bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revision of Oligocene ‘Paraphiomys’ and an origin for crown Thryonomyoidea (Rodentia: Hystricognathi: Phiomorpha) near the Oligocene–Miocene boundary in Africa
Authors: Sallam Hesham M , Seiffert Erik R 
Published: October 2019

Abstract‘Paraphiomys’ simonsi is a phiomorph rodent from the early Oligocene of Egypt (~29–30 Mya) that has historically been aligned with much younger (&lt; ~20 Mya) Miocene species of the genera Paraphiomys and Neosciuromys. Here, we use Bayesian tip-dating analysis of a 109-character morphological matrix containing 57 living and extinct ctenohystricans to test these proposed placements for ‘Paraphiomys’ simonsi. Our analyses provide support for the exclusion of ‘Paraphiomys’ simonsi from both Paraphiomys and Neosciuromys and justify the establishment of a new genus (Monamys gen. nov.) for this stem thryonomyoid. These analyses also indicate that the divergence of the extant dassie rat Petromus from the extant cane rat Thryonomys (i.e. origin of crown Thryonomyoidea) occurred ~23.7 Mya, close to the Oligocene–Miocene boundary and in close agreement with recent molecular estimates for this split. Miocene Neosciuromys, Paraulacodus, Protohummus and the type species of Paraphiomys are identified as stem thryonomyids, whereas the Namibian species Apodecter stromeri, Tufamys woodi, ‘Paraphiomys’ australis and ‘Paraphiomys’ roessneri are identified for the first time as stem petromurids, raising the possibility of a long period of endemic petromurid evolution in south-west Africa. Comparison of molecular divergence estimates with our optimal tip-dated topology suggests that stem bathyergoids are most likely to have arisen from late Eocene and early Oligocene ‘phiomyids’.
Three-dimensional Structural Interrelations between Cells, Extracellular Matrix and Mineral in Vertebrate Mineralization
Authors: Zou Zhaoyong , Tang Tengteng , Macías-Sánchez Elena , Sviben Sanja , Landis William J. , Bertinetti Luca , Fratzl Peter 
Published: October 2019

AbstractThe spatial-temporal relationship between cells, extracellular matrices and mineral deposits is fundamental for an improved understanding mineralization mechanisms in vertebrate tissues. By utilizing focused ion beam-scanning electron microscopy with serial surface imaging, normally mineralizing avian tendons have been studied with nanometer resolution in three dimensions with volumes exceeding tens of microns in range. These parameters are necessary to yield fine ultrastructural details while encompassing tissue domains sufficient to provide a comprehensive overview of the interrelationships between the tissue structural constituents. Investigation reveals a novel complex cellular network in highly mineralized tendon aspects, where ∼100 nm diameter canaliculi emanating from cell (tenocyte) lacunae surround extracellular collagen fibril bundles. Canaliculi are linked to smaller channels of ∼40 nm diameter, occupying spaces between fibrils. Close to the tendon mineralization front, calcium-rich globules appear between the fibrils and, with time, mineral propagates along and within collagen. These close associations between tenocytes, canaliculi, small channels, collagen and mineral suggest a new concept for the mineralization process, where ions and/or mineral precursors may be transported through spaces between fibrils before they crystallize along the surface of and within the fibrils.Significance StatementThe basic mechanism by which vertebrate collagenous tissues are mineralized is still not fully elucidated, despite the importance of this process for skeletal formation and regeneration. Through three-dimensional imaging of the cellular network together with the extracellular matrix and mineral deposits, the present work investigates normally mineralizing avian leg tendon as a model system for vertebrates in general. The data support a mechanism where mineral ions and possible mineral precursors are initially present in interfibrillar collagen spaces and are subsequently translocated to neighboring collagen fibrils. Mineral particles then nucleate in association with collagen to form the well known collagen-mineral composite material of the skeleton.
Positioning Personal Polygenic Risk score against the population background
Authors: Leonenko Ganna , Baker Emily , Schmidt Karl Michael , Escott-Price Valentina ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

AbstractThe polygenic risk scores (PRS) approach has been widely used across different traits for estimating polygenic risk, pleiotropy and disease prediction, but mostly in European populations. The predictive ability of the PRS in non-European populations is currently limited due to the lack of genetic research performed in populations of non-European ancestry. One of the main challenges of the practical use of PRS is to place an individual’s personal score in the context of the PRS distribution in the underlying population. In this paper we present an approach for estimating the parameters of the PRS distribution in a population using summary information from public data.Unstandardized PRS are usually not directly comparable even between European studies. Our approach can be used for standardisation whilst accounting for genotyping platforms, data quality and ancestry. It can be applied to assessing polygenic disease risk for individuals from a European population for any complex genetic disorder and, assuming that most of the disease risk loci are likely to be shared between populations, to estimating the disease risk for individuals from other populations. We demonstrate the precision of our method with simulations. We show the utility of our estimates in application to Alzheimer’s disease in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. We present population specific PRSs for different populations using 1000 Genomes data.
Test-time augmentation for deep learning-based cell segmentation on microscopy images
Authors: Moshkov Nikita , Mathe Botond , Kertesz-Farkas Attila , Hollandi Reka , Horvath Peter 
Published: October 2019

AbstractRecent advancements in deep learning have revolutionized the way microscopy images of cells are processed. Deep learning network architectures have a large number of parameters, thus, in order to reach high accuracy, they require massive amount of annotated data. A common way of improving accuracy builds on the artificial increase of the training set by using different augmentation techniques. A less common way relies on test-time augmentation (TTA) which yields transformed versions of the image for prediction and the results are merged. In this paper we describe incorporating the test-time argumentation prediction method into two major segmentation approaches used in the single-cell analysis of microscopy images, namely semantic segmentation using U-Net and instance segmentation using Mask R-CNN models. Our findings show that even using only simple test-time augmentations, such as rotation or flipping and proper merging methods, will result in significant improvement of prediction accuracy. We utilized images of tissue and cell cultures from the Data Science Bowl (DSB) 2018 nuclei segmentation competition and other sources. Additionally, boosting the highest-scoring method of the DSB with TTA, we could further improve and our method has reached an ever-best score at the DSB.
Improving cell distribution on 3D additive manufactured scaffolds through engineered seeding media density and viscosity
Authors: Cámara-Torres M. , Sinha R. , Mota C. , Moroni L. 
Published: October 2019

AbstractIn order to ensure the long-termin vitroandin vivofunctionality of cell-seeded 3D scaffolds, an effective and reliable method to control cell seeding efficiency and distribution is crucial. Static seeding on 3D additive manufactured scaffolds made of synthetic polymers still remains challenging, as it often results in poor cell attachment, high cell sedimentation and non-uniform cell distribution, due to gravity and to the intrinsic macroporosity and surface chemical properties of the scaffolds. In this study, the bio-inert macromolecules dextran and Ficoll were used for the first time as temporary supplements to alter the viscosity and density of the seeding media, respectively, and improve the static seeding output. The addition of these macromolecules drastically reduced the cell sedimentation velocities, allowing for homogeneous cell attachment to the scaffold filaments. Both dextran- and Ficoll-based seeding methods supported human mesenchymal stromal cells viability and osteogenic differentiation post-seeding. Interestingly, the improved cell distribution led to increased matrix production and mineralization compared to scaffolds seeded by conventional static method. These results suggest a simple and universal method for an efficient seeding of 3D additive manufactured scaffolds, independent of their material and geometrical properties, and applicable for bone and various other tissue regeneration.
What would it take to describe the global diversity of parasites?
Authors: Carlson Colin J. , Dallas Tad A. , Alexander Laura W. , Phelan Alexandra L. , Phillips Anna J. 
Published: October 2019

AbstractHow many parasites are there on Earth? Here, we use helminth parasites to high-light how little is known about parasite diversity, and how insufficient our current approach will be to describe the full scope of life on Earth. Using the largest database of host-parasite associations and one of the world’s largest parasite collections, we estimate a global total of roughly 100,000 to 350,000 species of helminth endoparasites of vertebrates, of which 85% to 95% are unknown to science. The parasites of amphibians and reptiles remain the most poorly described, but the majority of undescribed species are likely parasites of birds and bony fish. Missing species are disproportionately likely to be smaller parasites of smaller hosts in undersampled countries. At current rates, it would take centuries to comprehensively sample, collect, and name vertebrate helminths. While some have suggested that macroecology can work around existing data limitations, we argue that patterns described from a small, biased sample of diversity aren’t necessarily reliable, especially as host-parasite networks are increasingly altered by global change. In the spirit of moon-shots like the Human Genome Project and the Global Virome Project, we consider the idea of a Global Parasite Project: a global effort to transform parasitology and inventory parasite diversity at an unprecedented pace.
Single-cell sequencing of mouse thymocytes reveals mutational landscape shaped by replication errors, mismatch repair and H3K36me3
Authors: Aska Elli-Mari , Dermadi Bebek Denis , Kauppi Liisa 
Published: October 2019

ABSTRACTBackgroundDNA mismatch repair (MMR) safeguards genome stability by correcting errors made during DNA replication.In vitroevidence indicates that the MMR machinery is recruited to chromatin via H3K36me3, a histone mark enriched in 3’ exons of genes and associated with transcriptional activity. To dissect how replication errors, abundance of H3K36me3 and MMR together shape the mutational landscape in normal mammalian cells, we applied single-cell exome sequencing to thymic T cells isolated from MMR-proficient (Mlh1+/+) and MMR-deficient (Mlh1−/−) mice.ResultsUsing single-cell exome sequencing we identified short deletions as sensitive and quantifiable reporters of MMR-dependent mutations. We found H3K36me3-enrichedHuwe1andMcm7genes to be mutational hotspots exclusive toMlh1−/−T cells. InMlh1+/+cells, exons of H3K36me3-enriched genes had a lower mutation frequency compared to H3K36me3-depleted genes. Moreover, within transcriptionally active genes, 3’ exons, often H3K36me3-enriched, rather than 5’ exons had significantly fewer MMR-dependent mutations, indicating that MMR operates more efficiently within 3’ exons inMlh1+/+T cells.ConclusionsOur results provide evidence that H3K36me3 confers preferential MMR-mediated protection from transcription-associated deleterious replication errors. This offers an attractive concept of thrifty MMR targeting, where genes critical for the development of given cell type are preferentially shielded fromde novomutations by H3K36me3-guided MMR.
Pleiotropy of Bcl-2 family proteins is an ancient trait in the metazoan evolution
Authors: Popgeorgiev Nikolay , Jabbour Lea , Nguyen Trang Thi Minh , Ralchev Nikola , Gadet Rudy , Manon Stéphen , Osigus Hans-Jürgen , Schierwater Bernd , Rimokh Ruth , Gillet Germain 
Published: October 2019

ABSTRACTIn the animal kingdom, proteins of the Bcl-2 family are widely recognized as regulators of mitochondrial outer membrane permeabilization (MOMP), leading to apoptotic cell death. These proteins were recently also shown to control IP3-dependent calcium fluxes at the level of the endoplasmic reticulum (ER). However, the origin and evolution of these pleiotropic functions remain elusive. Here, we molecularly characterized the four members of the Bcl-2 family (trBcl-2L1 to -2L4) in the most primitive metazoan, namely Trichoplax adhaerens. Primary structure and phylogenetic analyses demonstrated that all four trBcl-2 homologs belong to the multidomain Bcl-2 group and presented a conserved C-terminus transmembrane (TM) domain. TrBcl-2L1 and trBcl-2L2 are highly divergent proteins clustering with the anti-apoptotic Bcl-2 members, whereas trBcl-2L3 and trBcl-2L4 were homologous to the pro-apoptotic Bax (trBax) and Bak (trBak). Interestingly, at the functional level, trBak operates as a BH3 only sensitizer repressing the anti-apoptotic activities of trBcl-2L1 and trBcl-2L2, whereas trBax leads to MOMP, similarly to the well-known indirect model of Bax activation. Finally, we found that trBcl-2L1 had a dual ER and mitochondrial subcellular localization and was able to bind to IP3R. By generating two TM domain mutants we demonstrated that trBcl-2L1 targeted to the ER was able to control IP3-dependent calcium fluxes, whereas Mito-trBcl-2L1 represses trBax-dependent MOMP, suggesting that Bcl-2 pleiotropy appeared early and was conserved throughout metazoan evolution.
Interaction between myricetin aggregates and lipase under simplified intestinal conditions
Authors: Bustos Atma-Sol , Håkansson Andreas , Linares-Pastén Javier A. , Nilsson Lars 
Published: October 2019

AbstractMyricetin, a flavonoid found in the plant kingdom, has previously been identified as a food molecule with beneficial effects against obesity. This property has been related with its potential to inhibit lipase, the enzyme responsible of fat digestion. In this study we investigate the interaction between myricetin and lipase under simplified intestinal conditions from a colloidal point of view. The results show that myricetin form aggregates in aqueous medium and under simplified intestinal condition, where it was found that lipase is in its monomeric form. Although lipase inhibition by myricetin at a molecular level has been reported previously, the results of this study suggest that myricetin aggregates inhibit lipase by a sequestering mechanism as well. The size of these aggregates was determined to be in the range of a few nm to >200 nm.
Vibriopore-forming leukocidin activates pyroptotic cell death via the NLRP3 inflammasome
Authors: Baram Noam , Cohen Hadar , Edry-Botzer Liat , Salomon Dor , Gerlic Motti 
Published: October 2019

ABSTRACTCell death mechanisms are central to combat infectious microbes and to drive pathological inflammation. One such mechanism, the inflammasome, controls infection through either activation of caspase-1 and the subsequent secretion of the mature pro-inflammatory cytokine, interleukin 1β (IL-1β), or by stopping the dissemination of intracellular pathogens by inducing pyroptotic cell death in infected cells. Hemolysins, which are pore-forming toxins (PFTs), target the host cell plasma membrane by producing pores with different diameters. These pores alter the permeability of the target membrane, often leading to cell death. We previously discovered a functional and potent pore-forming, leukocidin domain-containing hemolysin produced by the Gram-negative marine bacteriumVibrio proteolyticus(V. proteolyticus), termed VPRH. Although leukocidin domains are found in other known PFTs, VPRH constitutes a distinct, understudied class within the leukocidin superfamily. Since PTFs of other pathogens were shown to induce cell death by activating the inflammasome pathway, we hypothesized that VPRH-induced cell death is mediated by direct activation of the inflammasome in mammalian immune host cells. Indeed, we found that VPRH induced a two-step cell death in primary macrophages. The first, a rapid step, was mediated by activating the NLRP3 inflammasome, leading to caspase-1 activation and GSDMD cleavage that resulted in IL-1β secretion and pyroptotic cell death. The second step was independent of the inflammasome; however, its mechanism remains unknown. This study sets the foundation for better understanding the immunological consequences of inflammasome activation by a new leukocidin class of toxins.
Quantile normalization of single-cell RNA-seq read counts without unique molecular identifiers
Authors: Townes F. William , Irizarry Rafael A. 
Published: October 2019

AbstractSingle-cell RNA-seq (scRNA-seq) profiles gene expression of individual cells. Unique molecular identifiers (UMIs) remove duplicates in read counts resulting from polymerase chain reaction, a major source of noise. For scRNA-seq data lacking UMIs, we propose quasi-UMIs: quantile normalization of read counts to a compound Poisson distribution empirically derived from UMI datasets. When applied to ground-truth datasets having both reads and UMIs, quasi-UMI normalization has higher accuracy than alternatives such as census counts. Using quasi-UMIs enables methods designed specifically for UMI data to be applied to non-UMI scRNA-seq datasets.
Developmental variability drives mouse molar evolution along an evolutionary line of least resistance
Authors: Hayden Luke , Lochovska Katerina , Sémon Marie , Renaud Sabrina , Delignette-Muller Marie-Laure , Vilcot Maurine , Peterkova Renata , Hovorakova Maria , Pantalacci Sophie 
Published: October 2019

AbstractDevelopmental systems may preferentially produce certain types of variation and, thereby, bias phenotypic evolution. This is a central issue in evolutionary developmental biology, albeit somewhat understudied. Here we focus on the shape of the first upper molar which shows a clear, repeated tendency for anterior elongation at different scales from within mouse populations to between species of the Mus genus. In contrast, the lower molar displays more evolutionary stability. We compared upper and lower molar development of mouse strains representative of this fine variation (DUHi: elongated molars and FVB: short molars). Using a novel quantitative approach to examine small-scale developmental variation, we identified temporal, spatial and functional differences in tooth signaling centers between the two strains, likely due to different tuning of the activation-inhibition mechanisms ruling signaling center patterning. Based on the spatio-temporal dynamics of signaling centers and their lineage tracing, we show an intrinsic difference in the fate of signaling centers between lower and upper jaw of both strains. This can explain why variations in activation-inhibition parameters between strains are turned into anterior elongation in the upper molar only. Finally, although the “elongated” DUHi strain was inbred, first molar elongation was variable in adults, and we found high levels of intra-strain developmental variation in upper molar development. This is consistent with the inherent developmental instability of the upper molar system enabling the morphological variability of the tooth phenotype.In conclusion, we have uncovered developmental properties that underlie the molar’s capacity for repeated phenotypic change, or said differently, that underlie a “line of least resistance”. By focusing on the developmental basis of fine phenotypic variation, our study also challenges some common assumptions and practices in developmental and evolutionary developmental biology.
Predicting FinTech innovation adoption in South Africa: the case of cryptocurrency
Authors: Mazambani Last , Mutambara Emmanuel 
Published: October 2019

PurposeFinancial technology innovation within the developed world is driving financial markets, yet its adoption is lagging among consumers in emerging markets. At the same time, most African economies continue to be at the tail end of global financial innovations adoption. Given lagging consumer adoption of cryptocurrency in South Africa, the purpose of this paper is to apply the theory of planned behaviour (TPB) to predict behavioural intention to adopt cryptocurrency.Design/methodology/approachA survey instrument based on the TPB was used to collect quantitative data for predicting adoption from adult distance students at the Mancosa, Cape Town campus. For data analysis, the two-step structural equation modelling approach was used.FindingsThe findings indicate that attitude and perceived behavioural control positively impact the intention to adopt cryptocurrency. Subjective norm showed a negative non-significant influence. Overall, the results of the study show that the model has a good model fit and can be used to explain the theory.Research limitations/implicationsThe results of this study may not be generalisable to the wider population as it is only based on a cross-sectional study of a sample of adult students at a single institute in South Africa.Originality/valueThe contribution of this paper is threefold: it is one of a few studies on the behavioural intention to adopt cryptocurrency in South Africa using the TPB model, it contributes towards the use of predictive behavioural economics models in understanding consumer behaviour critical to accelerating the adoption of financial innovations, and the results of the study also inform behaviour change strategies that can be applied by practitioners or policymakers to improve adoption. Studies of this nature may lead to the development of financial innovation in emerging markets through a nuanced understanding of consumer behaviour.
Enabling supply chain agility through process integration and supply flexibility
Authors: Irfan Muhammad , Wang Mingzheng , Akhtar Naeem 
Published: October 2019

Purpose
The purpose of this paper is to emphasize the underlying mechanism through which firms can achieve supply chain agility and augment business performance from the vendor’s perspective.

Design/methodology/approach
Drawing on dynamic capability view and contingency theory, the study conceptualizes a moderated mediation model to investigate the underlying influence of process integration (PI), supply flexibility and product-related complexity on supply chain agility and the subsequent effect of supply chain agility on firm’s business performance. Survey data from a sample of 148 firms, in the garment manufacturing industry, in Pakistan were analyzed using partial least square methods.

Findings
The results revealed that supply flexibility (i.e. volume and mix) mediates the effect of PI on supply chain agility. Supply chain agility, in turn, influences a firm’s business performance. Furthermore, the competence‒capability framework is not consistent across the varying degrees of product complexity such as product complexity hinders the effect of supply flexibility on supply chain agility, whereas it amplifies the impact of PI on supply chain agility. The conditional indirect effects suggest that the indirect effect of PI on supply chain agility through supply flexibility becomes stronger when product complexity is high.

Originality/value
The study is novel in the context of an emerging economy to educate fashion vendors to tune their competencies and capabilities to regain the market share in the global market place.