β‐Defensins are antibiotic peptides involved in host defense at the epithelial surface. Three human β‐defensins (hBDs)‐‐hBD‐1, hBD‐2, and hBD‐3‐‐have been identified so far. We have characterized a new member of the β‐defensin family, hBD‐4, based on screening of genomic sequences and subsequent functional analysis. In contrast to hBD‐1, hBD‐2, and hBD‐3, which are diffusely expressed throughout many organs, hBD‐4 mRNA expression is confined to testis, stomach, uterus, neutrophils, thyroid, lung, and kidney. hBD‐4 expression was up‐regulated by infection with gram‐positive and gram‐negative bacteria in human respiratory epithelial cells, and in response to phorbol 12‐myristate 13‐acetate, but not in response to other inflammatory factors that up‐regulate the expression of hBD‐2 or hBD‐3. Synthetic hBD‐4 exhibits a selective, salt‐sensitive spectrum of antimicrobial activity, and it represents one of the most active antimicrobial peptides against Pseudomonas aeruginosa (minimal inhibitory concentration: 4.1 μg/ml) known to date. This new defensin is chemotactic for human blood monocytes, but it is inactive on neutrophils and eosinophils. These findings demonstrate the existence of a family of β‐defensin genes with different functions against diverse classes of microorganisms, regulated by different stimuli, and specific signal pathways, and confirm the relevance of antimicrobial peptides in host defense.

BackgroundOverweight is among the major challenging health risk factors. It has been claimed that birth weight, being a critical indicator of prenatal developmental conditions, is related to long-term overweight risk. In order to check this important assumption of developmental and preventive medicine, we performed a systematic review and comprehensive meta-analysis.Methods and FindingsRelevant studies published up to January 2011 that investigated the relation between birth weight and later risk of overweight were identified through literature searches using MEDLINE and EMBASE. For meta-analysis, 66 studies from 26 countries and five continents were identified to be eligible, including 643,902 persons aged 1 to 75 years. We constructed random-effects and fixed-effects models, performed subgroup-analyses, influence-analyses, assessed heterogeneity and publication bias, performed meta-regression analysis as well as analysis of confounder adjusted data. Meta-regression revealed a linear positive relationship between birth weight and later overweight risk (p<0.001). Low birth weight (<2,500 g) was found to be followed by a decreased risk of overweight (odds ratio (OR) = 0.67; 95% confidence interval (CI) 0.59–0.76). High birth weight (>4,000 g) was associated with increased risk of overweight (OR = 1.66; 95% CI 1.55–1.77). Results did not change significantly by using normal birth weight (2,500–4,000 g) as reference category (OR = 0.73, 95% CI 0.63–0.84, and OR = 1.60, 95% CI 1.45–1.77, respectively). Subgroup- and influence-analyses revealed no indication for bias/confounding. Adjusted estimates indicate a doubling of long-term overweight risk in high as compared to normal birth weight subjects (OR = 1.96, 95% CI 1.43–2.67).ConclusionsFindings demonstrate that low birth weight is followed by a decreased long-term risk of overweight, while high birth weight predisposes for later overweight. Preventing in-utero overnutrition, e.g., by avoiding maternal overnutrition, overweight and/or diabetes during pregnancy, might therefore be a promising strategy of genuine overweight prevention, globally.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has emerged as a key technology for label-free bioanalysis of the spatial distribution of biomolecules, pharmaceuticals and other xenobiotics in tissue sections. Recent advances in instrumentation, sample preparation, multimodal workflows, quantification, analytical standardization and 'big data' processing have led to widespread utilization of MALDI MSI in pharmaceutical research. These developments have led to applications of the technology in drug discovery beyond drug disposition analysis, most notably in pharmacodynamic biomarker research and in toxicology.

Previous studies have shown the implication of beta-defensins in host defense of the human body. The human beta-defensins 1 and 2 (hBD-1, hBD-2) have been isolated by biochemical methods. Here we report the identification of a third human beta-defensin, called human beta-defensin 3 (hBD-3; cDNA sequence, Genbank accession no. AF295370), based on bioinformatics and functional genomic analysis. Expression of hBD-3 is detected throughout epithelia of many organs and in non-epithelial tissues. In contrast to hBD-2, which is upregulated by microorganisms or tumor necrosis factor-alpha (TNF-alpha), hBD-3 expression is increased particularly after stimulation by interferon-gamma. Synthetic hBD-3 exhibits a strong antimicrobial activity against gram-negative and gram-positive bacteria and fungi, including Burkholderia cepacia. In addition, hBD-3 activates monocytes and elicits ion channel activity in biomembranes, specifically in oocytes of Xenopus laevis. This paper also shows that screening of genomic sequences is a valuable tool with which to identify novel regulatory peptides. Human beta-defensins represent a family of antimicrobial peptides differentially expressed in most tissues, regulated by specific mechanisms, and exerting physiological functions not only related to direct host defense.

Monitoring qHBsAg after successful HBV DNA suppression might be useful to identify patients who clear HBsAg, implicating finite NA treatment. The role of IP-10 as predictive marker for HBsAg loss should be further evaluated.

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Multimodal imaging combines complementary platforms for spatially resolved tissue analysis that are poised for application in life science and personalized medicine. Unlike established clinical in vivo multimodality imaging, automated workflows for in-depth multimodal molecular ex vivo tissue analysis that combine the speed and ease of spectroscopic imaging with molecular details provided by mass spectrometry imaging (MSI) are lagging behind. Here, we present an integrated approach that utilizes non-destructive Fourier transform infrared (FTIR) microscopy and matrix assisted laser desorption/ionization (MALDI) MSI for analysing single-slide tissue specimen. We show that FTIR microscopy can automatically guide high-resolution MSI data acquisition and interpretation without requiring prior histopathological tissue annotation, thus circumventing potential human-annotation-bias while achieving >90% reductions of data load and acquisition time. We apply FTIR imaging as an upstream modality to improve accuracy of tissue-morphology detection and to retrieve diagnostic molecular signatures in an automated, unbiased and spatially aware manner. We show the general applicability of multimodal FTIR-guided MALDI-MSI by demonstrating precise tumor localization in mouse brain bearing glioma xenografts and in human primary gastrointestinal stromal tumors. Finally, the presented multimodal tissue analysis method allows for morphology-sensitive lipid signature retrieval from brains of mice suffering from lipidosis caused by Niemann-Pick type C disease.