Clustering in surgical trials : database of intracluster correlations

PMID: 22217216 [PubMed - indexed for MEDLINE] PMCID: PMC3311136 Free PMC ArticlePeer reviewedPublisher PD

Ocean acidification changes the male fitness landscape.

Sperm competition is extremely common in many ecologically important marine taxa. Ocean acidification (OA) is driving rapid changes to the marine environments in which freely spawned sperm operate, yet the consequences of OA on sperm performance are poorly understood in the context of sperm competition. Here, we investigated the impacts of OA (+1000 μatm pCO2) on sperm competitiveness for the sea urchin Paracentrotus lividus. Males with faster sperm had greater competitive fertilisation success in both seawater conditions. Similarly, males with more motile sperm had greater sperm competitiveness, but only under current pCO2 levels. Under OA the strength of this association was significantly reduced and there were male sperm performance rank changes under OA, such that the best males in current conditions are not necessarily best under OA. Therefore OA will likely change the male fitness landscape, providing a mechanism by which environmental change alters the genetic landscape of marine species.We acknowledge Catherina Artikis and Yueling Hao for their contributions to the molecular analysis. We thank the team at Exeter Biosciences for their help and support. A.L.C. was supported by a Natural Environment Research Council (NERC) PhD studentship to Exeter, and received additional funding from Exeter CLES PREF and a Santander Postgraduate Research Award (2014/2015). C.L. was supported by a UK-OARP NERC consortium grant NE/H017496/1 and a NERC UK Fellowship: NE/G014728/1. DRL was supported by funding from the United States, National Science Foundation (Grant DEB 1354272) which helped to fund the molecular analysis

Divergence of photosynthetic strategies amongst marine diatoms.

Marine phytoplankton, and in particular diatoms, are responsible for almost half of all primary production on Earth. Diatom species thrive from polar to tropical waters and across light environments that are highly complex to relatively benign, and so have evolved highly divergent strategies for regulating light capture and utilization. It is increasingly well established that diatoms have achieved such successful ecosystem dominance by regulating excitation energy available for generating photosynthetic energy via highly flexible light harvesting strategies. However, how different light harvesting strategies and downstream pathways for oxygen production and consumption interact to balance excitation pressure remains unknown. We therefore examined the responses of three diatom taxa adapted to inherently different light climates (estuarine Thalassioisira weissflogii, coastal Thalassiosira pseudonana and oceanic Thalassiosira oceanica) during transient shifts from a moderate to high growth irradiance (85 to 1200 μmol photons m-2 s-1). Transient high light exposure caused T. weissflogii to rapidly downregulate PSII with substantial nonphotochemical quenching, protecting PSII from inactivation or damage, and obviating the need for induction of O2 consuming (light-dependent respiration, LDR) pathways. In contrast, T. oceanica retained high excitation pressure on PSII, but with little change in RCII photochemical turnover, thereby requiring moderate repair activity and greater reliance on LDR. T. pseudonana exhibited an intermediate response compared to the other two diatom species, exhibiting some downregulation and inactivation of PSII, but high repair of PSII and induction of reversible PSII nonphotochemical quenching, with some LDR. Together, these data demonstrate a range of strategies for balancing light harvesting and utilization across diatom species, which reflect their adaptation to sustain photosynthesis under environments with inherently different light regimes

Large centric diatoms allocate more cellular nitrogen to photosynthesis to counter slower RUBISCO turnover rates

© 2014 Wu, Jeans, Suggett, Finkel and Campbell. Diatoms contribute ~40% of primary production in the modern ocean and encompass the largest cell size range of any phytoplankton group. Diatom cell size influences their nutrient uptake, photosynthetic light capture, carbon export efficiency, and growth responses to increasing pCO2. We therefore examined nitrogen resource allocations to the key protein complexes mediating photosynthesis across six marine centric diatoms, spanning 5 orders of magnitude in cell volume, under past, current and predicted future pCO2 levels, in balanced growth under nitrogen repletion. Membrane bound photosynthetic protein concentrations declined with cell volume in parallel with cellular concentrations of total protein, total nitrogen and chlorophyll. Larger diatom species, however, allocated a greater fraction (by 3.5-fold) of their total cellular nitrogen to the soluble Ribulose-1,5-bisphosphate Carboxylase Oxygenase (RUBISCO) carbon fixation complex than did smaller species. Carbon assimilation per unit of RUBISCO large subunit (C RbcL-1 s-1) decreased with cell volume, from ~8 to ~2 C RbcL-1 s-1 from the smallest to the largest cells. Whilst a higher allocation of cellular nitrogen to RUBISCO in larger cells increases the burden upon their nitrogen metabolism, the higher RUBISCO allocation buffers their lower achieved RUBISCO turnover rate to enable larger diatoms to maintain carbon assimilation rates per total protein comparable to small diatoms. Individual species responded to increased pCO2, but cell size effects outweigh pCO2 responses across the diatom species size range examined. In large diatoms a higher nitrogen cost for RUBISCO exacerbates the higher nitrogen requirements associated with light absorption, so the metabolic cost to maintain photosynthesis is a cell size-dependent trait

Dynamic compression can inhibit chondrogenesis of mesenchymal stem cells

Funding was provided by Science Foundation Ireland (07-RFP-ENMF142) and Enterprise Ireland (PC/2006/384)

Roadmaps and Detours: Active Chlorophyll- a Assessments of Primary Productivity Across Marine and Freshwater Systems

Copyright © 2018 American Chemical Society. Assessing phytoplankton productivity over space and time remains a core goal for oceanographers and limnologists. Fast Repetition Rate fluorometry (FRRf) provides a potential means to realize this goal with unprecedented resolution and scale yet has not become the "go-to" method despite high expectations. A major obstacle is difficulty converting electron transfer rates to equivalent rates of C-fixation most relevant for studies of biogeochemical C-fluxes. Such difficulty stems from methodological inconsistencies and our limited understanding of how the electron requirement for C-fixation (φ e,C ) is influenced by the environment and by differences in the composition and physiology of phytoplankton assemblages. We outline a "roadmap" for limiting methodological bias and to develop a more mechanistic understanding of the ecophysiology underlying φ e,C . We 1) re-evaluate core physiological processes governing how microalgae invest photosynthetic electron transport-derived energy and reductant into stored carbon versus alternative sinks. Then, we 2) outline steps to facilitate broader uptake and exploitation of FRRf, which could transform our knowledge of aquatic primary productivity. We argue it is time to 3) revise our historic methodological focus on carbon as the currency of choice, to 4) better appreciate that electron transport fundamentally drives ecosystem biogeochemistry, modulates cell-to-cell interactions, and ultimately modifies community biomass and structure

Osteoblast-Restricted Disruption of the Growth Hormone Receptor in Mice Results in Sexually Dimorphic Skeletal Phenotypes

Growth hormone (GH) exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 (IGF-1) in liver and skeletal tissues. To examine the requirement for the GH receptor (GHR) in osteoblast function in bone, we used Cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions. Osteoblasts lacking GHR exhibited reduced IGF-1-induced Erk and Akt phosphorylation and attenuated IGF-1-induced proliferation and anti-apoptotic action. In addition, differentiation was modestly impaired in osteoblasts lacking GHR, as demonstrated by reduced alkaline phosphatase staining and calcium deposition. In order to determine the requirement for the GHR in bone in vivo, we generated mice lacking the GHR specifically in osteoblasts (ΔGHR), which were born at the expected Mendelian frequency, had a normal life span and were of normal size. Three week-old, female ΔGHR mice had significantly reduced osteoblast numbers, consistent with the in vitro data. By six weeks of age however, female ΔGHR mice demonstrated a marked increase in osteoblasts, although mineralization was impaired; a phenotype similar to that observed previously in mice lacking IGF-1R specifically in osteoblasts. The most striking phenotype occurred in male mice however, where disruption of the GHR from osteoblasts resulted in a feminization of bone geometry in 16 week-old mice, as observed by μCT. These results demonstrate that the GHR is required for normal postnatal bone development in both sexes. GH appears to serve a primary function in modulating local IGF-1 action. However, the changes in bone geometry observed in male ΔGHR mice suggest that, in addition to facilitating IGF-1 action, GH may function to a greater extent than previously appreciated in establishing the sexual dimorphism of the skeleton

Insulin therapy and dietary adjustments to normalize glycaemia and prevent nocturnal hypoglycaemia after evening exercise in type 1 diabetes: a randomized controlled trial

Introduction Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes. Methods Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, β-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise. Results Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar. Conclusions Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances

Gut microbiota of Type 1 diabetes patients with good glycaemic control and high physical fitness is similar to people without diabetes: an observational study

Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type 1 diabetes. This study compared the gut microbiota of patients with Type 1 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes.Ten males with Type 1 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO2max ), and exercise habits. Stool samples were analysed using next-generation sequencing of the 16S rRNA gene to obtain bacterial profiles from each individual. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was implemented to predict the functional content of the bacterial operational taxonomic units.Faecalibacterium sp., Roseburia sp. and Bacteroides sp. were typically the most abundant members of the community in both patients with Type 1 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type 1 diabetes compared with controls. The functional profiles were more conserved and the Type 1 diabetes group were comparable with the control group.We show that both gut microbiota and resulting functional bacterial profiles from patients with long-standing Type 1 diabetes in good glycaemic control and high physical fitness levels are comparable with those of matched people without diabetes. This article is protected by copyright. All rights reserved