A Bayesian palaeoenvironmental transfer function model for acidified lakes

A Bayesian approach to palaeoecological environmental reconstruction deriving from the unimodal responses generally exhibited by organisms to an environmental gradient is described. The approach uses Bayesian model selection to calculate a collection of probability-weighted, species-specific response curves (SRCs) for each taxon within a training set, with an explicit treatment for zero abundances. These SRCs are used to reconstruct the environmental variable from sub-fossilised assemblages. The approach enables a substantial increase in computational efficiency (several orders of magnitude) over existing Bayesian methodologies. The model is developed from the Surface Water Acidification Programme (SWAP) training set and is demonstrated to exhibit comparable predictive power to existing Weighted Averaging and Maximum Likelihood methodologies, though with improvements in bias; the additional explanatory power of the Bayesian approach lies in an explicit calculation of uncertainty for each individual reconstruction. The model is applied to reconstruct the Holocene acidification history of the Round Loch of Glenhead, including a reconstruction of recent recovery derived from sediment trap data.The Bayesian reconstructions display similar trends to conventional (Weighted Averaging Partial Least Squares) reconstructions but provide a better reconstruction of extreme pH and are more sensitive to small changes in diatom assemblages. The validity of the posteriors as an apparently meaningful representation of assemblage-specific uncertainty and the high computational efficiency of the approach open up the possibility of highly constrained multiproxy reconstructions

Maternal microchimerism in the livers of patients with Biliary atresia

BACKGROUND: Biliary atresia (BA) is a neonatal cholestatic disease of unknown etiology. It is the leading cause of liver transplantation in children. Many similarities exist between BA and graft versus host disease suggesting engraftment of maternal cells during gestation could result in immune responses that lead to BA. The aim of this study was to determine the presence and extent of maternal microchimerism (MM) in the livers of infants with BA. METHODS: Using fluorescent in situ hybridization (FISH), 11 male BA & 4 male neonatal hepatitis (NH) livers, which served as controls, were analyzed for X and Y-chromosomes. To further investigate MM in BA, 3 patients with BA, and their mothers, were HLA typed. Using immunohistochemical stains, the BA livers were examined for MM. Four additional BA livers underwent analysis by polymerase chain reaction (PCR) for evidence of MM. RESULTS: By FISH, 8 BA and 2 NH livers were interpretable. Seven of eight BA specimens showed evidence of MM. The number of maternal cells ranged from 2–4 maternal cells per biopsy slide. Neither NH specimen showed evidence of MM. In addition, immunohistochemical stains confirmed evidence of MM. Using PCR, a range of 1–142 copies of maternal DNA per 25,000 copies of patients DNA was found. CONCLUSIONS: Maternal microchimerism is present in the livers of patients with BA and may contribute to the pathogenesis of BA

Follow-up care for men with prostate cancer and the role of primary care: a systematic review of international guidelines

The optimal role for primary care in providing follow-up for men with prostate cancer is uncertain. A systematic review of international guidelines was undertaken to help identify key elements of existing models of follow-up care to establish a theoretical basis for evaluating future complex interventions. Many guidelines provide insufficient information to judge the reliability of the recommendations. Although the PSA test remains the cornerstone of follow-up, the diversity of recommendations on the provision of follow-up care reflects the current lack of research evidence on which to base firm conclusions. The review highlights the importance of transparent guideline development procedures and the need for robust primary research to inform future evidence-based models of follow-up care for men with prostate cancer

Understanding Sensory Nerve Mechanotransduction through Localized Elastomeric Matrix Control

BACKGROUND: While neural systems are known to respond to chemical and electrical stimulation, the effect of mechanics on these highly sensitive cells is still not well understood. The ability to examine the effects of mechanics on these cells is limited by existing approaches, although their overall response is intimately tied to cell-matrix interactions. Here, we offer a novel method, which we used to investigate stretch-activated mechanotransduction on nerve terminals of sensory neurons through an elastomeric interface. METHODOLOGY/PRINCIPAL FINDINGS: To apply mechanical force on neurites, we cultured dorsal root ganglion neurons on an elastic substrate, polydimethylsiloxane (PDMS), coated with extracellular matrices (ECM). We then implemented a controlled indentation scheme using a glass pipette to mechanically stimulate individual neurites that were adjacent to the pipette. We used whole-cell patch clamping to record the stretch-activated action potentials on the soma of the single neurites to determine the mechanotransduction-based response. When we imposed specific mechanical force through the ECM, we noted a significant neuronal action potential response. Furthermore, because the mechanotransduction cascade is known to be directly affected by the cytoskeleton, we investigated the cell structure and its effects. When we disrupted microtubules and actin filaments with nocodozale or cytochalasin-D, respectively, the mechanically induced action potential was abrogated. In contrast, when using blockers of channels such as TRP, ASIC, and stretch-activated channels while mechanically stimulating the cells, we observed almost no change in action potential signalling when compared with mechanical activation of unmodified cells. CONCLUSIONS/SIGNIFICANCE: These results suggest that sensory nerve terminals have a specific mechanosensitive response that is related to cell architecture

Ocean Acidification Affects Prey Detection by a Predatory Reef Fish

Changes in olfactory-mediated behaviour caused by elevated CO2 levels in the ocean could affect recruitment to reef fish populations because larval fish become more vulnerable to predation. However, it is currently unclear how elevated CO2 will impact the other key part of the predator-prey interaction – the predators. We investigated the effects of elevated CO2 and reduced pH on olfactory preferences, activity levels and feeding behaviour of a common coral reef meso-predator, the brown dottyback (Pseudochromis fuscus). Predators were exposed to either current-day CO2 levels or one of two elevated CO2 levels (∼600 µatm or ∼950 µatm) that may occur by 2100 according to climate change predictions. Exposure to elevated CO2 and reduced pH caused a shift from preference to avoidance of the smell of injured prey, with CO2 treated predators spending approximately 20% less time in a water stream containing prey odour compared with controls. Furthermore, activity levels of fish was higher in the high CO2 treatment and feeding activity was lower for fish in the mid CO2 treatment; indicating that future conditions may potentially reduce the ability of the fish to respond rapidly to fluctuations in food availability. Elevated activity levels of predators in the high CO2 treatment, however, may compensate for reduced olfactory ability, as greater movement facilitated visual detection of food. Our findings show that, at least for the species tested to date, both parties in the predator-prey relationship may be affected by ocean acidification. Although impairment of olfactory-mediated behaviour of predators might reduce the risk of predation for larval fishes, the magnitude of the observed effects of elevated CO2 acidification appear to be more dramatic for prey compared to predators. Thus, it is unlikely that the altered behaviour of predators is sufficient to fully compensate for the effects of ocean acidification on prey mortality

The Toxic Effects of Cigarette Additives. Philip Morris' Project Mix Reconsidered: An Analysis of Documents Released through Litigation

Stanton Glantz and colleagues analyzed previously secret tobacco industry documents and peer-reviewed published results of Philip Morris' Project MIX about research on cigarette additives, and show that this research on the use of cigarette additives cannot be taken at face value

Ocean Acidification at High Latitudes: Potential Effects on Functioning of the Antarctic Bivalve Laternula elliptica

Ocean acidification is a well recognised threat to marine ecosystems. High latitude regions are predicted to be particularly affected due to cold waters and naturally low carbonate saturation levels. This is of concern for organisms utilising calcium carbonate (CaCO3) to generate shells or skeletons. Studies of potential effects of future levels of pCO2 on high latitude calcifiers are at present limited, and there is little understanding of their potential to acclimate to these changes. We describe a laboratory experiment to compare physiological and metabolic responses of a key benthic bivalve, Laternula elliptica, at pCO2 levels of their natural environment (430 µatm, pH 7.99; based on field measurements) with those predicted for 2100 (735 µatm, pH 7.78) and glacial levels (187 µatm, pH 8.32). Adult L. elliptica basal metabolism (oxygen consumption rates) and heat shock protein HSP70 gene expression levels increased in response both to lowering and elevation of pH. Expression of chitin synthase (CHS), a key enzyme involved in synthesis of bivalve shells, was significantly up-regulated in individuals at pH 7.78, indicating L. elliptica were working harder to calcify in seawater undersaturated in aragonite (ΩAr = 0.71), the CaCO3 polymorph of which their shells are comprised. The different response variables were influenced by pH in differing ways, highlighting the importance of assessing a variety of factors to determine the likely impact of pH change. In combination, the results indicate a negative effect of ocean acidification on whole-organism functioning of L. elliptica over relatively short terms (weeks-months) that may be energetically difficult to maintain over longer time periods. Importantly, however, the observed changes in L. elliptica CHS gene expression provides evidence for biological control over the shell formation process, which may enable some degree of adaptation or acclimation to future ocean acidification scenarios