bluuebunny/crossref_metadata_2025_split huggingface dataset:
VE-cadherin endocytosis controls vascular integrity and patterning during development
Authors: Grimsley-Myers Cynthia M. , Isaacson Robin H. , Cadwell Chantel M. , Campos Jazmin , Hernandes Marina S. , Myers Kenneth R. , Seo Tadahiko , Giang William , Griendling Kathy K. , Kowalczyk Andrew P. 
Published: September 2019

AbstractTissue morphogenesis requires dynamic intercellular contacts that are subsequently stabilized as tissues mature. The mechanisms governing these competing adhesive properties are not fully understood. Using gain- and loss-of-function approaches, we tested the role of p120-catenin (p120) and VE-cadherin (VE-cad) endocytosis in vascular development using mouse mutants that exhibit increased (VE-cadGGG/GGG) or decreased (VE-cadDEE/DEE) internalization. VE-cadGGG/GGGmutant mice exhibited reduced VE-cad-p120 binding, reduced VE-cad levels, microvascular hemorrhaging, and decreased survival. By contrast, VE-cadDEE/DEEmutants exhibited normal vascular permeability but displayed microvascular patterning defects. Interestingly, VE-cadDEE/DEEmutant mice did not require endothelial p120, demonstrating that p120 is dispensable in the context of a stabilized cadherin.In vitro, VE-cadDEE mutant cells displayed defects in polarization and cell migration that were rescued by uncoupling VE-cadDEE from actin. These results indicate that cadherin endocytosis coordinates cell polarity and migration cues through actin remodeling. Collectively, our results indicate that regulated cadherin endocytosis is essential for both dynamic cell movements and establishment of stable tissue architecture.Summary StatementThis study uses mouse genetic andin vitroapproaches to demonstrate that cadherin endocytosis is critical for the formation of blood vessels during development by promoting actin-dependent collective cell migration, whereas the inhibition of this endocytosis by p120 binding is essential for vessel stabilization.
Parasite transmission in aquatic ecosystems under climate change: joint effects of temperature, host behavior and elimination of parasite larvae by predators
Authors: Gopko M. , Mironova E. , Pasternak A. , Mikheev V. , Taskinen J. 
Published: September 2019

AbstractA moderate raise in temperature was suggested to enhance the impact of parasites on aquatic ecosystems. Under higher temperatures, poikilothermic animals (e.g. fish), increase their activity, which can result in a more frequent encounter with parasites. However, temperature increase may also trigger processes counteracting an increased risk of parasitic infections. For instance, removal of free-living stages of parasites by filter-feeding organisms can increase with temperature and potentially mitigate disease risk in ecosystems under climate change.In our study, we aimed to find out whether an increased infection transmission under higher temperatures can be, at least, partly compensated by the increased removal of parasitic larvae be aquatic predators. In addition, we planned to reveal the behavioral mechanism underlying the more successful transmission of the parasite at higher temperatures.We experimentally studied how temperature, the behavior of fish host (rainbow trout) and the presence of filter-feeding mussels in the environment influence transmission success of trematode larvae (Diplostomum pseudospathaceumcercariae) to fish host.We found that temperature raise increased, while presence of filter-feeding mussels in the environment decreased infection intensities in fish. However, the effect of mussel’s presence was constant within the tested range of water temperatures (15-23ºC), which suggests that it cannot compensate for the observed increased transmission of parasites under temperature raise. The difference in fish individual behavior (swimming activity) before the exposure to parasites was a substantial factor the affecting host’s vulnerability to infection. However, fish motor activity only weakly correlated with temperature, therefore, it is unlikely to be responsible for the increased infection success under warmer conditions. After exposure to parasites, fish strongly decreased their activity. This decrease was temperature-dependent and more pronounced in bolder (more active) fish, which leads to lower variability in activity of fish exposed to parasites compared with the safe environment. Post-exposure activity did not influence the infection intensity.In general, we showed that the elimination of trematode larvae by filter-feeders is unlikely to deter the potential effects of global warming on host-parasite interactions in temperate freshwater ecosystems.
Causal inference for the effect of environmental chemicals on chronic kidney disease
Authors: Zhao Jing , Hinton Paige , Ma Qin 
Published: September 2019

AbstractThere is evidence from a limited number of statistical and animal studies that suggest that perfluoroalkyl acids (PFAs) are linked to a decline in kidney function. Thus, PFA exposure may be a modifiable risk factor for chronic kidney disease (CKD). As PFA is pervasive throughout our environment, determining its health effects is an important public health concern. We examined cross-sectional data from the 2009-2010 cycle of NHANES using generalized propensity score (GPS) analysis and univariate and multivariate ordinary least squares (OLS) regression to determine the link between urinary PFA concentration and estimated glomerular filtration rate (eGFR). GPS estimation methods used were Hirano-Imbens, additive spline, and a generalized additive model. Each of the statistical models used associated an increase in PFA concentration with a decline in eGFR, though the eGFR fit using the multivariate regression model were consistently higher than from the other four models. We conclude that PFA is a modifiable risk factor for CKD and GPS analysis produces credible results in estimating the effect of chemical exposures on continuous measure of kidney functions such as eGFR.Graphical abstract
Do cooperatively breeding mammals live longer? A re-appraisal
Authors: Thorley Jack 
Published: September 2019

ABSTRACTRecent comparative studies have suggested that cooperative breeding is associated with increases in maximum lifespan among mammals, replicating a pattern also seen in birds and insects. In this study, I re-examine the case for increased lifespan in mammalian cooperative breeders by analysing a large dataset of maximum longevity records. Unlike one previous study, I found no consistent, strong evidence that cooperative breeders have longer lifespans than other mammals, after having controlled for variation in body mass, mode of life and data quality. The only exception to this general trend was displayed by the African mole-rats (the Bathyergid family): all members of this family are relatively long-lived, but the social, cooperatively breeding species appear to be much longer-lived than the solitary species, the latter having not been known to live beyond 11 years in captivity. However, solitary mole-rat species have rarely been kept in captivity or followed longitudinally in the wild, and so it seems likely that their maximum lifespan has been grossly underestimated when compared to the highly researched social species. As few other subterranean species have received much attention in a captive or wild setting, I also suggest that current data also makes it impossible to rule out a causal role of subterranean living on lifespan extension in mammals, and that any future studies wanting to test for such an association should wait until more high quality longevity data is available from a wider range of permanently subterranean species.
Remodeling of the H3 nucleosomal landscape during mouse aging
Authors: Chen Yilin , Bravo Juan I. , Benayoun Bérénice A. 
Published: September 2019

AbstractIn multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin: cellular chromatin states (i.e. the ‘epigenome’) can tune transcriptional profiles, and, in line with the prevalence of transcriptional alterations with aging, accumulating evidence suggests that the chromatin landscape is altered with aging across cell types and species. However, though alterations in the chromatin make-up of cells are considered to be a hallmark of aging, little is known of the genomic loci that are specifically affected by age-related chromatin state remodeling and of their biological significance. Here, we report the analysis of genome-wide profiles of core histone H3 occupancy in aging male mice tissues (i.e. heart, liver, cerebellum and olfactory bulb) and primary cultures of neural stem cells. We find that, although no drastic changes in H3 levels are observed, local changes in H3 occupancy occur with aging across tissues and cells with both regions of increased or decreased occupancy. These changes are compatible with a general increase in chromatin accessibility at pro-inflammatory genes and may thus mechanistically underlie known shift in gene expression programs with aging.
Characterization of OA development between sexes in the rat medial meniscal transection model
Authors: Pucha Krishna A. , McKinney Jay M. , Fuller Julia M. , Willett Nick J. 
Published: September 2019

AbstractObjectiveOsteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While there are clear sex differences in OA development in humans, most pre-clinical research has been conducted solely in male animals thus limiting the ability of these findings to be generalized to both sexes in the context of this disease. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical animal model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery.DesignA MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure.ResultsQuantitative analysis of the medial 1/3 articular cartilage via EPIC-μCT showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Additionally, both male and female animals in the MMT group had increased subchondral bone mineral density and larger total osteophyte volumes due to MMT.ConclusionThese data demonstrate that OA can be induced in both sexes using the rat MMT model. Moving forward, adding sex as a factor in preclinical OA studies should be standard practice in pre-clinical studies in order to elucidate more inclusive and translatable results into the clinic.
Mosquito species and age influence thermal performance of traits relevant to malaria transmission
Authors: Miazgowicz KL , Mordecai EA , Ryan SJ , Hall RJ , Owen J , Adanlawo T , Balaji K , Murdock CC 
Published: September 2019

AbstractModels predicting disease transmission are a vital tool in the control of mosquito populations and malaria reduction as they can target intervention efforts. We compared the performance of temperature-dependent transmission models when mosquito life history traits were allowed to change across the lifespan of Anopheles stephensi, the urban malaria mosquito, to models parameterized with commonly derived estimates of lifetime trait values. We conducted an experiment on adult female An. stephensi to generate daily per capita values for lifespan, egg production, and biting rate at six constant temperatures. Both temperature and age significantly affected trait values. Further, we found quantitative and qualitative differences between temperature-trait relationships estimated based on daily rates versus directly observed lifetime values. Incorporating these temperature-trait relationships into an expression governing transmission suitability, relative R0(T), model resulted in minor differences in the breadth of suitable temperatures for Plasmodium falciparum transmission between the two models constructed from only An. stephensi trait data, but a substantial increase in breadth compared to a previously published model consisting of trait data from multiple mosquito species. Overall this work highlights the importance of considering how mosquito trait values vary with mosquito age and mosquito species when generating temperature-based environmental suitability predictions of transmission.
Proteostasis and Energetics as Proteome Hallmarks of Aging and Influenza Challenge in Pulmonary Disease
Authors: Loguercio Salvatore , Hutt Darren M. , Campos Alexandre Rosa , Stoeger Thomas , Grant Rogan A. , McQuattie-Pimentel Alexandra C , Abdala-Valencia Hiam , Lu Ziyan , Joshi Nikita , Ridge Karen , Chandel Navdeep S , Sznajder Jacob I. , Morimoto Richard I , Misharin Alexander V. , Budinger G.R. Scott , Balch William E. 
Published: September 2019

AbstractAging is associated with an increased risk for the development of many diseases. This is exemplified by the increased incidence of lung injury, muscle dysfunction and cognitive impairment in the elderly following influenza infection. Because the infectious cycle of flu is dependent upon the properties of the host, we examined the proteome ofalveolarmacrophages (AM) and type 2 cells (AT2) obtained from young (3 months) and old (18 months) naïve mice and mice exposed to influenza A. Our proteomics data show that there is a maladaptive collapse of the proteostasis network (PN) and changes in mitochondrial pathways in the aged naïve AM and AT2 proteomes. The mitochondrial imbalance and proteostatic collapse seen in aged cells places an excessive folding burden on these cells, which is further exacerbated following exposure to influenza A. Specifically, we see an imbalance in Hsp70 co-chaperones involved in protein folding and Hsp90 co-chaperones important for stress signaling pathways that are essential for cellular protection during aging. The acute challenge of influenza A infection of young and aged AM and AT2 cells reveals that age-associated changes in the chaperome affect the ability of these cells to properly manage the infection and post-infection biology, contributing to cytotoxicity. We posit that proteomic profiling of individual cell type specific responses provides a high impact approach to pinpoint fundamental molecular relationships that may contribute to the susceptibility to aging and environmental stress, providing a platform to identify new targets for therapeutic intervention to improve resiliency in the elderly.
Evolutionary dynamics of the SKN-1 → MED → END-1,3 regulatory gene cascade inCaenorhabditisendoderm specification
Authors: Maduro Morris F. 
Published: September 2019

ABSTRACTGene regulatory networks (GRNs) with GATA factors are important in animal development, and evolution of such networks is an important problem in the field. In the nematode,Caenorhabditis elegans, the endoderm (gut) is generated from a single embryonic precursor, E. The gut is specified by an essential cascade of transcription factors in a GRN, with the maternal factor SKN-1 at the top, activating expression of the redundantmed-1,2divergent GATA factor genes, with the combination of all three contributing to activation of the paralogousend-3andend-1canonical GATA factor genes. In turn, these factors activate the GATA factors geneselt-2andelt-7to regulate intestinal fate. In this work, genome sequences from over two dozen species within theCaenorhabditisgenus are used to identify putative orthologous genes encoding the MED and END-1,3 factors. The predictions are validated by comparison of gene structure, protein conservation, and putativecis-regulatory sites. The results show that all three factors occur together, but only within the Elegans supergroup of related species. While all three factors share similar DNA-binding domains, the MED factors are the most diverse as a group and exhibit unexpectedly high gene amplifications, while the END-1 orthologs are highly conserved and share additional extended regions of conservation not found in the other GATA factors. The MEME algorithm identified both known and previously unrecognizedcis-regulatory motifs. The results suggest that all three genes originated at the base of the Elegans supergroup and became fixed as an essential embryonic gene regulatory network with several conserved features, although each of the three factors is under different evolutionary constraints. Based on the results, a model for the origin and evolution of the network is proposed. The set of identified MED, END-3 and END-1 factors form a robust set of factors defining an essential embryonic gene network that has been conserved for tens of millions of years, that will serve as a basis for future studies of GRN evolution.
Aggregatibacter actinomycetemcomitansLtxA hijacks endocytic trafficking pathways in human lymphocytes
Authors: Lally Edward T , Boesze-Battaglia Kathleen , Dhingra Anuradha , Gomez Nestor M , Mitchell Claire H , Giannakakis Alexander , Fahim Syed A , Benz Roland , Balashova Nataliya 
Published: September 2019

ABSTRACTLeukotoxin (LtxA) from oral pathogenAggregatibacter actinomycetemcomitansis a secreted membrane-damaging protein. LtxA is internalized by β2 integrin LFA-1 (CD11a/CD18) expressing leukocytes and ultimately causes cell death; however toxin localization in the host cell is poorly understood and these studies fill this void. We investigated LtxA trafficking using multi-fluor confocal imaging, flow cytometry and Rab5 knockdown in human T lymphocyte Jurkat cells. Planar lipid bilayers were used to characterize LtxA pore-forming activity at different pH. Our results demonstrate that LtxA/LFA-1 complex gains an access to the cytosol of Jurkat cells without evidence of plasma membrane damage utilizing dynamin-dependent and clathrin-independent mechanism. Upon internalization LtxA follows the LFA-1 endocytic trafficking pathways as identified by co-localization experiments with endosomal and lysosomal markers (Rab5, Rab11A, Rab7, and Lamp2) and CD11a. Knockdown of Rab5a resulted in loss of susceptibility of Jurkat cells to LtxA cytotoxicity suggesting that late events of LtxA endocytic trafficking are required for toxicity. The toxin trafficking via the degradation endocytic pathway may culminate in delivery of the protein to lysosomes or its accumulation in Rab11A-dependent recycling endosomes. The ability of LtxA to form pores at acidic pH may result in permeabilization of the endosomal and lysosomal membranes.
De Novo Protein Design for Novel Folds using Guided Conditional Wasserstein Generative Adversarial Networks (gcWGAN)
Authors: Karimi Mostafa , Zhu Shaowen , Cao Yue , Shen Yang 
Published: September 2019

AbstractMotivationFacing data quickly accumulating on protein sequence and structure, this study is addressing the following question: to what extent could current data alone reveal deep insights into the sequence-structure relationship, such that new sequences can be designed accordingly for novel structure folds?ResultsWe have developed novel deep generative models, constructed low-dimensional and generalizable representation of fold space, exploited sequence data with and without paired structures, and developed ultra-fast fold predictor as an oracle providing feedback. The resulting semi-supervised gcWGAN is assessed with the oracle over 100 novel folds not in the training set and found to generate more yields and cover 3.6 times more target folds compared to a competing data-driven method (cVAE). Assessed with structure predictor over representative novel folds (including one not even part of basis folds), gcWGAN designs are found to have comparable or better fold accuracy yet much more sequence diversity and novelty than cVAE. gcWGAN explores uncharted sequence space to design proteins by learning from current sequence-structure data. The ultra fast data-driven model can be a powerful addition to principle-driven design methods through generating seed designs or tailoring sequence space.AvailabilityData and source codes will be available upon request.Contactyshen@tamu.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Sex Lability and Dimorphism in Dioecious Palmer Amaranth (Amaranthus palmeri)
Authors: Mesgaran Mohsen B. , Matzrafi Maor , Ohadi Sara 
Published: September 2019

AbstractDioecious weeds (separate sexes) may benefit from a maximized outcrossing and optimal sex-specific resource allocation but there are costs associated with the evolution of this breeding system which can be exploited for long-term management of dioecious weeds. That is, seed production in dioecious species is contingent upon the co-occurrence and co-flowering of the two genders and can be further complicated by biases in sex ratio. We therefore explored the sex ratio and dimorphism in secondary sex characters in three populations of Palmer amaranth (Amaranthus palmeri) from California, Kansas and Texas and tested if water stress can change the sex expression and/or the synchrony of flowering (anthesis) between male and female plants. Sex ratio (proportion of males) was balanced and did not deviate from 1:1 in all experiments and populations (California, Kansas, Texas) when plants received normal watering. Male and female plants of A. palmeri did not differ in timing of emergence, plant height and relative growth rate. While the initiation of flowering (emergence of inflorescence) occurred earlier in males than females, females preceded males in timing of anthesis. Water stress delayed anthesis in males to a larger extent than females giving rise to an anthesis mismatch as large as seven days between the two sexes. Water stress induced a female sex expression in Kansas population giving rise to a female to male ratio of 1.78 which significantly differed from the equal 1:1 sex ratio. Our data provide the first evidence of sex lability and environment sex determination (ESD) in A. palmeri, suggesting manipulation of sex expression and phenological asynchrony as novel tools for ecological management of dioecious weeds.