Host protection from infection relies on the recognition of pathogens by innate pattern-recognition receptors such as Toll-like receptors (TLRs). Here, we show that the orphan receptor TLR13 in mice recognizes a conserved 23S ribosomal RNA (rRNA) sequence that is the binding site of macrolide, lincosamide, and streptogramin group (MLS) antibiotics (including erythromycin) in bacteria. Notably, 23S rRNA from clinical isolates of erythromycin-resistant Staphylococcus aureus and synthetic oligoribonucleotides carrying methylated adenosine or a guanosine mimicking a MLS resistance-causing modification failed to stimulate TLR13. Thus, our results reveal both a natural TLR13 ligand and specific mechanisms of antibiotic resistance as potent bacterial immune evasion strategy, avoiding recognition via TLR13.

Dictyostelium NE81 is the first protein found in a lower eukaryote with properties justifying its denomination as a lamin-like protein. Knockout and overexpression mutants revealed an important role for NE81 in nuclear integrity, chromatin organization, and mechanical stability of cells.

No abstract

Contrary to the findings of Herbert et al. (Reports, 14 April 2006, p. 279), homozygous carriers of the C allele of the rs7566605 variant near the INSIG2 gene did not exhibit a significantly increased risk for obesity in a large population-based cross-sectional German study. A subgroup analysis, however, revealed that this allele significantly increased the risk for obesity in already overweight individuals.O besity is a leading health problem in many countries and results from a complex and dynamic interaction of social, environmental, and genetic factors. Herbert et al.(1) recently reported the association of the C allele in the rs7566605 polymorphism located near the INSIG2 gene with obesity in four different human samples. In a fifth sample, however, a large cohort of the Nurses Health Study (NHS), no such association was detectable (1). Therefore, we examined this association in the Study of Health in Pomerania (SHIP), a crosssectional population-based health survey from the northeastern area of Germany comprising 4310 unrelated German individuals, collected in 12 five-year age strata from 20 to 79 years (2-4). SHIP was designed to address general health and community medicine issues, with obesity as a main focus. In SHIP, 66.1% of all participants were overweight [body mass index (BMI) ≥ 25 kg/m 2 ] and 25.4% were obese (BMI ≥ 30 kg/m 2 ). Genotyping of the rs7566605 polymorphism was successful in 4089 of 4304 individuals (in six subjects, data sets were incomplete). Excluded individuals and the entire study sample did not differ with respect to age, gender, and BMI. Genotype frequencies (45.5% GG, 44.4% GC, 10.1% CC) were compatible with a HardyWeinberg equilibrium (P = 0.6769) and similar to the Caucasian samples reported in (1). Logistic regression analyses (dependent variable, obesity) and linear models (dependent variable, BMI) were performed on adjustments for age and gender. Table 1 details BMI stratified by genotype, gender, and the genotype distribution in predefined BMI strata.Mean adjusted BMI for the whole sample amounted to 27.38 ± 0.22 kg/m 2 (means ± SE; linear model), 27.16 ± 0.11 kg/m 2 , and 27.18 ± 0.10 kg/m 2 for CC, GC, and GG genotypes, respectively, and rs7566605 genotypes were not associated with BMI [P = 0.6531; 2 degrees of freedom (df)]. Odds ratios (ORs) for obesity were 1.13 (95% CI 0.97 to 1.31) and 1.20 (95% CI 0.94 to 1.54) for carriers of the GC and CC genotypes compared with GG genotypes, and thus were not significantly different (P = 0.1782, 2 df, logistic regression). This observation for obesity did not change in a recessive model (CC versus GC + GG), as pursued by Herbert et al.(1), with OR of 1.13 (95% CI 0.90 to 1.43; P = 0.2916). Likewise, the age-and gender-adjusted mean BMI of CC carriers did not differ significantly (difference from GC + GG carriers, 0.21 ± 0.23 kg/m 2 ; mean ± SE; P = 0.3593). Taken together, our data indicate that the rs7566605 variant is not associated with the overall risk for obesity in SHIP.The current scenario suggests that the rs7566605 v...

Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration. Direct contact to hydrogels, but not contact to hydrolytic or enzymatic hydrogel degradation products, resulted in enhanced cyclooxygenase-2 (COX-2) expression in all cell types, indicating a weak inflammatory activation in vitro. Only Mɸ altered their cytokine secretion profile after direct hydrogel contact, indicating a comparably pronounced inflammatory activation. On the other hand, in HAEC the expression of tight junction proteins, as well as cytokine and matrix metalloproteinase secretion were not influenced by the hydrogels, suggesting a maintained endothelial cell function. This was in line with the finding that in HAEC increased thrombomodulin synthesis but no thrombomodulin membrane shedding occurred. First in vivo data obtained after subcutaneous implantation of the materials in immunocompetent mice revealed good integration of implants in the surrounding tissue, no progredient fibrous capsule formation, and no inflammatory tissue reaction in vivo. Overall, the study demonstrates the potential of gelatin-based hydrogels for temporal replacement and functional regeneration of damaged soft tissue.