657 research outputs found
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Alternative Splicing Control of Abiotic Stress Responses
Full text linkThe deposited article is a post-print version and has been submitted to peer review.This publication hasn't any creative commons license associated.This deposit is composed by the main article, and it hasn't any supplementary materials associated.There is no public supplementary material available for this publication.Alternative splicing, which generates multiple transcripts from the same gene, is an important modulator of gene expression that can increase proteome diversity and regulate mRNA levels. In plants, this post-transcriptional mechanism is markedly induced in response to environmental stress, and recent studies have identified alternative splicing events that allow rapid adjustment of the abundance and function of key stress-response components. In agreement, plant mutants defective in splicing factors are severely impaired in their response to abiotic stress. Notably, mounting evidence indicates that alternative splicing regulates stress responses largely by targeting the abscisic acid (ABA) pathway. We review here current understanding of post-transcriptional control of plant stress tolerance via alternative splicing and discuss research challenges for the near future.Marie Skłodowska-Curie Individual Fellowship: (MSCA-IF-2015; grant 706274 ); EMBO Long-Term Fellowship: (ALTF 1576-2016 ); Fundação para a Ciência e a Tecnologia grant: (PTDC/BIA-PLA/1084/2014); GREEN-it research unit grant: (UID/Multi/04551/2013).info:eu-repo/semantics/publishedVersio
Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance
Full text linkThe deposited review is a post-print version and has been submitted to peer review.This publication hasn't any creative commons license associated.This deposit is composed by the review, and it hasn't any supplementary materials associated.The publication deposited was in a state of Epub Ahead of Print, at the time when the upload was made.Antibiotics target essential cellular functions but bacteria can become resistant by acquiring either exogenous resistance genes or chromosomal mutations. Resistance mutations typically occur in genes encoding essential functions; these mutations are therefore generally detrimental in the absence of drugs. However, bacteria can reduce this handicap by acquiring additional mutations, known as compensatory mutations. Genetic interactions (epistasis) either with the background or between resistances (in multiresistant bacteria) dramatically affect the fitness cost of antibiotic resistance and its compensation, therefore shaping dissemination of antibiotic resistance mutations. This Review summarizes current knowledge on the evolutionary mechanisms influencing maintenance of resistance mediated by chromosomal mutations, focusing on their fitness cost, compensatory evolution, epistasis, and the effect of the environment on these processes.PD and RB were supported by Fundação para a Ciência e Tecnologia (FCT), fellowships SFRH/BPD/118474/2016 and SFRH/BPD/109517/2015, respectively. Current research is supported by project JPIAMR/0001/2016-ERA NET and ONEIDA project (LISBOA-01-0145-FEDER-016417) co-funded by FEEI – ‘Fundos Europeus Estruturais e de Investimento’ from ‘Programa Operacional Regional Lisboa 2020’, and by national funds from FCT – ‘Fundação para a Ciência e a Tecnologia’.info:eu-repo/semantics/acceptedVersio
Noncanonical Biogenesis of Centrioles and Basal Bodies
Full text linkThe deposited article is a pre-print version.The deposited article version is the Epub Ahead of Print version of the article, posted online 23 April 2018, provided by Cold Spring Harbor Laboratory Press. It hasn't peer-review.This deposit is composed by the main article, and it hasn't any supplementary materials associated.Centrioles and basal bodies (CBBs) organize centrosomes and cilia within eukaryotic cells. These organelles are composed of microtubules and hundreds of proteins performing multiple functions such as signaling, cytoskeleton remodeling, and cell motility. The CBB is present in all branches of the eukaryotic tree of life and, despite its ultrastructural and protein conservation, there is diversity in its function, occurrence (i.e., presence/absence), and modes of biogenesis across species. In this review, we provide an overview of the multiple pathways through which CBBs are formed in nature, with a special focus on the less studied, noncanonical ways. Despite the differences among each mechanism herein presented, we highlighted some of their common principles. These principles, governing different steps of biogenesis, ensure that CBBs may perform a multitude of functions in a huge diversity of organisms but yet retained their robustness in structure throughout evolution.European Research Council Consolidator Grant: (CoG683528__Centriole-BirthDeath); Boehringer Ingelheim Fonds; Fundação para a Ciência e Tecnologia grant: (PD/BD/114350/2016).info:eu-repo/semantics/acceptedVersio
FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence
No full textThis deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.nature.com/articles/s41467-018-05258-6This deposit is composed by the main article and the supplementary materials are present in the publisher's page in the following link: https://www.nature.com/articles/s41467-018-05258-6#Sec36Aneuploidy, an abnormal chromosome number, has been linked to aging and age-associated diseases, but the underlying molecular mechanisms remain unknown. Here we show, through direct live-cell imaging of young, middle-aged, and old-aged primary human dermal fibroblasts, that aneuploidy increases with aging due to general dysfunction of the mitotic machinery. Increased chromosome mis-segregation in elderly mitotic cells correlates with an early senescence-associated secretory phenotype (SASP) and repression of Forkhead box M1 (FoxM1), the transcription factor that drives G2/M gene expression. FoxM1 induction in elderly and Hutchison-Gilford progeria syndrome fibroblasts prevents aneuploidy and, importantly, ameliorates cellular aging phenotypes. Moreover, we show that senescent fibroblasts isolated from elderly donors' cultures are often aneuploid, and that aneuploidy is a key trigger into full senescence phenotypes. Based on this feedback loop between cellular aging and aneuploidy, we propose modulation of mitotic efficiency through FoxM1 as a potential strategy against aging and progeria syndromes.E.L. holds an FCT Investigator Postdoctoral Grant (IF/00916/2014) from FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior). FCT Fellowships (SFRH/BD/74002/2010; SFRH/BD/125017/2016; PD/BD/128000/2016) supported J.C.M., S.V., and R.R. The following project grants supported this work: National Funds through FCT under the project PTDC/BEX-BCM/
2090/2014 ; NORTE-01-0145-FEDER-000029 funded by North Regional Operational Program (NORTE2020) under PORTUGAL 2020 Partnership Agreement through Regional Development Fund (FEDER); NORTE-07-0124-FEDER-000003 co-funded by North Regional Operational Program (ON.2) through FEDER and by FCT; and POCI-01-0145-FEDER-007274 i3S framework project co-funded by COMPETE 2020/PORTUGAL
2020 through FEDER and by FCT; Foundation Pediatric Oncology Groningen grant and Dutch Cancer Society grant 2012-RUG-5549 to F.F.info:eu-repo/semantics/publishedVersio
Bacterial Call to Arms for Warfare at the Infection Site
Full text linkBacterial sensing is important for perceiving environmental cues and activating responses. In this issue of Cell Host & Microbe, Hertzog et al. (2018) show that group A Streptococcus can couple the ability to respond to host cues with autoinduction of a quorum sensing system, leading to killing of bacterial competitors.info:eu-repo/semantics/publishedVersio
Genetic basis of thermal plasticity variation in Drosophila melanogaster body size
Full text linkThis deposit is composed by the main article. The supplementary materials can be found on-line through the following link: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007686#sec017Body size is a quantitative trait that is closely associated to fitness and under the control of both genetic and environmental factors. While developmental plasticity for this and other traits is heritable and under selection, little is known about the genetic basis for variation in plasticity that can provide the raw material for its evolution. We quantified genetic variation for body size plasticity in Drosophila melanogaster by measuring thorax and abdomen length of females reared at two temperatures from a panel representing naturally segregating alleles, the Drosophila Genetic Reference Panel (DGRP). We found variation between genotypes for the levels and direction of thermal plasticity in size of both body parts. We then used a Genome-Wide Association Study (GWAS) approach to unravel the genetic basis of inter-genotype variation in body size plasticity, and used different approaches to validate selected QTLs and to explore potential pleiotropic effects. We found mostly "private QTLs", with little overlap between the candidate loci underlying variation in plasticity for thorax versus abdomen size, for different properties of the plastic response, and for size versus size plasticity. We also found that the putative functions of plasticity QTLs were diverse and that alleles for higher plasticity were found at lower frequencies in the target population. Importantly, a number of our plasticity QTLs have been targets of selection in other populations. Our data sheds light onto the genetic basis of inter-genotype variation in size plasticity that is necessary for its evolution.Financial support for this work was provided by the Portuguese science funding agency, Fundação para a Ciência e Tecnologia, FCT: PhD fellowship to EL (SFRH/BD/52171/2013), and research grant to PB (PTDC/BIA-EVF/0017/2014); French research funding agency, Agence Nationale de la Recherche, ANR: Laboratory of Excellence TULIP, ANR-10-LABX-41 and ANR-11-IDEX-0002-02 (support for DD and PB) and French research centre, Centre National de la Recherche Scientifique, CNRS: International Associated Laboratory, LIA BEEG-B (support for DD and PB), and the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement (PCOFUND-GA-2013-609102), through the PRESTIGE programme coordinated by Campus France (support for DD). This work was developed with the support of the research infrastructure Congento, project LISBOA 01-0145-FEDER-022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and Foundation for Science and Technology (FCT,Portugal). The funders had no role in study design,data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio
Differential regulation of transition zone and centriole proteins contributes to ciliary base diversity
No full textCilia are evolutionarily conserved structures with many sensory and motility-related functions. The ciliary base, composed of the basal body and the transition zone, is critical for cilia assembly and function, but its contribution to cilia diversity remains unknown. Hence, we generated a high-resolution structural and biochemical atlas of the ciliary base of four functionally distinct neuronal and sperm cilia types within an organism, Drosophila melanogaster. We uncovered a common scaffold and diverse structures associated with different localization of 15 evolutionarily conserved components. Furthermore, CEP290 (also known as NPHP6) is involved in the formation of highly diverse transition zone links. In addition, the cartwheel components SAS6 and ANA2 (also known as STIL) have an underappreciated role in basal body elongation, which depends on BLD10 (also known as CEP135). The differential expression of these cartwheel components contributes to diversity in basal body length. Our results offer a plausible explanation to how mutations in conserved ciliary base components lead to tissue-specific diseases.info:eu-repo/semantics/publishedVersio
Deconstructing the molecular mechanisms shaping the vertebrate body plan
Full text linkThe large display of body shapes and sizes observed among vertebrates ultimately represent variations of a common basic body plan. This likely results from the use of homologous developmental schemes, just differentially tinkered both in amplitude and timing by natural selection. In this review, we will revisit, discuss and combine old ideas with new concepts to update our view on how the vertebrate body is built. Recent advances, particularly at the molecular level, will guide our deconstruction of the individual developmental modules that sequentially produce head, neck, trunk and tail structures, and the transitions between them.info:eu-repo/semantics/publishedVersio
Reassessing the Role of Hox Genes during Vertebrate Development and Evolution
Full text linkSince their discovery Hox genes have been at the core of the established models explaining the development and evolution of the vertebrate body plan as well as its paired appendages. Recent work brought new light to their role in the patterning processes along the main body axis. These studies show that Hox genes do not control the basic layout of the vertebrate body plan but carry out region-specific patterning instructions loaded on the derivatives of axial progenitors by Hox-independent processes. Furthermore, the finding that Hox clusters are embedded in functional chromatin domains, which critically impacts their expression, has significantly altered our understanding of the mechanisms of Hox gene regulation. This new conceptual framework has broadened our understanding of both limb development and the evolution of vertebrate paired appendages.info:eu-repo/semantics/publishedVersio
Antibodies aggravate the development of ischemic heart failure
Full text linkHeart-specific antibodies have been widely associated with myocardial infarction (MI). However, it remains unclear whether autoantibodies mediate disease progression or are a byproduct of cardiac injury. To disambiguate the role of immunoglobulins in MI, we characterized the development of ischemic heart failure in agammaglobulinemic mice (AID-/-μS-/-). Although these animals can produce functional B cells, they cannot synthesize secretory IgM (μS-/-) or perform Ig class switching (AID-/-), leading to complete antibody deficiency. Agammaglobulinemia did not affect overall post-MI survival but resulted in a significant reduction in infarct size. Echocardiographic analyses showed that, compared with wild-type infarcted control mice, AID-/-μS-/- mice exhibited improved cardiac function and reduced remodeling on day 56 post-MI. These differences remained significant even after animals with matched infarct sizes were compared. Infarcted AID-/-μS-/- mice also showed reduced myocardial expression levels of transcripts known to promote adverse remodeling, such as matrix metalloproteinase-9, collagen type I a1, collagen type III a1, and IL-6. An unbiased screening of the heart reactivity potential in the plasma of wild-type MI animals revealed the presence of antibodies that target the myocardial scar and collagenase-sensitive epitopes. Moreover, we found that IgG accumulated within the scar tissues of infarcted mice and remained in close proximity with cells expressing Fcγ receptors (CD16/32), suggesting the existence of an in situ IgG-Fcγ receptor axis. Collectively, our study results confirm that antibodies contribute to ischemic heart failure progression and provide novel insights into the mechanisms underlying this phenomenon. NEW & NOTEWORTHY Our study sheds some light on the long-standing debate over the relevance of autoantibodies in heart failure and might stimulate future research in the field. The observation of extracellular matrix-specific antibodies and the detection of Fcγ receptor-expressing cells within the scar provide novel insights into the mechanisms by which antibodies may contribute to adverse remodeling.info:eu-repo/semantics/publishedVersio