Genomewide and Enzymatic Analysis Reveals Efficient d-Galacturonic Acid Metabolism in the Basidiomycete Yeast Rhodosporidium toruloides.

Biorefining of renewable feedstocks is one of the most promising routes to replace fossil-based products. Since many common fermentation hosts, such as Saccharomyces cerevisiae, are naturally unable to convert many component plant cell wall polysaccharides, the identification of organisms with broad catabolism capabilities represents an opportunity to expand the range of substrates used in fermentation biorefinery approaches. The red basidiomycete yeast Rhodosporidium toruloides is a promising and robust host for lipid- and terpene-derived chemicals. Previous studies demonstrated assimilation of a range of substrates, from C5/C6 sugars to aromatic molecules similar to lignin monomers. In the current study, we analyzed the potential of R. toruloides to assimilate d-galacturonic acid, a major sugar in many pectin-rich agricultural waste streams, including sugar beet pulp and citrus peels. d-Galacturonic acid is not a preferred substrate for many fungi, but its metabolism was found to be on par with those of d-glucose and d-xylose in R. toruloides A genomewide analysis by combined transcriptome sequencing (RNA-seq) and RB-TDNA-seq revealed those genes with high relevance for fitness on d-galacturonic acid. While R. toruloides was found to utilize the nonphosphorylative catabolic pathway known from ascomycetes, the maximal velocities of several enzymes exceeded those previously reported. In addition, an efficient downstream glycerol catabolism and a novel transcription factor were found to be important for d-galacturonic acid utilization. These results set the basis for use of R. toruloides as a potential host for pectin-rich waste conversions and demonstrate its suitability as a model for metabolic studies with basidiomycetes.IMPORTANCE The switch from the traditional fossil-based industry to a green and sustainable bioeconomy demands the complete utilization of renewable feedstocks. Many currently used bioconversion hosts are unable to utilize major components of plant biomass, warranting the identification of microorganisms with broader catabolic capacity and characterization of their unique biochemical pathways. d-Galacturonic acid is a plant component of bioconversion interest and is the major backbone sugar of pectin, a plant cell wall polysaccharide abundant in soft and young plant tissues. The red basidiomycete and oleaginous yeast Rhodosporidium toruloides has been previously shown to utilize a range of sugars and aromatic molecules. Using state-of-the-art functional genomic methods and physiological and biochemical assays, we elucidated the molecular basis underlying the efficient metabolism of d-galacturonic acid. This study identified an efficient pathway for uronic acid conversion to guide future engineering efforts and represents the first detailed metabolic analysis of pectin metabolism in a basidiomycete fungus

Free to help? An experiment on free will belief and altruism

How does belief in free will affect altruistic behavior? In an online experiment we undermine subjects' belief in free will through a priming task. Subjects subsequently conduct a series of binary dictator games in which they can distribute money between themselves and a charity that supports low-income people in developing countries. In each decision task, subjects choose between two different distributions, one of which is more generous towards the charity. In contrast to previous experiments that report a negative effect of undermining free will on honest behavior and self-reported willingness to help, we find an insignificant average treatment effect. However, we do find that our treatment reduces charitable giving among non-religious subjects, but not among religious subjects. This could be explained by our finding that religious subjects associate more strongly with social norms that prescribe helping the poor, and might therefore be less sensitive to the effect of reduced belief in free will. Taken together, these findings indicate that the effects of free will belief on prosocial behavior are more nuanced than previously suggested

Understanding early inhibitory development : distinguishing two ways that children use inhibitory control

Inhibitory control is the capacity to suppress inappropriate responses. It is regarded as a unitary construct, central to executive function and effortful control, as well as many aspects of child development. There are, nevertheless, significant gaps in our understanding of inhibition’s early development, and several robust findings that remain hard to explain. These findings are outlined, and a new perspective on inhibitory control presented, which explains them by distinguishing between two ways that inhibitory control is used. According to the ‘strength/endurance account’, responses which are highly prepotent tax inhibitory strength; whereas, those which remain active for a long time tax inhibitory endurance. The review considers when and how these aspects of inhibition mature, before discussing their impact on development

Identification and characterization of a galacturonic acid transporter from Neurospora crassa and its application for Saccharomyces cerevisiae fermentation processes

BackgroundPectin-rich agricultural wastes potentially represent favorable feedstocks for the sustainable production of alternative energy and bio-products. Their efficient utilization requires the conversion of all major constituent sugars. The current inability of the popular fermentation host Saccharomyces cerevisiae to metabolize the major pectic monosaccharide D-galacturonic acid (D-GalA) significantly hampers these efforts. While it has been reasoned that the optimization of cellular D-GalA uptake will be critical for the engineering of D-GalA utilization in yeast, no dedicated eukaryotic transport protein has been biochemically described. Here we report for the first time such a eukaryotic D-GalA transporter and characterize its functionality in S. cerevisiae.ResultsWe identified and characterized the D-GalA transporter GAT-1 out of a group of candidate genes obtained from co-expression analysis in N. crassa. The N. crassa Δgat-1 deletion strain is substantially affected in growth on pectic substrates, unable to take up D-GalA, and impaired in D-GalA-mediated signaling events. Moreover, expression of a gat-1 construct in yeast conferred the ability for strong high-affinity D-GalA accumulation rates, providing evidence for GAT-1 being a bona fide D-GalA transport protein. By recombinantly co-expressing D-galacturonate reductase or uronate dehydrogenase in yeast we furthermore demonstrated a transporter-dependent conversion of D-GalA towards more reduced (L-galactonate) or oxidized (meso-galactaric acid) downstream products, respectively, over a broad concentration range.ConclusionsBy utilizing the novel D-GalA transporter GAT-1 in S. cerevisiae we successfully generated a transporter-dependent uptake and catalysis system for D-GalA into two products with high potential for utilization as platform chemicals. Our data thereby provide a considerable first step towards a more complete utilization of biomass for biofuel and value-added chemicals production

Engineering <i>Saccharomyces cerevisiae</i> for co-utilization of D-galacturonic acid and D-glucose from citrus peel waste

Pectin-rich agricultural byproducts are ideal feedstocks for biobased chemicals production. Here, the authors engineer the yeast, S. cerevisiae, in several steps to co-utilize d-galacturonic acid and d-glucose and demonstrate the potential of producing meso-galactaric acid from industrial orange peel

Structural validity evidence for the Oxford Utilitarianism Scale across 15 languages

Background: The Psychological Science Accelerator (PSA) recently completed a large-scale moral psychology study using translated versions of the Oxford Utilitarianism Scale (OUS). However, the translated versions have no validity evidence. Objective: The study investigated the structural validity evidence of the OUS across 15 translated versions and produced version-specific validity reports. Methods: We analyzed OUS data from the PSA, which was collected internationally on a centralized online questionnaire. We also collected qualitative feedback from experts for each translated version. Results: For each version, we produced version-specific psychometric reports which include the following: (1) descriptive item and demographics analyses, (2) factor structure evidence using confirmatory factor analyses, (3) measurement invariance testing across languages using multiple-group confirmatory factor analyses and alignment optimization, and (4) reliability analyses using coefficients ? and ?.info:eu-repo/semantics/publishedVersio

An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias

BackgroundIn 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs.PurposeThe objective of this statement is to update the 2002 ATS/ERS classification of IIPs.MethodsAn international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011.ResultsSubstantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment.ConclusionsThis update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation

A Multilab Replication of the Induced-Compliance Paradigm of Cognitive Dissonance

According to cognitive-dissonance theory, performing counterattitudinal behavior produces a state of dissonance that people are motivated to resolve, usually by changing their attitude to be in line with their behavior. One of the most popular experimental paradigms used to produce such attitude change is the induced-compliance paradigm. Despite its popularity, the replication crisis in social psychology and other fields, as well as methodological limitations associated with the paradigm, raise concerns about the robustness of classic studies in this literature. We therefore conducted a multilab constructive replication of the induced-compliance paradigm based on Croyle and Cooper (Experiment 1). In a total of 39 labs from 19 countries and 14 languages, participants (N = 4,898) were assigned to one of three conditions: writing a counterattitudinal essay under high choice, writing a counterattitudinal essay under low choice, or writing a neutral essay under high choice. The primary analyses failed to support the core hypothesis: No significant difference in attitude was observed after writing a counterattitudinal essay under high choice compared with low choice. However, we did observe a significant difference in attitude after writing a counterattitudinal essay compared with writing a neutral essay. Secondary analyses revealed the pattern of results to be robust to data exclusions, lab variability, and attitude assessment. Additional exploratory analyses were conducted to test predictions from cognitive-dissonance theory. Overall, the results call into question whether the induced-compliance paradigm provides robust evidence for cognitive dissonance.publishedVersio