bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying systematic variation at the single-cell level by leveraging low-resolution population-level data
Authors: Rahmani Elior , Jordan Michael I. , Yosef Nir 
Published: January 2022

AbstractA major limitation in single-cell genomics is a lack of ability to conduct cost-effective population-level studies. As a result, much of the current research in single-cell genomics focuses on biological processes that are broadly conserved across individuals, such as cellular organization and tissue development. This limitation prevents us from studying the etiology of experimental or clinical conditions that may be inconsistent across individuals owing to molecular variation and a wide range of effects in the population. In order to address this gap, we developed “kernel of integrated single cells” (Keris), a novel model-based framework to inform the analysis of single-cell gene expression data with population-level effects of a condition of interest. By inferring cell-type-specific moments and their variation across conditions using large tissue-level bulk data representing a population, Keris allows us to generate testable hypotheses at the single-cell level that would otherwise require collecting single-cell data from a large number of donors. Within the Keris framework, we show how the combination of low-resolution, large bulk data with small but high-resolution single-cell data enables the identification of changes in cell-subtype compositions and the characterization of subpopulations of cells that are affected by a condition of interest. Using Keris we estimate linear and non-linear age-associated changes in cell-type expression in large bulk peripheral blood mononuclear cells (PBMC) data. Combining with three independent single-cell PBMC datasets, we demonstrate that Keris can identify changes in cell-subtype composition with age and capture cell-type-specific subpopulations of senescent cells. This demonstrates the promise of enhancing single-cell data with population-level information to study compositional changes and to profile condition-affected subpopulations of cells, and provides a potential resource of targets for future clinical interventions.
Differential cellular stiffness contributes to tissue elongation on an expanding surface
Authors: Koyama Hiroshi , Suzuki Makoto , Yasue Naoko , Sasaki Hiroshi , Ueno Naoto , Fujimori Toshihiko 
Published: January 2022

AbstractPattern formation and morphogenesis of cell populations is essential for successful embryogenesis. Steinberg proposed the differential adhesion hypothesis (DAH), and differences in cell–cell adhesion and interfacial tension have proven to be critical for cell sorting. Standard theoretical models such as the vertex model consider not only cell–cell adhesion/tension but also area elasticity of apical cell surfaces and viscous friction forces. However, the potential contributions of the latter two parameters to pattern formation and morphogenesis remain to be determined. In this theoretical study, we analyzed the effect of both area elasticity and the coefficient of friction on pattern formation and morphogenesis. We assumed the presence of two cell populations, one population of which is surrounded by the other. Both populations were placed on the surface of a uniformly expanding environment analogous to growing embryos, in which friction forces are exerted between cell populations and their expanding environment. When the area elasticity or friction coefficient in the cell cluster was increased relative to that of the surrounding cell population, the cell cluster was elongated. In comparison with experimental observations, elongation of the notochord in mice is consistent with the hypothesis based on the difference in area elasticity but not the difference in friction coefficient. Because area elasticity is an index of cellular stiffness, we propose that differential cellular stiffness may contribute to tissue elongation within an expanding environment.
mucG, mucH, and mucI modulate production of mutanocyclin and reutericyclins in Streptococcus mutans B04Sm5
Authors: Baker Jonathon L. , Tang Xiaoyu , LaBonte Sandra , Uranga Carla , Edlund Anna 
Published: January 2022

AbstractStreptococcus mutans is considered a primary etiologic agent of dental caries, which is the most common chronic infectious disease worldwide. S. mutans B04Sm5 was recently shown to produce reutericyclins and mutanocyclin through the muc biosynthetic gene cluster, and to utilize reutericyclins to inhibit the growth of neighboring commensal Streptococci. In this study, examination of S. mutans and muc phylogeny suggested evolution of an ancestral S. mutans muc into three lineages within one S. mutans clade, and then horizontal transfer of muc to other S. mutans clades. The roles of the mucG and mucH transcriptional regulators, and the mucI transporter, were also examined. mucH was demonstrated to encode a transcriptional activator of muc. mucH deletion reduced production of mutanocyclin and reutericyclins, and eliminated the impaired growth and inhibition of neighboring Streptococci phenotypes which are associated with reutericyclin production. ΔmucG had increased mutanocyclin and reutericyclin production, which impaired growth and increased the ability to inhibit neighboring Streptococci. However, deletion of mucG also caused reduced expression of mucD, mucE, and mucI. Deletion of mucI reduced mutanocyclin and reutericylin production, but enhanced growth, suggesting that mucI may not transport reutericyclin as its homolog does in Limosilactobacillus reuteri. Further research is needed to determine the roles of mucG and mucI, and to identify any co-factors affecting the activity of the mucG and mucH regulators. Overall, this study provided pangenome and phylogenetic analysis that serves as a resource for S. mutans research, and began elucidation of the regulation of reutericyclins and mutanocyclin production in S. mutans.ImportanceS. mutans must be able to outcompete neighboring organisms in its ecological niche in order to cause dental caries. S. mutans B04Sm5 inhibited the growth of neighboring commensal Streptococci through production of reutericyclins via the muc biosynthetic gene cluster. In this study, carriage of muc was examined across S. mutans, which showed that 35 of 244 RefSeq S. mutans genomes encoded muc and provided a valuable update to the S. mutans pangenome and phylogeny. The roles of the mucG and mucH transcriptional regulators, and the mucI transporter, were also examined. All 3 genes impacted production of mutanocyclin and reutericyclins, which affected the growth rates, transcriptomes, and the ability of the S. mutans strains to inhibit the growth of neighboring commensals.
Genomic and phylogenetic analysis of the first myovirus isolated from Oceanospirillaceae, representing a novel viral cluster prevalent in polar oceans
Authors: Zhang Wenjing , Liu Yundan , Xing Jinyan , Zheng Kaiyang , Li Qian , Gu Chengxiang , Wang Ziyue , Shao Hongbing , Guo Cui , He Hui , Wang Hualong , Sung Yeong Yik , Mok Wen Jye , Wong Li Lian , Liang Yantao , McMinn Andrew , Wang Min 
Published: January 2022

AbstractThe marine bacterial family Oceanospirillaceae, which is abundant in the deep-seas and polar oceans, is closely associated with algal blooms and petroleum hydrocarbons degradation. However, only a few Oceanospirillaceae-infecting phages have so far been reported. Here we report on a novel Oceanospirillum phage, vB_OsaM_PD0307, which is the first myovirus to be found that infects Oceanospirillaceae. vB_OsaM_PD0307 with a 44,421 bp linear dsDNA genome. Phylogenetic analysis and average nucleotide sequence identities suggest that vB_OsaM_PD0307 is different from other phage isolates and represents a novel genus-level myoviral cluster with two high-quality uncultured viral genomes, designed as Oceanospimyovirus. Additionally, the biogeographical distribution of the vB_OsaM_PD0307 cluster suggests that they are widespread in the oceans and abundant in polar areas. In summary, our findings expand the current understanding of the phylogenetic diversity, genomic characteristic and function of Oceanospimyovirus phages, and highlight the role of the vB_OsaM_PD0307 phage as a major ecological agent that can infect certain key bacterial groups associated with polar algal blooms.ImportanceOceanospirillumphage vB_OsaM_PD0307 is the first myovirus found to infect Oceanospirillaceae and represents a novel viral genus, Oceanospimyovirus. This study provides insights into the genomic, phylogenetic, and ecological characteristics of myoviruses infecting Oceanospirillaceae and improves our understanding of the interactions between Oceanospirillaceae and their phages in the oceans.
The limits of metabolic heredity in protocells
Authors: Palmeira Raquel Nunes , Colnaghi Marco , Harrison Stuart A , Pomiankowski Andrew , Lane Nick 
Published: January 2022

AbstractThe universal core of metabolism could have emerged from thermodynamically favoured prebiotic pathways at the origin of life. Starting with H2and CO2, the synthesis of amino acids and mixed fatty acids, which self-assemble into protocells, is favoured under warm anoxic conditions. Here we address whether it is possible for protocells to evolve greater metabolic complexity, through positive feedbacks involving nucleotide catalysis. Using mathematical simulations to model metabolic heredity in protocells, based on branch points in proto-metabolic flux, we show that nucleotide catalysis can indeed promote protocell growth. This outcome only occurs when nucleotides directly catalyse CO2fixation. Strong nucleotide catalysis of other pathways (e.g. fatty acids, amino acids) generally unbalances metabolism and slows down protocell growth, and when there is competition between catalytic functions cell growth collapses. Autocatalysis of nucleotide synthesis can promote growth but only if nucleotides also catalyse CO2fixation; autocatalysis alone leads to the accumulation of nucleotides at the expense of CO2fixation and protocell growth rate. Our findings offer a new framework for the emergence of greater metabolic complexity, in which nucleotides catalyse broad-spectrum processes such as CO2fixation, hydrogenation and phosphorylation important to the emergence of genetic heredity at the origin of life.
Phenotypic and transcriptomic responses of the sun- and shade-loving plants to sunlight and dim-light conditions
Authors: Zhang Yu-Xin , Niu Yu-Qian , Wang Xin-Feng , Wang Zhen-Hui , Wang Meng-Li , Yang Ji , Wang Yu-Guo , Zhang Wen-Ju , Song Zhi-Ping , Li Lin-Feng 
Published: January 2022

AbstractElucidating how plant species respond to variable light conditions is important to understanding the ecological adaptation to heterogeneous natural habitats. However, the phenotypic responses and gene regulatory network of shade-loving plants under distinct light conditions have remained largely unclear. In this study, we assessed the differences in phenotypic and transcriptomic responses between Arabidopsis (sun-loving) and Panax ginseng (shade-loving) to sunlight and dim-light conditions. Our results showed that, compared to the Arabidopsis, ginseng plants not only exhibited a lower degree of phenotypic plasticity in response to distinct light conditions, but also showed higher photosynthetic efficiency under dim-light conditions. Further time-course transcriptome profiling and gene structural analyses revealed that differentially transcriptional regulation together with increased copy number of the photosynthesis-related genes (i.e., electron transfer and carbon fixation) may improve the photosynthetic efficiency of ginseng plants under dim-light conditions. In contrast, the loss-function and inactivation of phytochrome-interacting factors are potentially associated with the observed low degree of phenotypic plasticity of ginseng plants under the changing light conditions. Our study provides new insights on how shade-loving plants respond to variable light conditions. Candidate genes related to shade adaptation in ginseng provide valuable genetic resources for future molecular breeding of high-density planting crops.HighlightThe shade-loving species Panax ginseng possesses lower phenotypic plasticity under distinct light conditions and shows high photosynthesis efficiency under dim-light condition.
LuminoCell: a versatile and affordable luminometer platform for monitoring in-cell luciferase-based reporters
Authors: Weissová Kamila , Fafílek Bohumil , Radaszkiewicz Tomasz , Celiker Canan , Macháčková Petra , Čechová Tamara , Šebestíková Jana , Hampl Aleš , Bryja Vítězslav , Krejčí Pavel , Bárta Tomáš 
Published: January 2022

AbstractLuciferase reporter assays represent a simple and sensitive experimental system in cell and molecular biology to study multiple biological processes. However, the application of these assays is often limited by the costs of conventional luminometer instruments and the versatility of their use in different experimental conditions. Therefore, we aimed to develop a small, affordable luminometer allowing continuous measurement of luciferase activity, designed for inclusion into various kinds of tissue culture incubators. Here we introduce LuminoCell - an open-source platform for the construction of an affordable, sensitive, and portable luminometer capable of realtime monitoring in-cell luciferase activity. The LuminoCell costs $40, requires less than 1 hour to assemble, and it is capable of performing real-time sensitive detection of both magnitude and duration of the activity of major signalling pathways in cell cultures, including receptor tyrosine kinases (EGF, FGF), WNT/β-catenin, and NF-κB. Additionally, we show that the LuminoCell is suitable to be used in cytotoxicity assays as well as for monitoring periodic circadian gene expression.
Integrating top-down and bottom-up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone
Authors: Stankowski Sean , Chase Madeline A. , McIntosh Hanna , Streisfeld Matthew A. 
Published: January 2022

AbstractUnderstanding the phenotypic and genetic architecture of reproductive isolation is a longstanding goal of speciation research. In many systems, candidate barrier traits and loci have been identified, but causal connections between them are rarely made. In this study, we combine ‘top-down’ and ‘bottom-up’ approaches with demographic modeling toward an integrated understanding of speciation across a monkeyflower hybrid zone. Previous work in this system suggests that pollinator-mediated reproductive isolation is a primary barrier to gene flow between two divergent red- and yellow-flowered ecotypes ofMimulus aurantiacus. Several candidate floral traits contributing to pollinator isolation have been identified, including a difference in flower color, which is caused primarily by a single large-effect locus (MaMyb2). Other anonymous SNP loci, potentially contributing to pollinator isolation, also have been identified, but their causal relationships remain untested. Here, we performed demographic analyses, which indicate that this hybrid zone formed by secondary contact, but that subsequent gene flow was restricted in a large fraction of the genome by barrier loci. Using a cline-based genome scan (our bottom-up approach), we demonstrate that candidate barrier loci are broadly distributed across the genome, rather than mapping to one or a few ‘islands of speciation.’ A QTL analysis (our top-down approach) revealed most floral traits are highly polygenic, with little evidence that QTL co-localize, indicating that most traits are largely genetically independent. Finally, we find little convincing evidence for the overlap of QTL and candidate barrier loci, suggesting that some loci contribute to other forms of reproductive isolation. Our findings highlight the challenges of understanding the genetic architecture of reproductive isolation and reveal that barriers to gene flow aside from pollinator isolation may play an important role in this system.
The role of preterm birth and postnatal stress in neonatal structural brain development
Authors: Lammertink Femke , Benders Manon J.N.L. , Hermans Erno J. , Tataranno Maria L. , Dudink Jeroen , Vinkers Christiaan H. , den Heuvel Martijn P. van 
Published: January 2022

AbstractPreterm birth disrupts the emerging foundations of the brain’s architecture, and the continuum of early-life stress-provoked alterations reaches from a healthy adaptation with resilience to severe vulnerability and maladjustment with psychopathology. The current study examined how structural brain development is affected by a stressful extra-uterine environment and whether changes in topological architecture at term-equivalent age could explain the increased vulnerability for behavioral symptoms during early childhood. Longitudinal changes in structural brain connectivity were quantified using diffusion-weighted imaging (DWI) and tractography in preterm born infants (gestational age <28 weeks), imaged at 30 and/or 40 weeks of gestation (N=145, 43.5% female). A global index of postnatal stress was based on invasive procedures during hospitalization (e.g., heel lance). Infants were classified as vulnerable and resilient based on having more or less internalizing symptoms at 2-5 years of age (n=71). Findings were replicated in an independent validation sample (N=123, 39.8% female, n=91 with follow-up). Higher stress levels impaired structural connectivity growth in the amygdala, insula, hippocampus, and posterior cingulate cortex. The hippocampus, amygdala, and subthalamic nucleus showed lower global connectivity in vulnerable relative to resilient individuals. The distinct characteristics of the resilient brain allowed for a good predictive accuracy of group membership using local network measures (80%, p<10−5, κ=0.61). These findings emphasize the detrimental impact of postnatal stress and, more importantly, the relative plasticity of the preterm brain. Resilience following postnatal stress appertains to a potential compensatory or innate ability to propagate global information flow.Significance StatementThe underdeveloped preterm brain is exposed to various external stimuli following birth. Although the importance of early adversity has been widely recognized, the essential understanding of the effects of early chronic stress on neonatal brain networks as well as the remarkable degree of resilience is not well understood. We aim to provide an increased understanding of the impact of postnatal stress on brain development between 30 and 40 weeks of gestation and describe the topological architecture of a resilient brain. We observed global alteration in neonatal brain networks following postnatal stress and identified key contributive regions conferring resilience to the development of future internalizing symptoms.
Blood flow modeling under LVAD physiology. From global circulation to local hemodynamics☆
Authors: Blanco Pablo J. , Grinstein Jonathan , Bulant Carlos A. , Torii Ryo , Bourantas Christos V. , Lemos Pedro A. , García-García Héctor M. 
Published: January 2022

AbstractThis document presents the modeling strategy to address the in-silico study of different LVAD patho-physiological scenarios. The proposed approach employs a closed-loop lumped-parameter compartmental representation of the global circulation in the cardiovascular system (CVS). The CVS is coupled to a HeartMate 3 LVAD, and different cardiovascular conditions are proposed by modification of model parameters. Once the simulation for these conditions are performed, the cardiac function is analyzed in detail, and the global circulation model delivers flow rate waveforms which are employed as boundary conditions in a 3D hemodynamic simulation. This local circulation model is built using a patient-specific geometry of the aortic arch, containing 7 inlet/outlet boundaries, namely: LVAD cannula, aortic root, left and right subclavian arteries, left and right common carotid arteries and thoracic aorta. This model is exploited to investigate the impact of global cardiovascular conditions in the local hemodynamic features, particularly the wall shear stress (WSS) in different spatial regions.
Fitness costs and benefits in response to artificial artesunate selection inPlasmodium
Authors: Villa Manon , Berthomieu Arnaud , Rivero Ana 
Published: January 2022

AbstractDrug resistance is a major issue in the control of malaria. Mutations linked to drug resistance often target key metabolic pathways and are therefore expected to be associated with biological costs. The spread of drug resistance depends on the balance between the benefits that these mutations provide in the drug-treated host and the costs they incur in the untreated host. The latter may therefore be expressed both in the vertebrate host and in the vector. Research on the costs of drug resistance focusses on interactions with vertebrate host, yet whether they are also expressed in the vector has been overlooked. In this study, we aim to identify the costs and benefits of resistance against artesunate (AS), one of the main artemisinin derivatives used in malaria-endemic countries. For this purpose, we compared different AS-selected lines of the avian malaria parasitePlasmodium relictumto their ancestral (unselected) counterpart. We tested their within host dynamics and virulence both in the vertebrate host and in its natural vector, the mosquitoCulex quinquefasciatus. The within-host dynamics of the AS-selected lines in the treated birds was consistent with the phenotype of resistance described in humanP. falciparummalaria: a clearance delay during the treatment followed by a recrudescence once the treatment was interrupted. In the absence of treatment, however, we found no significant costs of resistance in the bird. The results of the two experiments to establish the infectivity of the lines to mosquitoes point towards a decreased infectivity of the drug-selected lines as compared to the ancestral, reference one. We discuss the potential implication of these results on the spread of artesunate resistance in the field.
Sex-specific transcription and DNA methylation landscapes of the Asian citrus psyllid, a vector of huanglongbing pathogens
Authors: Yu Xiudao , Marshall Hollie , Liu Yan , Xiong Yu , Zeng Xiangdong , Yu Haizhong , Chen Wei , Zhou Guchun , Zhu Bo , Ross Laura , Lu Zhanjun 
Published: January 2022

AbstractThe relationship of DNA methylation and sex-biased gene expression is of high interest, it allows research into mechanisms of sexual dimorphism and the development of potential novel strategies for insect pest control. The Asian citrus psyllid, Diaphorina citri Kuwayama, is a major vector for the causative agents of Huanglongbing (HLB), which presents an unparalleled challenge to citrus production worldwide. Here, we identify the X chromosome of D. citri and investigate differences in the transcription and DNA methylation landscapes between adult virgin males and females. We find a large number of male-biased genes on the autosomes and a depletion of such on the X chromosome. We have also characterised the methylome of D. citri, finding low genome-wide levels, which is unusual for an hemipteran species, as well as evidence for both promoter and TE methylation. Overall, DNA methylation profiles are similar between the sexes but with a small number of differentially methylated genes found to be involved in sex differentiation. There also appears to be no direct relationship between differential DNA methylation and differential gene expression. Our findings lay the groundwork for the development of novel epigenetic-based pest control methods, and given the similarity of the D. citri methylome to other insect species, these methods could be applicable across agricultural insect pests.