bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eco-evolutionary drivers of avian migratory connectivity
Authors: Fattorini Niccolò , Costanzo Alessandra , Romano Andrea , Rubolini Diego , Baillie Stephen , Bairlein Franz , Spina Fernando , Ambrosini Roberto 
Published: July 2022

AbstractUnderstanding how individuals redistribute after migration assists in the conservation and management of mobile species, yet the eco-evolutionary drivers of migratory connectivity remain unclear. Taking advantage of an exceptionally large (~150,000 individuals, 83 species) and more-than-a-century long dataset of bird ringing encounters, we investigated determinants of avian migratory connectivity on both short- and long-distance migrants. Most species exhibited significant connectivity likely due to the large intraspecific variability in migration strategies, which often led to the identification of distinct migratory populations. Migratory connectivity was strongly predicted by geography, especially migration distance, but it was evolutionary labile and weakly influenced by biological traits due to flexibility in migratory behaviour. By unravelling determinants of migratory connectivity we improve knowledge about the resilience of migrants to ecological perturbations. Also, our population-level analysis provides a critical tool to inform transboundary conservation and management strategies by explicitly considering the large intraspecific variability of avian migration.
Towards solving the conundrum of plasmid mobility: networks of functional dependencies shape plasmid transfer
Authors: Ares-Arroyo Manuel , Coluzzi Charles , Rocha Eduardo P.C. 
Published: July 2022

AbstractPlasmids are key drivers of bacterial evolution by transferring genes between cells via conjugation. Yet, half of the plasmids lack all protein coding genes for this process. We searched to solve this conundrum by identifying conjugative origins of transfer over thousands of plasmids and chromosomes ofEscherichia coliandStaphylococcus aureus. We found that plasmids carrying these sequences are very abundant and have the highest densities of antimicrobial resistance genes. They are hyper-parasites that directly hijack conjugative or mobilizable elements, but not both. These functional dependencies explain the co-occurrence of each type of plasmid in cells and illuminate the evolutionary relationships between the elements. We characterized systematically the genetic traits of plasmids in relation to conjugation and alternative mechanisms of transfer, and can now propose a confident putative mechanism of transfer for ca. 90% of them. The few exceptions could be passively mobilized by other processes. We conclude there is no conundrum concerning plasmid mobility.
Receptor levels determine binding affinity of WNT-3A to Frizzled 7 in a colorectal cancer model
Authors: Grätz Lukas , Sajkowska-Kozielewicz Joanna J. , Wesslowski Janine , Petzold Katja , Davidson Gary , Schulte Gunnar , Kozielewicz Paweł 
Published: July 2022

ABSTRACTWNT binding to Frizzleds (FZD) is a crucial step that leads to the initiation of signalling cascades governing multiple processes during embryonic development, stem cell regulation and adult tissue homeostasis. Recent efforts have enabled us to shed light on WNT-FZD pharmacology in overexpressed HEK293 cell systems. However, it is important to assess ligand binding at endogenous receptor levels as there might be differential binding behaviour in a native environment. Here, we focus on one FZD paralogue: FZD7, and study its interactions with WNT-3A in a CRISPR-Cas9-edited SW480 colorectal cancer model. SW480 cells were CRISPR-Cas9-edited to insert a HiBiT-tag on the N-terminus of FZD7, preserving the native signal peptide. Subsequently, these cells were used to study eGFP-WNT-3A association to endogenous and overexpressed HiBiT-FZD7using NanoBiT/BRET to measure ligand binding and quantification of NanoBiT-emitted luminescence to assess receptor internalization. eGFP-WNT-3A bound to endogenous HiBiT-FZD7with significantly higherkonand with lowerKdthan to overexpressed receptors. Importantly, as the fluorescent probe is an agonist, experiments performed in cell lysates demonstrated that eGFP-WNT-3A/HiBiT-FZD7binding assessment is not altered by receptor internalization. In conclusion, binding affinities of eGFP-WNT-3A to HiBiT-FZD7decreased with increasing receptor concentrations suggesting that HiBiT-FZD7overexpression fails to recapitulate ligand binding behaviour in a (patho-)physiologically relevant context where endogenous receptor expression levels are lower.
Pollinator mosaics mirror floral trait divergence within and between species ofCastilleja
Authors: Wenzell Katherine E. , Skogen Krissa A. , Fant Jeremie B. 
Published: July 2022

AbstractPollinator interactions are important in the evolution of floral traits, given that pollinators can directly influence plant fitness and mating patterns through interactions with flowers. However, geographic variation in both plant traits and floral visitors across multiple populations is largely understudied, despite being ubiquitous. This study explores whether a geographic mosaic of ecological interactions underlies observed patterns of floral divergence 1) among species of theCastilleja purpureacomplex (C. purpurea, C. citrina, andC. lindheimeri) and the congenerC. sessiliflora, as well as 2) withinC. sessiliflora, across its wide geographic range. We sampled floral visitors and floral traits (morphology and color) at 23 populations across a 1900 km study area in 1-3 years, with reproductive fitness (fruit set) data for 18 of these populations.We documented a wide diversity of pollinator functional groups visiting the four focal species, including bees, butterflies, hawkmoths, and hummingbirds. Visitor assemblages varied among species and across geography in the composition and diversity of floral visitors. We found relationships between floral traits and visitation by certain pollinator groups, which often aligned with syndrome-associated predictions. Additionally, we found evidence that visitation from pollinators predicted via syndromes was associated with increased reproductive fitness for two species: the red-floweredC. lindheimeriand hummingbird visitors, and the long-floral-tubedC. sessilifloraand hawkmoths.Beyond these cases, we found that pollinator functional groups were not restricted to plant species, and instead pollinators were largely generalist in their foraging behavior, suggesting the likelihood for incomplete reproductive isolation and the potential for ongoing gene flow among plant species where their ranges overlap.This study provides a large-scale exploration of how variation in pollinator assemblages across distributions may underlie floral trait divergence within and among recently diverged species, even when characterized by largely generalized modes of pollination. Our extensive sampling of 23 populations over multiple years across a large geographic area highlights the value of range-wide studies for characterizing patterns of divergence and speciation mediated by ecological interactions.
Seed reserve mobilization and seedling morphology in a bioassay for the detection of genetically modified soybean
Authors: Lopes Costa Francisco Cleilson , López Peña Samanda , Andrade Pereira Welison 
Published: July 2022

AbstractGermination and initial seedling development are physiological processes that determine the establishment of crops. During heterotrophic growth, each seedling develops from the biomass of its seeds. Thus, verifying the potential of genotypes to mobilize reserves under stress has been important. The aim of this study was to investigate how glyphosate affects the mobilization of reserves and seedling morphology. Two tolerant and two herbicide-sensitive cultivars were submitted to germination, seedling length and reserve mobilization tests, including treatments with glyphosate solutions (0, 0.06 and 0.12 %). The hypocotyl / radicle ratio and the efficiency of conversion of reserves to seedlings were also verified. The data were submitted to analysis of variance and test of means. It was observed that the percentage of normal seedlings and length seedlings were affected due to the concentration of the herbicide in the treatments, being the consequences more pronounced for sensitive cultivars; the glyphosate-tolerant genotype and with the best physiological quality mobilized more reserves and was more efficient in converting biomass to seedlings; in morphology, the average length of the seedlings was reduced due to the herbicide, being the roots affected in such a way that they became smaller than the hypocotyls. The herbicide affects the morphology of the seedlings mainly the radicle, and the mobilization of the reserves discriminates the genotypes regarding tolerance to glyphosate.
Identification of a sensory neuron Cav2.3 inhibitor within a new superfamily of macro-conotoxins
Authors: Hackney Celeste M. , Salcedo Paula Flórez , Mueller Emilie , Koch Thomas Lund , Kjelgaard Lau D. , Watkins Maren , Zachariassen Linda Grønborg , Tuelund Pernille Sønderby , McArthur Jeffrey R. , Adams David J. , Kristensen Anders S. , Olivera Baldomero , Finol-Urdaneta Rocio K. , Safavi-Hemami Helena , Morth Jens Preben , Ellgaard Lars 
Published: July 2022

AbstractAnimal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, that defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and two additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of voltage-gated ion channels, Mu8.1 preferentially inhibited the R-type (Cav2.3) calcium channel. Ca2+signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K+(Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study demonstrates the feasibility of large, disulfide-rich venom-component investigation, an endeavor that will lead to the discovery of novel structures and functions in the previously underexplored group of macro-conotoxins.
Executed and imagined grasping movements can be decoded from lower dimensional representation of distributed non-motor brain areas
Authors: Ottenhoff Maarten C. , Verwoert Maxime , Goulis Sophocles , Colon Albert J. , Wagner Louis , Tousseyn Simon , van Dijk Johannes P. , Kubben Pieter L. , Herff Christian 
Published: July 2022

AbstractUsing brain activity directly as input for assistive tool control can circumvent muscular dysfunction and increase functional independence for physically impaired people. Most invasive motor decoding studies focus on decoding neural signals from the primary motor cortex, which provides a rich but superficial and spatially local signal. Initial non-primary motor cortex decoding endeavors have used distributed recordings to demonstrate decoding of motor activity by grouping electrodes in mesoscale brain regions. While these studies show that there is relevant and decodable movement related information outside the primary motor cortex, these methods are still exclusionary to other mesoscale areas, and do not capture the full informational content of the motor system. In this work, we recorded intracranial EEG of 8 epilepsy patients, including all electrode contacts except those contacts in or adjacent to the central sulcus. We show that executed and imagined movements can be decoded from non-motor areas; combining all non-motor contacts into a lower dimensional representation provides enough information for a Riemannian decoder to reach an area under the curve of 0.83 ± 0.11. Additionally, by training our decoder on executed and testing on imagined movements, we demonstrate that between these two conditions there exists shared distributed information in the beta frequency range. By combining relevant information from all areas into a lower dimensional representation, the decoder was able to achieve high decoding results without information from the primary motor cortex. This representation makes the decoder more robust to perturbations, signal non-stationarities and neural tissue degradation. Our results indicate to look beyond the motor cortex and open up the way towards more robust and more versatile brain-computer interfaces.
Monoallelically-expressed Noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression
Authors: Hao Qinyu , Liu Minxue , Daulatabad Swapna Vidhur , Gaffari Saba , Srivastava Rajneesh , Song You Jin , Bhaskar Shivang , Moitra Anurupa , Mangan Hazel , Tseng Elizabeth , Gilmore Rachel B. , Freier Susan M. , Chen Xin , Wang Chengliang , Huang Sui , Chamberlain Stormy , Jin Hong , Korlach Jonas , McStay Brian , Sinha Saurabh , Janga Sarath Chandra , Prasanth Supriya G. , Prasanth Kannanganattu V. 
Published: July 2022

ABSTRACTOut of the several hundred copies of rRNA genes that are arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, ∼50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to differential expression of rRNAs. However, the mechanism(s), controlling the dosage of active versus inactive rRNA genes in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influences rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosome. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs that by forming constrained nucleolar territories on individual NORs contribute to rRNA expression.
Integrating analog and digital modes of gene expression at Arabidopsis FLC
Authors: Antoniou-Kourounioti Rea L. , Meschichi Anis , Reeck Svenja , Berry Scott , Menon Govind , Zhao Yusheng , Fozard John A. , Holmes Terri L. , Wang Huamei , Hartley Matthew , Dean Caroline , Rosa Stefanie , Howard Martin 
Published: July 2022

AbstractQuantitative gene regulation at the cell population-level can be achieved by two fundamentally different modes of regulation at individual gene copies. A “digital” mode involves binary ON/OFF expression states, with population-level variation arising from the proportion of gene copies in each state, while an “analog” mode involves graded expression levels at each gene copy. At the Arabidopsis floral repressor FLOWERING LOCUS C (FLC), “digital” Polycomb silencing is known to facilitate quantitative epigenetic memory in response to cold. However, whether FLC regulation before cold involves analog or digital modes is unknown. Using quantitative fluorescent imaging of FLC mRNA and protein, together with mathematical modelling, we find that FLC expression before cold is regulated by both analog and digital modes. We observe a temporal separation between the two modes, with analog preceding digital. The analog mode can maintain intermediate expression levels at individual FLC gene copies, before subsequent digital silencing, consistent with the copies switching OFF stochastically and heritably without cold. This switch leads to a slow reduction in FLC expression at the cell population-level. These data present a new paradigm for gradual repression, elucidating how analog transcriptional and digital epigenetic memory pathways can be integrated.
Single-cell multi-omics enabled discovery of alkaloid biosynthetic pathway genes in the medical plant Catharanthus roseus
Authors: Li Chenxin , Wood Joshua C. , Vu Anh Hai , Hamilton John P. , Rodriguez Lopez Carlos Eduardo , Payne Richard M. E. , Serna Guerrero Delia Ayled , Yamamoto Kotaro , Vaillancourt Brieanne , Caputi Lorenzo , O’Connor Sarah E. , Buell C. Robin 
Published: July 2022

ABSTRACTAdvances in omics technologies now permit generation of highly contiguous genome assemblies, detection of transcripts and metabolites at the level of single cells, and high-resolution determination of gene regulatory features including 3-dimensional chromatin interactions. Using a complementary, multi-omics approach, we interrogated the monoterpene indole alkaloid (MIA) biosynthetic pathway in Catharanthus roseus, a source of leading anti-cancer drugs. We identified not only new clusters of genes involved in MIA biosynthesis on the eight C. roseus chromosomes but also rampant gene duplication including paralogs of MIA pathway genes. Clustering was not limited to the linear genome and through chromatin interaction data, MIA pathway genes were shown to be present within the same topologically associated domain, permitting identification of a secologanin transporter. Single cell RNA-sequencing revealed exquisite and sequential cell-type specific partitioning of the leaf MIA biosynthetic pathway that, when coupled with a newly developed single cell metabolomics approach, permitted identification of a reductase that yields the bis-indole alkaloid anhydrovinblastine. Last, we revealed cell-type specific expression in the root MIA pathway that is conferred in part by neo- and sub-functionalization of paralogous MIA pathway genes. This study highlights how a suite of omic approaches, including single cell gene expression and metabolomics, can efficiently link sequence with function in complex, specialized metabolic pathways of plants.
Directed Differentiation of Human iPSCs to Functional Ovarian Granulosa-Like Cells via Transcription Factor Overexpression
Authors: Smela Merrick Pierson , Kramme Christian , Fortuna Patrick , Adams Jessica , Dong Edward , Kobayashi Mutsumi , Brixi Garyk , Tysinger Emma , Kohman Richie. E. , Shioda Toshi , Chatterjee Pranam , Church George M. 
Published: July 2022

AbstractAn in vitro model of human ovarian follicles would greatly benefit the study of female reproduction. Ovarian development requires the combination of germ cells and their supporting somatic cells, known as granulosa cells. Whereas efficient protocols exist for generating human primordial germ cell-like cells (hPGCLCs) from human iPSCs, a method of generating granulosa cells has been elusive. Here we report that simultaneous overexpression of two transcription factors (TFs) can direct the differentiation of human iPSCs to granulosa-like cells. We elucidate the regulatory effects of several granulosa-related TFs, and establish that overexpression of NR5A1 and either RUNX1 or RUNX2 is necessary and sufficient to generate granulosa-like cells. Our granulosa-like cells form ovary-like organoids (ovaroids) when aggregated with hPGCLCs, and recapitulate key ovarian phenotypes including support of germ cell maturation, follicle formation, and steroidogenesis. This model system will provide unique opportunities for studying human ovarian biology, and may enable the development of therapies for female reproductive health.
Effect of Charge Distribution on the Dynamics of Polyampholytic Disordered Proteins
Authors: Devarajan Dinesh Sundaravadivelu , Rekhi Shiv , Nikoubashman Arash , Kim Young C. , Howard Michael P. , Mittal Jeetain 
Published: July 2022

AbstractThe stability and physiological function of many biomolecular coacervates depend on the structure and dynamics of intrinsically disordered proteins (IDPs) that typically contain a significant fraction of charged residues. Although the effect of relative arrangement of charged residues on IDP conformation is a well-studied problem, the associated changes in dynamics are far less understood. In this work, we systematically interrogate the effects of charge distribution on the chain-level and segmental dynamics of polyampholytic IDPs in dilute solutions. We study a coarse-grained model polyampholyte consisting of an equal fraction of two oppositely charged residues (glutamic acid and lysine) that undergoes a transition from an ideal chain-like conformation for uniformly charge-patterned sequences to a semi-compact conformation for highly charge-segregated sequences. Changes in the chain-level dynamics with increasing charge segregation correlate with changes in conformation. The chain-level and segmental dynamics conform to simple homopolymer models for uniformly charge-patterned sequences but deviate with increasing charge segregation, both in the presence and absence of hydrodynamic interactions. We discuss the significance of these findings, obtained for a model polyampholyte, in the context of a charge-rich intrinsically disordered region of the naturally occurring protein LAF-1. Our findings have important implications for understanding the effects of charge patterning on the dynamics of polyampholytic IDPs in dilute conditions using polymer scaling theories.
Phylogenomic analysis of the Neocallimastigomycota: Proposal of Caecomycetaceae fam. nov., Piromycetaceae fam. nov., and emended description of the families Neocallimastigaceae and Anaeromycetaceae
Authors: Hanafy Radwa A. , Wang Yan , Stajich Jason E. , Pratt Carrie J. , Youssef Noha H. , Elshahed Mostafa H. 
Published: July 2022

AbstractThe anaerobic gut fungi (AGF) represent a coherent phylogenetic clade within the Mycota. Twenty genera have been described so far. Currently, the phylogenetic and evolutionary relationships between AGF genera remain poorly understood. Here, we utilized 53 transcriptomic datasets from 14 genera to resolve AGF inter-genus relationships using phylogenomics, and to provide a quantitative estimate (amino acid identity) for intermediate rank assignments. We identify four distinct supra-genus clades, encompassing genera producing polyflagellated zoospores, bulbous rhizoids, the broadly circumscribed genus Piromyces, and the Anaeromyces and affiliated genera. We also identify the genus Khoyollomyces as the earliest evolving AGF genus. Concordance between phylogenomic outputs and RPB1 and D/D2 LSU, but not RPB2, MCM7, or ITS1, phylogenies was observed. We combine phylogenomic analysis, and AAI outputs with informative phenotypic traits to propose accommodating 13/20 AGF genera into four families: Caecomycetaceae fam. nov. (encompassing genera Caecomyces and Cyllamyces), Piromycetaceae fam. nov. (encompassing the genus Piromyces), emend the description of fam. Neocallimastigaceae to only encompass genera Neocallimastix, Orpinomyces, Pecramyces, Feramyces, Ghazallomyces, and Aestipascuomyces, as well as the family Anaeromycetaceae to include the genera Oontomyces, Liebetanzomyces, and Capellomyces in addition to Anaeromyces. We refrain from proposing families for the deeply branching genus Khoyollomyces, and for genera with uncertain position (Buwchfawromyces, Joblinomyces, Tahromyces, Agriosomyces, Aklioshbomyces, and Paucimyces) pending availability of additional isolates and sequence data. Our results establish an evolutionary- grounded Linnaean taxonomic framework for the AGF, provide quantitative estimates for rank assignments, and demonstrate the utility of RPB1 as additional informative marker in Neocallimastigomycota taxonomy.