The interplay between regeneration and scavenging fluxes drives ocean iron cycling

Despite recent advances in observational data coverage, quantitative constraints on how different physical and biogeochemical processes shape dissolved iron distributions remain elusive, lowering confidence in future projections for iron-limited regions. Here we show that dissolved iron is cycled rapidly in Pacific mode and intermediate water and accumulates at a rate controlled by the strongly opposing fluxes of regeneration and scavenging. Combining new data sets within a watermass framework shows that the multidecadal dissolved iron accumulation is much lower than expected from a meta-analysis of iron regeneration fluxes. This mismatch can only be reconciled by invoking significant rates of iron removal to balance iron regeneration, which imply generation of authigenic particulate iron pools. Consequently, rapid internal cycling of iron, rather than its physical transport, is the main control on observed iron stocks within intermediate waters globally and upper ocean iron limitation will be strongly sensitive to subtle changes to the internal cycling balance

Non-lethal control of the cariogenic potential of an agent-based model for dental plaque

Dental caries or tooth decay is a prevalent global disease whose causative agent is the oral biofilm known as plaque. According to the ecological plaque hypothesis, this biofilm becomes pathogenic when external challenges drive it towards a state with a high proportion of acid-producing bacteria. Determining which factors control biofilm composition is therefore desirable when developing novel clinical treatments to combat caries, but is also challenging due to the system complexity and the existence of multiple bacterial species performing similar functions. Here we employ agent-based mathematical modelling to simulate a biofilm consisting of two competing, distinct types of bacterial populations, each parameterised by their nutrient uptake and aciduricity, periodically subjected to an acid challenge resulting from the metabolism of dietary carbohydrates. It was found that one population was progressively eliminated from the system to give either a benign or a pathogenic biofilm, with a tipping point between these two fates depending on a multiplicity of factors relating to microbial physiology and biofilm geometry. Parameter sensitivity was quantified by individually varying the model parameters against putative experimental measures, suggesting non-lethal interventions that can favourably modulate biofilm composition. We discuss how the same parameter sensitivity data can be used to guide the design of validation experiments, and argue for the benefits of in silico modelling in providing an additional predictive capability upstream from in vitro experiments

In silico modelling to differentiate the contribution of sugar frequency versus total amount in driving biofilm dysbiosis in dental caries

Dental caries is the most prevalent infection globally and a substantial economic burden in developed countries. Dietary sugars are the main risk factor, and drive increased proportions of acid-producing and acid-tolerating (aciduric) bacterial species within dental bio lms. Recent longitudinal studies have suggested that caries is most strongly correlated with total sugar intake, contrasting with the prevailing view that intake frequency is the primary determinant. To explore this possibility, we employed a computational model for supragingival plaque to systematically sample combinations of sugar frequency and total amount, allowing their independent contributions on the ratio of aciduric (i.e. cariogenic) to non-aciduric bacteria to be unambiguously determined. Sugar frequency was found to be irrelevant for either very high or very low daily total amounts as the simulated bio lm was predicted to be always or never cariogenic, respectively. Frequency was a determining factor for intermediate total amounts of sugar, including the estimated average human consumption. An increased risk of caries (i.e. high prevalence of aciduric/non-aciduric species) was predicted for high intake frequencies. Thus, both total amount and frequency of sugar intake may combine to in uence plaque cariogenicity. These ndings could be employed to support public guidance for dietary change, leading to improved oral healthcare

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Biotic and abiotic retention, recycling and remineralization of metals in the ocean

Trace metals shape both the biogeochemical functioning and biological structure of oceanic provinces. Trace metal biogeochemistry has primarily focused on modes of external supply of metals from aeolian, hydrothermal, sedimentary and other sources. However, metals also undergo internal transformations such as abiotic and biotic retention, recycling and remineralization. The role of these internal transformations in metal biogeochemical cycling is now coming into focus. First, the retention of metals by biota in the surface ocean for days, weeks or months depends on taxon-specific metal requirements of phytoplankton, and on their ultimate fate: that is, viral lysis, senescence, grazing and/or export to depth. Rapid recycling of metals in the surface ocean can extend seasonal productivity by maintaining higher levels of metal bioavailability compared to the influence of external metal input alone. As metal-containing organic particles are exported from the surface ocean, different metals exhibit distinct patterns of remineralization with depth. These patterns are mediated by a wide range of physicochemical and microbial processes such as the ability of particles to sorb metals, and are influenced by the mineral and organic characteristics of sinking particles. We conclude that internal metal transformations play an essential role in controlling metal bioavailability, phytoplankton distributions and the subsurface resupply of metals

Diet and asthma: looking back, moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant's immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma

Co-Orientation of Replication and Transcription Preserves Genome Integrity

In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus subtilis slows replication elongation, and we proposed that this effect contributes to the evolutionary pressure selecting the transcription-replication co-orientation bias. This selection might have been based purely on selection for speedy replication; alternatively, the slowed replication might actually represent an average of individual replication-disruption events, each of which is counter-selected independently because genome integrity is selected. To differentiate these possibilities and define the precise forces driving this aspect of genome organization, we generated new strains with inversions either over ∼1/4 of the chromosome or at ribosomal RNA (rRNA) operons. Applying mathematical analysis to genomic microarray snapshots, we found that replication rates vary dramatically within the inverted genome. Replication is moderately impeded throughout the inverted region, which results in a small but significant competitive disadvantage in minimal medium. Importantly, replication is strongly obstructed at inverted rRNA loci in rich medium. This obstruction results in disruption of DNA replication, activation of DNA damage responses, loss of genome integrity, and cell death. Our results strongly suggest that preservation of genome integrity drives the evolution of co-orientation of replication and transcription, a conserved feature of genome organization

Outcomes research in the development and evaluation of practice guidelines

BACKGROUND: Practice guidelines have been developed in response to the observation that variations exist in clinical medicine that are not related to variations in the clinical presentation and severity of the disease. Despite their widespread use, however, practice guideline evaluation lacks a rigorous scientific methodology to support its development and application. DISCUSSION: Firstly, we review the major epidemiological foundations of practice guideline development. Secondly, we propose a chronic disease epidemiological model in which practice patterns are viewed as the exposure and outcomes of interest such as quality or cost are viewed as the disease. Sources of selection, information, confounding and temporal trend bias are identified and discussed. SUMMARY: The proposed methodological framework for outcomes research to evaluate practice guidelines reflects the selection, information and confounding biases inherent in its observational nature which must be accounted for in both the design and the analysis phases of any outcomes research study