bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in local adaptation: what can we learn from reciprocal transplant experiments?
Authors: Svensson Erik I. , Goedert Debora , Gómez-Llano Miguel A. , Spagopoulou Foteini , Nava-Bolaños Angela , Booksmythe Isobel 
Published: August 2018

Local adaptation is of fundamental interest to evolutionary biologists. Traditionally, local adaptation has been studied using reciprocal transplant experiments to quantify fitness differences between residents and immigrants in pairwise transplants between study populations. Previous studies have detected local adaptation in some cases, but others have shown lack of adaptation or even maladaptation. Recently, the importance of different fitness components, such as survival and fecundity, to local adaptation have been emphasized. Here, we address another neglected aspect in studies of local adaptation: sex differences. Given the ubiquity of sexual dimorphism in life histories and phenotypic traits, this neglect is surprising, but may be partly explained by differences in research traditions and terminology in the fields of local adaptation and sexual selection. Studies that investigate differences in mating success between resident and immigrants across populations tend to be framed in terms of reproductive and behavioural isolation, rather than local adaptation. We briefly review the published literature that bridges these areas and suggest that reciprocal transplant experiments could benefit from quantifying both male and female fitness components. Such a more integrative research approach could clarify the role of sex differences in the evolution of local adaptations.
This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences'.
The geography of sex: sexual conflict, environmental gradients and local loss of sex in facultatively parthenogenetic animals
Authors: Burke Nathan W. , Bonduriansky Russell 
Published: August 2018

Obligately asexual organisms tend to occur at higher altitudes or latitudes and occupy larger ranges than their obligately sexual relatives—a phenomenon called geographical parthenogenesis. Some facultatively parthenogenetic organisms that reproduce both sexually and asexually also exhibit spatial variation in reproductive mode. Theory suggests that sexual conflict and mate limitation can determine the relative frequency of sex in facultative parthenogens, but the effect of these dynamics on spatial distributions is unknown. Here, we use individual-based models to investigate whether these dynamics can generate local differences in the reproductive mode in a facultatively parthenogenetic metapopulation occupying an environmental gradient. We find that selection for resistance and high fecundity creates positive epistasis in virgin females between a mutant allele for parthenogenesis and alleles for resistance, resulting in female-biased sex ratios and higher resistance and coercion towards the productive ‘core’ of the metapopulation. However, steeper environmental gradients, which lead to lower density and less mating at the ‘edge’, generate female bias without promoting coercion or resistance. Our analysis shows that local adaptation of facultatively parthenogenetic populations subject to sexual conflict and productivity gradients can generate striking spatial variation suggesting new patterns for empirical investigation. These findings could also help to explain the rarity of facultative parthenogenesis in animals.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences'.
Abandoning the ship using sex, dispersal or dormancy: multiple escape routes from challenging conditions
Authors: Gerber Nina , Kokko Hanna 
Published: August 2018

Natural populations often experience environments that vary across space and over time, leading to spatio-temporal variation of the fitness of a genotype. If local conditions are poor, organisms can disperse in space (physical movement) or time (dormancy, diapause). Facultatively sexual organisms can switch between asexual and sexual reproduction, and thus have a third option available to deal with maladaptedness: they can engage in sexual reproduction in unfavourable conditions (an ‘abandon-ship’ response). Sexual reproduction in facultatively sexual organisms is often coupled with dispersal and/or dormancy, while bet-hedging theory at first sight predicts sex, dispersal and dormancy to covary negatively, as they represent different escape mechanisms that could substitute for each other. Here we briefly review the observed links between sex, dormancy and dispersal, and model the expected covariation patterns of dispersal, dormancy and the reproductive mode in the context of local adaptation to spatio-temporally fluctuating environments. The correlations between sex, dormancy and dispersal evolve differently within species versus across species. Various risk-spreading strategies are not completely interchangeable, as each has dynamic consequences that can feed back into the profitability of others. Our results shed light on the discrepancy between previous theoretical predictions on covarying risk-spreading traits and help explain why sex often associates with other means of escaping unfavourable situations.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences’.
Evolution of female choice under intralocus sexual conflict and genotype-by-environment interactions
Authors: Li Xiang-Yi , Holman Luke 
Published: August 2018

In many species, females are hypothesized to obtain ‘good genes’ for their offspring by mating with males in good condition. However, female preferences might deplete genetic variance and make choice redundant. Additionally, high-condition males sometimes produce low-fitness offspring, for example because of environmental turnover and gene-by-environment interactions (GEIs) for fitness, or because fit males carry sexually antagonistic alleles causing them to produce unfit daughters. Here, we extend previous theory by investigating the evolution of female mate choice in a spatially explicit evolutionary simulation implementing both GEIs and intralocus sexual conflict (IASC), under sex-specific hard or soft selection. We show that IASC can weaken female preferences for high-condition males or even cause a preference for males in low condition, depending on the relative benefits of producing well-adapted sons versus daughters, which in turn depends on the relative hardness of selection on males and females. We discuss the relevance of our results to conservation genetics and empirical evolutionary biology.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences’.
On the role of sex differences for evolution in heterogeneous and changing fitness landscapes: insights from pygmy grasshoppers
Authors: Forsman Anders 
Published: August 2018

Much research has been devoted to study evolution of local adaptations by natural selection, and to explore the roles of neutral processes and developmental plasticity for patterns of diversity among individuals, populations and species. Some aspects, such as evolution of adaptive variation in phenotypic traits in stable environments, and the role of plasticity in predictable changing environments, are well understood. Other aspects, such as the role of sex differences for evolution in spatially heterogeneous and temporally changing environments and dynamic fitness landscapes, remain elusive. An increased understanding of evolution requires that sex differences in development, physiology, morphology, life-history and behaviours are more broadly considered. Studies of selection should take into consideration that the relationships linking phenotypes to fitness may vary not only according to environmental conditions but also differ between males and females. Such opposing selection, sex-by-environment interaction effects of selection and sex-specific developmental plasticity can have consequences for population differentiation, local adaptations and for the dynamics of polymorphisms. Integrating sex differences in analytical frameworks and population comparisons can therefore illuminate neglected evolutionary drivers and reconcile unexpected patterns. Here, I illustrate these issues using empirical examples from over 20 years of research on colour polymorphicTetrix subulataandTetrix undulatapygmy grasshoppers, and summarize findings from observational field studies, manipulation experiments, common garden breeding experiments and population genetics studies.This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences’.
Modeling motor neuron resilience in ALS using stem cells
Authors: Allodi Ilary , Nijssen Jik , Benitez Julio Aguila , Schweingruber Christoph , Fuchs Andrea , Bonvicini Gillian , Cao Ming , Kiehn Ole , Hedlund Eva 
Published: August 2018

SUMMARYOculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeledin vitro. Towards this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of Phox2a in neuronal progenitors. We demonstrate, using electrophysiology, immunocytochemistry and RNA sequencing, thatin vitrogenerated neurons arebona fideoculomotor neurons based on their cellular properties and similarity to theirin vivocounterpart in rodent and man. We also show thatin vitrogenerated oculomotor neurons display a robust activation of survival-promoting Akt signaling and are more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. Thus, we can generatebona fideoculomotor neuronsin vitrowhich display a resilience similar to that seenin vivo.
α2-adrenergic signaling disrupts β cell BDNF-TrkB receptor tyrosine kinase signaling
Authors: Kalwat Michael A. , Huang Zhimin , Binns Derk D. , McGlynn Kathleen , Cobb Melanie H. 
Published: August 2018

AbstractAdrenergic signaling is a well-known input into pancreatic islet function. Specifically, the insulin-secreting islet β cell expresses the Gi/o-linked α2-adrenergic receptor, which upon activation suppresses insulin secretion. The use of adrenergic agonist epinephrine at micromolar doses may have supraphysiological effects. We found that pretreating β cells with micromolar concentrations of epinephrine differentially inhibited activation of receptor tyrosine kinases. We chose TrkB as an example because of its relative sensitivity to the effects of epinephrine and due to its potential regulatory role in the β cell. Our characterization of brain-derived neurotrophic factor (BDNF)-TrkB signaling in MIN6 β cells showed that TrkB is activated by BDNF as expected, leading to canonical TrkB autophosphorylation and subsequent downstream signaling, as well as chronic effects on β cell growth. Micromolar, but not nanomolar, concentrations of epinephrine blocked BDNF-induced TrkB autophosphorylation and downstream mitogen-activated protein kinase pathway activation, suggesting an inhibitory phenomenon at the receptor level. We determined epinephrine-mediated inhibition of TrkB activation to be Gi/o-dependent using pertussis toxin, arguing against an off-target effect of high dose epinephrine. Published data suggested that inhibition of potassium channels or phosphoinositide-3-kinase signaling may abrogate the negative effects of epinephrine, however these did not rescue TrkB signaling in our experiments. Taken together, these results show that 1) TrkB kinase signaling occurs in β cells and 2) use of epinephrine in studies of insulin secretion requires careful consideration of concentration-dependent effects. BDNF-TrkB signaling in β cells may underlie pro-survival or growth signaling and warrants further study.
Human pancreatic islet 3D chromatin architecture provides insights into the genetics of type 2 diabetes
Authors: Miguel-Escalada Irene , Bonàs-Guarch Silvia , Cebola Inês , Joan Ponsa-Cobas , Mendieta-Esteban Julen , Rolando Delphine M.Y. , Javierre Biola M. , Atla Goutham , Farabella Irene , Morgan Claire C. , García-Hurtado Javier , Beucher Anthony , Morán Ignasi , Pasquali Lorenzo , Ramos Mireia , Appel Emil V.R. , Linneberg Allan , Gjesing Anette P. , Witte Daniel R. , Pedersen Oluf , Grarup Niels , Ravassard Philippe , Torrents David , Mercader Josep Maria , Piemonti Lorenzo , Berney Thierry , Koning de Eelco J.P. , Kerr-Conte Julie , Pattou François , Fedko Iryna O. , Prokopenko Inga , Hansen Torben , Marti-Renom Marc A. , Fraser Peter , Ferrer Jorge 
Published: August 2018

AbstractGenetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer regions (enhancer clusters, stretch enhancers or super-enhancers). So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in 3D-space. Furthermore, their target genes are generally unknown. We have now created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers with their target genes, often located hundreds of kilobases away. It further revealed sets of islet enhancers, super-enhancers and active promoters that form 3D higher-order hubs, some of which show coordinated glucose-dependent activity. Hub genetic variants impact the heritability of insulin secretion, and help identify individuals in whom genetic variation of islet function is important for T2D. Human islet 3D chromatin architecture thus provides a framework for interpretation of T2D GWAS signals.
Pirfenidone attenuates lung fibrotic fibroblast-mediated fibrotic responses to transforming growth factor-β1
Authors: Jin Jin , Togo Shinsaku , Kadoya Kotaro , Tulafu Miniwan , Namba Yukiko , Iwai Moe , Watanabe Junko , Nagahama Kumi , Okabe Takahiro , Hidayat Moulid , Kodama Yuzo , Kitamura Hideya , Ogura Takashi , Kitamura Norikazu , Ikeo Kazuho , Sasaki Shinichi , Tominaga Shigeru , Takahashi Kazuhisa 
Published: August 2018

AbstractPirfenidone, an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis (IPF), functions by inhibiting myofibroblast differentiation, which is involved in transforming growth factor (TGF)-β1-induced IPF pathogenesis. However, unlike normal lung fibroblasts, the relationship between pirfenidone responses of TGF-β1-induced human fibrotic lung fibroblasts and lung fibrosis is unknown. Here, we investigated the effect of pirfenidone on the functions of two new targets, collagen triple helix repeat containing protein 1 (CTHRC1) and four-and-a-half LIM domain protein 2 (FHL2), which included fibroblast activity, collagen gel contraction, and migration toward fibronectin. Compared to control lung fibroblasts, pirfenidone restored TGF-β1-stimulated fibroblast-mediated collagen gel contraction, migration, and CTHRC1 release in lung fibrotic fibroblasts. Furthermore, pirfenidone attenuated TGF-β1- and CTHRC1-induced fibroblast activity, bone morphogenic protein-4/Gremlin1 upregulation, and α-smooth muscle actin, fibronectin, and FHL2 downregulation, similar to that observed post-CTHRC1 inhibition. In contrast, FHL2 inhibition suppressed migration and fibronectin expression but did not downregulate CTHRC1. Overall, pirfenidone suppressed fibrotic fibroblast-mediated fibrotic processes via inverse regulation of CTHRC1-induced lung fibroblast activity. Thus, CTHRC1 can be used for predicting pirfenidone response and developing new therapeutic target for lung fibrosis.Summary statementPirfenidone suppressed TGF-β1-mediated fibrotic processes in fibrotic lung fibroblasts by attenuating CTHRC1 expression, suggesting that CTHRC1 may be a novel therapeutic target for treating patients with lung fibrosis.
Quantifying local malignant adaptation in tissue-specific evolutionary trajectories by harnessing cancer’s repeatability at the genetic level
Authors: Tokutomi N , Moyret-Lalle C , Puisieux A , Sugano S , Martinez P 
Published: August 2018

AbstractCancer is a potentially lethal disease, in which patients with nearly identical genetic backgrounds can develop a similar pathology through distinct combinations of genetic alterations. We aimed to reconstruct the evolutionary process underlying tumour initiation, using the combination of convergence and discrepancies observed across 2,742 cancer genomes from 9 tumour types. We developed a framework using the repeatability of cancer development to score the local malignant adaptation (LMA) of genetic clones, as their potential to malignantly progress and invade their environment of origin. Using this framework, we found that pre-malignant skin and colorectal lesions appeared specifically adapted to their local environment, yet insufficiently for full cancerous transformation. We found that metastatic clones were more adapted to the site of origin than to the invaded tissue, suggesting that genetics may be more important for local progression than for the invasion of distant organs. In addition, we used network analyses to investigate evolutionary properties at the system-level, highlighting that different dynamics of malignant progression can be modelled by such a framework in tumour-type-specific fashion. We find that occurrence-based methods can be used to specifically recapitulate the process of cancer initiation and progression, as well as to evaluate the adaptation of genetic clones to given environments. The repeatability observed in the evolution of most tumour types could therefore be harnessed to better predict the trajectories likely to be taken by tumours and pre-neoplastic lesions in the future.
Cyclodextrin triggers MCOLN1-dependent endo-lysosome secretion in Niemann-Pick type C cells
Authors: Vacca Fabrizio , Vossio Stefania , Mercier Vincent , Moreau Dimitri , Johnson Shem , Montoya Jonathan Paz , Moniatte Marc , Gruenberg Jean 
Published: August 2018

ABSTRACTIn specialized cell types, lysosome-related organelles support regulated secretory pathways, while in non-specialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptionally and promote clearance in lysosome storage diseases. In addition, evidence is also accumulating that low concentrations of cyclodextrins reduce the cholesterol storage phenotype in cells and animals with the cholesterol storage disease Niemann-Pick type C, via an unknown mechanism. Here, we report that cyclodextrin triggers the secretion of the endo/lysosomal content in non-specialized cells, and that this mechanism is responsible for the decreased cholesterol overload in Niemann-Pick type C cells. We also find that that the secretion of the endo/lysosome content occurs via a mechanism dependent on the endosomal calcium channel MCOLN1, as well as FYCO1, the AP1 adaptor and its partner Gadkin. We conclude that endolysosomes in non-specialized cells can acquire secretory functions elicited by cyclodextrin, and that this pathway is responsible for the decrease in cholesterol storage in Niemann-Pick C cells.
Centromere repositioning induced by inner kinetochore impairment generates a meiosis barrier
Authors: Lu Min , He Xiangwei 
Published: August 2018

AbstractCentromeres dictate the sites for kinetochore assembly on chromosomes, while their own position on each chromosome is determined epigenetically by a specific histone H3 variant CENP-A. For all eukaryotic species, the chromosomal position of each centromere is distinct and inherited with high fidelity, although the mechanisms underlying the epigenetic stability and its functional significance remain largely unknown. Here in the fission yeast Schizosaccharomyces pombe, we show that mutations in inner kinetochore components influence centromeric chromatin organization to various levels. In extreme cases, a single deletion of wip1, mhf1 and mhf2 (the conserved CENP-T-W-S-X complex subunits) or double deletions of cnp3 (a homologue of mammalian CENP-C) and fta6 (a pombe specific component) induce centromere repositioning - inactivation of the original centromere and formation of a neocentromere - in one of the three chromosomes at random. Neocentromeres tend to locate in pericentromeric heterochromatin regions, although heterochromatin is not required for centromere inactivation. Cells carrying a neocentromere are competent in mitosis and in meiosis of homozygotes. However, when these cells are crossed to cells carrying the original centromere, the progeny suffers severe lethality due to defects in meiotic chromosome segregation. These results recapitulate a meiosis barrier that could initiate genetic divergence between two populations with mismatched centromeres, documenting a potential role of the Evolutionary New Centromeres (ENCs) in speciation.Significance StatementIn eukaryotes, centromeres are chromosomal regions where kinetochores are assembled and the positions of centromeres are accurately inherited. While the centromere and kinetochore assembly are extensively studied, the mechanisms that each centromere maintain its identity on chromosomes are still not well understood. In this study, we demonstrated that the inner kinetochore is required for the normal centromere identity as single depletion of the inner kinetochore CENP-T-W-S-X complex or double deletions of cnp3/CENP-C and fta6 induce centromere repositioning. We further showed cells carrying a neocentromere are reproductively isolated from the wildtype population carrying the original centromere. Taken together, these results suggest that induced centromere repositioning mimics the evolutionary new centromeres and is sufficient to cause reproductive isolation.
Antimicrobial, Antioxidant and Anti-Inflammatory Activities of Proteins of Phaseoulus lunatus (Fabaceae) Baby Lima Beans Produced in Ecuador
Authors: Tamayo J. , Poveda T. , Paredes M. , Vásquez G. , Calero-Cáceres W. 
Published: August 2018

ABSTRACTPhaseoulus lunatus L., a variety of baby lima bean, which is produced in the coastal region of Ecuador, is a profitable crop of that country. Various cultivars of this common bean are considered a sources for nutraceutical compounds, such as bioactive peptides. To assess the potential biologic activities of protein isolates and hydrolysates of P. lunatus baby lima beans, this study evaluates the proteins antimicrobial, antioxidant and anti-inflammatory activities. Antioxidant activity was measured by the TBARS method. In-vitro anti-inflammatory activity was measured by the inhibition of denatured protein as well as a diffusion method, according with CLSI guidelines by antimicrobial activity. Both fractions (isolate and hydrolysates) showed anti-inflammatory and antioxidant activity. However, protein hydrolysates (pH 5) had a better performance than protein isolates. The same effect was observed in antimicrobial activity, when protein hydrolysates had a broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria. These preliminary studies suggest that P. lunatus baby lima beans could have a considerable biological activity for nutraceutical applications.