OBJECTIVE: To investigate the relationship between breast-feeding and obesity in childhood. DESIGN: Systematic review and meta-analysis of published epidemiological studies (cohort, case-control or cross-sectional studies) comparing early feeding-mode and adjusting for potential confounding factors. Electronic databases were searched and reference lists of relevant articles were checked. Calculations of pooled estimates were conducted in fixed-and random-effects models. Heterogeneity was tested by Q-test. Publication bias was assessed from funnel plots and by a linear regression method. OUTCOME MEASURES: Odds ratio (OR) for obesity in childhood defined as body mass index (BMI) percentiles. RESULTS: Nine studies with more than 69 000 participants met the inclusion criteria. The meta-analysis showed that breastfeeding reduced the risk of obesity in childhood significantly. The adjusted odds ratio was 0.78, 95% CI (0.71, 0.85) in the fixed model. The assumption of homogeneity of results of the included studies could not be refuted (Q-test for heterogeneity, P40.3), stratified analyses showed no differences regarding different study types, age groups, definition of breast-feeding or obesity and number of confounding factors adjusted for. A dose-dependent effect of breast-feeding duration on the prevalence of obesity was reported in four studies. Funnel plot regression gave no indication of publication bias. CONCLUSION: Breast-feeding seems to have a small but consistent protective effect against obesity in children.

The ribosome and protein synthesis are major targets within the cell for inhibition by antibiotics, such as the tetracyclines. The tetracycline family of antibiotics represent a large and diverse group of compounds, ranging from the naturally produced chlortetracycline, introduced into medical usage in the 1940s, to second and third generation semi-synthetic derivatives of tetracycline, such as doxycycline, minocycline and more recently the glycylcycline tigecycline. Here we describe the mode of interaction of tetracyclines with the ribosome and mechanism of action of this class of antibiotics to inhibit translation. Additionally, we provide an overview of the diverse mechanisms by which bacteria obtain resistance to tetracyclines, ranging from efflux, drug modification, target mutation and the employment of specialized ribosome protection proteins.

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In bacteria, ribosome-stalling during translation of ErmBL leader peptide occurs in the presence of the antibiotic erythromycin and leads to induction of expression of the downstream macrolide resistance methyltransferase ErmB. The lack of structures of drug-dependent stalled ribosome complexes (SRCs) has limited our mechanistic understanding of this regulatory process. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmBL-SRC. The structure reveals that the antibiotic does not interact directly with ErmBL, but rather redirects the path of the peptide within the tunnel. Furthermore, we identify a key peptide-ribosome interaction that defines an important relay pathway from the ribosomal tunnel to the peptidyltransferase center (PTC). The PTC of the ErmBL-SRC appears to adopt an uninduced state that prevents accommodation of Lys-tRNA at the A-site, thus providing structural bases for understanding how the drug and the nascent peptide cooperate to inhibit peptide-bond formation and induce translation arrest.

SUMMARY During protein synthesis, nascent polypeptide chains within the ribosomal tunnel can act in cis to induce ribosome stalling and regulate expression of downstream genes. The Staphylococcus aureus ErmCL leader peptide induces stalling in the presence of clinically important macrolide antibiotics, such as erythromycin, leading to the induction of the downstream macrolide resistance methyltransferase ErmC. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmCL-stalled ribosome at 3.9 Å resolution. The structure reveals how the ErmCL nascent chain directly senses the presence of the tunnel-bound drug and thereby induces allosteric conformational rearrangements at the peptidyltransferase center (PTC) of the ribosome. ErmCL-induced perturbations of the PTC prevent stable binding and accommodation of the aminoacyl-tRNA at the A-site leading to inhibition of peptide bond formation and translation arrest.