bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hedgehog signalling regulates patterning of the murine and human dentitions through Gas1 co-receptor function
Authors: Seppala Maisa , Thivichon-Prince Beatrice , Xavier Guilherme M. , Shaffie Nina , Sangani Indiya , Birjandi Anahid A. , Rooney Joshua , Lau Jane N. S. , Dhalivar Rajveer , Rossi Ornella , Riaz Adeel , Stonehouse-Smith Daniel , Wang Yiran , Viriot Laurent , Cobourne Martyn T. 
Published: November 2020

ABSTRACTThe mammalian dentition exhibits wide numerical and morphological variation between different species. The regulation of dental pattern is achieved through complex reiterative molecular signalling interactions that occur through multiple stages of tooth development. We show that mice with loss-of-function in the Hedgehog co-receptor Gas1 have variation in size, morphology and number of teeth within the molar dentition. Specifically, premolar-like supernumerary teeth are present with high penetrance, arising through survival and continued development of vestigial tooth germs. We further demonstrate that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt signalling in vestigial tooth germs through facilitation of Shh signalling. Moreover, regulation of tooth number is independent of the additional Hedgehog co-receptors Cdon and Boc. Interestingly, further reduction of Shh pathway activity in aGas1mutant background leads to fusion of the molar field and ultimately, developmental arrest of tooth development rather than exacerbating the supernumerary phenotype. Finally, we demonstrate defective coronal morphology in the molar dentition of human subjects carryingGAS1missense mutations, suggesting that regulation of Hedgehog signalling through GAS1 is also essential for normal patterning of the human dentition.
Reciprocal social ties drive stability within a social network
Authors: Dakin Roslyn , Clunis Paisley , Cornthwaite Emily M. , Ryder T. Brandt 
Published: November 2020

ABSTRACTSocial reciprocity is thought to be the most important driver of cooperation among non-kin, but its effects within complex social networks where individuals choose their partners have not been studied. Here, we test whether reciprocation can explain social dynamics in a bird species where males form coalitions to court females, the wire-tailed manakin (Pipra filicauda). In our study population, approximately a third of male-male social interactions involve one male leaving his territory to interact and display with the owner of another territory; this directional behaviour provides benefits to the recipient at a cost to the visiting male. We characterize social ties among pairs of territory holders according to the directionality of their interactions, and show here that territory holding males engaged in far more reciprocated (bidirectional) partnerships with other territory holders than expected by chance. Reciprocated partnerships were also stronger (i.e., the partners interacted more frequently) than non-reciprocated partnerships, controlling for spatial proximity of the territories. An individual-level analysis revealed that a male’s social contribution to a given partner was predictive of the number of social interactions he received from that same partner. Finally, we show that reciprocation predicted the long-term stability of social partnerships one year later. Together, these results demonstrate that reciprocity is associated with stability in complex social networks where partner choice is flexible.LAY SUMMARYWhen animals are free to choose their partners, how does reciprocity influence social dynamics?In the wire-tailed manakin, males form coalitions with other males to help attract mates. We tracked male social networks and found that some males form reciprocal partnerships where each male leaves its territory to display at the other’s territory. These bidirectional partnerships are particularly strong and stable, indicating that reciprocity is associated with stability in complex social networks.
A Cell Atlas of Microbe-Responsive Processes in the Zebrafish Intestine
Authors: Willms Reegan J. , Jones Lena Ocampo , Hocking Jennifer C. , Foley Edan 
Published: November 2020

ABSTRACTGut microbial products direct growth, differentiation, and development in the animal host. Disruptions to host-microbe interactions have profound health consequences, that include onset of chronic inflammatory illnesses. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled transcriptional activity in individual cells from the intestine, and associated tissue, of zebrafish larvae that we raised in the presence or absence of a microbiome. We uncovered extensive cellular heterogeneity in the conventional zebrafish intestinal epithelium, including previously undescribed cell types with known mammalian homologs. By comparing conventional to germ-free profiles, we mapped microbial impacts on transcriptional activity in each cell population. We revealed intricate degrees of cellular specificity in host responses to the microbiome that included regulatory effects on patterning, metabolic and immune activity. For example, we showed that removal of microbes hindered pro-angiogenic signals in the developing vasculature, resulting in impaired intestinal vascularization. Our work provides a high-resolution atlas of intestinal cellular composition in the developing fish gut and details the effects of the microbiome on each cell type. Furthermore, we provide a web-based resource for single-cell gene expression visualization under conventional and germ-free conditions to facilitate exploration of this dataset.
Discordance between the predicted vs. the actually recognized CD8+ T cell epitopes of HCMV pp65 antigen and aleatory epitope dominance
Authors: Lehmann Alexander , Zhang Ting , Reche Pedro A , Lehmann Paul V. 
Published: November 2020

AbstractCD8+ T cell immune monitoring aims at measuring the numbers and functions of antigen-specific CD8+ T cell populations engaged during immune responses, providing insights into the magnitude and quality of cell-mediated immunity operational in a test subject. The selection of peptides forex vivoCD8+ T cell detection is critical, however, because for each restricting HLA class I molecule present in a human individual there is a multitude of potential epitopes within complex antigens, and HLA diversity between the test subjects predisposes CD8+ T cell responses to individualized epitope recognition profiles. We report here on a brute force CD8+ T cell epitope mapping approach for the human cytomegalovirus (HCMV) pp65 antigen on ten HLA-A*02:01-matched HCMV infected human subjects. In this approach, in each test subject, every possible CD8+ T cell epitope was systematically tested; that is 553 individual peptides that walk the sequence of the HCMV pp65 protein in steps of single amino acids. Highly individualized CD8+ T cell response profiles with aleatory epitope recognition patterns were observed. We compared the actually detected epitope utilization in each individual with epitope prediction ranking for the shared HLA-A*02:01 allele, and for additional HLA class I alleles expressed by each individual. No correlation was found between epitopes’ ranking on the prediction scale and their actual immune dominance. The data suggest that accurate CD8+ T cell immune monitoring might depend on the agnostic reliance on mega peptide pools, or brute force mapping, rather than individualized epitope predictions.
Genetic demultiplexing of pooled single-cell RNA-sequencing samples in cancer facilitates effective experimental design
Authors: Weber Lukas M. , Hippen Ariel A. , Hickey Peter F. , Berrett Kristofer C. , Gertz Jason , Doherty Jennifer Anne , Greene Casey S. , Hicks Stephanie C. 
Published: November 2020

AbstractBackgroundPooling cells from multiple biological samples prior to library preparation within the same single-cell RNA sequencing experiment provides several advantages, including lower library preparation costs and reduced unwanted technological variation, such as batch effects. Computational demultiplexing tools based on natural genetic variation between individuals provide a simple approach to demultiplex samples, which does not require complex additional experimental procedures. However, these tools have not been evaluated in cancer, where somatic variants, which could differ between cells from the same sample, may obscure the signal in natural genetic variation.ResultsHere, we performedin silicobenchmark evaluations by combining raw sequencing reads from multiple single-cell samples in high-grade serous ovarian cancer, which has a high copy number burden, and lung adenocarcinoma, which has a high tumor mutational burden. Our results confirm that genetic demultiplexing tools can be effectively deployed on cancer tissue using a pooled experimental design, although high proportions of ambient RNA from cell debris reduce performance.ConclusionsThis strategy provides significant cost savings through pooled library preparation. To facilitate similar analyses at the experimental design phase, we provide freely accessible code and a reproducible Snakemake workflow built around the best-performing tools found in ourin silicobenchmark evaluations, available athttps://github.com/lmweber/snp-dmx-cancer.
Genomic and phenotypic analysis of COVID-19-associated pulmonary aspergillosis isolates ofAspergillus fumigatus
Authors: Steenwyk Jacob L. , Mead Matthew E. , de Castro Patrícia Alves , Valero Clara , Damasio André , dos Santos Renato A. C. , Labella Abigail L. , Li Yuanning , Knowles Sonja L. , Raja Huzefa A. , Oberlies Nicholas H. , Zhou Xiaofan , Cornely Oliver A. , Fuchs Frieder , Koehler Philipp , Goldman Gustavo H. , Rokas Antonis 
Published: November 2020

AbstractThe ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) first described from Wuhan, China. A subset of COVID-19 patients has been reported to have acquired secondary infections by microbial pathogens, such as fungal opportunistic pathogens from the genusAspergillus. To gain insight into COVID-19 associated pulmonary aspergillosis (CAPA), we analyzed the genomes and characterized the phenotypic profiles of four CAPA isolates ofAspergillus fumigatusobtained from patients treated in the area of North Rhine-Westphalia, Germany. By examining the mutational spectrum of single nucleotide polymorphisms, insertion-deletion polymorphisms, and copy number variants among 206 genes known to modulateA. fumigatusvirulence, we found that CAPA isolate genomes do not exhibit major differences from the genome of the Af293 reference strain. By examining virulence in an invertebrate moth model, growth in the presence of osmotic, cell wall, and oxidative stressors, and the minimum inhibitory concentration of antifungal drugs, we found that CAPA isolates were generally, but not always, similar toA. fumigatusreference strains Af293 and CEA17. Notably, CAPA isolate D had more putative loss of function mutations in genes known to increase virulence when deleted (e.g., in theFLEAgene, which encodes a lectin recognized by macrophages). Moreover, CAPA isolate D was significantly more virulent than the other three CAPA isolates and theA. fumigatusreference strains tested. These findings expand our understanding of the genomic and phenotypic characteristics of isolates that cause CAPA.
Structurally distinct duplex telomere repeat-binding proteins inUstilago maydisexecute specialized, non-overlapping functions in telomere recombination and telomere protection
Authors: Yu Eun Young , Zahid Syed , Hsu Min , Sutherland Jeanette , Holloman William K. , Lue Neal F. 
Published: November 2020

AbstractDuplex telomere binding proteins exhibit considerable structural and functional diversity in different phyla. Herein we address the distinct properties and functions of two Myb-containing, duplex telomere repeat-binding factors inUstilago maydis, a basidiomycete fungus that is evolutionarily distant from the standard budding and fission yeasts. The two telomere-binding proteins inU. maydis, namedUmTrf1 andUmTrf2, have different domain organizations and belong to distinct protein families with different phylogenetic distributions. Despite these differences, they exhibit comparable affinities and similar sequence specificity for the canonical, 6-base-pair telomere repeats. Deletion oftrf1triggers preferential loss of long telomere tracts, suggesting a role for the encoded protein in promoting telomere replication. Trf1 loss also partially suppresses the ALT-like phenotypes ofku70-deficient mutants, suggesting a novel role for a telomere protein in stimulating ALT-related pathways. In keeping with these ideas, we found that purified Trf1 can modulate the helicase activity of Blm, a conserved telomere replication and recombination factor. In contrast,trf2appears to be essential and transcriptional repression of this gene leads to severe growth defects and profound telomere aberrations that encompass telomere length heterogeneity, accumulation of extrachromosomal telomere repeats such as C-circles, and high levels of single-stranded telomere DNA. These observations support a critical role forUmTrf2 in telomere protection. Together, our findings point to a unique, unprecedented division of labor between the two major duplex telomere repeat-binding factors inUstilago maydis. Comparative analysis ofUmTrf1 homologs in different phyla reveals a high degree of functional diversity for this protein family, and provides a case study for how a sequence-specific DNA binding protein can acquire and lose functions at different chromosomal locations.
Phylogenomics of scorpions reveal a co-diversification of scorpion mammalian predators and mammal-specific sodium channel toxins
Authors: Santibáñez-López Carlos E. , Aharon Shlomi , Ballesteros Jesús A. , Gainett Guilherme , Baker Caitlin M. , González-Santillán Edmundo , Harvey Mark S. , Hassan Mohamed K. , Abu-Almaaty Ali Hussin , Aldeyarbi Shorouk Mohamed , Monod Lionel , Ojanguren-Affilastro Andrés , Raven Robert J. , Pinto-Da-Rocha Ricardo , Zvik Yoram , Gavish-Regev Efrat , Sharma Prashant P. 
Published: November 2020

AbstractScorpions constitute a charismatic lineage of arthropods and comprise more than 2,500 described species. Found throughout various tropical and temperate habitats, these predatory arachnids have a long evolutionary history, with a fossil record that began in the Silurian. While all scorpions are venomous, the asymmetrically diverse family Buthidae harbors nearly half the diversity of extant scorpions, and all but one of the 58 species that are medically significant to humans. Many aspects of scorpion evolutionary history are unclear, such as the relationships of the most toxic genera and their constituent venom peptides. Furthermore, the diversification age of toxins that act specifically on mammalian ion channels have never been inferred. To redress these gaps, we assembled a large-scale phylogenomic dataset of 100 scorpion venom transcriptomes and/or genomes, emphasizing the sampling of highly toxic buthid genera. To infer divergence times of venom gene families, we applied a phylogenomic node dating approach for the species tree in tandem with phylostratigraphic bracketing to estimate minimum ages of mammal-specific toxins. Our analyses establish a robustly supported phylogeny of scorpions, particularly with regard to relationships between medically significant taxa. Analysis of venom gene families shows that mammal-specific sodium channel toxins have independently evolved in five lineages within Buthidae. The temporal windows of mammal-specific toxin origins are contiguous with the basal diversification of major scorpion mammal predators such as carnivores, shrews, bats and rodents. These results suggest an evolutionary arms race model comprised of co-diversification of mammalian predators and NaTx homologs in buthid venom.
Cerebellum models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment
Authors: Chang Xuebin , Jia Xiaoyan , Dong Debo , Wang Yulin 
Published: November 2020

AbstractTo comprehensively investigate the white matter (WM) features of cerebellum in patients with schizophrenia, and further assess the correlation between altered WM features and clinical and cognitive assessments. Forty-two patients and fifty-two matched healthy controls (HCs) of the Collaborative Informatics and Neuroimaging Suite Data Exchange tool were involved in this study. The cerebellar WM volume was calculated by voxel-based morphometry. And tract-based spatial statistics was used to analysis the diffusion changes in patients when compared to HCs. Furthermore, we investigated the correlation between altered imaging feature and clinical, cognitive assessments. Compared to HCs, the schizophrenia patients did not reveal difference in cerebellar WM volume and schizophrenia patients showed decreased fractional anisotropy and increased radial diffusivity in left middle cerebellar peduncles and inferior cerebellar peduncles in voxel-wise but not in tract-wise. Critically, these cerebellar changes were associated with disease duration in schizophrenia patients. And significant correlation between the altered cerebellar WM features and cognitive assessments only revealed in HCs but disrupted in schizophrenia patients. The present findings suggested that the voxel-wise WM integrity analysis might was the more sensitive way to investigate the structural abnormalities in schizophrenia patients. Middle cerebellar peduncles and inferior cerebellar peduncles may be a crucial neurobiological substrate of cognition and thus might be regarded as a biomarker for treatment.
The unintended consequences of a surge in antibiotic resistance when removing wastewater drain biofilm
Authors: Kotay Shireen M , Parikh Hardik I , Gweon Hyun S , Barry Katie , Stoesser Nicole , Walker A Sarah , Crook Derrick W , Vegesana Kasi , Mathers Amy J 
Published: November 2020

SUMMARYThe prevalence and proliferation of antimicrobial resistant bacteria is considered one of the critical issues of our time. Wastewater is a habitat for complex microbial communities where bacteria share genes of antimicrobial resistance through horizontal gene transfer. Hospital wastewater drainage systems are an ideal reservoir for environmental and pathogenic bacteria to interface and exchange genes of antimicrobial resistance1. Highly resistant Enterobacterales are of the greatest concern because they not only cause human infections but can also thrive in the environment2,3and have shown to transmit from sink drains to patients4. Replacement of contaminated plumbing may be the most intuitive and widely deployed response once highly resistant potentially pathogenic bacteria are identified in a sink drain. Here we show using shotgun metagenomic sequencing of sink drain biofilms (in 6 intensive care patient rooms, 36 subsamples) paired with microbial culture analysis, an evident shift of biofilm community structure towards increased abundance of Enterobacteriaceae in the newly replaced sink plumbing. Significant increase in resistome load and abundance of clinically relevant resistance and typically mobile genes in the newly replaced plumbing was also observed. Findings from this study demonstrate that exchanging contaminated plumbing for new plumbing may actually have the unexpected consequence of increased abundance of Enterobacterales and genes of antimicrobial resistance in the sink drains. Disruption of preexisting complex environmental biofilms may result in an unintended increase in the amount of antimicrobial resistant Enterobacterales which are targeted for elimination. Temporal variability is an important attribute of ecosystems affecting colonization dynamics and biotic interactions (composition of introduced and resident communities) are key to functional outcomes. Absence of competition within an ecosystem favors invasion.
Propagandist or objective observer? Independent documentaries in/on Hong Kong's recent social movements
Authors: Van den Troost Kristof 
Published: November 2020

PurposeThis article explores recent changes in Hong Kong’s independent documentary filmmaking during a decade of escalating protests in the territory, focusing in particular on cinema's role in Hong Kong's “movement field.”Design/methodology/approachThe article focuses on Ying E Chi, an important distributor and promoter of Hong Kong independent films; the annual Hong Kong Independent Film Festival it organizes; three recent documentaries it distributes that are relevant to the 2019–2020 protests. The findings in this article are based on interviews, the textual analysis of relevant films and participant observation at film screenings.FindingsThis study argues that independent documentaries function in Hong Kong's “movement field” in three main ways: by contributing to and providing a space for civic discourse, by facilitating international advocacy and by engaging in memory work. Its contributions to civic culture, it asserts, are reflected in the films' observational aesthetic, which invites reflection and discussion. Public screenings and lengthy post-screening discussions are important ways in which these functions are realized.Originality/valueThis article builds on existing literature to propose a new way of thinking about cinema's role in Hong Kong social movements. It also analyses three important recent films that have not yet been covered much in existing academic literature.
International trade and innovation: delving in Latin American commerce
Authors: Vallina-Hernandez Ana María , de la Fuente-Mella Hanns , Fuentes-Solís Rodrigo 
Published: November 2020

PurposeThe purpose of this paper is to compare and contrast the international trade characteristics of commerce between Latin American countries and some of the top economies in the world, in order to identify new business opportunities for LATAM firms in dynamical external markets.Design/methodology/approachA triple indexed gravity model, correcting with robust standardized errors clustered, and a panel data analysis was used to obtain the relationship between Latin American countries and advanced and other emerging economies.FindingsThe main finding of this paper is that innovation overcomes gravity effects and parameters typical of a knowledge society are the significant ones to explain trade among different regions. The model that includes an innovation proxy accommodates with the new international theories of trade. Besides, communication capacity is essential to reach consumers abroad with newer and more complex products. Moreover, the constant is significant when innovation is included, which may imply intersectoral trade that behaves relatively stable in bilateral trade.Practical implicationsThe findings suggest that the economies that have some relevance in trade, have increasing numbers regarding patents. Thus, the empirical findings relate to the theoretical models which state that comparative advantages may be dynamic due to technological innovation.Originality/valueThis paper shows that innovation is a central parameter to engage in intratrade and develop a knowledge-based economy. Latin America sometimes appears to be a puzzle as to how to improve its economic performance and overcome its social and economic problems. Intratrade seems to be the route to increase Latin American business participation in world trade.