Molecular danger signals attract neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) to sites of infection. The G protein-coupled receptor (GPR) 43 recognizes propionate and butyrate and ...is abundantly expressed on PMNs. The functional role of GPR43 activation for in vivo orchestration of immune response is unclear. We examined dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammatory response in wild-type and Gpr43-deficient mice. The severity of colonic inflammation was assessed by clinical signs, histological scoring, and cytokine production. Chemotaxis of wild-type and Gpr43-deficient PMNs was assessed through transwell cell chemotactic assay. A reduced invasion of PMNs and increased mortality due to septic complications were observed in acute DSS colitis. In chronic DSS colitis, Gpr43(-/-) animals showed diminished PMN intestinal migration, but protection against inflammatory tissue destruction. No significant difference in PMN migration and cytokine secretion was detected in a sterile inflammatory model. Ex vivo experiments show that GPR43-induced migration is dependent on activation of the protein kinase p38alpha, and that this signal acts in cooperation with the chemotactic cytokine keratinocyte chemoattractant. Interestingly, shedding of L-selectin in response to propionate and butyrate was compromised in Gpr43(-/-) mice. These results indicate a critical role for GPR43-mediated recruitment of PMNs in containing intestinal bacterial translocation, yet also emphasize the bipotential role of PMNs in mediating tissue destruction in chronic intestinal inflammation.
What strategy should an individual follow in a heterogeneous environment when its phenotype is not optimized for its current environment: make changes to the environment (habitat construction), move ...to a different place (habitat choice), or both? Scheiner et al. used an individual‐based model to investigate the interaction of habitat choice and habitat construction. In most situations, habitat construction was superior to either habitat selection or a mixed strategy.
We performed a genome-wide association study of 19,779 nonsynonymous SNPs in 735 individuals with Crohn disease and 368 controls. A total of 7,159 of these SNPs were informative. We followed up on ...all 72 SNPs with P ≤ 0.01 with an allele-based disease association test in 380 independent Crohn disease trios, 498 Crohn disease singleton cases and 1,032 controls. Disease association of rs2241880 in the autophagy-related 16-like 1 gene (ATG16L1) was replicated in these samples (P = 4.0 × 10−8) and confirmed in a UK case-control sample (P = 0.0004). By haplotype and regression analysis, we found that marker rs2241880, a coding SNP (T300A), carries virtually all the disease risk exerted by the ATG16L1 locus. The ATG16L1 gene encodes a protein in the autophagosome pathway that processes intracellular bacteria. We found a statistically significant interaction with respect to Crohn disease risk between rs2241880 and the established CARD15 susceptibility variants (P = 0.039). Together with the lack of association between rs2241880 and ulcerative colitis (P > 0.4), these data suggest that the underlying biological process may be specific to Crohn disease.
This article develops empirically based guidelines to assist managers in selecting or modifying package designs for achieving desired consumer responses. Seven studies identify the key types of ...package designs, including the factors that differentiate those package designs, and determine how these holistic designs are related to consumer brand impressions. The selection of package designs can be simplified with the use of five holistic types: massive, contrasting, natural, delicate, and nondescript designs. Sincere brands should have natural package designs, exciting brands should have contrasting designs, competent brands should have delicate designs, sophisticated brands should have natural or delicate designs, and rugged brands should have contrasting or massive designs. The authors discuss the potential trade-offs among the impressions created by holistic design types and illustrate their findings with numerous real packages. PUBLICATION ABSTRACT
What strategy should an individual follow when faced with a suboptimal environment: change the environment, adapt to the environment, or both? Scheiner et al. used an individual-based model to ...address the interaction of plasticity and habitat construction with different life histories in a heterogeneous environment. In most situations, habitat construction was superior to either plasticity or a mixed strategy, but not always, and specific conditions may favor plasticity.
The magnetic fields of Earth and Jupiter, along with those of rapidly rotating, low-mass stars, are generated by convection-driven dynamos that may operate similarly (the slowly rotating Sun ...generates its field through a different dynamo mechanism). The field strengths of planets and stars vary over three orders of magnitude, but the critical factor causing that variation has hitherto been unclear. Here we report an extension of a scaling law derived from geodynamo models to rapidly rotating stars that have strong density stratification. The unifying principle in the scaling law is that the energy flux available for generating the magnetic field sets the field strength. Our scaling law fits the observed field strengths of Earth, Jupiter, young contracting stars and rapidly rotating low-mass stars, despite vast differences in the physical conditions of the objects. We predict that the field strengths of rapidly rotating brown dwarfs and massive extrasolar planets are high enough to make them observable.
Visual appeal is an important consideration in the design of interior service environments because attractiveness influences consumer behavior. Employing both an experiment and a field study, we show ...that visual complexity reduces a service environment’s attractiveness. Furthermore, we find that the complexity-attractiveness relationship is mediated by processing fluency and its instantaneous affective companion, pleasure. Our findings provide novel insights into the underlying process mechanism involved in channeling the effect of visual complexity on attractiveness. Furthermore, both studies confirm that customers’ field dependence moderates the complexity-fluency relationship and that shopping motivation (i.e., hedonic vs. utilitarian shopping goals) moderates the fluency-pleasure relationship. Our findings suggest that it is generally better to reduce the complexity of interior service environments. To achieve this, service firms should reduce the number of objects in the environment, enhance the visual organization and symmetry of their arrangement, and use fewer colors, textures, and materials.
Mercury has a global magnetic field of internal origin and it is thought that a dynamo operating in the fluid part of Mercury's large iron core is the most probable cause. However, the low intensity ...of Mercury's magnetic field-about 1% the strength of the Earth's field-cannot be reconciled with an Earth-like dynamo. With the common assumption that Coriolis and Lorentz forces balance in planetary dynamos, a field thirty times stronger is expected. Here I present a numerical model of a dynamo driven by thermo-compositional convection associated with inner core solidification. The thermal gradient at the core-mantle boundary is subadiabatic, and hence the outer region of the liquid core is stably stratified with the dynamo operating only at depth, where a strong field is generated. Because of the planet's slow rotation the resulting magnetic field is dominated by small-scale components that fluctuate rapidly with time. The dynamo field diffuses through the stable conducting region, where rapidly varying parts are strongly attenuated by the skin effect, while the slowly varying dipole and quadrupole components pass to some degree. The model explains the observed structure and strength of Mercury's surface magnetic field and makes predictions that are testable with space missions both presently flying and planned.
For many published dynamo models an Earth-like magnetic field has been claimed. However, it has also been noted that as the Ekman number (viscosity) is lowered to less unrealistic values, the ...magnetic field tends to become less Earth-like. Here we define quantitative criteria for the degree of semblance of a model field with the geomagnetic field, based on the field morphology at the core–mantle boundary. We consider the ratio of the power in the axial dipole component to that in the rest if the field, the ratios between equatorially symmetric and antisymmetric and between zonal and non-zonal non-dipole components, and a measure for the degree of spatial concentration of magnetic flux at the core surface. We also briefly discuss shortcomings of possible other criteria for an Earth-like model. We test the compliance with our criteria for a large number of dynamo models driven by imposed temperatures at their inner and outer boundaries that cover the accessible parameter space. We order models according to their magnetic Reynolds number
Rm (ratio of advection to diffusion of magnetic field) and magnetic Ekman number
E
η
(ratio between rotation period and magnetic diffusion time). Requirements for an Earth-like field morphology are that
E
η
<
10
−
4
and that
Rm falls into a limited range that depends on
E
η
. Higher values of
Rm are required at low values of
E
η
. Extrapolating the boundaries of compliant dynamos in this parameter space to the Earth's value of
E
η
suggests that Earth-like dynamos exist all the way between present model values and parameter values of the geodynamo. We also study a more limited set of dynamo models with flux boundary conditions. The nature of the boundary condition and the distribution of sources and sinks of buoyancy have a secondary influence on the field morphology.
Mucosal epithelial cell layers are constantly exposed to a complex resident microflora. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich ...proteins and is considered to be involved in host defense by pathogen binding. This report describes the regulation and function of DMBT1 in intestinal epithelial cells, which form the primary immunological barrier for invading pathogens. We report that intestinal epithelial cells up-regulate DMBT1 upon proinflammatory stimuli (e.g., TNF-alpha, LPS). We demonstrate that DMBT1 is a target gene for the intracellular pathogen receptor NOD2 via NF-kappaB activation. DMBT1 is strongly up-regulated in the inflamed intestinal mucosa of Crohn's disease patients with wild-type, but not with mutant NOD2. We show that DMBT1 inhibits cytoinvasion of Salmonella enterica and LPS- and muramyl dipeptide-induced NF-kappaB activation and cytokine secretion in vitro. Thus, DMBT1 may play an important role in the first line of mucosal defense conferring immune exclusion of bacterial cell wall components. Dysregulated intestinal DMBT1 expression due to mutations in the NOD2/CARD15 gene may be part of the complex pathophysiology of barrier dysfunction in Crohn's disease.
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