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1,440 result(s) for "Roche, David"
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Comparative genomic analysis of Ralstonia solanacearum reveals candidate genes for host specificity
Background Ralstonia solanacearum is a vascular soil-borne plant pathogen with an unusually broad host range. This economically destructive and globally distributed bacterium has thousands of distinct lineages within a heterogeneous and taxonomically disputed species complex. Some lineages include highly host-adapted strains (ecotypes), such as the banana Moko disease-causing strains, the cold-tolerant potato brown rot strains (also known as R3bv2) and the recently emerged Not Pathogenic to Banana (NPB) strains. Results These distinct ecotypes offer a robust model to study host adaptation and the emergence of ecotypes because the polyphyletic Moko strains include lineages that are phylogenetically close to the monophyletic brown rot and NPB strains. Draft genomes of eight new strains belonging to these three model ecotypes were produced to complement the eleven publicly available R. solanacearum genomes. Using a suite of bioinformatics methods, we searched for genetic and evolutionary features that distinguish ecotypes and propose specific hypotheses concerning mechanisms of host adaptation in the R. solanacearum species complex. Genome-wide, few differences were identified, but gene loss events, non-synonymous polymorphisms, and horizontal gene transfer were identified among type III effectors and were associated with host range differences. Conclusions This extensive comparative genomics analysis uncovered relatively few divergent features among closely related strains with contrasting biological characteristics; however, several virulence factors were associated with the emergence of Moko, NPB and brown rot and could explain host adaptation.
Functional expression of a Mo-dependent formate dehydrogenase in Escherichia coli under aerobic conditions
Oxygen tolerant complex metal-dependent formate dehydrogenases hold potential for biotechnological applications. In this work, we report the functional expression of the complex, molybdenum-dependent soluble formate dehydrogenase encoded by the fdsGBACD operon from Cupriavidus necator (CnFDH) in Escherichia coli. Expression of the operon from plasmids or from a copy integrated in the chromosome enabled growth of an energy-auxotrophic selection strain on formate as sole energy source under aerobic conditions. Growth could be accelerated in turbidostat, leading to a drop of the generation time of 1 hour. While no mutation was found in the operon of evolved isolates, genome sequencing revealed non-synonymous point mutations in the gene focA coding for a bidirectional formate transporter carried in all isolates sequenced. Reverting the mutations led to a drop in the growth rate demonstrating the focA gene as principal target of continuous culture adaptation. A member of the oxygen-tolerant subclass of complex FDH showed stable formate oxidation activity when expressed in the heterologous host E. coli, a model organism of biotechnology. The integration of the operon in the chromosome offers the possibility of structure/function studies and activity enhancements through in vivo mutagenesis, which can also be applied to CO2 reduction in appropriate selection hosts.
Making and Remaking Horror in the 1970s and 2000s
InMaking and Remaking Horror in the 1970s and 2000sauthor David Roche takes up the assumption shared by many fans and scholars that original horror movies are more \"disturbing,\" and thus better than the remakes. He assesses the qualities of movies, old and recast, according to criteria that include subtext, originality, and cohesion. With a methodology that combines a formalist and cultural studies approach, Roche sifts aspects of the American horror movie that have been widely addressed (class, the patriarchal family, gender, and the opposition between terror and horror) and those that have been somewhat neglected (race, the Gothic, style, and verisimilitude). Containing seventy-eight black and white illustrations, the book is grounded in a close comparative analysis of the politics and aesthetics of four of the most significant independent American horror movies of the 1970s--The Texas Chain Saw Massacre, The Hills Have Eyes, Dawn of the Dead,andHalloween--and their twenty-first-century remakes. To what extent can the politics of these films be described as \"disturbing\" insomuch as they promote subversive subtexts that undermine essentialist perspectives? Do the politics of the film lie on the surface or are they wedded to the film's aesthetics? Early in the book, Roche explores historical contexts, aspects of identity (race, ethnicity, and class), and the structuring role played by the motif of the American nuclear family. He then asks to what extent these films disrupt genre expectations and attempt to provoke emotions of dread, terror, and horror through their representations of the monstrous and the formal strategies employed? In this inquiry, he examines definitions of the genre and its metafictional nature. Roche ends with a meditation on the extent to which the technical limitations of the horror films of the 1970s actually contribute to this \"disturbing\" quality. Moving far beyond the genre itself,Making and Remaking Horrorstudies the redux as a form of adaptation and enables a more complete discussion of the evolution of horror in contemporary American cinema.
Risky behaviours and injuries amongst Catalan children with ADHD: does pharmacological treatment improve outcomes?
Background Attention-Deficit/Hyperactivity Disorder (ADHD) prevalence rates are around 5–10% of school-aged children. We test whether medication use for ADHD decreases the likelihood of risky behaviour (sexual behaviour, alcohol, tobacco, and drug consumption) and injuries amongst children aged 6–18. Methods We use a large administrative dataset for the whole population of Catalan children in Spain who were born between 1998 and 2012. We apply a scale that contains alternative definitions of ADHD so that over-diagnosis is also identified and estimate a count data model to explain the number of visits whilst accounting for confounding. Our identification strategy relies on instrumenting medication using an average indicator of the probability of prescribing medication for each most visited healthcare centre provider. Results Our results suggest that medication use significantly reduced the number of visits of children diagnosed with ADHD for injuries but not risky behaviour. This finding is robust irrespective of the considered span or the grace period after including ADHD-related comorbidities as controls. Conclusion In line with previous literature, medication use amongst children with ADHD reduces the prevalence of injuries but not risky behaviours.
Interpreting a Sudden Population Decline in a Long‐Lived Species (Malaclemys terrapin rhizophorarum)
Long‐term ecological studies are critical for providing insight into population dynamics and detecting population declines, particularly for species of conservation concern. However, spatiotemporal variation and logistical challenges make the identification of sudden population declines difficult. We conducted an in‐water capture‐mark‐recapture study of mangrove diamond‐backed terrapins (Malaclemys terrapin rhizophorarum) within Big Sable Creek, in Everglades National Park, Florida. We used an 18‐year dataset (2001 to 2019) incorporating year, sex, hurricane occurrence, and sampling effort to estimate survival using Cormack–Jolly–Seber (CJS) models in Program Mark. Annual survivorship estimates were high from 2001 to 2003 for both sexes (91%–96%) and variable from 2006 to 2014 (77%–92%). Beginning in 2015, survival estimates exhibited a steeper decline (females: 65%, males 75%), and dropped to below 36% by 2018. Because the driver of this apparent population decline is unknown, we created a population projection matrix and used model‐estimated annual survival to simulate annual terrapin population size. We then generated competing scenarios of low survival at various age classes to attempt to reproduce a simulated decline mirroring what we observed from our capture data. A scenario of low adult survival (75%–85%) from 2012 to 2018, possibly in conjunction with no reproduction after 2010, provides estimates of abundance that appear to match simulated annual population size and may indicate that adult emigration/human removal or a drastic drop in recruitment could be responsible for the apparent decline in survival. We explore reasons for this apparent decline and highlight difficulties common to long‐term studies that may influence how declines are interpreted. Annual sex‐specific survival estimates for mangrove diamond‐backed terrapins (Malaclemys terrapin rhizophorarum) in Everglades National Park from 2001 to 2019.
Identifying non‐adult attention‐deficit/hyperactivity disorder individuals using a stacked machine learning algorithm using administrative data population registers in a universal healthcare system
Background This research project aims to build a Machine Learning algorithm (ML) to predict first‐time ADHD diagnosis, given that it is the most frequent mental disorder for the non‐adult population. Methods We used a stacked model combining 4 ML approaches to predict the presence of ADHD. The dataset contains data from population health care administrative registers in Catalonia comprising 1,225,406 non‐adult individuals for 2013–2017, linked to socioeconomic characteristics and dispensed drug consumption. We defined a measure of proper ADHD diagnoses based on medical factors. Results We obtained an AUC of 79.6% with the stacked model. Significant variables that explain the ADHD presence are the dispersion across patients' visits to healthcare providers; the number of visits, diagnoses related to other mental disorders and drug consumption; age, and sex. Conclusions ML techniques can help predict ADHD early diagnosis using administrative registers. We must continuously investigate the potential use of ADHD early detection strategies and intervention in the health system. We considered a large‐scale population‐based study applying Machine Learning (ML) to ADHD disease in non‐adults in Catalonia, Spain. The Spanish healthcare system provides free universal healthcare, so we cover all healthcare providers. Our findings show an overall prediction accuracy of more than 84% predicting ADHD diagnosis based on demographic data and health system records. The possible early detection of ADHD is very relevant because of its prevalence of 3.4% of the child‐adolescent population.
Exploring the association of antibiotic consumption on resistance: evidence from Catalonia (Spain) using a threshold regression approach
IntroductionThis study aims to empirically identify key predictors of antibiotic resistance at the individual level and to evaluate how the relationship between antibiotic use and resistance evolves as accumulated antibiotic-defined daily dose (DDD) levels exceed specific thresholds. To capture these non-linear dynamics, we apply a threshold regression framework.MethodsA longitudinal population-based observational study using a comprehensive administrative dataset from Catalonia (2014–2021), focusing on 2 924 590 individuals born before 1965 under a universal healthcare system. Antibiotic resistance was identified using diagnostic codes and was observed among 17 466 individuals (0.6%) during the study period. Antibiotic exposure was defined as the number of dispensed systemic antibiotics (ATC J01) per DDD, calculated as the sum of cumulative consumption and the maximum use over six consecutive months. Machine learning techniques (logistic regression, decision trees, random forests and gradient-boosting, combined in a stacked ensemble) were employed to identify factors associated with antibiotic resistance, while accounting for sociodemographic characteristics, morbidity status, regional factors and antibiotic consumption. Model performance was evaluated using standard classification metrics. Threshold regression models, optimised using genetic algorithms, were applied to detect non-linearities in the relationship between cumulative antibiotic consumption and resistance.ResultsMachine learning models demonstrated good predictive performance (area under the curve 0.90, 95% CI 0.90 to 0.91; 0.83, 95% CI 0.82 to 0.83) in the stacked model. Antibiotic consumption emerged as one of the strongest predictors of resistance. Threshold regression revealed substantial heterogeneity in the association between accumulated antibiotic use and diminishing marginal effects beyond specific DDD thresholds, indicating that additional consumption at high levels was associated with smaller increases in resistance.ConclusionsThese findings suggest that interventions targeting excessive antibiotic use, particularly below identified threshold levels, and tailored to specific sociodemographic and regional contexts, may be effective in mitigating antibiotic resistance. Accounting for non-linear consumption–resistance dynamics is essential for informing antibiotic stewardship policies.
Transnationalism and Imperialism
-- This book redefines American productions of the Western genre as an expression of a transnational ideology and culture of imperialism. Reviewers agree that this collection offers the most impressive sampling of the vast number of global Westerns produced from the silent era to the present day, compared to other publications in recent years on the Western. -- IUP is a leading publisher in areas of film and media studies related to this book including early and silent film, national cinemas, and Italian and French film. This fulfills a goal outlined in IUP's strategic plan to bring an international scope to the discipline. -- The audience is scholarly and the book is highly likely to be recommended as a library purchase. It will reach scholars and students studying the Western genre, critical film theory, and the cultural history of colonialism and imperialism.
Change in Cofactor Specificity of Oxidoreductases by Adaptive Evolution of an Escherichia coli NADPH-Auxotrophic Strain
In the cell, NAD(H) and NADP(H) cofactors have different functions. The former mainly accepts electrons from catabolic reactions and carries them to respiration, while the latter provides reducing power for anabolism. The nicotinamide cofactor specificity of enzymes plays a key role in regulating metabolic processes and attaining cellular homeostasis. Multiple studies have used enzyme engineering tools or a directed evolution approach to switch the cofactor preference of specific oxidoreductases. However, whole-cell adaptation toward the emergence of novel cofactor regeneration routes has not been previously explored. To address this challenge, we used an Escherichia coli NADPH-auxotrophic strain. We continuously cultivated this strain under selective conditions. After 500 to 1,100 generations of adaptive evolution using different carbon sources, we isolated several strains capable of growing without an external NADPH source. Most isolated strains were found to harbor a mutated NAD + -dependent malic enzyme (MaeA). A single mutation in MaeA was found to switch cofactor specificity while lowering enzyme activity. Most mutated MaeA variants also harbored a second mutation that restored the catalytic efficiency of the enzyme. Remarkably, the best MaeA variants identified this way displayed overall superior kinetics relative to the wild-type variant with NAD + . In other evolved strains, the dihydrolipoamide dehydrogenase (Lpd) was mutated to accept NADP + , thus enabling the pyruvate dehydrogenase and 2-ketoglutarate dehydrogenase complexes to regenerate NADPH. Interestingly, no other central metabolism oxidoreductase seems to evolve toward reducing NADP + , which we attribute to several biochemical constraints, including unfavorable thermodynamics. This study demonstrates the potential and biochemical limits of evolving oxidoreductases within the cellular context toward changing cofactor specificity, further showing that long-term adaptive evolution can optimize enzyme activity beyond what is achievable via rational design or directed evolution using small libraries. IMPORTANCE In the cell, NAD(H) and NADP(H) cofactors have different functions. The former mainly accepts electrons from catabolic reactions and carries them to respiration, while the latter provides reducing power for anabolism. Correspondingly, the ratio of the reduced to the oxidized form differs for NAD + (low) and NADP + (high), reflecting their distinct roles. We challenged the flexibility of E. coli ’s central metabolism in multiple adaptive evolution experiments using an NADPH-auxotrophic strain. We found several mutations in two enzymes, changing the cofactor preference of malic enzyme and dihydrolipoamide dehydrogenase. Upon deletion of their corresponding genes we performed additional evolution experiments which did not lead to the emergence of any additional mutants. We attribute this restricted number of mutational targets to intrinsic thermodynamic barriers; the high ratio of NADPH to NADP + limits metabolic redox reactions that can regenerate NADPH, mainly by mass action constraints.