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In search of the Goldilocks zone for hybrid speciation
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.The supplementary materials can also be accessed through the following link: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007613#sec021Hybridization has recently gained considerable interest both as a unique opportunity for observing speciation mechanisms and as a potential engine for speciation. The latter remains a controversial topic. It was recently hypothesized that the reciprocal sorting of genetic incompatibilities from parental species could result in hybrid speciation, when the hybrid population maintains a mixed combination of the parental incompatibilities that prevents further gene exchange with both parental populations. However, the specifics of the purging/sorting process of multiple incompatibilities have not been examined theoretically. We here investigate the allele-frequency dynamics of an isolated hybrid population that results from a single hybridization event. Using models of two or four loci, we investigate the fate of one or two genetic incompatibilities of the Dobzhansky-Muller type (DMIs). We study how various parameters affect both the sorting/purging of the DMIs and the probability of observing hybrid speciation by reciprocal sorting. We find that the probability of hybrid speciation is strongly dependent on the linkage architecture (i.e. the order and recombination rate between loci along chromosomes), the population size of the hybrid population, and the initial relative contributions of the parental populations to the hybrid population. We identify a Goldilocks zone for specific linkage architectures and intermediate recombination rates, in which hybrid speciation becomes highly probable. Whereas an equal contribution of parental populations to the hybrid population maximizes the hybrid speciation probability in the Goldilocks zone, other linkage architectures yield unintuitive asymmetric maxima. We provide an explanation for this pattern, and discuss our results both with respect to the best conditions for observing hybrid speciation in nature and their implications regarding patterns of introgression in hybrid zones.This research was supported by the Fundação Calouste Gulbenkian. 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
Conflict between heterozygote advantage and hybrid incompatibility in haplodiploids (and sex chromosomes)
Full text linkThe deposited article version is a post-print and is the "Accepted Author Manuscript" provided by Wiley and posted online on 12th January 2018.This publication hasn't any creative commons license associated.This deposit is composed by the main article plus the supplementary materials of the publication.In many diploid species the sex chromosomes play a special role in mediating reproductive isolation. In haplodiploids, where females are diploid and males haploid, the whole genome behaves similarly to the X/Z chromosomes of diploids. Therefore, haplodiploid systems can serve as a model for the role of sex chromosomes in speciation and hybridization. A previously described population of Finnish Formica wood ants displays genome-wide signs of ploidally and sexually antagonistic selection resulting from hybridization. Here, hybrid females have increased survivorship but hybrid males are inviable. To understand how the unusual hybrid population may be maintained, we developed a mathematical model with hybrid incompatibility, female heterozygote advantage, recombination, and assortative mating. The rugged fitness landscape resulting from the co-occurrence of heterozygote advantage and hybrid incompatibility results in a sexual conflict in haplodiploids, which is caused by the ploidy difference. Thus, whereas heterozygote advantage always promotes long-term polymorphism in diploids, we find various outcomes in haplodiploids in which the population stabilizes either in favor of males, females, or via maximizing the number of introgressed individuals. We discuss these outcomes with respect to the potential long-term fate of the Finnish wood ant population, and provide approximations for the extension of the model to multiple incompatibilities. Moreover, we highlight the general implications of our results for speciation and hybridization in haplodiploids versus diploids, and how the described fitness relationships could contribute to the outstanding role of sex chromosomes as hotspots of sexual antagonism and genes involved in speciation. This article is protected by copyright. All rights reserved.Fundação Calouste Gulbenkian; National Science Foundation grant: (NSF PHY-1125915); Human Frontier Science Program; Finnish Cultural Foundation; Academy of Finland grant: (252411).info:eu-repo/semantics/acceptedVersio
Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance
No full textThis deposit is composed by a publication in which the IGC' 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 could only be accessed by two ways: either by requesting a legal copy to the author (the email contact present in this deposit) or by visiting the following link: http://www.jimmunol.org/content/200/1/101.long#ack-1This publication hasn't any creative commons license associated.It has been shown that dominant tolerance, namely in transplantation, requires Foxp3+regulatory T cells. Although most tolerance-inducing regimens rely on regulatory T cells, we found that induction of tolerance to proteins in aluminum hydroxide can be achieved in Foxp3-deficient mice using nondepleting anti-CD4 Abs. This type of tolerance is Ag specific, and tolerant mice retain immune competence to respond to unrelated Ags. We demonstrated with chicken OVA-specific TCR-transgenic mice that the same tolerizing protocol (CD4 blockade) and the same target Ag (OVA) achieves Foxp3-dependent transplantation tolerance to OVA-expressing skin grafts, but Foxp3-independent tolerance when the Ag is provided as OVA-aluminum hydroxide. In the latter case, we found that tolerance induction triggered recessive mechanisms leading to elimination of effector cells and, simultaneously, a dominant mechanism associated with the emergence of an anergic and regulatory CTLA-4+IL-2lowFoxp3-T cell population, where the tolerance state is IL-10 dependent. Such Foxp3-independent mechanisms can improve the efficacy of tolerance-inducing protocols.Fundacao para a Ciencia e Tecnologia grant: (HMSP-ICT/0034/2013); FEDER through POR Lisboa 2020–Programa Operacional Regional de Lisboa grant: (LISBOA-01-0145-FEDER-007391).info:eu-repo/semantics/publishedVersio
Author Correction: Human Sexual Cycles are Driven by Culture and Match Collective Moods
Full text linkThis deposit is composed simultaneously by the original published article and also by the "correction" for the published article (erratum).This deposit is composed by the main article plus the supplementary materials of the publication.The link for the original article: https://www.nature.com/articles/s41598-017-18262-5A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.Human reproduction does not happen uniformly throughout the year and what drives human sexual cycles is a long-standing question. The literature is mixed with respect to whether biological or cultural factors best explain these cycles. The biological hypothesis proposes that human reproductive cycles are an adaptation to the seasonal (hemisphere-dependent) cycles, while the cultural hypothesis proposes that conception dates vary mostly due to cultural factors, such as holidays. However, for many countries, common records used to investigate these hypotheses are incomplete or unavailable, biasing existing analysis towards Northern Hemisphere Christian countries. Here we show that interest in sex peaks sharply online during major cultural and religious celebrations, regardless of hemisphere location. This online interest, when shifted by nine months, corresponds to documented human births, even after adjusting for numerous factors such as language and amount of free time due to holidays. We further show that mood, measured independently on Twitter, contains distinct collective emotions associated with those cultural celebrations. Our results provide converging evidence that the cyclic sexual and reproductive behavior of human populations is mostly driven by culture and that this interest in sex is associated with specific emotions, characteristic of major cultural and religious celebrations.National Institutes of Health grant: (01LM011945-01); Fundação para a Ciência e a Tecnologia grant: (PTDC IVC ESCT 5337 2012); Welcome DFRH WIIA 60 2011; Marie Curie Actions; Defense Advanced Research Projects Agency (DARPA) - NGS2 program grant: (#D17AC00005); Economic Development Agency grant: (ED17HDQ3120040); NSF Award grant: (IIS-0811994).info:eu-repo/semantics/publishedVersio
Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage and Mirrors Severe Shifts in Kupffer Cells
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.Dipeptidyl peptidase-4 (DPP-4 or clusters of differentiation [CD]26) is a multifunctional molecule with established roles in metabolism. Pharmacologic inhibition of DPP-4 is widely used to improve glycemic control through regulation of the incretin effect. Colaterally, CD26/DPP-4 inhibition appears to be beneficial in many inflammatory conditions, namely in delaying progression of liver pathology. Nevertheless, the exact implications of CD26/DPP-4 enzymatic activity in liver dysfunction remain unclear. In this work, we investigated the involvement of CD26/DPP-4 in experimental mouse models of induced hepatocyte damage that severely impact Kupffer cell (KC) populations. Liver dysfunction was evaluated in CD26 knockout (KO) and B6 wild-type mice during acute liver damage induced by acetaminophen, chronic liver damage induced by carbon tetrachloride, and KC-depleting treatment with clodronate-loaded liposomes. We found that necrosis resolution after hepatotoxic injury was delayed in CD26KO mice and in B6 mice treated with the CD26/DPP-4 inhibitor sitagliptin, suggesting that DPP-4 enzymatic activity plays a role in recovering from acute liver damage. Interestingly, the severe KC population reduction in acute and chronic liver injury was concomitant with increased CD26/DPP-4 serum levels. Remarkably, both chronic liver damage and noninflammatory depletion of KCs by clodronate liposomes were marked by oscillation in CD26/DPP-4 serum activity that mirrored the kinetics of liver KC depletion/recovery. Conclusion:CD26/DPP-4 enzymatic activity contributes to necrosis resolution during recovery from acute liver injury. Serum CD26/DPP-4 is elevated when severe perturbations are imposed on KC populations, regardless of patent liver damage. We propose that serum CD26/DPP-4 is a potential systemic surrogate marker of severe impairments in the KC population imposed by clinical and subclinical liver conditions.FundingSupported by the Fundação para a Ciência e Tecnologia (grant no. PTDC/BIM‐MET/0486/2012), iNOVA4Health (UID/Multi/04462/2013), the European Commission Marie Skłodowska‐Curie Actions H2020 (grant agreements no. 722619 and no. 734719), the Sociedade Portuguesa de Diabetologia Bolsa Charneco da Costa 2017, and a Fundação para a Ciência e Tecnologia fellowship no. PD/BD/105997/2014 to I.C.info:eu-repo/semantics/publishedVersio
PLK4 is a microtubule-associated protein that self assembles promoting de novo MTOC formation
Full text linkThe deposited article version is the Epub Ahead of Print version of the article (the "Accepted Manuscript"), posted online 20th September 2018, provided by Company of Biologists. It has peer-review.The deposited article version contains attached the supplementary materials within the pdf.The centrosome is an important microtubule-organizing centre (MTOC) in animal cells. It consists of two barrel-shaped structures, the centrioles, surrounded by the pericentriolar material (PCM), which nucleates microtubules. Centrosomes can form close to an existing structure (canonical duplication) or de novo How centrosomes form de novo is not known. The master driver of centrosome biogenesis, PLK4, is critical to recruit several centriole components. Here, we investigate the beginning of centrosome biogenesis, taking advantage of Xenopus egg extracts, where PLK4 can induce de novo MTOC formation (Eckerdt et al., 2011; Zitouni et al., 2016). Surprisingly, we observe that in vitro, PLK4 can self-assemble into condensates that recruit α/β-tubulin. In Xenopus extracts, PLK4 assemblies additionally recruit PLK4's substrate, STIL, and the microtubule nucleator, γ-tubulin, forming acentriolar MTOCs de novo The assembly of these robust microtubule asters is independent of dynein, similarly to centrosomes. We suggest a new mechanism of action for PLK4, where it forms a self-organizing catalytic scaffold that recruits centriole components, PCM factors and α/β-tubulin, leading to MTOC formation.We are thankful to Anna Akhmanova, Raquel Oliveira and Jeffrey B.Woodruff for reading and discussing the manuscript. We are also thankful to Catarina Nabais for the GFP control construct and Vladimir Joukov for the Xenopus Cep192 antibody. S.M.G was funded by an EMBO Long term fellowship ALTF 1088-2009, a Marie curie Intra-European fellowship (#253373) and a FCT postdoctoral fellowship. The collaboration with J.L. laboratory in the USA was supported by a The Company of Biologists travel grant. S.Z is funded by ERC grant ERC-COG-683258. Research in JL lab was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. M.B-D. Laboratory is supported by an ERC grant ERC-COG-683258 and FCT Investigator to MBD.info:eu-repo/semantics/acceptedVersio
Genetic analyses favour an ancient and natural origin of elephants on Borneo
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.The origin of the elephant on the island of Borneo remains elusive. Research has suggested two alternative hypotheses: the Bornean elephant stems either from a recent introduction in the 17th century or from an ancient colonization several hundreds of thousands years ago. Lack of elephant fossils has been interpreted as evidence for a very recent introduction, whereas mtDNA divergence from other Asian elephants has been argued to favor an ancient colonization. We investigated the demographic history of Bornean elephants using full-likelihood and approximate Bayesian computation analyses. Our results are at odds with both the recent and ancient colonization hypotheses, and favour a third intermediate scenario. We find that genetic data favour a scenario in which Bornean elephants experienced a bottleneck during the last glacial period, possibly as a consequence of the colonization of Borneo, and from which it has slowly recovered since. Altogether the data support a natural colonization of Bornean elephants at a time when large terrestrial mammals could colonise from the Sunda shelf when sea levels were much lower. Our results are important not only in understanding the unique history of the colonization of Borneo by elephants, but also for their long-term conservation.Fundação para a Ciência e a Tecnologia grants: (SFRH/BPD/64837/2009, PTDC/BIA-BDE/71299/2006); Laboratoire d’Excellence (LABEX) grant: (ANR -10-LABX-41); Laboratoire International Associé (BEEG-B); Darwin Initiative for the Survival of Species grant: (09/016); US Fish and Wildlife Service; Asian Elephant Conservation Fund; Elephant Family and Columbus Zoo; Danish Research Council (DFF-FNU); Villum Foundation Young Investigator grant; Leverhulme Trust grant: (F/00 212/AM).info:eu-repo/semantics/publishedVersio
Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation
Full text linkThis deposit is composed by the main article plus the supplementary materials of the publication.Centrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas. Moreover, we identify another recurrent feature of cancer cells: centriole size deregulation. Further experiments demonstrate that severe centriole over-elongation can promote amplification through both centriole fragmentation and ectopic procentriole formation. Furthermore, we show that overly long centrioles form over-active centrosomes that nucleate more microtubules, a known cause of invasiveness, and perturb chromosome segregation. Our screen establishes centriole amplification and size deregulation as recurrent features of cancer cells and identifies novel causes and consequences of those abnormalities.FCT- Harvard Medical School Program Portugal grant: (HMSP-CT/SAU-ICT/0075/2009); Fundação para a Ciência e a Tecnologia grants: (SFRH/BPD/98439/2013, SFRH/BPD/82420/2011, POCI-01-0145-FEDER-016390, PTDC/BIM-ONC/6858/2014); EMBO installation grant; ERC grant: (ERC-2010-StG-261344).info:eu-repo/semantics/publishedVersio
CANA: A python package for quantifying control and canalization in Boolean Networks
Full text linkThis deposit is composed by the main article. The supplementary materials can be accessed through the following link: github.com/rionbr/CANALogical models offer a simple but powerful means to understand the complex dynamics of biochemical regulation, without the need to estimate kinetic parameters. However, even simple automata components can lead to collective dynamics that are computationally intractable when aggregated into networks. In previous work we demonstrated that automata network models of biochemical regulation are highly canalizing, whereby many variable states and their groupings are redundant (Marques-Pita and Rocha, 2013). The precise charting and measurement of such canalization simplifies these models, making even very large networks amenable to analysis. Moreover, canalization plays an important role in the control, robustness, modularity and criticality of Boolean network dynamics, especially those used to model biochemical regulation (Gates and Rocha, 2016; Gates et al., 2016; Manicka, 2017). Here we describe a new publicly-available Python package that provides the necessary tools to extract, measure, and visualize canalizing redundancy present in Boolean network models. It extracts the pathways most effective in controlling dynamics in these
models, including their effective graph and dynamics canalizing map, as well as other tools to uncover minimum sets of control variables.RC was supported by CAPES Foundation grant 18668127, Instituto Gulbenkian de Ciência (IGC), and Indiana University Precision Health to Population Health (P2P) Study. LR was partially funded by the National Institutes of Health, National Library of Medicine Program, grant 01LM011945-01, by a Fulbright Commission fellowship, and by NSF-NRT grant 1735095, Interdisciplinary Training in Complex Networks and Systems. 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
Estimating Attractor Reachability in Asynchronous Logical Models
Full text linkThis deposit is composed by the main article. The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphys.2018.01161/full#supplementary-material.Logical models are well-suited to capture salient dynamical properties of regulatory networks. For networks controlling cell fate decisions, cell fates are associated with model attractors (stable states or cyclic attractors) whose identification and reachability properties are particularly relevant. While synchronous updates assume unlikely instantaneous or identical rates associated with component changes, the consideration of asynchronous updates is more realistic but, for large models, may hinder the analysis of the resulting non-deterministic concurrent dynamics. This complexity hampers the study of asymptotical behaviors, and most existing approaches suffer from efficiency bottlenecks, being generally unable to handle cyclical attractors and quantify attractor reachability. Here, we propose two algorithms providing probability estimates of attractor reachability in asynchronous dynamics. The first algorithm, named Firefront, exhaustively explores the state space from an initial state, and provides quasi-exact evaluations of the reachability probabilities of model attractors. The algorithm progresses in breadth, propagating the probabilities of each encountered state to its successors. Second, Avatar is an adapted Monte Carlo approach, better suited for models with large and intertwined transient and terminal cycles. Avatar iteratively explores the state space by randomly selecting trajectories and by using these random walks to estimate the likelihood of reaching an attractor. Unlike Monte Carlo simulations, Avatar is equipped to avoid getting trapped in transient cycles and to identify cyclic attractors. Firefront and Avatar are validated and compared to related methods, using as test cases logical models of synthetic and biological networks. Both algorithms are implemented as new functionalities of GINsim 3.0, a well-established software tool for logical modeling, providing executable GUI, Java API, and scripting facilities.This work was supported by Fundação para a Ciência e a Tecnologia (FCT, Portugal), grants PTDC/EIA-CCO/099229/2008, UID/CEC/50021/2013, IF/01333/2013, and PTDC/EEI-CTP/2914/2014.info:eu-repo/semantics/publishedVersio