bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstructing the transcriptional ontogeny of maize and sorghum supports an inverse hourglass model of inflorescence development
Authors: Leiboff Samuel , Hake Sarah 
Published: April 2019

AbstractAssembling meaningful comparisons between species is a major limitation in studying the evolution of organismal form. To understand development in maize and sorghum, closely-related species with architecturally distinct inflorescences, we collected RNAseq profiles encompassing inflorescence body plan specification in both species. We reconstructed molecular ontogenies from 40 B73 maize tassels and 47 BT×623 sorghum panicles and separated them into transcriptional stages. To discover new markers of inflorescence development, we used random forest machine learning to determine stage by RNAseq. We used two descriptions of transcriptional conservation to identify hourglass-like developmental stages. Despite short evolutionary ancestry of 12 million years, we found maize and sorghum inflorescences are most different during their hourglass-like stages of development, following an ‘inverse-hourglass’ model of development. We discuss if agricultural selection may account for the rapid divergence signatures in these species and the observed separation of evolutionary pressure and developmental reprogramming.HighlightsTranscript dynamics identify maize tassel and sorghum panicle developmental stagesRandom forest predicts developmental age by gene expression, providing molecular markers and anin silicostaging applicationMaize and sorghum inflorescences are most similar when committing stem cells to a determinant fateExpression conservation identifies hourglass-like stage, but transcriptomes diverge, similar to ‘inverse hourglass’ observations in cross-phyla animal embryo comparisons
ABioTrans: A Biostatistical tool for Transcriptomics Analysis
Authors: Yutong Zou , Thuy Tien Bui , Selvarajoo Kumar 
Published: April 2019

AbstractHere we report a bio-statistical/informatics tool, ABioTrans, developed in R for gene expression analysis. The tool allows the user to directly read RNA-Seq data files deposited in the Gene Expression Omnibus or GEO database. Operated using any web browser application, ABioTrans provides easy options for multiple statistical distribution fitting, Pearson and Spearman rank correlations, PCA, k-means and hierarchical clustering, differential expression analysis, Shannon entropy and noise (square of coefficient of variation) analyses, as well as Gene ontology classifications.Availability and implementationABioTrans is available at https://github.com/buithuytien/ABioTransOperating system(s): Platform independent (web browser)Programming language: R (R studio)Other requirements: Bioconductor genome wide annotation databases, R-packages (shiny, LSD, fitdistrplus, actuar, entropy, moments, RUVSeq, edgeR, DESeq2, NOISeq, AnnotationDbi, ComplexHeatmap, circlize, clusterProfiler, reshape2, DT, plotly, shinycssloaders, dplyr, ggplot2). These packages will automatically be installed when the ABioTrans.R is executed in R studio.No restriction of usage for non-academic.
CCDC186 controls dense-core vesicle cargo sorting by exit
Authors: Cattin-Ortolá Jérôme , Topalidou Irini , Lau Ho-Tak , Hummer Blake , Asensio Cedric S. , Ong Shao-En , Ailion Michael 
Published: April 2019

ABSTRACTThe regulated release of peptide hormones depends on their packaging into dense-core vesicles (DCVs). Two models have been proposed for DCV cargo sorting. The “sorting by entry” model proposes that DCV cargos selectively enter nascent DCVs at the trans-Golgi network (TGN). The “sorting by exit” model proposes that sorting occurs by the post-TGN removal of non-DCV cargos and retention of mature DCV cargos. Here we show that the coiled-coil protein CCDC186 controls sorting by exit.Ccdc186KO insulinoma cells secrete less insulin, fail to retain insulin and carboxypeptidase E in mature DCVs at the cell periphery, and fail to remove carboxypeptidase D from immature DCVs. A mutation affecting the endosome-associated recycling protein (EARP) complex causes similar defects in DCV cargo retention and removal. CCDC186 and EARP may act together to control the post-Golgi retention of cargos in mature DCVs.
Zebrafish GPR161 Contributes to Basal Hedgehog Repression in a Tissue-specific Manner
Authors: Tschaikner Philipp , Regele Dominik , Salvenmoser Willi , Geley Stephan , Stefan Eduard , Aanstad Pia 
Published: April 2019

AbstractHedgehog (Hh) ligands act as morphogens to direct patterning and proliferation during embryonic development. Protein kinase A (PKA) is a central negative regulator of Hh signalling, and in the absence of Hh ligands, PKA activity prevents inappropriate expression of Hh target genes. The Gαs- coupled receptor Gpr161 contributes to the basal Hh repression machinery by activating PKA, although the extent of this contribution is unclear. Here we show that loss of Gpr161 in zebrafish leads to constitutive activation of low-, but not high-level Hh target gene expression in the neural tube. In contrast, in the myotome, both high- and low-level Hh signalling is constitutively activated in the absence of Gpr161 function. Our results suggest that the relative contribution of Gpr161 to basal repression of Hh signalling is tissue-specific. Distinct combinations of G-protein-coupled receptors may allow the fine-tuning of PKA activity to ensure the appropriate sensitivity to Hh across different tissues.
Neuronal aging potentiates beta-amyloid generation via amyloid precursor protein endocytosis
Authors: Burrinha Tatiana , Gomes Ricardo , Terrasso Ana Paula , Almeida Cláudia Guimas 
Published: April 2019

AbstractAging increases the risk of Alzheimer’s disease (AD). During normal aging synapses decline and β-Amyloid (Aβ) accumulates. An Aβ defective clearance with aging is postulated as responsible for Aβ accumulation, although a role for increased Aβ production with aging can also lead to Aβ accumulation. To test this hypothesis, we established a long-term culture of primary mouse neurons that mimics neuronal aging (lysosomal lipofuscin accumulation and synapse decline). Intracellular endogenous Aβ42 accumulated in aged neurites due to increased amyloid-precursor protein (APP) processing. We show that APP processing is up-regulated by a specific age-dependent increase in APP endocytosis. Endocytosed APP accumulated in early endosomes that, in turn were found augmented in aged neurites. APP processing and early endosomes up-regulation was recapitulated in vivo. Finally, we found that inhibition of Aβ production reduced the decline in synapses in aged neurons. We propose that potentiation of APP endocytosis by neuronal aging increases Aβ production, which contributes to aging-dependent decline in synapses.SummaryHow aging increases the risk of Alzheimer’s disease is not clear. We show that normal neuronal aging increases the intracellular production of β-amyloid, due to an upregulation of the amyloid precursor protein endocytosis. Importantly, increased Aβ production contributes to the aging-dependent synapse loss.
Split-Belt walking induces changes in active, but not passive, perception of step length
Authors: Sombric Carly , Gonzalez-Rubio Marcela , Torres-Oviedo Gelsy 
Published: April 2019

AbstractThe estimation of limbs’ position is critical for motor control. While motor adaptation changes the estimation of limb position in volitional arm movements, this has not been observed in locomotion. We hypothesized that split-belt walking with the legs moving at different speeds changes the estimation of the legs’ position when taking a step. Thus, we assessed young subjects’ perception of step length (i.e., inter-feet distance at foot landing) when they moved their legs (active perception) or these were moved by the experimenter (passive perception). Step length’s active, but not passive perception was altered by split-belt walking; indicating that adapted efferent inputs changed the perceived limbs’ position without changing information from sensory signals. These perceptual shifts were sensitive to how they were tested: they were observed in the trailing, but not the leading leg, and they were more salient when tested with short than long step lengths. Our results suggest that sensory changes following motor adaptation might arise from mismatched limb position estimates from different sensory sources (i.e., proprioception and vision), which is less prominent in walking. We also speculate that split-belt walking could improve the deficient perception of step length post-stroke, which contributes to their gait asymmetry impairing patients’ mobility.
An in vitro model maintaining taxon-specific functional activities of the gut microbiome
Authors: Li Leyuan , Abou-Samra Elias , Ning Zhibin , Zhang Xu , Mayne Janice , Wang Janet , Cheng Kai , Walker Krystal , Stintzi Alain , Figeys Daniel 
Published: April 2019

AbstractThe gut microbiome is a new target for therapeutics. In vitro high-throughput culture models could provide time-and-cost saving solutions to discover microbiome responses to drugs. Unfortunately, there has been no report of in vitro models capable of maintaining functional and compositional profiles resembling the in vivo gut microbiome. Here, we developed and validated a high-throughput culturing model named Mipro to maintain individuals’ microbiomes. The Mipro model quintupled viable bacteria count while maintained the functional and compositional profiles of individuals’ gut microbiomes. Comparison of taxon-specific functions between pre -and-post culture microbiomes showed Pearson’s correlation coefficient r of 0.83 ± 0.03. Moreover, the Mipro model also exhibited a high degree of in vitro – in vivo correlation (Pearson’s r of 0.68 ± 0.09) in microbial responses to metformin in mice fed a high-fat diet. Mipro provides a highly simulated gut microbiome for high-throughput investigation of drug-microbiome interactions.
Quantifying the Payments for Ecosystem Services among hydrologic units in Zhujiang River Basin, China based on the indicator of Optional Capacity Value
Authors: Yang Haile , Zhao Bin , Chen Jiakuan 
Published: April 2019

AbstractEcosystem services (ES) are fundamental to human being’s livelihoods, production and survival. However, the spatial mismatch between ES supply and demand is a common phenomenon. Payments for Ecosystem Services (PES) provide a way to promote the complementary advantages and benefits equilibrium between ES supplier and beneficiary. At present, PES is mainly based on the tradeoff between the profit and loss of ecological conservation. The quantifying of PES mainly uses the opportunity cost of ES supplier and follows the principle of additionality, which neglects the benefits that arise from the basic (contrast to additional) ES experienced by ES beneficiary and ignores the rights and interests of ES supplier who supplies the basic ES. To resolve this problem, we proposed that we should set the value of ES experienced by ES beneficiary as the quantitative indicator of PES. Here, we introduced a new indicator (optional capacity value, OCV) to implement this idea. The ES OCV indicates the optional capacity of supporting the total value produced by human being’s economic and social activities provided by the total volume of an ES. In this paper, we calculated the ES OCV of water provision in Zhujiang River Basin (Pearl River Basin), China. Then, we discussed three scenarios of quantifying PES, based on the principles of (1) interests sharing and responsibilities bearing and (2) equal pay for equal work. The results showed that the ES OCV could describe the conditions that water resources in a hydrologic unit not only provide benefits to the hydrologic unit itself, but also provide benefits to downstream hydrologic units, and then could be a quantitative indicator for PES. This research provides a new PES scheme which would promote the coordinated development and ecological conservation among the regions with mismatch between ES supply and demand.
The MADS-box transcription factor PHERES1 controls imprinting in the endosperm by binding to domesticated transposons
Authors: Batista Rita A. , Moreno-Romero Jordi , Qiu Yichun , van Boven Joram , Santos-González Juan , Figueiredo Duarte D. , Köhler Claudia 
Published: April 2019

AbstractMADS-box transcription factors are ubiquitous in eukaryotic organisms and play major roles during plant development. Nevertheless, their function in seed development remains largely unknown. Here we show that the imprinted Arabidopsis thaliana MADS-box TF PHERES1 (PHE1) is a master regulator of paternally expressed imprinted genes, as well as of non-imprinted key regulators of endosperm development. PHE1 binding sites show distinct epigenetic modifications on maternal and paternal alleles, correlating with parental-specific transcriptional activity. Importantly, we show that the CArG-box-like DNA-binding motifs bound by PHE1 have been distributed by RC/Helitron transposable elements. Our data provide an example of molecular domestication of these elements, which by distributing PHE1 binding sites throughout the genome, have facilitated the recruitment of crucial endosperm regulators into a single transcriptional network.
Genetic analysis of the transition from wild to domesticated cotton (G. hirsutumL.)
Authors: Grover Corrinne E. , Yoo Mi-Jeong , Lin Meng , Murphy Matthew D. , Harker David B. , Byers Robert L. , Lipka Alexander E. , Hu Guanjing , Yuan Daojun , Conover Justin L. , Udall Joshua A. , Paterson Andrew H. , Gore Michael A. , Wendel Jonathan F. 
Published: April 2019

AbstractThe evolution and domestication of cotton is of great interest from both economic and evolutionary standpoints. Although many genetic and genomic resources have been generated for cotton, the genetic underpinnings of the transition from wild to domesticated cotton remain poorly known. Here we generated an intraspecific QTL mapping population specifically targeting domesticated cotton phenotypes. We used 466 F2individuals derived from an intraspecific cross between the wildGossypium hirsutumvar.yucatanense(TX2094) and the elite cultivarG. hirsutumcv. Acala Maxxa, in two environments, to identify 120 QTL associated with phenotypic changes under domestication. While the number of QTL recovered in each subpopulation was similar, only 22 QTL were considered coincident (i.e., shared) between the two locations, eight of which shared peak markers. Although approximately half of QTL were located in the A-subgenome, many key fiber QTL were detected in the D-subgenome, which was derived from a species with unspinnable fiber. We found that many QTL are environment-specific, with few shared between the two environments, indicating that QTL associated withG. hirsutumdomestication are genomically clustered but environmentally labile. Possible candidate genes were recovered and are discussed in the context of the phenotype. We conclude that the evolutionary forces that shape intraspecific divergence and domestication in cotton are complex, and that phenotypic transformations likely involved multiple interacting and environmentally responsive factors.SummaryAn F2population between wild and domesticated cotton was used to identify QTL associated with selection under domestication. Multiple traits characterizing domesticated cotton were evaluated, and candidate genes underlying QTL are described for all traits. QTL are unevenly distributed between subgenomes of the domesticated polyploid, with many fiber QTL located on the genome derived from the D parent, which does not have spinnable fiber, but a majority of QTL overall located on the A subgenome. QTL are many (120) and environmentally labile. These data, together with candidate gene analyses, suggest recruitment of many environmentally responsive factors during cotton domestication.
Concurrence of Porin Loss and Modular Amplification of β-Lactamase Encoding Genes Drives Carbapenem Resistance in a Cohort of Recurrent Enterobacterales Bacteremia
Authors: Shropshire William C. , Aitken Samuel L. , Pifer Reed , Kim Jiwoong , Bhatti Micah M. , Li Xiqi , Kalia Awdhesh , Galloway-Peña Jessica , Sahasrabhojane Pranoti , Arias Cesar A. , Greenberg David E. , Hanson Blake M. , Shelburne Samuel A. 
Published: April 2019

ABSTRACTBackgroundCarbapenem resistant Enterobacterales (CRE) remain urgent antimicrobial resistance threats. Approximately half of CRE clinical isolates lack carbapenem hydrolyzing enzymes and develop carbapenem resistance through alternative mechanisms. The purpose of this study was to elucidate the development of carbapenem resistance mechanisms from clonal, recurrent extended-spectrum β-lactamase positive Enterobacterales (ESBL-E) bacteremia isolates in a vulnerable patient population.MethodsThis study investigated a historical, retrospective cohort of ESBL-E bacteremia cases in the University of Texas MD Anderson Cancer Center (MDACC) from January 2015 to July 2016. Phylogenetic and comparative genomic analyses were performed to identify clonal, recurrent ESBL-E isolates developing carbapenem resistance. Oxford Nanopore Technology (ONT) long-read and Illumina short-read sequencing data were used to generate consensus assemblies and to identify signatures of mobile genetic element mediated amplification and transposition of antimicrobial resistance genes. Serial passaging experiments were performed on a set of clinical ST131 ESBL-E isolates to recapitulate in vivo observations. qPCR and qRT-PCR were used to determine respective copy number and transcript levels of β-lactamase genes.Results116 ESBL-E bacteremia cases were identified, 16 of which had documented recurrent infections. Four serial, recurrent isolates displayed a carbapenem resistant phenotype, three without the acquisition of a known carbapenemase. These three isolates had non-carbapenemase-producing CRE (non-CP-CRE) mechanisms driven by IS26- and ISEcp1-mediated amplification of respective translocatable units (TU) and transposition units (TPU) harboring both blaOXA-1 and blaCTX-M variants with concomitant outer membrane porin disruption. The TU and TPU structures inserted into the open reading frames of outer membrane porin genes in a subset of non-CP-CRE isolates. Serial passage of an index ST131 ESBL-E isolate under selective carbapenem exposure resulted in chromosomal amplification of modular, TUs harboring β-lactamase genes with concomitant porin inactivation, recapitulating the in vivo carbapenem resistance progression. Long-read sequencing of two additional MDACC bacteremia strains identified similar non-CP-CRE mechanisms observed in the serial isolates.ConclusionsNon-CP-CRE de novo mechanisms were the primary driver of CRE development in recurrent bacteremia cases within this vulnerable patient population. The incorporation of long-read ONT data into AMR surveillance platforms is critical to identify high-risk CRE isolates that are difficult to identify with low-resolution phenotypic and molecular characterization methods.
Distinct Structural Features of the Lon Protease Drive Conserved Hand-over-Hand Substrate Translocation
Authors: Shin Mia , Asmita Ananya , Puchades Cristina , Adjei Eric , Wiseman R. Luke , Karzai A. Wali , Lander Gabriel C. 
Published: April 2019

AbstractHand-over-hand translocation is emerging as the conserved mechanism by which ATP hydrolysis drives substrate translocation within the classical clade of AAA+ proteins. However, the operating principles of the distantly related HCLR clade, which includes the important quality control protease Lon, remains poorly defined. We determined a cryo-electron microscopy structure ofY. pestisLon trapped in the act of processing substrate. This structure revealed that sequential ATP hydrolysis and hand-over-hand substrate translocation are conserved in this AAA+ protease. However, Lon processes substrates through a distinct molecular mechanism involving structural features unique to the HCLR clade. Our findings define a previously unobserved translocation mechanism that is likely conserved across HCLR proteins and reveal how fundamentally distinct structural configurations of distantly-related AAA+ enzymes can power hand-over-hand substrate translocation.
Information processing by endoplasmic reticulum stress sensors
Authors: Stroberg Wylie , Eilertsen Justin , Schnell Santiago 
Published: April 2019

AbstractThe unfolded protein response (UPR) is a collection of cellular feedback mechanisms that seek to maintain protein folding homeostasis in the endoplasmic reticulum (ER). When the ER is “stressed”, either through high protein folding demand or undersupply of chaperones and foldases, stress sensing proteins in the ER membrane initiate the UPR. Recently, experiments have indicated that these signaling molecules detect stress by being both sequestered by free chaperones and activated by free unfolded proteins. However, it remains unclear what advantage this bidirectional sensor control offers stressed cells. Here, we show that combining positive regulation of sensor activity by unfolded proteins with negative regulation by chaperones allows the sensor to make a more informative measurement of ER stress. The increase in the information capacity of the combined sensing mechanism stems from stretching of the active range of the sensor, at the cost of increased uncertainty due to the integration of multiple signals. These results provide a possible rationale for the evolution of the observed stress sensing mechanism.
Statistical modeling, estimation, and remediation of sample index hopping in multiplexed droplet-based single-cell RNA-seq data
Authors: Farouni Rick , Djambazian Haig , Ragoussis Jiannis , Najafabadi Hamed S. 
Published: April 2019

AbstractWe introduce a probabilistic model for estimation of sample index-hopping rate in multiplexed droplet-based single-cell RNA sequencing data and for inference of the true sample of origin of the hopped reads. Across the datasets we analyzed, we estimate the sample index hopping probability to range between 0.003–0.009, a small number that counter-intuitively gives rise to a large fraction of ‘phantom molecules’ – as high as 85% in a given sample. We demonstrate that our model-based approach can correct for this artifact by accurately purging the majority of phantom molecules from the data. Code and reproducible analysis notebooks are available at https://github.com/csglab/phantom_purge.StructureSection 1 provides a concise summary of the paper. Section 2 provides a brief historical and technical overview of the phenomenon of sample index hopping and an explanation of related concepts. The three sections that follow describe the statistical modeling approach and correspond to the following three goals. (1) Building a generative model that probabilistically describes the phenomenon of sample index hopping of multiplexed sample reads (Section 3). (2) Estimating the index hopping rate from empirical experimental data (Section 4). (3) Correcting for the effects of sample index hopping through a principled probabilistic procedure that reassigns reads to their true sample of origin and discards predicted phantom molecules by optimally minimizing the false positive rate (Section 5). Next, Section 6 details the results of the analyses performed on empirical and experimental validation datasets. The Supplementary Notes consists of three sections: (1) Mathematical Derivations, (2) Overview of Computational Workflow, (3) Method’s Limitations.