The evolution of trait correlations constrains phenotypic adaptation to high CO2 in a eukaryotic alga

Microbes form the base of food webs and drive biogeochemical cycling. Predicting the effects of microbial evolution on global elemental cycles remains a significant challenge due to the sheer number of interacting environmental and trait combinations. Here, we present an approach for integrating multivariate trait data into a predictive model of trait evolution. We investigated the outcome of thousands of possible adaptive walks parameterized using empirical evolution data from the alga Chlamydomonas exposed to high CO2. We found that the direction of historical bias (existing trait correlations) influenced both the rate of adaptation and the evolved phenotypes (trait combinations). Critically, we use fitness landscapes derived directly from empirical trait values to capture known evolutionary phenomena. This work demonstrates that ecological models need to represent both changes in traits and changes in the correlation between traits in order to accurately capture phytoplankton evolution and predict future shifts in elemental cycling

Identifying Health Economic Considerations to Include in the Research Protocol of a Randomized Controlled Trial (the REDUCE-RISK Trial): Systematic Literature Review and Assessment.

BACKGROUND: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years). OBJECTIVE: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished. METHODS: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD's National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected. RESULTS: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children's school attendance and parents' productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument. CONCLUSIONS: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children's and parents' QoL (EuroQol 5-Dimension questionnaires), children's school attendance, and parents' productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02852694; https://clinicaltrials.gov/ct2/show/NCT02852694

Multivariate trait analysis reveals diatom plasticity constrained to a reduced set of biological axes

AbstractTrait-based approaches to phytoplankton ecology have gained traction in recent decades as phenotypic traits are incorporated into ecological and biogeochemical models. Here, we use high-throughput phenotyping to explore both intra- and interspecific constraints on trait combinations that are expressed in the cosmopolitan marine diatom genus Thalassiosira. We demonstrate that within Thalassiosira, phenotypic diversity cannot be predicted from genotypic diversity, and moreover, plasticity can create highly divergent phenotypes that are incongruent with taxonomic grouping. Significantly, multivariate phenotypes can be represented in reduced dimensional space using principal component analysis with 77.7% of the variance captured by two orthogonal axes, here termed a ‘trait-scape’. Furthermore, this trait-scape can be recovered with a reduced set of traits. Plastic responses to the new environments expanded phenotypic trait values and the trait-scape, however, the overall pattern of response to the new environments was similar between strains and many trait correlations remained constant. These findings demonstrate that trait-scapes can be used to reveal common constraints on multi-trait plasticity in phytoplankton with divergent underlying phenotypes. Understanding how to integrate trait correlational constraints and trade-offs into theoretical frameworks like biogeochemical models will be critical to predict how microbial responses to environmental change will impact elemental cycling now and into the future.</jats:p

A day in the life of marine sulfonates

Lab-based studies, combined with metatranscriptomic and metabolomic field analyses, reveal important diel-linked roles for sulfonates in the major classes of phytoplankton that produce them, and in the environment in which they feed ubiquitous heterotrophic bacteri

Antiphospholipid Antibodies Bind ATP: A putative Mechanism for the Pathogenesis of Neuronal Dysfunction

Antiphospholipid antibodies (aPL) generated in experimental animals cross-react with ATP. We therefore examined the possibility that aPL IgG from human subjects bind to ATP by affinity column and an enzyme linked immunosorbent assay (ELISA). Sera with high levels of aPL IgG were collected from 12 patients with the antiphospholipid syndrome (APS). IgG fractions from 10 of 12 APS patients contained aPL that could be affinity-bound to an ATP column and completely eluted with NaCl 0.5 M. A significant (>50%) inhibition of aPL IgG binding by ATP 5 mM was found in the majority. Similar inhibition was obtained with ADP but not with AMP or cAMP. All the affinity purified anti-ATP antibodies also bound β2-glycoprotein-I (β2-GPI, also known as apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding depends on this serum cofactor. We further investigated this possibility and found that the binding of β2-GPI to the ATP column was similar to that of aPL IgG in that most was reversed by NaCl 0.5 M. Furthermore, addition of β2-GPI to aPL IgG significantly increased the amount of aPL binding to an ATP column. We conclude that aPL IgG bind ATP, probably through β2-GPI. This binding could interfere with the normal extracellular function of ATP and similar neurotransmitters

Ecosystem heterogeneity and diversity mitigate Amazon forest resilience to frequent extreme droughts

© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust The impact of increases in drought frequency on the Amazon forest's composition, structure and functioning remain uncertain. We used a process- and individual-based ecosystem model (ED2) to quantify the forest's vulnerability to increased drought recurrence. We generated meteorologically realistic, drier-than-observed rainfall scenarios for two Amazon forest sites, Paracou (wetter) and Tapajós (drier), to evaluate the impacts of more frequent droughts on forest biomass, structure and composition. The wet site was insensitive to the tested scenarios, whereas at the dry site biomass declined when average rainfall reduction exceeded 15%, due to high mortality of large-sized evergreen trees. Biomass losses persisted when year-long drought recurrence was shorter than 2–7 yr, depending upon soil texture and leaf phenology. From the site-level scenario results, we developed regionally applicable metrics to quantify the Amazon forest's climatological proximity to rainfall regimes likely to cause biomass loss > 20% in 50 yr according to ED2 predictions. Nearly 25% (1.8 million km2) of the Amazon forests could experience frequent droughts and biomass loss if mean annual rainfall or interannual variability changed by 2σ. At least 10% of the high-emission climate projections (CMIP5/RCP8.5 models) predict critically dry regimes over 25% of the Amazon forest area by 2100

The developmental effects of media-ideal internalization and self-objectification processes on adolescents’ negative body-feelings, dietary restraint, and binge eating

Despite accumulated experimental evidence of the negative effects of exposure to media-idealized images, the degree to which body image, and eating related disturbances are caused by media portrayals of gendered beauty ideals remains controversial. On the basis of the most up-to-date meta-analysis of experimental studies indicating that media-idealized images have the most harmful and substantial impact on vulnerable individuals regardless of gender (i.e., “internalizers” and “self-objectifiers”), the current longitudinal study examined the direct and mediated links posited in objectification theory among media-ideal internalization, self-objectification, shame and anxiety surrounding the body and appearance, dietary restraint, and binge eating. Data collected from 685 adolescents aged between 14 and 15 at baseline (47 % males), who were interviewed and completed standardized measures annually over a 3-year period, were analyzed using a structural equation modeling approach. Results indicated that media-ideal internalization predicted later thinking and scrutinizing of one’s body from an external observer’s standpoint (or self-objectification), which then predicted later negative emotional experiences related to one’s body and appearance. In turn, these negative emotional experiences predicted subsequent dietary restraint and binge eating, and each of these core features of eating disorders influenced each other. Differences in the strength of these associations across gender were not observed, and all indirect effects were significant. The study provides valuable information about how the cultural values embodied by gendered beauty ideals negatively influence adolescents’ feelings, thoughts and behaviors regarding their own body, and on the complex processes involved in disordered eating. Practical implications are discussed

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Myocardial Autophagy after Severe Burn in Rats

Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn.Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function.Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function.Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction