bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strong phylogenetic signal despite high phylogenomic complexity in an Andean plant radiation (Freziera,Pentaphylacaceae)
Authors: Frost Laura , Bedoya Ana M. , Lagomarsino Laura 
Published: July 2021

AbstractThe Andes mountains of western South America are a globally important biodiversity hotspot, yet there is a paucity of resolved phylogenies for plant clades from this region. Filling an important gap to our understanding of the World’s richest flora, we present the first phylogeny ofFreziera(Pentaphylacaceae), an Andean-centered, cloud forest radiation. Our dataset was obtained via hybrid-enriched target sequence capture of Angiosperms353 universal loci for 50 of the ca. 75 spp., obtained almost entirely from herbarium specimens. We identify high phylogenomic complexity inFreziera, including the presence of data artifacts. Via by-eye observation of gene trees, detailed examination of warnings from recently improved assembly pipelines, and gene tree filtering, we identified that artifactual orthologs (i.e., the presence of only one copy of a multi-copy gene due to differential assembly) were an important source of gene tree heterogeneity that had a negative impact on phylogenetic inference and support. These artifactual orthologs may be common in plant phylogenomic datasets, where multiple instances of genome duplication are common. After accounting for artifactual orthologs as source of gene tree error, we identified a significant, but non-specific signal of introgression using Patterson’s D and f4 statistics. Despite phylogenomic complexity, we were able to resolveFrezierainto nine well-supported subclades whose evolution has been shaped by multiple evolutionary processes, including incomplete lineage sorting, historical gene flow, and gene duplication. Our results highlight the complexities of plant phylogenomics, which are heightened in Andean radiations, and show the impact of filtering data processing artifacts and standard filtering approaches on phylogenetic inference.
We get by with a little help from our friends: shared adaptive variation provides a bridge to novel ecological specialists during adaptive radiation
Authors: Richards Emilie J. , Martin Christopher H. 
Published: July 2021

AbstractAdaptive radiations involve astounding bursts of phenotypic, ecological, and species diversity. However, the microevolutionary processes that underlie the origins of these bursts are still poorly understood. We report the discovery of an intermediate ‘wide-mouth’ scale-eating ecomorph in a sympatric radiation of Cyprinodon pupfishes, illuminating the transition from a widespread algae-eating generalist to a novel microendemic scale-eating specialist. We first show that this ecomorph occurs in sympatry with generalist C. variegatus and scale-eating specialist C. desquamator on San Salvador Island, Bahamas, but is genetically differentiated, morphologically distinct, and often consumes scales. We then compared the timing of selective sweeps on shared and unique adaptive variants in trophic specialists to characterize their adaptive walk. Shared adaptive regions swept first in both the specialist desquamator and the intermediate ‘wide-mouth’ ecomorph, followed by unique sweeps of introgressed variation in ‘wide-mouth’ and de novo variation in desquamator. The two scale-eating populations additionally shared 9% of their hard selective sweeps with molluscivores C. brontotheroides, despite no single common ancestor among specialists. Our work provides a new microevolutionary framework for investigating how major ecological transitions occur and illustrates how both shared and unique genetic variation can provide a bridge for multiple species to access novel ecological niches.
The spatial transcriptomic landscape of the healing intestine following damage
Authors: Parigi Sara M. , Larsson Ludvig , Das Srustidhar , Ramirez Flores Ricardo O. , Frede Annika , Tripathi Kumar P. , Diaz Oscar E. , Selin Katja , Morales Rodrigo A. , Luo Xinxin , Monasterio Gustavo , Engblom Camilla , Gagliani Nicola , Saez-Rodriguez Julio , Lundeberg Joakim , Villablanca Eduardo J. 
Published: July 2021

AbstractThe intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics (ST) to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we used our resource to map transcriptomics modules associated with human diseases demonstrating that ST can be used to inform clinical practice. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.
FishExp: a comprehensive database and analysis platform for gene expression and alternative splicing of fish species
Authors: Tan Suxu , Wang Wenwen , Jie Wencai , Liu Jinding 
Published: July 2021

AbstractThe publicly archived RNA-seq data has grown exponentially, but its valuable information has not yet been fully discovered and utilized, especially for alternative splicing. This is true for fish species, which play important roles in ecology, research, and the food industry. To mitigate this, we present FishExp, a web-based data platform covering gene expression and alternative splicing in 26,081 RNA-seq experiments from 44 fishes. In addition to searching by gene identifiers and symbols, FishExp allows users to query the data using various functional terms and BLAST alignment. Notably, the user can customize experiments and tools to perform differential/specific expression and alternative splicing analysis, provided with functional enrichments. The results of retrieval and analysis can be visualized on the gene-, transcript- and splicing event-level webpage in a highly interactive and intuitive manner. The manually curated sample information, uniform data processing and visualization tools make it efficient for users to gain new insights from these large datasets. All data in FishExp can be downloaded for more in-depth analysis. FishExp is freely accessible at https://bioinfo.njau.edu.cn/fishExp.
Inducible Yeast Two-Hybrid with Quantitative Measures
Authors: Hernandez Jesus , Ross Kevin D. , Hamilton Bruce A. 
Published: July 2021

ABSTRACTThe yeast two-hybrid (Y2H) assay has long been used to identify new protein-protein interaction pairs and to compare relative interaction strengths. Traditional Y2H formats may be limited, however, by use of constitutive strong promoters if expressed proteins have toxic effects or post-transcriptional expression differences in yeast among a comparison group. As a step toward more quantitative Y2H assays, we modified a common vector to use an inducible CUP1 promoter, which showed quantitative induction of several “bait” proteins with increasing copper concentration. Using mouse Nxf1 (homologous to yeast Mex67p) as a model bait, copper titration achieved levels that bracket levels obtained with the constitutive ADH1 promoter. Using a liquid growth assay for an auxotrophic reporter in multiwell plates allowed log-phase growth rate to be used as a measure of interaction strength. These data demonstrate the potential for quantitative comparisons of protein-protein interactions using the Y2H system.
Characterizing collaborative transcription regulation with a graph-based deep learning approach
Authors: Zhang Zhenhao , Feng Fan , Yao Yuan , Liu Jie 
Published: July 2021

AbstractHuman epigenome and transcription activities have been characterized by a number of sequence-based deep learning approaches which only utilize the DNA sequences. However, transcription factors interact with each other, and their collaborative regulatory activities go beyond the linear DNA sequence. Therefore leveraging the informative 3D chromatin organization to investigate the collaborations among transcription factors is critical. We developed ECHO, a graph-based neural network, to predict chromatin features and characterize the collaboration among them by incorporating 3D chromatin organization from 200-bp high-resolution Micro-C contact maps. ECHO predicts 2, 583 chromatin features with significantly higher average AUROC and AUPR than the best sequence-based model. We observed that chromatin contacts of different distances affected different types of chromatin features’ prediction in diverse ways, suggesting complex and divergent collaborative regulatory mechanisms. Moreover, ECHO was interpretable via gradient-based attribution methods. The attributions on chromatin contacts identify important contacts relevant to chromatin features. The attributions on DNA sequences identify TF binding motifs and TF collaborative binding. Furthermore, combining the attributions on contacts and sequences reveals important sequence patterns in the neighborhood which are relevant to target sequence’s chromatin feature prediction. The attribution results that reveal TF collaboration activities are provided on a website https://echo.dcmb.med.umich.edu/echo/.
Evolution and diversity of bat and rodent Paramyxoviruses from North America
Authors: Larsen Brendan B. , Gryseels Sophie , Otto Hans W. , Worobey Michael 
Published: July 2021

AbstractParamyxoviruses are a diverse group of negative-sense, single-stranded RNA viruses of which several species cause significant mortality and morbidity. In recent years the collection of paramyxoviruses sequences detected in wild mammals has substantially grown, however little is known about paramyxovirus diversity in North American mammals. To better understand natural paramyxovirus diversity, host range, and host specificity, we sought to comprehensively characterize paramyxoviruses across a range of diverse co-occurring wild small mammals in Southern Arizona. We used highly degenerate primers to screen fecal and urine samples and obtained a total of 55 paramyxovirus sequences from 12 rodent species and 6 bat species. We also performed illumina RNA-seq and de novo assembly on 14 of the positive samples to recover a total of 5 near full-length viral genomes. We show there are at least 2 clades of rodent-borne paramyxoviruses in Arizona, while bat-associated paramyxoviruses formed a putative single clade. Using structural homology modeling of the viral attachment protein, we infer that three of the five novel viruses likely bind sialic acid in a manner similar to other Respiroviruses, while the other two viruses from Heteromyid rodents likely bind a novel host receptor. We find no evidence for cross-species transmission, even among closely related sympatric host species. Taken together, these data suggest paramyxoviruses are a common viral infection in some bat and rodent species present in North America, and illuminate the evolution of these viruses.ImportanceThere are a number of viral lineages that are potential zoonotic threats to humans. One of these, paramyxoviruses, have jumped into humans multiple times from wild and domestic animals. We conducted one of the largest viral surveys of wild mammals in the United States to better understand paramyxovirus diversity and evolution.
Development and Validation of a High-Throughput Short Sequence Typing Scheme forSerratia marcescensPure Culture and Environmental DNA
Authors: Bourdin Thibault , Monnier Alizée , Benoit Marie-Ève , Bédard Emilie , Prévost Michèle , Quach Caroline , Déziel Eric , Constant Philippe 
Published: July 2021

AbstractMolecular typing methods are used to characterize the relatedness between bacterial isolates involved in infections. These approaches rely mostly on discrete loci or whole genome sequences (WGS) analyses of pure cultures. On the other hand, their application to environmental DNA profiling to evaluate epidemiological relatedness amongst patients and environments has received less attention. We developed a specific, high-throughput short sequence typing (HiSST) method for the opportunistic human pathogenSerratia marcescens. Genes displaying the highest polymorphism were retrieved from the core genome of 60S. marcescensstrains. Bioinformatics analyses showed that use of only three loci (withinbssA, gabRanddhaM) distinguished strains with the same level of efficiency than average nucleotide identity scores of whole genomes. This HiSST scheme was applied to an epidemiological survey ofS. marcescensin a neonatal intensive care unit (NICU). In a first case study, a strain responsible for an outbreak in the NICU was found in a sink drain of this unit, by using HiSST scheme and confirmed by WGS. The HiSST scheme was also applied to environmental DNA extracted from sink-environment samples. Diversity ofS. marcescenswas modest, with 11, 6 and 4 different sequence types (ST) ofgabR, bssAanddhaMloci amongst 19 sink drains, respectively. Epidemiological relationships amongst sinks were inferred on the basis of pairwise comparisons of ST profiles. Further research aimed at relating ST distribution patterns to environmental features encompassing sink location, utilization and microbial diversity is needed to improve the surveillance and management of opportunistic pathogens.
Loss of GdpP function in Staphylococcus aureus leads to β-lactam tolerance and enhanced evolution of β-lactam resistance
Authors: Poon Raymond , Basuino Li , Satishkumar Nidhi , Chatterjee Aditi , Mukkayyan Nagaraja , Buggeln Emma , Huang Liusheng , Nair Vinod , Argudín Maria A. , Datta Sandip K. , Chambers Henry F. , Chatterjee Som S. 
Published: July 2021

SynopsisBackgroundWe previously reported the presence of mutations in gdpP among Staphylococcus aureus strains that were obtained by serial passaging in β-lactam drugs. gdpP codes for a phosphodiesterase that cleaves cyclic-di-AMP (CDA), a newly discovered second messenger.ObjectivesWe sought to identify the role of gdpP in β-lactam resistance of S. aureus.MethodsCDA concentrations in bacterial cytosol were measured through mass-spectrometric analysis. gdpP deletion mutagenesis and their complemented strains were created in clinically relevant S. aureus strains to characterize its function.ResultsgdpP associated mutations among passaged strains were identified to cause loss of phosphodiesterase function, leading to increased CDA accumulation in the bacterial cytosol. Deletion of gdpP led to an enhanced ability of the bacteria to withstand a β-lactam challenge (two to three log increase in bacterial colony forming units) by promoting tolerance without enhancing MICs of β-lactam antibiotics. Our results demonstrate that increased drug tolerance due to loss of GdpP function can provide a selective advantage in acquisition of high-level β-lactam resistance and could lead to β-lactam treatment failure of S. aureus infections.ConclusionsLoss of GdpP function increases tolerance to β-lactams that can lead to its therapy failure and can permit β-lactam resistance to occur more readily.
Network diffusion model predicts neurodegeneration in limb-onset amyotrophic lateral sclerosis
Authors: Bhattarai Anjan , Chen Zhaolin , Chua Phyllis , Talman Paul , Mathers Susan , Chapman Caron , Howe James , Lee CM Sarah , Lie Yenni , Poudel Govinda R , Egan Gary F 
Published: July 2021

AbstractThe trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS. We measured degeneration in limb-onset ALS patients (n=14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n=12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. The cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Our findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.
Aboveground biomass increments over 26 years (1993–2019) in an old-growth cool-temperate forest in northern Japan
Authors: Noguchi Mahoko , Hoshizaki Kazuhiko , Matsushita Michinari , Sugiura Daiki , Yagihashi Tsutomu , Saitoh Tomoyuki , Itabashi Tomohiro , Kazuhide Ohta , Shibata Mitsue , Hoshino Daisuke , Masaki Takashi , Osumi Katsuhiro , Takahashi Kazunori , Suzuki Wajirou 
Published: July 2021

AbstractAssessing long-term changes in biomass of old-growth forests is critical in evaluating forest ecosystem functions under a changing climate. Long-term biomass changes are the result of accumulated short-term changes, which can be affected by endogenous processes such as gap filling in small-scale canopy openings. Here, we used 26 years (1993–2019) of repeated tree census data in an old-growth, cool-temperate, deciduous mixed forest that contains three topographic units (riparian, denuded slope, and terrace) in northern Japan to document decadal changes in aboveground biomass (AGB) and their processes in relation to endogenous processes and climatic factors. AGB increased steadily over the 26 years in all topographic units, but different tree species contributed to the increase among the topographic units. AGB gain within each topographic unit exceeded AGB loss via tree mortality in most of the measurement periods despite substantial temporal variation in AGB loss. At the local scale, variations in AGB gain were partially explained by compensating growth of trees around canopy gaps. Climate affected the local-scale AGB gain: the gain was larger in the measurement periods with higher mean temperature during the current summer but smaller in those with higher mean temperature during the previous autumn, synchronously in all topographic units. The decadal climate trends of warming are likely to have contributed to the steady increase in AGB in this old-growth forest.
Wild lab: A naturalistic free viewing experiment reveals previously unknown EEG signatures of face processing
Authors: Gert Anna L. , Ehinger Benedikt V. , Timm Silja , Kietzmann Tim C. , König Peter 
Published: July 2021

AbstractNeural mechanisms of face perception are predominantly studied in well-controlled experimental settings that involve random stimulus sequences and fixed eye positions. While powerful, the employed paradigms are far from what constitutes natural vision. Here, we demonstrate the feasibility of ecologically more valid experimental paradigms using natural viewing behavior, by combining a free viewing paradigm on natural scenes, free of photographer bias, with advanced data processing techniques that correct for overlap effects and co-varying nonlinear dependencies of multiple eye movement parameters. We validate this approach by replicating classic N170 effects in neural responses, triggered by fixation onsets (fERPs). Importantly, our more natural stimulus paradigm yielded smaller variability between subjects than the classic setup. Moving beyond classic temporal and spatial effect locations, our experiment furthermore revealed previously unknown signatures of face processing. This includes modulation of early fERP components, as well as category-specific adaptation effects across subsequent fixations that emerge even before fixation onset.
Mapping Protein Numbers in Living Cells
Authors: Thirstrup Derek J , Yao Jie , Sherman Jamie , Mueller Irina A , Wiegraebe Winfried 
Published: July 2021

AbstractWe introduce a new, robust method to map the numbers of proteins in living cells. The method can be applied to laser scanning, spinning disk, and lattice light-sheet microscopes in a robust, reproducible, and scalable fashion. The method uses calibrated EGFP solutions that are imaged with the appropriate microscope modality to create a calibration curve that is then applied to convert the fluorescence intensities from 3D microscope images into molecule numbers. We applied this method to human induced pluripotent stem cells in which proteins representing key cellular structures were endogenously tagged with mEGFP. We used the ratio of mEGFP-tagged proteins to total proteins to create 3D maps of live cells showing the density of total proteins measured in molecules per µm3. The method opens the door to new quantitative single cell analyses of cellular protein numbers in the context of single cell gene expression, associations with cellular complexes, and changes in cellular behaviors. The method is capable of quantifying protein numbers, over three orders of magnitude, in the cytoplasm or within various cellular structures while offering the unique advantages of each microscopy modality.
Eukaryotic stress induced mutagenesis is limited by a local control of Translesion Synthesis
Authors: Masłowska Katarzyna H. , Villafañez Florencia , Laureti Luisa , Iwai Shigenori , Pagès Vincent 
Published: July 2021

AbstractThe DNA Damage Response (DDR) preserves the genetic integrity of the cell by sensing and repairing damages after a genotoxic stress. Translesion Synthesis (TLS), an error-prone DNA damage tolerance pathway, is controlled by PCNA ubiquitination. In this report, we raise the question whether TLS is controlled locally, or globally. Using a recently developed method that allows to follow the bypass of a single lesion inserted into the yeast genome, we show that: i) TLS is controlled locally at each individual lesion by PCNA ubiquitination, ii) a single lesion is enough to induce PCNA ubiquitination, and iii) PCNA ubiquitination is an imperative requirement for TLS to occur. More importantly, we show that global PCNA ubiquitination that follows a genotoxic stress does not increase TLS at individual lesions. We conclude that unlike the SOS response in bacteria, the eukaryotic DDR does not promote TLS and mutagenesis.