114 research outputs found
Rapid Experimental Evolution of Pesticide Resistance in C. elegans Entails No Costs and Affects the Mating System
Pesticide resistance is a major concern in natural populations and a model trait to study adaptation. Despite the importance of this trait, the dynamics of its evolution and of its ecological consequences remain largely unstudied. To fill this gap, we performed experimental evolution with replicated populations of Caenorhabditis elegans exposed to the pesticide Levamisole during 20 generations. Exposure to Levamisole resulted in decreased survival, fecundity and male frequency, which declined from 30% to zero. This was not due to differential susceptibility of males. Rather, the drug affected mobility, resulting in fewer encounters, probably leading to reduced outcrossing rates. Adaptation, i.e., increased survival and fecundity, occurred within 10 and 20 generations, respectively. Male frequency also increased by generation 20. Adaptation costs were undetected in the ancestral environment and in presence of Ivermectin, another widely-used pesticide with an opposite physiological effect. Our results demonstrate that pesticide resistance can evolve at an extremely rapid pace. Furthermore, we unravel the effects of behaviour on life-history traits and test the environmental dependence of adaptation costs. This study establishes experimental evolution as a powerful tool to tackle pesticide resistance, and paves the way to further investigations manipulating environmental and/or genetic factors underlying adaptation to pesticides
Treatable Traits in COPD - A Proposed Approach
The well-recognized individual heterogeneity within COPD patients has led to a growing interest in greater personalization in the approach of these patients. Thus, the treatable traits strategy has been proposed as a further step towards precision medicine in the management of chronic airway disease, both in stable phase and acute exacerbations. The aim of this paper is to perform a critical review on the treatable traits strategy and propose a guide to approach COPD patients in the light of this new concept. An innovative stepwise approach is proposed - a multidisciplinary model based on two distinct phases, with the potential to be implemented in both primary care and hospital settings. The first phase is the initial and focused assessment of a selected subset of treatable traits, which should be addressed in all COPD patients in both settings (primary care and hospital). As some patients may present with advanced disease at diagnosis or may progress despite this initial treatment requiring a more specialized assessment, they should progress to a second phase, in which a broader approach is recommended. Beyond stable COPD, we explore how the treatable traits strategy may be applied to reduce the risk of future exacerbations and improve the management of COPD exacerbations. Since many treatable traits have already been related to exacerbation risk, the strategy proposed here represents an opportunity to be proactive. Although it still lacks prospective validation, we believe this is the way forward for the future of the COPD approach.info:eu-repo/semantics/publishedVersio
Hydrodynamic entrance length for laminar flow in microchannels with rectangular cross section
This work presents a detailed numerical investigation on the required development length (L=L/B) in laminar Newtonian fluid flow in microchannels with rectangular cross section and different aspect ratios (AR). The advent of new microfluidic technologies shifted the practical Reynolds numbers (Re) to the range of unitary (and even lower) orders of magnitude, i.e., creeping flow conditions. Therefore, accurate estimations of L at Re≤O(1) are important for microsystem design. At such low Reynolds numbers, in which inertial forces are less dominant than viscous forces, flow characteristics become necessarily different from those at the macroscale where Re is typically much larger. A judicious choice of mesh refinement and adequate numerical methods allowed obtaining accurate results and a general correlation for estimating L, valid in the ranges 0≤Re≤2000 and 0.1≤AR≤1, thus covering applications in both macro and microfluidics.The authors acknowledge the support by CEFT (Centro de Estudos de Fenómenos de
Transporte) and Project PTDC/EMS-ENE/3362/2014—POCI-01-0145-FEDER-016665, funded by
FEDER funds through COMPETE2020 “Programa Operacional Competitividade e Internacionaliza”
(POCI) and by national funds through FCT “Fundac ao para a Ciência e a Tecnologia”, I.P. L.L. Ferrás
would also like to thank FCT for financial support through scholarship SFRH/BPD/100353/2014 and
projects UIDB/00013/2020 and UIDP/00013/2020. A. Sucena, A. M. Afonso, M. M. Alves and F. T.
Pinho are also grateful to FCT for funding through projects UIDB/00532/2020 and UIDP/00532/2020.
A. Sucena thanks FCT for the Ph.D. Grant SFRH/BD/115547/201
Ploidy mosaicism and allele-specific gene expression differences in the allopolyploid Squalius alburnoides
<p>Abstract</p> <p>Background</p> <p><it>Squalius alburnoides </it>is an Iberian cyprinid fish resulting from an interspecific hybridisation between <it>Squalius pyrenaicus </it>females (P genome) and males of an unknown <it>Anaecypris hispanica-</it>like species (A genome). <it>S. alburnoides </it>is an allopolyploid hybridogenetic complex, which makes it a likely candidate for ploidy mosaicism occurrence, and is also an interesting model to address questions about gene expression regulation and genomic interactions. Indeed, it was previously suggested that in <it>S. alburnoides </it>triploids (PAA composition) silencing of one of the three alleles (mainly of the P allele) occurs. However, not a whole haplome is inactivated but a more or less random inactivation of alleles varying between individuals and even between organs of the same fish was seen.</p> <p>In this work we intended to correlate expression differences between individuals and/or between organs to the occurrence of mosaicism, evaluating if mosaics could explain previous observations and its impact on the assessment of gene expression patterns.</p> <p>Results</p> <p>To achieve our goal, we developed flow cytometry and cell sorting protocols for this system generating more homogenous cellular and transcriptional samples. With this set-up we detected 10% ploidy mosaicism within the <it>S. alburnoides </it>complex, and determined the allelic expression profiles of ubiquitously expressed genes (<it>rpl8</it>; <it>gapdh </it>and <it>β-actin</it>) in cells from liver and kidney of mosaic and non-mosaic individuals coming from different rivers over a wide geographic range.</p> <p>Conclusions</p> <p>Ploidy mosaicism occurs sporadically within the <it>S. alburnoides </it>complex, but in a frequency significantly higher than reported for other organisms. Moreover, we could exclude the influence of this phenomenon on the detection of variable allelic expression profiles of ubiquitously expressed genes (<it>rpl8</it>; <it>gapdh </it>and <it>β-actin</it>) in cells from liver and kidney of triploid individuals. Finally, we determined that the expression patterns previously detected only in a narrow geographic range is not a local restricted phenomenon but is pervasive in rivers where <it>S. pyrenaicus </it>is sympatric with <it>S. alburnoides</it>.</p> <p>We discuss mechanisms that could lead to the formation of mosaic <it>S. alburnoides </it>and hypothesise about a relaxation of the mechanisms that impose a tight control over mitosis and ploidy control in mixoploids.</p
Pretreatment of plastic waste: Removal of colorants from hdpe using biosolvents
UIDB/50011/2020 UIDP/50011/2020 CA18220, 2020.00647.CEECIND UIDB/50006/2020 UIDP/50006/2020Plastics recycling remains a challenge due to the relatively low quality of the recycled material, since most of the developed recycling processes cannot deal with the additives present in the plastic matrix, so the recycled products end up in lower-grade applications. The application of volatile organic solvents for additives removal is the preferred choice. In this study, pretreatment of plastic packaging waste to remove additives using biosolvents was investigated. The plastic waste used was high-density polyethylene (HDPE) with blue and orange colorants (pigment and/or dye). The first step was to identify the type of colorants present in the HDPE, and we found that both plastics presented only one colorant that was actually a pigment. Then, limonene, a renewable solvent, was used to solubilize HDPE. After HDPE dissolution, a wide range of alcohols (mono-, di-, and tri-alcohols) was evaluated as antisolvents in order to selectively precipitate the polymer and maximize its purity. The use of limonene as solvent for plastic dissolution, in combination with poly-alcohols with an intermediate alkyl chain length and a large number of hydroxyl (OH) groups, was found to work best as an antisolvent (1,2,3-propanetriol and 1,2,4-butanetriol), leading to a removal of up to 94% and 100% of the blue and orange pigments, respectively. Finally, three cycles of extraction were carried out, proving the capability of the solvent and antisolvent to be recovered and reused, ensuring the economic viability and sustainability of the process. This pretreatment provides a secondary source of raw materials and revenue for the recycling process, which may lead to an increase in the quality of recycled polymers, contributing to the development of an economical and sustainable recycling process.publishersversionpublishe
Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma
The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities’ associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.We would like to thank all patients for donating their samples and for collaborating in this study. IPATIMUP integrates the i3S Research Unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT). This work was supported by the Portuguese Foundation for Science and Technology (FCT), financed by the European Social Funds (COMPETE-FEDER) and National Funds through the FCT (projects PEstC/SAU/LA0003/2013 and POCI-01-0145-FEDER-007274, fellowships SFRH/BPD/77646/2011 and SFRH/BPD/120777/2016 to S.G. and P.I.M., respectively, grant PTDC/BEXGMG/0242/2012 to S.S. and by Programa Operacional Regional do Norte (ON.2 – O Novo Norte and Norte 2020), through FEDER funds under the Quadro de Referência Estratégico Nacional (QREN; projects NORTE-07-0162-FEDER-00018 and NORTE-070162-FEDER-000067, and NORTE-01-0145-FEDER-000029)
Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project
Background: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. Method: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. Results: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. Conclusions: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. Trial registration: www.clinicaltrials.gov (ID: NCT04180319)
Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity
The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al
Role of alpha-1 antitrypsin genotypes in the progression of adult liver disease
info:eu-repo/semantics/publishedVersio
Alternative Splicing and Gene Duplication in the Evolution of the FoxP Gene Subfamily
The FoxP gene subfamily of transcription factors is defined by its characteristic 110 amino acid long DNA-binding forkhead domain and plays essential roles in vertebrate biology. Its four members, FoxP1–P4, have been extensively characterized functionally. FoxP1, FoxP2, and FoxP4 are involved in lung, heart, gut, and central nervous system (CNS) development. FoxP3 is necessary and sufficient for the specification of regulatory T cells (Tregs) of the adaptive immune system
- …