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Building the right centriole for each cell type
Full text linkThe deposited article version is the publisher version, which is in a "Epub Ahead of Print” state at the moment of the deposit.This deposit is composed by the main article, and it hasn't any supplementary materials associated.The centriole is a multifunctional structure that organizes centrosomes and cilia and is important for cell signaling, cell cycle progression, polarity, and motility. Defects in centriole number and structure are associated with human diseases including cancer and ciliopathies. Discovery of the centriole dates back to the 19th century. However, recent advances in genetic and biochemical tools, development of high-resolution microscopy, and identification of centriole components have accelerated our understanding of its assembly, function, evolution, and its role in human disease. The centriole is an evolutionarily conserved structure built from highly conserved proteins and is present in all branches of the eukaryotic tree of life. However, centriole number, size, and organization varies among different organisms and even cell types within a single organism, reflecting its cell type-specialized functions. In this review, we provide an overview of our current understanding of centriole biogenesis and how variations around the same theme generate alternatives for centriole formation and function.Gulbenkian Foundation; European Research Council Consolidator Grant: (CoG683528); Fundaçao para a Ciencia e Tecnologia grant: (PTDC/BIM-ONC/6858/2014); National Institutes of Health; National Cancer Institute; Center for Cancer Research.info:eu-repo/semantics/publishedVersio
Online behavioral patterns in a health crisis setting: the 2009 pandemic.
Full text linkSeasonal flu places a heavy burden on both human populations and health care ser-
vices every year, warranting permanent surveillance. Online-based surveillance mod-
els harness the collective online search activity of flu-infected individuals to provide
real-time monitoring of flu activity. These models assume that most flu-related online
behavior is motivated by a flu infection. However, when the flu pandemic emerged
in 2009 it resulted in abnormal search behaviors that confounded these models, as
several reasons, beyond infection, can motivate individuals to seek flu information.
In practice, and despite their potential, current models cannot distinguish whether
such activity is related with actual flu infection or not, rendering them useless, at
least in pandemic settings.
If the different motives that prompt flu-related searches can be pinpointed, then this
information can be used to train the models to recognize what is infection-motivated
and what is not. Moreover, if online behaviors reflect real-life behaviors, then valuable
public health insights can be extracted by analyzing the public’s online response to
a pandemic.
To test these assumptions, we collected flu-related online search trends regarding
the pandemic period. We estimated real-life behaviors, anxiety and risk perception,
through data obtained from surveys conducted during the pandemic. As possible
explanatory variables of online search trends, we collected flu-related media coverage
as well as laboratory-confirmed flu cases.
We found that a specific set of search trends was more associated with media activity,
whereas another set of search trends was more associated with flu infections. The
media-related search trends proxied the public’s anxiety levels and the infection-
related search trends proxied the public’s risk perception.
Having determined which factors correlated with specific search trends, and what
real-life behaviors might have corresponded to these search trends, our findings place
online sources as suitable tools for monitoring the public’s response to a flu pandemic.
Our findings additionally support the possibility of separating search trends that are
more sensitive to media activity and search trends that are more sensitive to flu
activity. Thus, we provide proof-of-principle that it should be possible to infer human
behaviour from online behaviour and, in practical terms, our system is flexible and
general enough to be applied both to pandemic and seasonal flu, as well as to other
infectious settings.info:eu-repo/semantics/publishedVersio
Protein analysis and gene expression indicate differential vulnerability of Iberian fish species under a climate change scenario
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.Current knowledge on the biological responses of freshwater fish under projected scenarios of climate change remains limited. Here, we examine differences in the protein configuration of two endemic Iberian freshwater fish species, Squalius carolitertii and the critically endangered S. torgalensis that inhabit in the Atlantic-type northern and in the Mediterranean-type southwestern regions, respectively. We performed protein structure modeling of fourteen genes linked to protein folding, energy metabolism, circadian rhythms and immune responses. Structural differences in proteins between the two species were found for HSC70, FKBP52, HIF1α and GPB1. For S. torgalensis, besides structural differences, we found higher thermostability for two proteins (HSP90 and GBP1), which can be advantageous in a warmer environment. Additionally, we investigated how these species might respond to projected scenarios of 3° climate change warming, acidification (ΔpH = -0.4), and their combined effects. Significant changes in gene expression were observed in response to all treatments, particularly under the combined warming and acidification. While S. carolitertii presented changes in gene expression for multiple proteins related to folding (hsp90aa1, hsc70, fkbp4 and stip1), only one such gene was altered in S. torgalensis (stip1). However, S. torgalensis showed a greater capacity for energy production under both the acidification and combined scenarios by increasing cs gene expression and maintaining ldha gene expression in muscle. Overall, these findings suggest that S. torgalensis is better prepared to cope with projected climate change. Worryingly, under the simulated scenarios, disturbances to circadian rhythm and immune system genes (cry1aa, per1a and gbp1) raise concerns for the persistence of both species, highlighting the need to consider multi-stressor effects when evaluating climate change impacts upon fish. This work also highlights that assessments of the potential of endangered freshwater species to cope with environmental change are crucial to help decision-makers adopt future conservation strategies.Instituto da Conservação da Natureza e Florestas.info:eu-repo/semantics/publishedVersio
Phosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the Metalloprotease ADAM17/TACE
Full text linkCell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme), is responsible for cleavage ("shedding") of membrane-tethered signaling molecules, including the cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within the secretory pathway requires its binding to iRhom2, which mediates the exit of TACE from the endoplasmic reticulum. An important, but mechanistically unclear, feature of TACE biology is its ability to be stimulated rapidly on the cell surface by numerous inflammatory and growth-promoting agents. Here, we report a role for iRhom2 in TACE stimulation on the cell surface. TACE shedding stimuli trigger MAP kinase-dependent phosphorylation of iRhom2 N-terminal cytoplasmic tail. This recruits 14-3-3 proteins, enforcing the dissociation of TACE from complexes with iRhom2, promoting the cleavage of TACE substrates. Our data reveal that iRhom2 controls multiple aspects of TACE biology, including stimulated shedding on the cell surface.info:eu-repo/semantics/publishedVersio
Leptin Resistance and the Neuro-Adipose Connection
Full text linkThis article was submitted to Cellular Endocrinology, a section of the journal Frontiers in Endocrinology.Obesity is a public health concern affecting both genders at all ages around the world. The worldwide prevalence of obesity is rapidly increasing and has nearly doubled between 1980 and 2016. Consequently, it places a large financial burden on the economy due to the increased morbidity and mortality, as well as the reduced quality of life and development of chronic diseases. Obesity is typically characterized by excessive amounts of the hormone leptin, a cytokine-like molecule produced in white adipose tissue (WAT) that is secreted into the systemic circulation. The circulating levels of leptin are proportional to the amount of fat and function as the afferent signal in a negative feedback loop that seeks to maintain body fat in a very narrow range of variation. Leptin has a central role in body weight homeostasis due to its inhibition of food intake inhibition and stimulation of energy expenditure. The effect of leptin on body weight is attributed to its action in a specific brain region, the hypothalamus. Hence, leptin is released by adipocytes in proportion to the size of fat depots, enters the circulation, and reaches the central nervous system by crossing the blood-brain barrier (BBB) through receptor-mediated endocytosis in which it acts mainly through the arcuate nucleus of the hypothalamus to mediate most of its actions. Specifically, leptin modulates the activity of two types of neurons to inhibit appetite, through production of anorexigenic peptides by the pro-opiomelanocortin (POMC) neurons and suppression of the orexigenic agouti-related protein (AgRP) neurons. Besides acting on the hypothalamus to suppress appetite, leptin also induces lipolysis in WAT and thermogenesis in brown adipose tissue (BAT) and browning of WAT, via the activation of the sympathetic nervous system (SNS). However, in most obese subjects, despite its high serum levels, leptin fails to perform its physiological functions and consequently fails to reduce weight. This effect has been coined as leptin resistance.Fundação para Ciência e Tecnologia grants: (PD/BD/52437/2013, PTDC-BIM-MET-3750-2014); EMBO grant: (IG3077); Prémios Maratona Saúde 2015: (Diabetes); Human Frontiers Science Program grant:(RGY0070/2016).info:eu-repo/semantics/publishedVersio
Temporal variation in brain transcriptome is associated with the expression of female mimicry as a sequential male alternative reproductive tactic in fish
Full text linkThe deposited article is the accepted manuscript (post-print), posted online 7 November 2017. This publication hasn't any creative commons license associated. This deposit is composed by the main article plus the supplementary materials of the publication. Both raw data and transcriptome assembly were deposited in BioProject portal at NCBI (PRJNA329073).Distinct patterns of gene expression often underlie intra- and inter-sexual differences, and the study of this set of co-regulated genes is essential to understand the emergence of complex behavioural phenotypes. Here, we describe the development of a de novo transcriptome and brain gene expression profiles of wild-caught peacock blenny, Salaria pavo, an intertidal fish with sex-role reversal in courtship behaviour (i.e. females are the courting sex) and sequential alternative reproductive tactics in males (i.e. larger and older nest-holder males and smaller and younger sneaker males occur). Sneakers mimic both female's courtship behaviour and nuptial colouration to get access to nests and sneak fertilizations, and later in life transition into nest-holder males. Thus, this species offers the unique opportunity to study how the regulation of gene expression can contribute to intersex phenotypes and to the sequential expression of male and female behavioural phenotypes by the same individual. We found that at the whole brain level, expression of the sneaker tactic was paralleled by broader and divergent gene expression when compared to either females or nest-holder males, which were more similar between themselves. When looking at sex-biased transcripts, sneaker males are intersex rather than being either nest-holder or female-like, and their transcriptome is simultaneously demasculinized for nest-holder-biased transcripts and feminized for female-biased transcripts. These results indicate that evolutionary changes in reproductive plasticity can be achieved through regulation of gene expression, and in particular by varying the magnitude of expression of sex-biased genes, throughout the lifetime of the same individual. This article is protected by copyright. All rights reserved.Fundação para a Ciência e a Tecnologia grants: (PTDC/MAR/69749/2006, EXCL/BIA-ANM/0549/2012, SFRH/BD/89072/2012); Macao Science and Technology Development Fund grant: (012/2012/A1).info:eu-repo/semantics/acceptedVersio
Changes in Expression of the CLOCK Gene in Obstructive Sleep Apnea Syndrome Patients Are Not Reverted by Continuous Positive Airway Pressure Treatment
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressure (CPAP) treatment.Fundação para a Ciência e Tecnologia; European Research Council grant: (ERC-2014-CoG 647888-iPROTECTION).info:eu-repo/semantics/publishedVersio
Specific expression of heme oxygenase-1 by myeloid cells modulates renal ischemia-reperfusion injury
Full text linkThis work was presented in abstract form at the 17th Congress of the European Society for Organ Transplantation (ESOT) in Brussels, Belgium (Brief Oral Presentation, BOS04 – Ischemia, Reperfusion, Metabolism and Aging, abstract N°BO33; 13–16 September 2015) and at the 16th Congress of the European Association of Urology (EAU) in Munich, Germany (Poster Session 48, Kidney Transplant: From Bench to clinical practice, abstract n°603; 11–15 March 2016).Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1(M-KO)), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1(M-KO) exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1(M-KO) mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b(+) F4/80(lo) subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1(+) CD11b(+) F4/80(lo) myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1(M-KO) mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.Fonds de la Recherche Scientifique Médicale; Fonds Erasme pour la Recherche Médicale; Société Belge d’Urologie.info:eu-repo/semantics/publishedVersio
Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora), two signaling networks-the N-acyl homoserine lactone (AHL) quorum-sensing system and the Gac/Rsm signal transduction pathway-control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources.IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways.Fundação Para a Ciência e Tecnologia grants: (PTDC/BIA-BCM/101585/2008, SFRH/BD/33570/2008, SRFH/BD/113986/2015, PD/00133/2012); Marie Curie Intra-European grant: (PIEF-GA-2011-301365); Howard Hughes Medical Institute international early career scientist grant: (HHMI 55007436).info:eu-repo/semantics/publishedVersio
Adaptation to new nutritional environments: larval performance, foraging decisions, and adult oviposition choices in Drosophila suzukii
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.All data and scripts are available on Figshare (doi: 10.4225/03/58ca18ae80d1a) and all materials are available upon request. https://figshare.com/articles/Silva-Soares_et_al_2017/4757275Understanding how species adapt to new niches is a central issue in evolutionary ecology. Nutrition is vital for the survival of all organisms and impacts species fitness and distribution. While most Drosophila species exploit rotting plant parts, some species have diversified to use ripe fruit, allowing earlier colonization. The decomposition of plant material is facilitated by yeast colonization and proliferation. These yeasts serve as the main protein source for Drosophila larvae. This dynamic rotting process entails changes in the nutritional composition of the food and other properties, and animals feeding on material at different stages of decay are expected to have behavioural and nutritional adaptations.Instituto Gulbenkian de Ciência.info:eu-repo/semantics/publishedVersio