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Nakamura, G.

Publications and source records attributed to Nakamura, G..

8 recordsLinked to original sources

Combined antagonism of Oncostatin M (OSM) and Interleukin 6 (IL-6) provides both anti-fibrotic and anti-inflammatory benefit in pulmonary fibrosis

Interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated ILD (SSc-ILD), are irreversible fibrosing diseases with a mean survival time of less than 5 years for IPF. Poorly understood etiology and complex pathogenesis of these diseases have hampered the identification and development of effective therapeutics. Existing treatments can slow progressive fibrosis and lung function decline but do not stop it entirely, resulting in a minimal impact on patient survival. Thus, novel therapeutic interventions are needed. Tocilizumab, an anti-IL-6 receptor antibody, was recently approved by FDA for the treatment of SSc-ILD based on evidence demonstrating a reduction in the rate of lung function decline. In this study, we have characterized an IL-6-driven feed-forward myeloid axis contributing to lung inflammation providing a mechanistic hypothesis for tocilizumab. Concomitantly we have identified an oncostatin M (OSM) orchestrated lung injury response contributing to epithelial and endothelial cell disruption, myofibroblast activation and fibrosis. Despite dysregulated expression of IL11 in IPF, SSc-ILD, and murine models of fibrosis, we found no evidence for a pro-fibrotic role for IL-11 in vitro or in vivo. Instead, in pre-clinical models of IPF we demonstrate that antagonism of OSM alone, or to a greater degree in combination with IL-6, reduced lung fibrosis and inflammation. Translating these observations, we validated gp130:OSMR, rather than gp130:LIFR, as the dominant human receptor complex used by OSM, identifying OSMR as a potential therapeutic target to stall fibrosis.

immunology↗

There and Back to the Present: An Evolutionary Tale on Biological Diversity

Ecologists often agree on the importance of macroevolution for niche-mediated distribution of biological diversity along environmental gradients. Yet, macroevolutionary diversification and dispersal in time and space generate uneven geographic distribution of phylogenetic pools, which affects the imprint let by macroevolution on local species pools. In this article we introduce an individual-based simulation approach coupled to Approximate Bayesian Computation (ABC) that allows to parameterize the adaptation rate of species niche positions along the evolution of a monophyletic lineage, and the intensity of dispersal limitation, associated with the distribution of biological diversity between assemblages potentially connected by dispersal (metacommunity). The analytical tool was implemented in an R package called mcfly. We evaluated the statistical performance of the analytical framework using simulated datasets, which confirmed the suitability of the analysis to estimate adaptation rate and dispersal limitation parameters. Further, we evaluated the role played by niche evolution and dispersal limitation on species diversity distribution of Phyllostomidae bats across the Neotropics. The framework proposed here shed light on the links between niche evolution, dispersal limitation and the distribution of biological diversity, and thereby improved our understanding of evolutionary imprints on ecological patterns. Perhaps more importantly, it offers new possibilities for solving the eco-evolutionary puzzle.

ecology↗

The Hidden Side Of Diversity: Effects Of Imperfect Detection On Multiple Dimensions Of Biodiversity

O_LIStudies on ecological communities often address patterns of species distribution and abundance, but few consider uncertainty in counts of both species and individuals when computing diversity measures. C_LIO_LIWe evaluated the extent to which imperfect detection may influence patterns of taxonomic, functional, and phylogenetic diversity in ecological communities. C_LIO_LIWe estimated the true abundance of fruit-feeding butterflies sampled in canopy and understory strata in a subtropical forest. We compared the diversity values calculated by observed and estimated abundance data through the hidden diversity framework. This framework evaluates the deviation of observed diversity when compared with diversities derived from estimated true abundances, and if such deviation represents a bias or a noise in the observed diversity pattern. C_LIO_LIThe hidden diversity values differed between strata for all diversity measures, except for functional richness. The taxonomic measure was the only one where we observed an inversion of the most diverse stratum when imperfect detection was included. Regarding phylogenetic and functional measures, the strata showed distinct responses to imperfect detection, despite the tendency to overestimate observed diversity. While the understory showed noise for the phylogenetic measure, since the observed pattern was maintained, the canopy had biased diversity for the functional metric. This bias occurred since no significant differences were found between strata for observed diversity, but rather for estimated diversity, with the canopy being more clustered. C_LIO_LIWe demonstrate that ignore imperfect detection may lead to unrealistic estimates of diversity and hence, to erroneous interpretations of patterns and processes that structure biological communities. For fruit-feeding butterflies, according to their phylogenetic position or functional traits, the undetected individuals triggered different responses in the relationship of the diversity measures to the environmental factor. This highlights the importance to evaluate and include the uncertainty in species detectability before calculating biodiversity measures to describe communities. C_LI

ecology↗

FishPhyloMaker: An R package to generate phylogenies for ray-finned fishes

Phylogenies summarize evolutionary information that is essential in the investigation of ecological and evolutionary causes of diversity patterns. They allow investigating hypotheses from trait evolution to the relationship between evolutionary diversity and ecosystem functioning. However, obtaining a comprehensive phylogenetic hypothesis can be difficult for some groups, especially those with a high number of species, that is the case for fishes, particularly tropical ones. The lack of species in phylogenetic hypotheses, called Darwinian shortfalls, can hinder ecological and evolutionary studies involving this group. To tackle this problem, we developed FishPhyloMaker, an R package that facilitates the generation of phylogenetic trees through a reliable and reproducible procedure, even for a large number of species. The package adopts well-known rules of insertion based on cladistic hierarchy, allowing its use by specialists and non-specialists in fish systematics. We tested the reliability of our algorithm in maintaining important properties of phylogenetic distances running a sensitivity analysis. We also exemplified the use of the FishPhyloMaker package by constructing complete phylogenies for fishes inhabiting the four richest freshwater ecoregions of the world. Furthermore, we proposed a new method to calculate Darwinian shortfalls and mapped this information for the major freshwater drainages of the world. FishPhyloMaker will expand the range of evolutionary and ecological questions that can be addressed using ray-finned fishes as study models, mainly in the field of community phylogenetics, by providing an easy and reliable way to obtain comprehensive phylogenies. Further, FishPhyloMaker presents the potential to be extended to other taxonomic groups that suffer from the same difficulty in the obtention of comprehensive phylogenetic hypothesis. HighlightsO_LIWe provide the first automated procedure to check species names, construct phylogenetic trees and calculate Darwinian shortfalls for ray-finned fishes (Actinopterygii) by the R package FishPhyloMaker. C_LIO_LIThis package provides functions to assemble phylogenies through a fast, reliable, and reproducible method, allowing its use and replicability by specialists and non-specialists in fish systematics. C_LIO_LIThe package also provides an interactive procedure that gives more flexibility to the user when compared with other existing tools that construct phylogenetic trees for other highly speciose groups. C_LIO_LIThe package includes a new method to compute Darwinian shortfalls for ray-finned fishes, but the rationale of the provided algorithm can be extended in future studies to be used in other groups of organisms C_LI

evolutionary biology↗

naturaList: a package to classify occurrence records in levels of confidence in species identification

O_LIThere is a big volume of occurrence records available in biodiversity databases, but researchers should guarantee its quality before use it in scientific studies. A problem that might compromise the quality of occurrence data is species misidentification. We address this issue by presenting naturaList, a R package designed to classify species occurrence data according to identification reliability. C_LIO_LInaturaList allows to classify species occurrences up to six levels of confidence in species identification, and to filter occurrence data accordingly. The highest level of confidence is assigned to records identified by a specialist, whose name must be provided by the user. The other five levels of confidence are derived from the occurrence data. We demonstrate naturaList functions using occurrences of Alsophila setosa, a tree fern species from Atlantic Forest, as example. We classified and filtered data in grid cells in order to maintain only the highest-level records in each cell. Then we selected only those records classified in the two highest levels of confidence. C_LIO_LIFrom 323 occurrences of Alsophila setosa displaying geographic coordinates, 69 (21%) were identified by a specialist. After filtering the highest-level records inside grid cells, 102 records remained. From these grid cell filtered data, 38 occurrences (37%) were classified into the highest confidence level. Three records were removed using an interactive map module, due to falling in sea sites or outside the native range size of the species. Since we selected only records classified in the two highest levels of confidence, the final dataset contained 94 occurrence records. C_LIO_LInaturaList guarantees the reproducibility of occurrence data processing and cleaning. Macroecologists, biogeographers and taxonomists might benefit from using naturaList package to evaluate the quality of species identification in occurrence data and by identify sites that need evaluation of taxonomic classification of species. C_LI

ecology↗

2MV/cm Pulsed Electric Fields Promote Transthyretin Amyloid Disintegration

Exposing transthyretin amyloid to 1000 sub-nanosecond 2 MV/cm pulsed electric fields (PEFs) promotes both amyloid disassembly and amyloid-derived transthyretin disintegration. The process produced no change in pH, and the resulting temperature increase was less than 1 {degrees}C. We conclude that PEFs physical effects facilitate amyloid disassembly, rather than thermal or chemical effects, and provoke amyloid-derived transthyretin disintegration, the latter of which is reported here for the first time.

biophysics↗

A multifaceted approach to analyzing taxonomic, functional and phylogenetic β-diversity

Ecological literature offers a myriad of methods for quantifying {beta}-diversity. One such methods is determining BDtotal (BD), which, unlike other methods, can be decomposed into meaningful components that indicate how unique a community is regarding its composition (local contribution) and how unique a species is regarding its occurrence in the metacommunity (species contribution). Despite this advantage, the original formulation of the BD metric only assesses taxonomic variation and neglects other important dimensions of biodiversity. We expanded the original formulation of BD to capture variation in the functional and phylogenetic dimensions of a metacommunity by computing two new metrics -- BDFun and BDPhy -- as well as their respective components that represent the local and species contribution. We tested the statistical performance of these new metrics for capturing variation in functional and phylogenetic composition through simulated metacommunities and illustrated the potential use of these new metrics by analyzing {beta}-diversity of stream fish communities. Our results demonstrated that BDPhy and BDFun have acceptable type I error and great power to detect the effect of deep evolutionary relationships and attributes mediating patterns of {beta}-diversity. The empirical example illustrates how BDPhy and BDFun reveal complementary aspects of {beta}-diversity relative to the original BD metric. These new metrics can be used to identify local communities that are of conservation importance because they represent unique functional, phylogenetic and taxonomic compositions. We conclude that BDPhy and BDFun are important tools for providing complementary information in the investigation of the structure of metacommunities.

ecology↗

The dimensionality of biological diversity revisited.

Biodiversity can be represented by a variety of different dimensions (e.g. functional diversity, phylogenetic diversity, genetic diversity and taxonomic diversity). While the many different representations of biodiversity can lead to a more complete description of communities, they also lead to a degree of fragmentation of the biodiversity concept. Developing a unified measure that integrates all the dimensions of biodiversity is a theoretical solution for this problem, however, it remains an operationally utopian task. Alternatively, quantifying the dimensionality of biodiversity is a way to integrate the different dimensions of biological diversity. This concept is explored in the present study. We define the dimensionality of diversity as the number of different diversity metrics needed to effectively describe biodiversity. We provide a solution that joins the two components of dimensionality (correlation and the variation of each diversity metric) in the same framework, allowing us to quantify dimensionality. We show, through a simulation study, that considering the correlation among dimensions with the variation of each dimension offers important information that is neglected when only correlation information (the component used in the current methodology to measure dimensionality) is considered. We demonstrate how to apply the proposed framework by investigating the dimensionality of South American small mammal communities (cricetids and marsupials). Our example demonstrates that the taxonomic dimension of diversity captures most of the spatial variation among these communities. We conclude by highlighting the greater understanding of dimensionality that is obtained through this method, as well as the insights it provides into the importance of each diversity metric to the whole biodiversity space, insights which can not be obtained through the current common method.

ecology↗