it>< 0.03). However, no significant difference was observed between LGL and HGL intervention groups in the amount of food and energy consumed during lunch.</p> <p>Conclusions</p> <p>Decreased hunger in children prior to lunch in LGL group is likely due to higher protein and fat content of LGL breakfast. Diets that are low in GL can be recommended as part of healthy diet for preschool children.</p

Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

BACKGROUND: Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. METHODS: Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry. RESULTS: RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. CONCLUSION: RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling

A high-resolution map of the Grp1 locus on chromosome V of potato harbouring broad-spectrum resistance to the cyst nematode species Globodera pallida and Globodera rostochiensis

The Grp1 locus confers broad-spectrum resistance to the potato cyst nematode species Globodera pallida and Globodera rostochiensis and is located in the GP21-GP179 interval on the short arm of chromosome V of potato. A high-resolution map has been developed using the diploid mapping population RHAM026, comprising 1,536 genotypes. The flanking markers GP21 and GP179 have been used to screen the 1,536 genotypes for recombination events. Interval mapping of the resistances to G. pallida Pa2 and G. rostochiensis Ro5 resulted in two nearly identical LOD graphs with the highest LOD score just north of marker TG432. Detailed analysis of the 44 recombinant genotypes showed that G. pallida and G. rostochiensis resistance could not be separated and map to the same location between marker SPUD838 and TG432. It is suggested that the quantitative resistance to both nematode species at the Grp1 locus is mediated by one or more tightly linked R genes that might belong to the NBS-LRR class

A genome-wide genetic map of NB-LRR disease resistance loci in potato

Like all plants, potato has evolved a surveillance system consisting of a large array of genes encoding for immune receptors that confer resistance to pathogens and pests. The majority of these so-called resistance or R proteins belong to the super-family that harbour a nucleotide binding and a leucine-rich-repeat domain (NB-LRR). Here, sequence information of the conserved NB domain was used to investigate the genome-wide genetic distribution of the NB-LRR resistance gene loci in potato. We analysed the sequences of 288 unique BAC clones selected using filter hybridisation screening of a BAC library of the diploid potato clone RH89-039-16 (S. tuberosum ssp. tuberosum) and a physical map of this BAC library. This resulted in the identification of 738 partial and full-length NB-LRR sequences. Based on homology of these sequences with known resistance genes, 280 and 448 sequences were classified as TIR-NB-LRR (TNL) and CC-NB-LRR (CNL) sequences, respectively. Genetic mapping revealed the presence of 15 TNL and 32 CNL loci. Thirty-six are novel, while three TNL loci and eight CNL loci are syntenic with previously identified functional resistance genes. The genetic map was complemented with 68 universal CAPS markers and 82 disease resistance trait loci described in literature, providing an excellent template for genetic studies and applied research in potato

Electrostatic Effects in the Folding of the SH3 Domain of the c-Src Tyrosine Kinase: pH-Dependence in 3D-Domain Swapping and Amyloid Formation

The SH3 domain of the c-Src tyrosine kinase (c-Src-SH3) aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i) its thermal stability; and (ii) its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid pH, while Gln128Lys and Gln128Arg mutants do not form these aggregates under any of the conditions assayed. We have also solved the crystallographic structures of the wild-type (WT) and Gln128Glu, Gln128Lys and Gln128Arg mutants from crystals obtained at different pHs. At pH 5.0, crystals belong to the hexagonal space group P6522 and the asymmetric unit is formed by one chain of the protomer of the c-Src-SH3 domain in an open conformation. At pH 7.0, crystals belong to the orthorhombic space group P212121, with two molecules at the asymmetric unit showing the characteristic fold of the SH3 domain. Analysis of these crystallographic structures shows that the residue at position 128 is connected to Glu106 at the diverging β-turn through a cluster of water molecules. Changes in this hydrogen-bond network lead to the displacement of the c-Src-SH3 distal loop, resulting also in conformational changes of Leu100 that might be related to the binding of proline rich motifs. Our findings show that electrostatic interactions and solvation of residues close to the folding nucleation site of the c-Src-SH3 domain might play an important role during the folding reaction and the amyloid fibril formation.This research was funded by the Spanish Ministry of Science and Innovation and Ministry of Economy and Competitiveness and FEDER (EU): BIO2009-13261-C02-01/02 (ACA); BIO2012-39922-C02-01/02 (ACA); CTQ2013-4493 (JLN) and CSD2008-00005 (JLN); Andalusian Regional Government (Spain) and FEDER (EU): P09-CVI-5063 (ACA); and Valentian Regional Government (Spain) and FEDER (EU): Prometeo 2013/018 (JLN). Data collection was supported by European Synchrotron Radiation Facility (ESRF), Grenoble, France: BAG proposals MX-1406 (ACA) and MX-1541 (ACA); and ALBA (Barcelona, Spain) proposals 2012010072 (ACA) and 2012100378 (ACA)

Prophylactic ciprofloxacin treatment prevented high mortality, and modified systemic and intestinal immune function in tumour-bearing rats receiving dose-intensive CPT-11 chemotherapy

Infectious complications are a major cause of morbidity and mortality from dose-intensive cancer chemotherapy. In spite of the importance of intestinal bacteria translocation in these infections, information about the effect of high-dose chemotherapy on gut mucosal immunity is minimal. We studied prophylactic ciprofloxacin (Cipro) treatment on irinotecan (CPT-11) toxicity and host immunity in rats bearing Ward colon tumour. Cipro abolished chemotherapy-related mortality, which was 45% in animals that were not treated with Cipro. Although Cipro reduced body weight loss and muscle wasting, it was unable to prevent severe late-onset diarrhoea. Seven days after CPT-11, splenocytes were unable to proliferate (stimulation index=0.10±0.02) and produce proliferative and inflammatory cytokines (i.e., Interleukin (IL)-2, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) IL-1β, IL-6) on mitogen stimulation in vitro (P<0.05 vs controls), whereas mesenteric lymph node (MLN) cells showed a hyper-proliferative response and a hyper-production of pro-inflammatory cytokines on mitogen stimulation. This suggests compartmentalised effects by CPT-11 chemotherapy on systemic and intestinal immunity. Cipro normalised the hyper-responsiveness of MLN cells, and in the spleen, it partially restored the proliferative response and normalised depressed production of IL-1β and IL-6. Taken together, Cipro prevented infectious challenges associated with immune hypo-responsiveness in systemic immune compartments, and it may also alleviate excessive pro-inflammatory responses mediating local gut injury

Connecting Planetary Composition with Formation

The rapid advances in observations of the different populations of exoplanets, the characterization of their host stars and the links to the properties of their planetary systems, the detailed studies of protoplanetary disks, and the experimental study of the interiors and composition of the massive planets in our solar system provide a firm basis for the next big question in planet formation theory. How do the elemental and chemical compositions of planets connect with their formation? The answer to this requires that the various pieces of planet formation theory be linked together in an end-to-end picture that is capable of addressing these large data sets. In this review, we discuss the critical elements of such a picture and how they affect the chemical and elemental make up of forming planets. Important issues here include the initial state of forming and evolving disks, chemical and dust processes within them, the migration of planets and the importance of planet traps, the nature of angular momentum transport processes involving turbulence and/or MHD disk winds, planet formation theory, and advanced treatments of disk astrochemistry. All of these issues affect, and are affected by the chemistry of disks which is driven by X-ray ionization of the host stars. We discuss how these processes lead to a coherent end-to-end model and how this may address the basic question.Comment: Invited review, accepted for publication in the 'Handbook of Exoplanets', eds. H.J. Deeg and J.A. Belmonte, Springer (2018). 46 pages, 10 figure