bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic and spatial determinants of leaf endophyte microbiomes in the flowering plant genusHeuchera(Saxifragaceae)
Authors: Pantinople Dexcem J. , Conner Reagan , Sutton-Dauber Stephanie , Broussard Kelli , Siniscalchi Carolina M. , Engle-Wrye Nicholas J. , Jordan Heather R. , Folk Ryan A. 
Published: May 2023

AbstractPremise: Endophytic plant-microbe interactions range from mutualistic relationships that confer important ecological and agricultural traits to neutral or quasi-parasitic relationships. In contrast to root-associated endophytes, the role of environmental and host-related factors for acquiring leaf endophyte communities remains relatively unexplored. Here we assess leaf endophyte diversity to test the hypothesis that membership of these microbial communities is driven primarily by abiotic environment and host phylogeny.Methods:We used a broad geographic coverage of North America in the genus,Heuchera(Saxifragaceae). Bacterial and fungal communities were characterized with 16S and ITS amplicon sequencing, using QIIME2 to call operational taxonomic units and calculate species richness, Shannon diversity, and phylogenetic diversity. We assembled environmental predictors for microbial diversity at collection sites including latitude, elevation, temperature, precipitation, and soil parameters.Results:We find differing assembly patterns for bacterial and fungal endophytes; we found that only host phylogeny is significantly associated with bacteria, while geographic distance alone was the best predictor of fungal community composition. Species richness and phylogenetic diversity are very similar across sites and species, with only fungi showing a response to aridity and precipitation for some metrics. Unlike what has been observed with root-associated microbial communities, in this system microbes show no relationship with pH or other soil factors.Conclusions:Host phylogeny and geographic distance independently influence different microbial communities, while aridity and precipitation determine fungal diversity within leaves ofHeuchera. Our results indicate the importance of detailed clade-based investigation of microbiomes and the complexity of microbiome assembly within specific plant organs.
Mapping QTL for vernalization requirement identified adaptive divergence of the candidate geneFlowering Locus Cin polyploidCamelina sativa
Authors: Chaudhary Raju , Higgins Erin E. , Eynck Christina , Sharpe Andrew G. , Parkin Isobel A. P. 
Published: May 2023

AbstractVernalization requirement is an integral component of flowering in winter-type plants. The availability of winter ecotypes amongCamelinaspecies facilitated the mapping of QTL for vernalization requirement inC. sativa. An inter- and intraspecific crossing scheme between relatedCamelinaspecies, where two different sources of the winter-type habit were used, resulted in the development of two segregating populations. Linkage maps generated with sequence-based markers identified three QTL associated with vernalization requirement inC. sativa; two from the inter-specific (chromosomes 13 and 20) and one from the intra-specific cross (chromosome 8). Notably, the three loci were mapped to different homologous regions of the hexaploidC. sativagenome. All three QTL were found in proximity toFLOWERING LOCUS C(FLC), variants of which have been reported to affect the vernalization requirement in plants. Temporal transcriptome analysis for winter-typeCamelina alyssumdemonstrated reduction in expression ofFLCon chromosomes 13 and 20 during cold treatment, which would trigger flowering, sinceFLCwould be expected to suppress floral initiation.FLCon chromosome 8 also showed reduced expression in theC. sativassp.pilosawinter parent upon cold treatment, but was expressed at very high levels across all time points in the spring-typeC. sativa. The chromosome 8 copy carried a deletion in the spring-type line, which could impact its functionality. Contrary to previous reports, all threeFLCloci can contribute to controlling the vernalization response inC. sativaand provide opportunities for manipulating this requirement in the crop.Significance StatementDeveloping winterC. sativagermplasm is an important breeding goal for this alternative oilseed, with application in the food, fuel and bioproduct industries. Studying the genetic architecture of the vernalization response has shown that contrary to previous reports all threeFLCloci inCamelinaspecies could be exploited to manipulate this important trait.
Vocal-visual combinations in wild chimpanzees
Authors: Mine Joseph G. , Wilke Claudia , Zulberti Chiara , Bejhati Melika , Stoll Sabine , Machanda Zarin , Manser Andri , Slocombe Katie. E , Townsend Simon W. 
Published: May 2023

AbstractHuman communication is strikingly multi-modal, relying on vocal utterances combined with visual gestures, facial expressions and more. Recent efforts to describe multi-modal signal production in our ape relatives have shed important light on the evolutionary trajectory of this core hallmark of human language. However, whilst promising, a systematic quantification of primate signal production which filters out random combinations produced across modalities is currently lacking. Here, through recording the communicative behaviour of wild chimpanzees from the Kibale forest, Uganda we address this issue and generate the first repertoire of non-random combined vocal and visual components. Using collocation analysis, we identify more than 100 vocal-visual combinations which occur more frequently than expected by chance. We also probe how multi-modal production varies in the population, finding no differences between individuals as a function of age, sex or rank. The number of visual components exhibited alongside vocalizations was, however, associated with vocalization type and duration. We demonstrate that chimpanzees produce a vast array of combined vocal and visual components, exhibiting a hitherto underappreciated level of combinatorial complexity. We conclude that a multi-modal approach is crucial to accurately representing the communicative abilities of non-human primates.
REGENERATIVE GENE THERAPY IN THE HYPOTHALAMUS PROLONGS FERTILITY IN FEMALE RATS
Authors: Gallardo Maria D. , Girard Mauricio , Bigres Araceli , Lehmann Marianne , Rodriguez Silvia S. , Goya Rodolfo G. 
Published: May 2023

ABSTRACTThere is substantial evidence that age-related ovarian failure in rats is preceded by abnormal responsiveness of the neuroendocrine axis to estrogen positive feedback. In middle-aged (M-A) female rats, we have demonstrated that intrahypothalamic gene therapy for insulin-like growth factor-I (IGF-I) started at 6 months of age extends the regular cyclicity of the animals beyond 10 month (the age at which MA rats stop ovulating) and preserves the integrity of the ovarian structure. Here, we implemented long-term regenerative gene therapy in the hypothalamus of young females. The goal was to extend fertility in the treated animals. We constructed a helper-dependent adenovector that harbors the green fluorescent protein (GFP) reporter gene as well as a gene tandem, termed STEMCCA, which harbors the 4 Yamanaka genes (oct4, sox2, klf4, and c-myc, OSKM), both under the control of a Tet-Off bidirectional promoter. An adenovector that only carries the gene for GFP was used as control. At 4 months of age 12 female rats received an intrahypothalamic injection of our OSKM-GFP vector (treated rats); 12 control rats a vector expressing GFP only (control rats). At 9.3 months of age control and treated rats were mated with young males. A group of 12 young intact female rats was also mated. The rate of pregnancy recorded was 83%, 8.3% and 25% for young, M-A control and M-A treated animals, respectively. Average litter size was 9, 3 and 3 for the corresponding groups. Mean pup BW was slightly higher in the M-A rats. In a preliminary study we confirmed that ovulation in our M-A females ceases at 10 months of age. Our results are in line with the evidence that viral vector-mediated delivery of the Yamanaka genes in the brain has strong regenerative effects without adverse side effects. The particular significance of the present results is that, for the first time, they show that long-term OSKM gene therapy in the hypothalamus is able to extend the functionality of such a complex system as the hypothalamo-pituitary-ovarian axis.
Integration of HLA-DR linkage disequilibrium to MHC class II predictions
Authors: Pedersen Mette Bøge , Asmussen Sarah Rosenberg , Sarfelt Freja Malou , Saksager Astrid Brix , Sackett Peter Wad , Nielsen Morten , Barra Carolina 
Published: May 2023

AbstractInsights into peptide binding to HLA class II molecules is essential when studying the biological mechanisms behind cellular immunity, autoimmune diseases, and the development of immunotherapies and peptide vaccines. Currently, most of the publicly available data used to train state-of-the-art binding prediction methods for HLA-DR only includes DRB1 information. The role of the paralogue alleles, HLA-DRB3/4/5, and their strong linkage disequilibrium to DRB1 is often omitted when typing HLA-II alleles. This leads to ambiguities when making disease associations and interpreting HLA-restricted immune data. To resolve this issue, we present HLAAssoc-1.0, a method to infer HLA-DRB3/4/5 alleles by linkage disequilibrium to HLA-DRB1. We illustrate the usage of the tool and the importance of the integration of HLA-DRB3/4/5 alleles in the data analysis in different case studies including the interpretation of immunopetidomics data. Additionally, we infer allele information for the data used for training of NetMHCIIpan lacking HLA-DRB3/4/5 allele information and demonstrate that the retrained method achieved improved performance. In all cases, inferring HLA-DRB3/4/5 allele presence in non-fully typed HLA-II assays resulted in improved allele and motif deconvolutions. HLAAssoc-1.0 is available athttps://services.healthtech.dtu.dk/service.php?HLAAssoc-1.0.
The impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication: insights from a BALB/c mouse model
Authors: Morris Dorothea R. , Qu Yue , Thomason Kerrie S. , Haas de Mello Aline , Preble Richard , Menachery Vineet D. , Casola Antonella , Garofalo Roberto P. 
Published: May 2023

AbstractRSV and SARS-CoV-2 are prone to co-infection with other respiratory viruses. In this study, we use RSV/SARS-CoV-2 co-infection to evaluate changes to clinical disease and viral replication in vivo. To consider the severity of RSV infection, effect of sequential infection, and the impact of infection timing, mice were co-infected with varying doses and timing. Compared with a single infection of RSV or SARS-CoV-2, the co-infection of RSV/SARS-CoV-2 and the primary infection of RSV followed by SARS-CoV-2 results in protection from SARS-CoV-2-induced clinical disease and reduces SARS-CoV-2 replication. Co-infection also augmented RSV replication at early timepoints with only the low dose. Additionally, the sequential infection of RSV followed by SARS-CoV-2 led to improved RSV clearance regardless of viral load. However, SARS-CoV-2 infection followed by RSV results in enhanced SARS-CoV-2-induced disease while protecting from RSV-induced disease. SARS-CoV-2/RSV sequential infection also reduced RSV replication in the lung tissue, regardless of viral load. Collectively, these data suggest that RSV and SARS-CoV-2 co-infection may afford protection from or enhancement of disease based on variation in infection timing, viral infection order, and/or viral dose. In the pediatric population, understanding these infection dynamics will be critical to treat patients and mitigate disease outcomes.Author SummaryInfants and young children are commonly affected by respiratory viral co-infections. While RSV and SARS-CoV-2 are two of the most prevalent respiratory viruses, their co-infection rate in children remains surprisingly low. In this study, we investigate the impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication using an animal model. The findings indicate that RSV infection either simultaneously or prior to SARS-CoV-2 infection in mice protect against SARS-CoV-2-induced clinical disease and viral replication. On the other hand, infection with SARS-CoV-2 followed by RSV results in worsening of SARS-CoV-2-induced clinical disease, but also protection from RSV-induced clinical disease. These results highlight a protective role for RSV exposure, given this occurs before infection with SARS-CoV-2. This knowledge could help guide vaccine recommendations in children and sets a basis for future mechanistic studies.Graphical Abstract
Spatio-temporal variation of bacterial community structure in two intertidal sediment types of Jiaozhou Bay
Authors: Chen Xuechao , Zhang Xinran , Yu Hao , Han Meiaoxue , Sun Jianhua , Liu Gang , Ji Yan , Zhai Chuan , Zhu Liyan , Shao Hongbing , Liang Yantao , McMinn Andrew , Wang Min 
Published: May 2023

AbstractThe intertidal sediment environment is dynamic and the biofilm bacterial community within it must constantly adjust, but an understanding of the differences in the biofilm bacterial community within sediments of different types is still relatively limited. In this study, the structure of the bacterial community in Jiaozhou Bay sediment biofilms are described using high-throughput 16S rRNA gene sequencing and the effects of temporal change and different sediment environment types are discussed. The Shannon index was significantly higher in sandy samples than in muddy samples. The co-occurrence network was tighter and more species were involved in community building in sandy samples. The principal coordinates analysis identified a significant separation between different sediment types and between stations (LiCun estuary, LC and ZhanQiao Pier, ZQ). Proteobacteria, which had a relative abundance of approximately 50% at all phylum levels, was significantly more abundant at ZQ, while Campilobacterota and Firmicutes were significantly more abundant at LC. The relative abundances of Bacteroidetes, Campilobacterota, Firmicutes, and Chloroflexi were significantly higher in the muddy samples, while Actinobacteria and Proteobacteria were higher in the sandy samples. There were different phylum-level biomarkers between sediment types at different stations. There were also different patterns of functional enrichment in biogeochemical cycles between sediment types and stations with the former having more gene families that differed significantly, highlighting their greater role in determining bacterial function. The RDA results, where each month’s samples were concentrated individually, showed reduced variation between months when the amplicon sequence variant was replaced by KEGG orthologs, presumably the temporal change had an impact on shaping the intertidal sediment bacterial community, although this was less clear at the gene family level. Random forest prediction yielded a combination of 43 family-level features that responded well to temporal change, reflecting the influence of temporal change on sediment biofilm bacteria.HighlightsSandy sediments have more bacterial species involved in community building.Different substrates from different stations have their own phylum biomarkers.Substrates have a greater influence on shaping bacterial function.Temporal changes have a greater shaping power on bacteria than on gene families.Graphic abstract
Mitochondrial temperature homeostasis resists external metabolic stresses
Authors: Terzioglu Mügen , Veeroja Kristo , Montonen Toni , Ihalainen Teemu O. , Salminen Tiina S. , Bénit Paule , Rustin Pierre , Chang Young-Tae , Nagai Takeharu , Jacobs Howard T. 
Published: May 2023

ABSTRACTBased on studies with a fluorescent reporter dye, Mito Thermo Yellow, and the genetically encoded gTEMP ratiometric fluorescent temperature indicator targeted to mitochondria, the temperature of active mitochondria in four mammalian and one insect cell-line was estimated to be up to 15 °C above that of the external environment to which the cells were exposed. High mitochondrial temperature was maintained in the face of a variety of metabolic stresses, including substrate starvation or modification, decreased ATP demand due to inhibition of cytosolic protein synthesis, inhibition of the mitochondrial adenine nucleotide transporter and, if an auxiliary pathway for electron transfer was available via the alternative oxidase, even respiratory poisons acting downstream of OXPHOS complex I. We propose that the high temperature of active mitochondria is an inescapable consequence of the biochemistry of oxidative phosphorylation and is homeostatically maintained as a primary feature of mitochondrial metabolism.IMPACT STATEMENTMitochondria are up to 15 °C hotter than their external environment in living cells. In response to diverse metabolic stresses, mitochondrial temperature re-adjusts to this value whenever possible.
Creating, curating and querying computer models of biological pathways for Inherited Metabolic Disorders
Authors: Slenter Denise N. , Willighagen Egon L. 
Published: May 2023

AbstractCollecting knowledge about Inherited Metabolic Disorders (IMDs) has the potential to support early diagnosis as well as foster research into treatment options. Biological pathway databases can be used to create an overview of relevant articles and books describing IMDs and collect, curate, and summarize knowledge about these disorders. Reuse of the information captured in these databases in research requires the knowledge to be accurate but also machine-readable. WikiPathways is a community-driven project to establish a machinereadable knowledge base of biological processes. We here describe how pathways models from WikiPathways were used to represent the underlying biological mechanisms of many IMDs collected by domain experts over a period of six years. This paper describes a standardized approach to depict IMDs in WikiPathways, shows the current limitations in creating machine-readable disease information, and introduces an approach to support data curation based on these machine-readable biological pathways. Furthermore, several SPARQL-queries were developed to analyze the biological content created in these models. Using this approach, 47 pathways were collected about 345 diseases, involving 877 metabolites, 421 annotated metabolic interactions, 262 genes, and 587 proteins related to these disorders.
A Generative Model for Creating Path Delineated Helical Proteins
Authors: Kibler Ryan D. , Wicky Basile , Coventry Brian , Woodall Nicholas B. 
Published: May 2023

AbstractEngineered proteins with precisely defined shapes can scaffold functional protein domains in 3D space to fine-tune their functions, such as the regulation of cellular signaling by ligand positioning or the design of self-assembling protein materials with specific forms. Methods for simply and efficiently generating the protein backbones to initiate these design processes remain limited. In this work, we develop a lightweight neural network to guide helix fragment assembly along a guideline using a GAN architecture and show that this approach can rapidly generate viable samples while being computationally inexpensive. Key to our approach is the transformation of the input structural data used for training into a parametric representation of helices to reduce the generator network size, which in turn facilitates rapid backpropagation to find specific helical arrangements during generation. This approach provides a method to quickly generate helical protein scaffolds.
ROCCO: A Robust Method for Detection of Open Chromatin via Convex Optimization
Authors: Hamilton Nolan H. , Furey Terrence S. 
Published: May 2023

AbstractMotivationAnalysis of open chromatin regions across multiple samples from two or more distinct conditions can determine altered gene regulatory patterns associated with biological phenotypes and complex traits. The ATAC-seq assay allows for tractable genome-wide open chromatin profiling of large numbers of samples. Stable, broadly applicable genomic annotations of open chromatin regions are not available. Thus, most studies first identify open regions using peak calling methods for each sample independently. These are then heuristically combined to obtain a consensus peak set. Reconciling sample-specific peak resultspost hocfrom larger cohorts is particularly challenging, and informative spatial features specific to open chromatin signals are not leveraged effectively.ResultsWe propose a novel method,ROCCO, that determines consensus open chromatin regions across multiple samples simultaneously.ROCCOemploys robust summary statistics and solves a constrained optimization problem formulated to account for both enrichment and spatial dependence of open chromatin signal data. We show this formulation admits attractive theoretical and conceptual properties as well as superior empirical performance compared to current methodology.Availability and ImplementationSource code, documentation, and usage demos forROCCOare available on GitHub at:https://github.com/nolan-h-hamilton/ROCCO.ROCCOcan also be installed as a standalone binary utility usingpip/PyPI.Contactnolanh@email.unc.eduortsfurey@email.unc.edu.Supplementary InformationSupplementary material is available with this submission. Additional resources that may aid readers are available in theROCCOGitHubrepository.
Improving the study of RNA dynamics through advances in RNA-seq with metabolic labeling and nucleotide-recoding chemistry
Authors: Zimmer Joshua T. , Vock Isaac W. , Schofield Jeremy A. , Kiefer Lea , Moon Michelle H. , Simon Matthew D. 
Published: May 2023

AbstractRNA metabolic labeling using 4-thiouridine (s4U) captures the dynamics of RNA synthesis and decay. The power of this approach is dependent on appropriate quantification of labeled and unlabeled sequencing reads, which can be compromised by the apparent loss of s4U-labeled reads in a process we refer to as dropout. Here we show that s4U-containing transcripts can be selectively lost when RNA samples are handled under sub-optimal conditions, but that this loss can be minimized using an optimized protocol. We demonstrate a second cause of dropout in nucleotide recoding and RNA sequencing (NR-seq) experiments that is computational and downstream of library preparation. NR-seq experiments involve chemically converting s4U from a uridine analog to a cytidine analog and using the apparent T-to-C mutations to identify the populations of newly synthesized RNA. We show that high levels of T-to-C mutations can prevent read alignment with some computational pipelines, but that this bias can be overcome using improved alignment pipelines. Importantly, kinetic parameter estimates are affected by dropout independent of the NR chemistry employed, and all chemistries are practically indistinguishable in bulk, short-read RNA-seq experiments. Dropout is an avoidable problem that can be identified by including unlabeled controls, and mitigated through improved sample handing and read alignment that together improve the robustness and reproducibility of NR-seq experiments.