The epidemiological literature published to date indicates that individuals with more sunlight exposure are at a significantly increased risk of AMD. The OR significantly decreased with increasing GDP per capita.
CX 3 CL1 (fractalkine) plays an important role in inflammation by acting as both chemoattractant and as an adhesion molecule. As for other chemokines, expression of CX 3 CL1 is known to be regulated at the level of transcription and translation. The unique transmembrane structure of CX 3 CL1 raises the possibility of additional functional regulation by altering its abundance at the cell surface. This could be accomplished in principle by changes in traffic between subcellular compartments. To analyze this possibility we examined the subcellular distribution of CX 3 CL1 in human ECV-304 cells stably expressing untagged or green fluorescent proteintagged forms of the chemokine. CX 3 CL1 was present in two distinct compartments, diffusely on the plasma membrane and in a punctate juxtanuclear compartment. The latter shared some features with, yet was distinct from the conventional endocytic pathway and may represent a specialized recycling subcompartment. Accordingly, surface CX 3 CL1 was found to be in dynamic equilibrium with the juxtanuclear vesicular compartment. Intracellular CX 3 CL1 co-localized with the SNARE (soluble N-ethylmaleimide factor attachment protein receptor) proteins syntaxin-13 and VAMP-3. Cleavage of VAMP-3 by tetanus toxin or impairment of syntaxin-13 function by expression of a dominant-negative allele inhibited the ability of internalized CX 3 CL1 to traffic back to the plasma membrane. These data demonstrate the existence of a dynamic, SNARE-mediated recycling of CX 3 CL1 from the cell surface to and from an endomembrane storage compartment. The intracellular storage depot may serve as a source of the chemokine that could be rapidly mobilized by stimuli.
In this paper, we propose an explicit closed-form Bayes factor for the problem of two-sample hypothesis testing. The proposed approach can be regarded as a Bayesian version of the pooled-variance t-statistic and has various appealing properties in practical applications. It relies on data only through the t-statistic and can thus be calculated by using an Excel spreadsheet or a pocket calculator. It avoids several undesirable paradoxes, which may be encountered by the previous Bayesian approach of Gönen et al. (2005). Specifically, the proposed approach can be easily taught in an introductory statistics course with an emphasis on Bayesian thinking. Simulated and real data examples are provided for illustrative purposes.
The chemokine CX 3 CL1 plays a key role in glomerulonephritis and can act as both chemoattractant and adhesion molecule. CX 3 CL1 also is upregulated in tubulointerstitial injury, but little is known about the subcellular distribution and function of CX 3 CL1 in renal tubular epithelial cells (RTEC). Unexpectedly, it was found that CX 3 CL1 is expressed predominantly on the apical surface of tubular epithelium in human renal transplant biopsy specimens with acute rejection or acute tubular necrosis. For studying the targeting of CX 3 CL1 in polarized RTEC, MDCK cells that expressed untagged or green fluorescent protein-tagged CX 3 CL1 were generated. The chemokine was present on the apical membrane and in subapical vesicles. Apical targeting of CX 3 CL1 was not due to signals that were conferred by its intracellular domain, to associations with lipid rafts, or to O-glycosylation but, rather, depended on N-linked glycosylation of the protein. With the use of fluorescence recovery after photobleaching, it was found that CX 3 CL1 is immobile in the apical membrane. However, CX 3 CL1 partitioned with the triton-soluble rather than -insoluble cellular fraction, indicating that it is not associated directly with the actin cytoskeleton or with lipid rafts. Accordingly, disruption of rafts through cholesterol depletion did not render CX 3 CL1 mobile. For exploration of potential functions of apical CX 3 CL1, binding of CX 3 CR1-expressing leukocytes to polarized RTEC was examined. Leukocyte adhesion to the luminal surface was enhanced significantly when CX 3 CL1 was present. These data demonstrate that CX 3 CL1 is expressed preferentially on the apical membrane of RTEC and suggest a novel function for the chemokine in recruitment and retention of leukocytes in tubulointerstitial inflammation.
Macropinocytosis is essential for myeloid cells to survey their environment and for growth of RAS-transformed cancer cells. Several growth factors and inflammatory stimuli are known to induce macropinocytosis, but its endogenous inhibitors have remained elusive. Stimulation of Roundabout receptors by Slit ligands inhibits directional migration of many cell types, including immune cells and cancer cells. We report that SLIT2 inhibits macropinocytosis in vitro and in vivo by inducing cytoskeletal changes in macrophages. In mice, SLIT2 attenuates the uptake of muramyl dipeptide, thereby preventing NOD2-dependent activation of NF-κB and consequent secretion of pro-inflammatory chemokine, CXCL1. Conversely, blocking the action of endogenous SLIT2 enhances CXCL1 secretion. SLIT2 also inhibits macropinocytosis in RAS-transformed cancer cells, thereby decreasing their survival in nutrient-deficient conditions which resemble tumor microenvironment. Our results identify SLIT2 as a physiological inhibitor of macropinocytosis and challenge the conventional notion that signals that enhance macropinocytosis negatively regulate cell migration, and vice versa.
The silkworm, Bombyx mori L. (Lepidoptera: Bombycidae), an oligophagous insect that mainly feeds on mulberry leaves, is susceptible to entomopathogen infection when reared with tricuspid cudrania leaves. A total of 56 dominant bacterial strains, classified into 12 phylotypes based on bacteriological properties and analysis of 16S rRNA genes, were isolated from the intestine of the fourth and fifth instar silkworm larvae. Ten and seven phylotypes exist in the intestine of the silkworm larvae reared with mulberry leaves and tricuspid cudrania leaves, respectively. Four of them are common in the intestine of the two treatment groups. By screening their lipolytic ability on a Rhodamine B agar plate, nine lipase-producing bacterial strains were obtained and classified into six genera, including Bacillus, Brevibacterium, Corynebacterium, Staphylococcus, Klebsiella, and Stenotrophomonas. Except for Stenotrophomonas, which is common in both, the other genera only exist in the intestine of the silkworm larvae fed with mulberry leaves. In addition, by culture and fermentation in vitro, the maximum cell density and lipase activity of lipase-producing bacteria were examined at about 48 hours. The results indicate that diet has a significant impact on the gut bacterial community, especially lipase-producing bacteria. We suggest that the difference of lipase-producing bacterial diversity might be related to disease resistance of the silkworm.
BACKGROUND: Root-knot nematodes (Meloidogyne spp.) are soilborne pathogens that can cause great damage to and economic loss of crops globally. Owing to the high toxicity of chemicals toward humans and the environment, the use of biocontrol bacteria, a promising method for controlling root-knot nematodes, has gained attention. RESULTS:To screen novel bacterial strains for their ability to control root-knot nematodes, 106 bacterial strains were isolated from soil. Eight of the obtained isolates exhibited satisfactory nematicidal activity against Meloidogyne incognita at 2-fold dilutions (approximately 3 × 10 12 CFU mL −1 ) after 12 h of exposure. Based on their physiological, biochemical and molecular (16S rRNA and gyrB gene sequences) characteristics, the eight strains were identified as Bacillus halotolerans, B. kochii, B. oceanisediminis, B. pumilus, B. toyonensis, B. cereus, Pseudomonas aeruginosa and B. pseudomycoides. In greenhouse and field experiments, the eight isolates suppressed M. incognita up to 69.96% compared to the control. Additionally, the yield of tomato increased 1.4-26.1% over that of the control. CONCLUSION: The strains of B. halotolerans DDWA, B. kochii DDWB, B. oceanisediminis DDWC and B. pseudomycoides JNC have potential to control M. incognita, which has not been previously reported.
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