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1.
Proc Natl Acad Sci U S A ; 119(44): e2203150119, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36306328

RESUMO

This study explores how researchers' analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers' expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each team's workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers' results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.


Assuntos
Análise de Dados , Pesquisadores , Humanos , Incerteza , Reprodutibilidade dos Testes
2.
J Pers ; 90(6): 846-872, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35000199

RESUMO

OBJECTIVE: Relations between the Big Five personality dispositions and individual differences in political trust and involvement in politics have been investigated in many studies. We aimed to systematically integrate these findings and further explore the correlations at different hierarchical levels of the Big Five and political trust and involvement. METHOD: We conducted a meta-analysis of 43 publications (N1  = 207,360 participants) and estimated latent correlations at different hierarchical levels using two additional samples (N2  = 988 and N3  = 795). RESULTS: The meta-analysis revealed substantial correlations between involvement and openness (+), extraversion (+), and neuroticism (-), but only small correlations between trust and the Big Five. We also found a substantial amount of inconsistency in findings across studies. Our additional analyses showed that (a) correlations with the Big Five were larger for higher-order factors of general political trust (as opposed to subdimensions such as trust in politicians) and general political involvement (as opposed to subdimensions such as political interest) and (b) correlational patterns within each Big Five domain differed across facets. CONCLUSION: Our analyses indicate that political involvement is more strongly linked to the Big Five than political trust. We discuss the theoretical and empirical relevance of hierarchical constructs.


Assuntos
Personalidade , Confiança , Humanos , Extroversão Psicológica , Neuroticismo , Inventário de Personalidade
3.
BMC Bioinformatics ; 16: 142, 2015 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-25933606

RESUMO

BACKGROUND: Recent advances in synthetic biology have provided tools to efficiently construct complex DNA molecules which are an important part of many molecular biology and biotechnology projects. The planning of such constructs has traditionally been done manually using a DNA sequence editor which becomes error-prone as scale and complexity of the construction increase. A human-readable formal description of cloning and assembly strategies, which also allows for automatic computer simulation and verification, would therefore be a valuable tool. RESULTS: We have developed pydna, an extensible, free and open source Python library for simulating basic molecular biology DNA unit operations such as restriction digestion, ligation, PCR, primer design, Gibson assembly and homologous recombination. A cloning strategy expressed as a pydna script provides a description that is complete, unambiguous and stable. Execution of the script automatically yields the sequence of the final molecule(s) and that of any intermediate constructs. Pydna has been designed to be understandable for biologists with limited programming skills by providing interfaces that are semantically similar to the description of molecular biology unit operations found in literature. CONCLUSIONS: Pydna simplifies both the planning and sharing of cloning strategies and is especially useful for complex or combinatorial DNA molecule construction. An important difference compared to existing tools with similar goals is the use of Python instead of a specifically constructed language, providing a simulation environment that is more flexible and extensible by the user.


Assuntos
Biologia Computacional/métodos , Simulação por Computador , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Software , Biologia Sintética/métodos , Biblioteca Gênica , Genômica , Humanos
4.
Sci Adv ; 10(6): eadj5778, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38324680

RESUMO

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.


Assuntos
Ciências do Comportamento , Mudança Climática , Humanos , Intenção , Políticas
5.
Metab Eng Commun ; 17: e00224, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37415783

RESUMO

Fatty acids are produced by eukaryotes like baker's yeast Saccharomyces cerevisiae mainly using a large multifunctional type I fatty acid synthase (FASI) where seven catalytic steps and a carrier domain are shared between one or two protein subunits. While this system may offer efficiency in catalysis, only a narrow range of fatty acids are produced. Prokaryotes, chloroplasts and mitochondria rely instead on a FAS type II (FASII) where each catalytic step is carried out by a monofunctional enzyme encoded by a separate gene. FASII is more flexible and capable of producing a wider range of fatty acid structures, such as the direct production of unsaturated fatty acids. An efficient FASII in the preferred industrial organism S. cerevisiae could provide a platform for developing sustainable production of specialized fatty acids. We functionally replaced either yeast FASI genes (FAS1 or FAS2) with a FASII consisting of nine genes from Escherichia coli (acpP, acpS and fab -A, -B, -D, -F, -G, -H, -Z) as well as three from Arabidopsis thaliana (MOD1, FATA1 and FATB). The genes were expressed from an autonomously replicating multicopy vector assembled using the Yeast Pathway Kit for in-vivo assembly in yeast. Two rounds of adaptation led to a strain with a maximum growth rate (µmax) of 0.19 h-1 without exogenous fatty acids, twice the growth rate previously reported for a comparable strain. Additional copies of the MOD1 or fabH genes resulted in cultures with higher final cell densities and three times higher lipid content compared to the control.

6.
Cogn Sci ; 47(2): e13255, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36807910

RESUMO

In cognitive science, there is a tacit norm that phenomena such as cultural variation or synaesthesia are worthy examples of cognitive diversity that contribute to a better understanding of cognition, but that other forms of cognitive diversity (e.g., autism, attention deficit hyperactivity disorder/ADHD, and dyslexia) are primarily interesting only as examples of deficit, dysfunction, or impairment. This status quo is dehumanizing and holds back much-needed research. In contrast, the neurodiversity paradigm argues that such experiences are not necessarily deficits but rather are natural reflections of biodiversity. Here, we propose that neurodiversity is an important topic for future research in cognitive science. We discuss why cognitive science has thus far failed to engage with neurodiversity, why this gap presents both ethical and scientific challenges for the field, and, crucially, why cognitive science will produce better theories of human cognition if the field engages with neurodiversity in the same way that it values other forms of cognitive diversity. Doing so will not only empower marginalized researchers but will also present an opportunity for cognitive science to benefit from the unique contributions of neurodivergent researchers and communities.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Cognição , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Ciência Cognitiva
7.
Injury ; 54 Suppl 6: 110783, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38143127

RESUMO

Vertically unstable pelvic injuries associated with sacroiliac disruption are challenging. Although percutaneous iliosacral fixation using two screws at S1 vertebral body has been shown beneficial, the use of two transiliac screws at S1 has been proposed to increase the fixation strength of the construct. In the herein study, the finite element method (FEM) was performed to analyse the biomechanical behaviour of five different constructions using iliosacral screws only, transiliac screws only, and combining an iliosacral and a transiliac screw. A vertically unstable AO 61C1.2 type pelvic injury was produced for the evaluation of the posterior pelvic displacement and implant stress, and the anterior implant stress using FEM. The symphysis pubis was fixed with a 3.5-mm reconstruction plate in all cases. The model was axially loaded with 800N applied in the centre of S1 body, perpendicular to the ground (Y-axis), simulating the bipodal stance moment. There was a statistically significant reduction in both posterior displacement and implant stresses in the groups fixed with at least one transiliac screw compared to the groups fixed with iliosacral screws. In our FEM study, the construct using two transiliac screws in S1 is biomechanically superior for stabilizing the sacroiliac joint in vertically unstable pelvic ring injuries compared to the other configurations. Lateral displacement, posterior displacement, and von Mises stress were reduced with this construct. A good option can be the use of one iliosacral screw and one transiliac screw in S1.


Assuntos
Fraturas Ósseas , Instabilidade Articular , Ossos Pélvicos , Humanos , Articulação Sacroilíaca/cirurgia , Articulação Sacroilíaca/lesões , Fixação Interna de Fraturas/métodos , Análise de Elementos Finitos , Parafusos Ósseos , Fraturas Ósseas/cirurgia , Fenômenos Biomecânicos , Ossos Pélvicos/cirurgia , Ossos Pélvicos/lesões , Sacro/cirurgia , Sacro/lesões
8.
Sci Data ; 10(1): 87, 2023 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-36774440

RESUMO

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.


Assuntos
COVID-19 , Humanos , Adaptação Psicológica , Comportamentos Relacionados com a Saúde , Pandemias , Inquéritos e Questionários
9.
R Soc Open Sci ; 10(5): 221255, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37206965

RESUMO

In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students' understanding of open research, consumption of science and the development of transferable skills); (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship.

10.
Sci Data ; 10(1): 272, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37169799

RESUMO

The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.


Assuntos
COVID-19 , Humanos , Atitude , COVID-19/psicologia , Princípios Morais , Pandemias , Inquéritos e Questionários , Mudança Social , Fatores Socioeconômicos
11.
Elife ; 122023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37994903

RESUMO

Reproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages researchers to integrate reproducible research and open science practices into their daily work. Here, we outline eleven strategies for making training in these practices the norm at research institutions. The strategies, which emerged from a virtual brainstorming event organized in collaboration with the German Reproducibility Network, are concentrated in three areas: (i) adapting research assessment criteria and program requirements; (ii) training; (iii) building communities. We provide a brief overview of each strategy, offer tips for implementation, and provide links to resources. We also highlight the importance of allocating resources and monitoring impact. Our goal is to encourage researchers - in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees - to think creatively about the many ways they can promote reproducible research and open science practices in their institutions.


Assuntos
Mentores , Médicos , Humanos , Reprodutibilidade dos Testes , Seleção de Pessoal , Pesquisadores
12.
Curr Opin Psychol ; 46: 101390, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35802986

RESUMO

Despite widespread scientific consensus on climate change, conspiracy theories about its causes and consequences are flourishing. In response, psychological research has started to investigate the consequences of espousing conspiracy beliefs about climate change. Although some scholars maintain that the evidence for a causal link between belief in conspiracy theories and behavior remains elusive, others have argued that climate change conspiracy theories undermine pro-climate action. To shed further light on this question across a range of outcome measures, we present a meta-analysis of 22 independent samples (Nparticipants = 20,765). Overall, we find clear evidence that climate conspiracy beliefs have moderate-to-large negative correlations with not only acceptance of (climate) science, trust, and pro-environmental concern, but also with behavioural intentions and policy support. Most of these effects were not moderated by design (experimental vs. correlational), political ideology, or prior conspiracy beliefs. However, we note publication bias and in several cases sufficient experimental data were lacking. Implications for addressing conspiracy theories about climate change are discussed.


Assuntos
Mudança Climática , Intenção , Humanos , Confiança/psicologia
13.
Public Underst Sci ; 31(4): 437-457, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35135408

RESUMO

We investigated pandemic denial in the general public in Germany after the first wave of COVID-19 in May 2020. Using latent class analysis, we compared patterns of disagreement with claims about (a) the origin, spread, or infectiousness of the SARS-CoV-2 virus and (b) the personal risk from COVID-19 between scientific laypersons (N = 1,575) and scientific experts (N = 128). Two groups in the general public differed distinctively from expert evaluations. The Dismissive (8%) are characterized by low-risk assessment, low compliance with containment measures, and mistrust in politicians. The Doubtful (19%) are characterized by low cognitive reflection, high uncertainty in the distinction between true and false claims, and high social media intake. Our research indicates that pandemic denial cannot be linked to a single and distinct pattern of psychological dispositions but involves different subgroups within the general population that share high COVID-19 conspiracy beliefs and low beliefs in epistemic complexity.


Assuntos
COVID-19 , Mídias Sociais , COVID-19/epidemiologia , Dissidências e Disputas , Humanos , Pandemias , SARS-CoV-2
14.
Comput Struct Biotechnol J ; 20: 779-787, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36284710

RESUMO

Malonyl-CoA is an energy-rich molecule formed by the ATP-dependent carboxylation of acetyl coenzyme A catalyzed by acetyl-CoA carboxylase. This molecule is an important precursor for many biotechnologically interesting compounds such as flavonoids, polyketides, and fatty acids. The yeast Saccharomyces cerevisiae remains one of the preferred cell factories, but has a limited capacity to produce malonyl-CoA compared to oleaginous organisms. We developed a new S. cerevisiae strain with a conditional allele of ACC1, the essential acetyl-CoA carboxylase (ACC) gene, as a tool to test heterologous genes for complementation. Yarrowia lipolytica is an oleaginous yeast with a higher capacity for lipid production than S. cerevisiae, possibly due to a higher capacity to produce malonyl-CoA. Measuring relative intracellular malonyl-CoA levels with an in-vivo biosensor confirmed that expression of Y. lipolytica ACC in S. cerevisiae leads to a higher accumulation of malonyl-CoA compared with overexpression of the native gene from an otherwise identical vector. The higher accumulation was generally accompanied by a decreased growth rate. Concomitant expression of both the homologous and heterologous ACC1 genes eliminated the growth defect, with a marginal reduction of malonyl-CoA accumulation.

15.
Cureus ; 14(6): e26202, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35891833

RESUMO

Various surgical treatments for supracondylar fracture in children remain the motive of research and study. A common factor in each technique is anatomic reduction, which is critical for the excellent recovery of the fracture. Anatomic reduction is preferably realized through closed and percutaneous approaches. This study aimed to present a closed percutaneous technique to treat Gartland III supracondylar fractures to aggregate a facilitating factor in the surgical approach to this condition. Our technique was applied to surgical patients in orthopedic and traumatology emergency care and illustrated by a synthetic elbow model, including soft tissue and intraoperative images.

16.
BMC Res Notes ; 15(1): 75, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193662

RESUMO

The UK House of Commons Science and Technology Committee has called for evidence on the roles that different stakeholders play in reproducibility and research integrity. Of central priority are proposals for improving research integrity and quality, as well as guidance and support for researchers. In response to this, we argue that there is one important component of research integrity that is often absent from discussion: the pedagogical consequences of how we teach, mentor, and supervise students through open scholarship. We justify the need to integrate open scholarship principles into research training within higher education and argue that pedagogical communities play a key role in fostering an inclusive culture of open scholarship. We illustrate these benefits by presenting the Framework for Open and Reproducible Research Training (FORRT), an international grassroots community whose goal is to provide support, resources, visibility, and advocacy for the adoption of principled, open teaching and mentoring practices, whilst generating conversations about the ethics and social impact of higher-education pedagogy. Representing a diverse group of early-career researchers and students across specialisms, we advocate for greater recognition of and support for pedagogical communities, and encourage all research stakeholders to engage with these communities to enable long-term, sustainable change.


Assuntos
Bolsas de Estudo , Estudantes , Humanos , Mentores , Reprodutibilidade dos Testes , Pesquisadores
17.
PNAS Nexus ; 1(3): pgac093, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35990802

RESUMO

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution-individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic.

18.
Nat Commun ; 13(1): 517, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35082277

RESUMO

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.


Assuntos
Pandemias/legislação & jurisprudência , Saúde Pública/legislação & jurisprudência , Conformidade Social , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , Comparação Transcultural , Comportamentos Relacionados com a Saúde , Humanos , Liderança , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , SARS-CoV-2 , Autorrelato , Identificação Social
19.
Yeast ; 28(1): 55-61, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20824890

RESUMO

Chromosomal DNA damage can be a result of several processes and agents of endogenous or exogenous origin. These cause strand breaks or oxidized bases that lead to strand breaks, which relax the normally supercoiled genomic DNA and increase its electrophoretic mobility. The extent of DNA damage can be assessed by single cell gel electrophoresis, where the chromosomal DNA migration distance correlates with the extent of DNA damage. This technique has been used for a variety of applications with several organisms, but only a few studies have been reported for Saccharomyces cerevisiae. A possible reason for this absence is that low cellular DNA content could hamper visualization. Here we report an optimization of the comet assay protocol for yeast cells that is robust and sensitive enough to reproducibly detect background DNA damage and oxidative damage caused by hydrogen peroxide. DNA repair was observed and quantified as diminishing comet tail length with time after oxidative stress removal in a process well described by first-order kinetics with a tail length half-life of 11 min at 37 °C. This is, to our knowledge, the first quantitative measurement of DNA repair kinetics in S. cerevisiae by this method. We also show that diet antioxidants protect from DNA damage, as shown by a three-fold decrease in comet tail length. The possibility of assessment of DNA damage and repair in individual cells applied to the model organism S. cerevisiae creates new perspectives for studying genotoxicity and DNA repair.


Assuntos
Ensaio Cometa/métodos , Dano ao DNA , Reparo do DNA , DNA Fúngico/metabolismo , Peróxido de Hidrogênio/metabolismo , Antioxidantes/metabolismo , Meia-Vida , Cinética , Oxirredução , Estresse Oxidativo , Saccharomyces cerevisiae/genética
20.
Biochem Soc Trans ; 39(5): 1533-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21936847

RESUMO

The yeast apoptosis field emerged with the finding that key components of the apoptotic machinery are conserved in these simple eukaryotes. Thus it became possible to exploit these genetically tractable organisms to improve our understanding of the intricate mechanisms of cell death in higher eukaryotes and of severe human diseases associated with apoptosis dysfunctions. Early on, it was recognized that a mitochondria-mediated apoptotic pathway showing similarities to the mammalian intrinsic pathway was conserved in yeast. Recently, lysosomes have also emerged as central players in mammalian apoptosis. Following LMP (lysosomal membrane permeabilization), lysosomal proteases such as cathepsins B, D and L are released into the cytosol and can trigger a mitochondrial apoptotic cascade. CatD (cathepsin D) can also have anti-apoptotic effects in some cellular types and specific contexts. Nonetheless, the mechanisms underlying LMP and the specific role of cathepsins after their release into the cytosol remain poorly understood. We have recently shown that yeast vacuoles, membrane-bound acidic organelles, which share many similarities to plant vacuoles and mammalian lysosomes, are also involved in the regulation of apoptosis and that the vacuolar protease Pep4p, orthologue of the human CatD, is released from the vacuole into the cytosol in response to acetic acid. Here, we discuss how the conservation of cell-death regulation mechanisms in yeast by the lysosome-like organelle and mitochondria may provide new insights into the understanding of the complex interplay between the mitochondria and lysosome-mediated signalling routes during mammalian apoptosis.


Assuntos
Apoptose/fisiologia , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/fisiologia , Transdução de Sinais/fisiologia , Vacúolos/metabolismo , Animais , Humanos , Proteínas de Saccharomyces cerevisiae/metabolismo
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