Universal response pattern of phytoplankton growth rates to increasing CO 2

Phytoplankton growth rate is a key variable controlling species succession and ecosystem structure throughout the surface ocean. Carbonate chemistry conditions are known to influence phytoplankton growth rates but there is no conceptual framework allowing us to compare growth rate responses across taxa. Here we analyse the literature to show that phytoplankton growth rates follow an optimum curve response pattern whenever the tested species is exposed to a sufficiently large gradient in proton (H+) concentrations. Based on previous findings with coccolithophores and diatoms, we argue that this ‘universal reaction norm’ is shaped by the stimulating influence of increasing inorganic carbon substrate (left side of the optimum) and the inhibiting influence of increase H+ (right side of the optimum). We envisage that exploration of carbonate chemistry-dependent optimum curves as a default experimental approach will boost our mechanistic understanding of phytoplankton responses to ocean acidification, like temperature curves have already boosted our mechanistic understanding to global warming

Adiposity is associated with blunted cardiovascular, neuroendocrine and cognitive responses to acute mental stress

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited - Copyright @ 2012 Jones et al.Obesity and mental stress are potent risk factors for cardiovascular disease but their relationship with each other is unclear. Resilience to stress may differ according to adiposity. Early studies that addressed this are difficult to interpret due to conflicting findings and limited methods. Recent advances in assessment of cardiovascular stress responses and of fat distribution allow accurate assessment of associations between adiposity and stress responsiveness. We measured responses to the Montreal Imaging Stress Task in healthy men (N=43) and women (N=45) with a wide range of BMIs. Heart rate (HR) and blood pressure (BP) measures were used with novel magnetic resonance measures of stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and arterial compliance to assess cardiovascular responses. Salivary cortisol and the number and speed of answers to mathematics problems in the task were used to assess neuroendocrine and cognitive responses, respectively. Visceral and subcutaneous fat was measured using T2*-IDEAL. Greater BMI was associated with generalised blunting of cardiovascular (HR:β=−0.50 bpm.unit−1, P=0.009; SV:β=−0.33 mL.unit−1, P=0.01; CO:β=−61 mL.min−1.unit−1, P=0.002; systolic BP:β=−0.41 mmHg.unit−1, P=0.01; TPR:β=0.11 WU.unit−1, P=0.02), cognitive (correct answers: r=−0.28, P=0.01; time to answer: r=0.26, P=0.02) and endocrine responses (cortisol: r=−0.25, P=0.04) to stress. These associations were largely determined by visceral adiposity except for those related to cognitive performance, which were determined by both visceral and subcutaneous adiposity. Our findings suggest that adiposity is associated with centrally reduced stress responsiveness. Although this may mitigate some long-term health risks of stress responsiveness, reduced performance under stress may be a more immediate negative consequence.This work is funded by the UK National Institute of Health Research (NIHR), Siemens Medical Systems, British Heart Foundation (BHF), NIHR Senior Research Fellowship & The Fondation Leducq, BHF Intermediate Fellowship

Isocyanide based multicomponent reactions of oxazolidines and related systems

N-Alkyloxazolidines react in a multicomponent reaction with carboxylic acids and isocyanides to give N-acyloxyethylamino acid amides. The previously reported reaction conditions were improved using a design of experiments approach (DoE). Under the optimised conditions, good yields of the N-acyloxyethylamino acid amide products are obtained both via a three- or four-component approach from N-alkylethanolamines, aldehydes/ketones, isocyanides and carboxylic acids. The reaction of oxazolidines without a nitrogen substituent was found to give either the expected Ugi products or the N-acyloxyethylamino acid amides depending on the choice of reaction conditions. Optimised reaction conditions were also developed for the ring-expansion of oxazolidines to morpholin-2-ones via reaction with an isocyanide followed by hydrolysis. The mechanistic pathway of the multicomponent reaction was briefly investigated using an O-18 labelling experiment. The carboxylic acid component can be replaced by a range of other acidic nucleophiles including thiobenzoic acid, thiophenol or 5-phenyltetrazole, which are incorporated via an alternative pathway. These latter reactions can also be applied to 2-aminotetrahydrofurans, 2-aminotetrahydropyrans or 4-hydroxybut-2-one, further extending the structural diversity of the multicomponent reaction products. (C) 2010 Elsevier Ltd. All rights reserved

Predicting sustainable arsenic mitigation using machine learning techniques.

This study evaluates state-of-the-art machine learning models in predicting the most sustainable arsenic mitigation preference. A Gaussian distribution-based Naïve Bayes (NB) classifier scored the highest Area Under the Curve (AUC) of the Receiver Operating Characteristic curve (0.82), followed by Nu Support Vector Classification (0.80), and K-Neighbors (0.79). Ensemble classifiers scored higher than 70% AUC, with Random Forest being the top performer (0.77), and Decision Tree model ranked fourth with an AUC of 0.77. The multilayer perceptron model also achieved high performance (AUC=0.75). Most linear classifiers underperformed, with the Ridge classifier at the top (AUC=0.73) and perceptron at the bottom (AUC=0.57). A Bernoulli distribution-based Naïve Bayes classifier was the poorest model (AUC=0.50). The Gaussian NB was also the most robust ML model with the slightest variation of Kappa score on training (0.58) and test data (0.64). The results suggest that nonlinear or ensemble classifiers could more accurately understand the complex relationships of socio-environmental data and help develop accurate and robust prediction models of sustainable arsenic mitigation. Furthermore, Gaussian NB is the best option when data is scarce

Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related)

Heat and fluid flow in a scraped-surface heat exchanger containing a fluid with temperature-dependent viscosity

Scraped-surface heat exchangers (SSHEs) are extensively used in a wide variety of industrial settings where the continuous processing of fluids and fluid-like materials is involved. The steady non-isothermal flow of a Newtonian fluid with temperature-dependent viscosity in a narrow-gap SSHE when a constant temperature difference is imposed across the gap between the rotor and the stator is investigated. The mathematical model is formulated and the exact analytical solutions for the heat and fluid flow of a fluid with a general dependence of viscosity on temperature for a general blade shape are obtained. These solutions are then presented for the specific case of an exponential dependence of viscosity on temperature. Asymptotic methods are employed to investigate the behaviour of the solutions in several special limiting geometries and in the limits of weak and strong thermoviscosity. In particular, in the limit of strong thermoviscosity (i.e., strong heating or cooling and/or strong dependence of viscosity on temperature) the transverse and axial velocities become uniform in the bulk of the flow with boundary layers forming either just below the blade and just below the stationary upper wall or just above the blade and just above the moving lower wall. Results are presented for the most realistic case of a linear blade which illustrate the effect of varying the thermoviscosity of the fluid and the geometry of the SSHE on the flow

Human helminth therapy to treat inflammatory disorders - where do we stand?

Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans

Using a quantitative quadruple immunofluorescent assay to diagnose isolated mitochondrial Complex I deficiency

Isolated Complex I (CI) deficiency is the most commonly observed mitochondrial respiratory chain biochemical defect, affecting the largest OXPHOS component. CI is genetically heterogeneous; pathogenic variants affect one of 38 nuclear-encoded subunits, 7 mitochondrial DNA (mtDNA)-encoded subunits or 14 known CI assembly factors. The laboratory diagnosis relies on the spectrophotometric assay of enzyme activity in mitochondrially-enriched tissue homogenates, requiring at least 50 mg skeletal muscle, as there is no reliable histochemical method for assessing CI activity directly in tissue cryosections. We have assessed a validated quadruple immunofluorescent OXPHOS (IHC) assay to detect CI deficiency in the diagnostic setting, using 10 µm transverse muscle sections from 25 patients with genetically-proven pathogenic CI variants. We observed loss of NDUFB8 immunoreactivity in all patients with mutations affecting nuclear-encoding structural subunits and assembly factors, whilst only 3 of the 10 patients with mutations affecting mtDNA-encoded structural subunits showed loss of NDUFB8, confirmed by BN-PAGE analysis of CI assembly and IHC using an alternative, commercially-available CI (NDUFS3) antibody. The IHC assay has clear diagnostic potential to identify patients with a CI defect of Mendelian origins, whilst highlighting the necessity of complete mitochondrial genome sequencing in the diagnostic work-up of patients with suspected mitochondrial disease

Perspectives of people in Mali toward genetically-modified mosquitoes for malaria control

Background: Genetically-modified (GM) mosquitoes have been proposed as part of an integrated vector control strategy for malaria control. Public acceptance is essential prior to field trials, particularly since mosquitoes are a vector of human disease and genetically modified organisms (GMOs) face strong scepticism in developed and developing nations. Despite this, in sub-Saharan Africa, where the GM mosquito effort is primarily directed, very little data is available on perspectives to GMOs. Here, results are presented of a qualitative survey of public attitudes to GM mosquitoes for malaria control in rural and urban areas of Mali, West Africa between the months of October 2008 and June 2009. Methods: The sample consisted of 80 individuals - 30 living in rural communities, 30 living in urban suburbs of Bamako, and 20 Western-trained and traditional health professionals working in Bamako and Bandiagara. Questions were asked about the cause of malaria, heredity and selective breeding. This led to questions about genetic alterations, and acceptable conditions for a release of pest-resistant GM corn and malaria-refractory GM mosquitoes. Finally, participants were asked about the decision-making process in their community. Interviews were transcribed and responses were categorized according to general themes. Results: Most participants cited mosquitoes as one of several causes of malaria. The concept of the gene was not widely understood; however selective breeding was understood, allowing limited communication of the concept of genetic modification. Participants were open to a release of pest-resistant GM corn, often wanting to conduct a trial themselves. The concept of a trial was reapplied to GM mosquitoes, although less frequently. Participants wanted to see evidence that GM mosquitoes can reduce malaria prevalence without negative consequences for human health and the environment. For several participants, a mosquito control programme was preferred; however a transgenic release that satisfied certain requirements was usually acceptable. Conclusions: Although there were some dissenters, the majority of participants were pragmatic towards a release of GM mosquitoes. An array of social and cultural issues associated with malaria, mosquitoes and genetic engineering became apparent. If these can be successfully addressed, then social acceptance among the populations surveyed seems promising

BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis

Regulation of BubR1 is central to the control of APC/C activity. We have found that BubR1 forms a complex with PCAF and is acetylated at lysine 250. Using mass spectrometry and acetylated BubR1-specific antibodies, we have confirmed that BubR1 acetylation occurs at prometaphase. Importantly, BubR1 acetylation was required for checkpoint function, through the inhibition of ubiquitin-dependent BubR1 degradation. BubR1 degradation began before the onset of anaphase. It was noted that the pre-anaphase degradation was regulated by BubR1 acetylation. Degradation of an acetylation-mimetic form, BubR1–K250Q, was inhibited and chromosome segregation in cells expressing BubR1–K250Q was markedly delayed. By contrast, the acetylation-deficient mutant, BubR1–K250R, was unstable, and mitosis was accelerated in BubR1–K250R-expressing cells. Furthermore, we found that APC/C–Cdc20 was responsible for BubR1 degradation during mitosis. On the basis of our collective results, we propose that the acetylation status of BubR1 is a molecular switch that converts BubR1 from an inhibitor to a substrate of the APC/C complex, thus providing an efficient way to modulate APC/C activity and mitotic timing