Role of hyaluronan and hyaluronan-binding proteins in lung pathobiology

Hyaluronan (HA) has diverse functions in normal lung homeostasis and pulmonary disease. HA constitutes the major glycosaminoglycan in lung tissue, with HA degradation products, produced by hyaluronidase enzymes and reactive oxygen species, being implicated in several lung diseases, including acute lung injury, asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. The differential activities of HA and its degradation products are due, in part, to regulation of multiple HA-binding proteins, including cluster of differentiation 44 (CD44), Toll-like receptor 4 (TLR4), HA-binding protein 2 (HABP2), and receptor for HA-mediated motility (RHAMM). Recent research indicates that exogenous administration of high-molecular-weight HA can serve as a novel therapeutic intervention for lung diseases, including lipopolysaccharide (LPS)-induced acute lung injury, sepsis/ventilator-induced lung injury, and airway hyperreactivity. This review focuses on the regulatory role of HA and HA-binding proteins in lung pathology and discusses the capacity of HA to augment and inhibit various lung diseases.     

Social class differences in secular trends in established coronary risk factors over 20 years: a cohort study of British men from 1978-80 to 1998-2000

Background

Coronary heart disease (CHD) mortality in the UK since the late 1970s has declined more markedly among higher socioeconomic groups. However, little is known about changes in coronary risk factors in different socioeconomic groups. This study examined whether changes in established coronary risk factors in Britain over 20 years between 1978–80 and 1998–2000 differed between socioeconomic groups.

Methods and Findings

A socioeconomically representative cohort of 7735 British men aged 40–59 years was followed-up from 1978–80 to 1998–2000; data on blood pressure (BP), cholesterol, body mass index (BMI) and cigarette smoking were collected at both points in 4252 survivors. Social class was based on longest-held occupation in middle-age. Compared with men in non-manual occupations, men in manual occupations experienced a greater increase in BMI (mean difference = 0.33 kg/m²; 95%CI 0.14–0.53; p for interaction = 0.001), a smaller decline in non-HDL cholesterol (difference in mean change = 0.18 mmol/l; 95%CI 0.11–0.25, p for interaction≤0.0001) and a smaller increase in HDL cholesterol (difference in mean change = 0.04 mmol/l; 95%CI 0.02–0.06, p for interaction≤0.0001). However, mean systolic BP declined more in manual than non-manual groups (difference in mean change = 3.6; 95%CI 2.1–5.1, p for interaction≤0.0001). The odds of being a current smoker in 1978–80 and 1998–2000 did not differ between non-manual and manual social classes (p for interaction = 0.51).

Conclusion

Several key risk factors for CHD and type 2 diabetes showed less favourable changes in men in manual occupations. Continuing priority is needed to improve adverse cardiovascular risk profiles in socially disadvantaged groups in the UK.     

The generation and maintenance of diversity in microbial communities

Microorganisms play a central role in the regulation of ecosystem processes, and they comprise the vast majority of species on Earth. With recent developments in molecular methods, it has become tractable to quantify the extent of microbial diversity in natural environments. Here we examine this revolution in our understanding of microbial diversity, and we explore the factors that contribute to the seemingly astounding numbers of microbial taxa found within individual environmental samples. We conducted a meta-analysis of bacterial richness estimates from a variety of ecosystems. Nearly all environments contained hundreds to thousands of bacterial taxa, and richness levels increased with the number of individuals in a sample, a pattern consistent with those reported for nonmicrobial taxa. A cursory comparison might suggest that bacterial richness far exceeds the richness levels typically observed for plant and animal taxa. However, the apparent diversity of bacterial communities is influenced by phylogenetic breadth and allometric scaling issues. When these features are taken into consideration, the levels of microbial diversity may appear less astounding. Although the fields of ecology and biogeography have traditionally ignored microorganisms, there are no longer valid excuses for neglecting microorganisms in surveys of biodiversity. Many of the concepts developed to explain plant and animal diversity patterns can also be applied to microorganisms once we reconcile the scale of our analyses to the scale of the organisms being observed. Furthermore, knowledge from microbial systems may provide insight into the mechanisms that generate and maintain species richness in nonmicrobial systems.     

Depth-Dependent Differences in Community Structure of the Human Colonic Microbiota in Health

Objective

The aims of this study were to develop techniques for spatial microbial assessment in humans and to establish colonic luminal and mucosal spatial ecology, encompassing longitudinal and cross-sectional axes.

Design

A microbiological protected specimen brush was used in conjunction with a biopsy forceps to sample the colon in nine healthy volunteers undergoing colonoscopy. Terminal Restriction Fragment Length Polymorphism analysis was used to determine the major variables in the spatial organization of the colonic microbiota.

Results

Protected Specimen Brush sampling retrieved region-specific, uncontaminated samples that were enriched for bacterial DNA and depleted in human DNA when compared to biopsy samples. Terminal Restriction Fragment Length Polymorphism analysis revealed a segmentation of bacterial communities between the luminal brush and biopsy-associated ecological niches with little variability across the longitudinal axis of the colon and reduced diversity in brush samples.

Conclusion

These results support the concept of a microbiota with little longitudinal variability but with some degree of segregation between luminal and mucosal communities.     

Diversity and metabolism of marine bacteria cultivated on dissolved DNA

Dissolved DNA (dDNA) is a potentially important source of energy and nutrients in aquatic ecosystems. However, little is known about the identity, metabolism, and interactions of the microorganisms capable of consuming dDNA. Bacteria from Eel Pond (Woods Hole, MA) were cultivated on low-molecular-weight (LMW) or high-molecular-weight (HMW) dDNA, which served as the primary source of carbon, nitrogen, and phosphorus. Cloning and sequencing of 16S rRNA genes revealed that distinct bacterial assemblages with comparable levels of taxon richness developed on LMW and HMW dDNA. Since the LMW and HMW dDNA used in this study were stoichiometrically identical, the results confirm that the size alone of dissolved organic matter can influence bacterial community composition. Variation in the growth and metabolism of isolates provided insight into mechanisms that may have generated differences in bacterial community composition. For example, bacteria from LMW dDNA enrichments generally grew better on LMW dDNA than on HMW dDNA. In contrast, bacteria isolated from HMW dDNA enrichments were more effective at degrading HMW dDNA than bacteria isolated from LMW dDNA enrichments. Thus, marine bacteria may experience a trade-off between their ability to compete for LMW dDNA and their ability to access HMW dDNA via extracellular nuclease production. Together, the results of this study suggest that dDNA turnover in marine ecosystems may involve a succession of microbial assemblages with specialized ecological strategies.     

Development of a novel PCR assay for detection of Prevotella oris in clinical specimens

Prevotella oris is a nonpigmented, Gram-negative, anaerobic bacterium that has been associated with several serious oral and systemic infections. Prevotella oris has been identified in clinical specimens by bacterial culture and biochemical tests, which are generally unreliable. The aim of this study was to develop a PCR assay for the direct detection of P. oris in clinical specimens. PCR primers specific for P. oris were identified by alignment of bacterial 16S rRNA genes from closely related species and selection of PCR primers specific for P. oris at their 3' ends. Amplification of a 1110-bp product indicated PCR positivity for P. oris. The primers were shown to be specific for P. oris DNA, because no PCR products were obtained when DNA from other oral bacteria, including closely related Prevotella species, were used as test species, and this was confirmed by digestion of PCR products with RsaI and MnlI. Prevotella oris DNA was detected in 17 (36.2%) of 47 pus samples from subjects with dentoalveolar abscesses and in all three pus samples from subjects with spreading odontogenic infections. This PCR assay provides a sensitive, specific and reliable method for identifying P. oris in clinical specimens.     

Diversity and Metabolism of Marine Bacteria Cultivated on Dissolved DNA

Dissolved DNA (dDNA) is a potentially important source of energy and nutrients in aquatic ecosystems. However, little is known about the identity, metabolism, and interactions of the microorganisms capable of consuming dDNA. Bacteria from Eel Pond (Woods Hole, MA) were cultivated on low-molecular-weight (LMW) or high-molecular-weight (HMW) dDNA, which served as the primary source of carbon, nitrogen, and phosphorus. Cloning and sequencing of 16S rRNA genes revealed that distinct bacterial assemblages with comparable levels of taxon richness developed on LMW and HMW dDNA. Since the LMW and HMW dDNA used in this study were stoichiometrically identical, the results confirm that the size alone of dissolved organic matter can influence bacterial community composition. Variation in the growth and metabolism of isolates provided insight into mechanisms that may have generated differences in bacterial community composition. For example, bacteria from LMW dDNA enrichments generally grew better on LMW dDNA than on HMW dDNA. In contrast, bacteria isolated from HMW dDNA enrichments were more effective at degrading HMW dDNA than bacteria isolated from LMW dDNA enrichments. Thus, marine bacteria may experience a trade-off between their ability to compete for LMW dDNA and their ability to access HMW dDNA via extracellular nuclease production. Together, the results of this study suggest that dDNA turnover in marine ecosystems may involve a succession of microbial assemblages with specialized ecological strategies.