bluuebunny/crossref_metadata_2025_split huggingface dataset:
A balanced measure shows superior performance of pseudobulk methods over mixed models and pseudoreplication approaches in single-cell RNA-sequencing analysis
Authors: Murphy Alan E , Skene Nathan G 
Published: February 2022

SummaryRecently, Zimmermanet al.,1highlighted the importance of accounting for the dependence between cells from the same individual when conducting differential expression analysis on single-cell RNA-sequencing data. Their work proved the inadequacy of pseudoreplication approaches for such analysis – This was an important step forward that was conclusively proven by them. A hierarchical single-cell expression simulation approach (hierarchicell) was developed by Zimmermanet al.,1to generate non-differentially expressed genes upon which performance was evaluated using the type 1 error rate; the proportion of non-differentially expressed genes indicated as differentially expressed by a model. However, evaluating such models on their type 1 or type 2 error rate in isolation is insufficient to determine their true performance – for example, a method with low type 1 error may have a high type 2 error rate. Moreover, because no seed was set for the pseudo-random number generator used in hierarchicell, the different methods evaluated by Zimmermanet al. were done so on different simulated datasets. Here, we corrected these issues, reran the author’s analysis and found pseudobulk methods outperformed mixed models.ContactAlan Murphy:a.murphy@imperial.ac.uk, Nathan Skene:n.skene@imperial.ac.ukCode availabilityThe modified version of hierarchicell which returns all error metrics, uses the same simulated data across approaches and has checkpointing capabilities (if runs are aborted or crashed) is available at:https://github.com/neurogenomics/hierarchicell.The benchmarking script along with the results are available at:https://github.com/Al-Murphy/reanalysis_scRNA_seq_benchmark.
modelRxiv: A platform for the dissemination and interactive display of models
Authors: Harris Keith D. , Hadari Guy , Greenbaum Gili 
Published: February 2022

AbstractModeling the dynamics of biological processes is ubiquitous across the ecological and evolutionary disciplines. However, the increasing complexity of these models poses a significant challenge to the dissemination of model-derived results. With the existing requirements of scientific publishing, most often only a small subset of model results are generated, presented in static figures or tables, and made available to the scientific community. Further exploration of the parameter space of a model, investigation of possible variations of a model, and validation of the results in relation to model assumptions commonly rely on local deployment of code supplied by the authors. This can pose a technical challenge due to the diversity of frameworks and environments in which models are developed, and preclude model validation and exploration by readers and reviewers. To address this issue, we developed a platform that serves as an interactive repository of biological models, calledmodelRxiv. The platform provides a unified interface for the analysis of models that does not require any technical understanding of the model implementation. To facilitate adding models tomodelRxiv, we utilize OpenAI large-language models (LLMs) to make code written in different programming languages compatible withmodelRxiv, making the platform language-agnostic.modelRxivis designed to serve as an interactive extension of published models, allowing users to regenerate model results under user-defined parameterizations of the model. By making published models accessible, this platform promises to significantly improve the accessibility, reproducibility, and validation of ecological and evolutionary models.
Phenotypic Characterization of indigenous goat population in Southern, Ethiopia
Authors: Muluneh Teshager , Tadesse Wondimagegn 
Published: February 2022

AbstractA study was conducted at Abaya and Yirgachafe districts to characterize indigenous goat types phenotypically. Data were collected through field measurements and visual observation of qualitative traits. Totally 540 goats were used for metric and morphometric measurement. Results of the study revealed that the goat populations found in Abaya and Yirgachafe district were different characteristics which are physically Abaya goats were closest with Arsi-Bale whereas yirgachafee with Woyto-Guji which are mostly distributed goat breeds in southern Ethiopia. The dominant coat color pattern in study area was plain, patchy, and spotted with proportions of 55.19, 37.04, and 7.78% and 46.67, 38.89, and 14.44% in Abaya and Yirgachafee district respectively. A strong and positive correlation(r = 0.83, 0.76) was observed between heart girth and body weight for male and female goat populations respectively. Generally, the indigenous goat population has its own difference in its morphological and morphometric traits. Traits have their own economic contribution. Therefore, identifying these important traits for further genetic improvements, conservation and sustainable utilization of the genetic resources of the diversified goat population is important.
Endocytosis-mediated vitellogenin absorption and lipid metabolism in the hindgut-derived pseudoplacenta of the viviparous teleost Xenotoca eiseni
Authors: Iida Atsuo , Nomura Jumpei , Yoshida Junki , Suzuki Takayuki , Yokoi Hayato , Hondo Eiichi 
Published: February 2022

AbstractCertain viviparous animals possess mechanisms for mother-to-embryo nutrient transport during gestation. Xenotoca eiseni is one such viviparous teleost species in which the mother supplies proteins and other components to the offspring developing in the ovary. The embryo possesses trophotenia, a hindgut-derived pseudoplacenta to receive the maternal supplement. However, the molecular mechanisms underlying viviparous non-mammalian animals remain elusive. We conducted this study to investigate the mechanism for nutrient absorption and degradation in trophoenia of X. eiseni. The tracer assay indicated that a lipid transfer protein, vitellogenin (Vtg), was absorbed into the epithelial layer cells of trophotaenia. Vtg uptake was significantly suppressed by Pitstop-2, an inhibitor of clathrin-mediated endocytosis. Gene expression analysis indicated that the genes involved in endocytosis-mediated lipolysis and lysosomal cholesterol transport were expressed in trophotaenia. In contrast, plasma membrane transporters expressed in the intestinal tract were not functional in trophotaenia. Our results suggested that endocytosis-mediated lysosomal lipolysis is one of the mechanisms underlying maternal component metabolism. Thus, our study demonstrated how viviparous teleost species have acquired a unique developmental system that is based on the hindgut-derived pseudoplacenta.
The Effect of Lipid Composition on the Dynamics of Tau Fibrils
Authors: Chowdhury Unmesh D. , Paul Arnav , Bhargava B. L. 
Published: February 2022

AbstractKnowledge of the interaction of the tau fibrils with the cell membrane is critical for the understanding of the underlying tauopathy pathogenesis. Lipid composition is found to effect the conformational ensemble of the tau fibrils. Using coarse grained and all-atom molecular dynamics simulations we have shown the effect of the lipid composition in modulating the tau structure and dynamics. Molecular dynamics simulations show that tau proteins interact differentially with the zwitterionic compared to the charged lipid membranes. The negatively charged POPG lipid membranes increase the binding affinity of the tau fibrils. The addition of cholesterol is also found to modify the tau binding to the membrane.
Multi-omics approach reveals dysregulation of protein phosphorylation correlated with lipid metabolism in mouse fatty liver
Authors: Kim Sora Q. , Mohallem Rodrigo , Franco Jackeline , Buhman Kimberly K. , Kim Kee-Hong , Aryal Uma K. 
Published: February 2022

AbstractObesity caused by overnutrition is a major risk factor for non-alcoholic fatty liver disease (NAFLD). Several lipid intermediates such as fatty acids, glycerophospholipids and sphingolipids are implicated in NAFLD, but detailed characterization of lipids and their functional links to proteome and phosphoproteome remain to be elucidated. To characterize this complex molecular relationship, we used multi-omics approach by conducting comparative proteomic, phoshoproteomic and lipidomic analyses of high fat (HFD) and low fat (LFD) diet fed mice livers. We quantified 2447 proteins and 1339 phosphoproteins containing 1650 class I phosphosites (with localization probability > 0.75), of which 669 phosphosites were significantly different between HFD and LFD mice livers. We detected alterations of proteins associated with cellular metabolic processes such as small molecule catabolic process, monocarboxylic acid, long- and medium-chain fatty acid, and ketone body metabolic processes, and peroxisome organization. We observed significant downregulation of protein phosphorylation in HFD fed mice liver in general. Untargeted lipidomics identified upregulation of triacylglycerols, glycerolipids and ether glycerophosphocholines and downregulation of glycerophospholipids such as lysoglycerophospholipids, as well as ceramides and acylcarnitines. Analysis of differentially regulated phosphosites revealed phosphorylation dependent deregulation of insulin signaling as well as lipogenic and lipolytic pathways during HFD induced obesity. Thus, this study reveals a molecular connection between decreased protein phosphorylation and lipolysis, as well as lipid-mediated signaling in diet-induced obesity.
CellNeighborEX: Deciphering Neighbor-Dependent Gene Expression from Spatial Transcriptomics Data
Authors: Kim Hyobin , Lövkvist Cecilia , Palma António M. , Martin Patrick , Kim Junil , Kumar Amit , Peixoto Maria Leonor , Madan Esha , Gogna Rajan , Won Kyoung Jae 
Published: February 2022

AbstractCells have evolved communication methods to sense their microenvironments and send biological signals. In addition to the communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach that identifiescell neighbor-dependent geneexpression (CellNeighborEX). After categorizing cells based on their microenvironment from spatial transcriptomics (ST) data, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. To categorize cells along with their environment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on the ST technology. We show that cells express different gene sets depending on the neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. These genes were associated with development (in embryos) or metastases (liver cancer). We further validate that gene expression can be induced by neighboring partners. The neighbor-dependent gene expression suggests new potential genes involved in cell-cell interactions beyond what ligand-receptor co-expression can discover.
A Bayesian Hierarchical Model for Signal Extraction from Protein Microarrays
Authors: Bérubé Sophie , Kobayashi Tamaki , Wesolowski Amy , Norris Douglas E. , Ruczinski Ingo , Moss William J. , Louis Thomas A. 
Published: February 2022

SummaryProtein microarrays are a promising technology that measure protein levels in serum or plasma samples. Due to the high technical variability of these assays and high variation in protein levels across serum samples in any population, directly answering biological questions of interest using protein microarray measurements is challenging. Using within-array ranks of protein levels for analysis can mitigate the impact of between-sample variation on downstream analysis. Although ranks are sensitive to pre-processing steps, ranking methods that accommodate uncertainty provide robust and loss-function optimal ranks. Such ranking methods require Bayesian modeling that produces full posterior distributions for parameters of interest. Bayesian models that produce such outputs have been developed for other assays, for example DNA microarrays, but those modeling assumptions are not appropriate for protein microarrays. We develop and evaluate a Bayesian model to extract a full posterior distribution of normalized fluorescent signals and associated ranks for protein microarrays, and show that it fits well to data from two studies that use protein microrarrays from different manufacturing processes. We validate the model via simulation and demonstrate the downstream impact of using estimates from this model to obtain optimal ranks.
Regulatory dynamics distinguishing desiccation tolerance strategies within resurrection grasses
Authors: Aubin Brian St. , Wai Ching Man , Kenchanmane Raju Sunil K. , Niederhuth Chad E. , VanBuren Robert 
Published: February 2022

AbstractDesiccation tolerance has evolved recurrently in grasses using two unique strategies to mitigate photooxidative damage under anhydrobiosis. The grassOropetium thomaeumprotects and retains chlorophyll, thylakoids, and the photosynthetic apparatus during desiccation (Homoiochlorophyly), whileEragrostis nindensisdegrades and resynthesizes these components under desiccation and rehydration (Poikilochlorophyly). Here, we surveyed chromatin architecture and gene expression during desiccation in these two closely related species to identify regulatory dynamics underlying the distinct desiccation tolerance strategies in grasses. In both grasses, we observed a strong association between nearby chromatin accessibility and gene expression in desiccated tissues compared to well-watered, reflecting an unusual chromatin stability under anhydrobiosis. Integration of chromatin accessibility (ATACseq) and expression data (RNAseq) revealed a core desiccation response across these two grasses including many genes with binding sites for the core seed development transcription factor ABI5.O. thomaeumhad a unique set of desiccation induced genes and regulatory elements associated with photoprotection, pigment biosynthesis, and response to high light, reflecting its adaptation of homoiochlorophyly. A tandem array of early light induced proteins (ELIPs) had massive shifts in gene expression and chromatin openness under desiccation in onlyO. thomaeum, and ELIPs acquired a novel desiccation related cis-regulatory motif, reflecting regulatory neofunctionalization during the evolution of desiccation tolerance. Together, our results highlight the complex regulatory and expression dynamics underlying desiccation tolerance in grasses.
ApiaceaeFNS Ioriginated fromF3Hthrough tandem gene duplication
Authors: Pucker Boas , Iorizzo Massimo 
Published: February 2022

AbstractBackgroundFlavonoids are specialized metabolites with numerous biological functions in stress response and reproduction of plants. Flavones are one subgroup that is produced by the flavone synthase (FNS). Two distinct enzyme families evolved that can catalyze the biosynthesis of flavones. While the membrane-bound FNS II is widely distributed in seed plants, one lineage of soluble FNS I appeared to be unique to Apiaceae species.ResultsWe show through phylogenetic and comparative genomic analyses that ApiaceaeFNS Ievolved through tandem gene duplication of flavanone 3-hydroxylase (F3H)followed by neofunctionalization. Currently available datasets suggest that this event happened within the Apiaceae in a common ancestor ofDaucus carotaandApium graveolens. The results also support previous findings thatFNS Iin the Apiaceae evolved independent ofFNS Iin other plant species.ConclusionWe validated a long standing hypothesis about the evolution of Apiaceae FNS I and predicted the phylogenetic position of this event. Our results explain how an Apiaceae-specificFNS Ilineage evolved and confirm independence from otherFNS Ilineages reported in non-Apiaceae species.
High variation in handling times confers 35-year stability to predator feeding rates despite altered prey abundances and apparent diet proportions
Authors: Novak Mark 
Published: February 2022

AbstractHistorical resurveys of ecological communities are important for placing the structure of modern ecosystems in context. Rarely, however, are snapshot surveys alone sufficient for providing direct insight into the rates of ecological processes that underlie how communities function, either now or in the past. In this study, I used a statistically-reasoned observational approach to estimate the feeding rates of a New Zealand intertidal predator,Haustrum haustorium, using diet surveys performed at several sites by Robert Paine in 1968–9 and by me in 2004. Comparisons between time periods reveal a remarkable consistency inH. haustorium’s prey-specific feeding rates, which contrasts with the changes I observed in prey abundances,H. haustorium’s body size distribution, and the proportional contributions ofH. haustorium’s prey to its apparent diet. Although these results imply accompanying and perhaps adaptive changes inH. haustorium’s prey preferences, they are nonetheless anticipated byH. haustorium’s high range of variation in prey-specific handling times that dictate not only its maximum possible feeding rates but also the probabilities with which feeding events may be detected during diet surveys. Similarly high variation in detection times (i.e. handling and digestion times) is evident in predator species throughout the animal kingdom. The potential disconnect between a predator’s apparent diet and its actual feeding rates suggests that much of the temporal and biogeographic variation that is perceived in predator diets and food-web structures may be of less functional consequence than currently assumed.
Enhanced photosynthetic efficiency for increased carbon assimilation and woody biomass production in hybrid poplar INRA 717-1B4
Authors:   Living Carbon Team, Tao Yumin , Chiu Li-Wei , Hoyle Jacob W. , Du Jessica , Rasmussen Karli , Mellor Patrick , Richey Christian , Kuiper Julie , Fried Madeline , Dewhirst Rebecca A. , Tucker Dominick , Crites Alex , Orr Gary A. , Heckert Matthew J. , Vidal Damaris G. , Orosco-Cardenas Martha L. , Hall Madeline E. 
Published: February 2022

ABSTRACTIncreasing CO2 levels in the atmosphere and the resulting negative impacts on climate change have compelled global efforts to achieve carbon neutrality or negativity. Most such efforts focus on carbon sequestration through chemical or physical approaches. We aim to harness the power of synthetic biology to enhance plants’ natural ability to draw down and sequester carbon, thereby positively affecting climate change. Past decades of scientific progress have shed light on strategies to overcome the intrinsic limitations of carbon drawdown and fixation through photosynthesis, particularly in row crops in hopes of improving agricultural productivity for food security. Incorporating a photorespiration bypass in C3 plants has shown promising results of increased biomass and grain yield. Despite their globally dominant role in atmospheric carbon flux, the drawdown rates of most trees are currently limited by their C3 photosynthetic metabolism, and efforts to improve the photosynthetic capacity of trees, such as by reducing energy loss in photorespiration, are currently lacking. Here, we selected a photorespiration bypass pathway and tested its effectiveness on photosynthetic enhancement in hybrid poplar INRA717-IB4. The design includes a RNAi strategy to reduce the transportation of the photorespiration byproduct, glycolate, out of chloroplast and a shunt pathway to metabolize the retained glycolate back to CO2 for fixation through the Calvin-Benson cycle. Molecular and physiological data collected from two repeated growth experiments indicates that transgenic plants expressing genes in the photorespiration bypass pathway have increased photosynthetic efficiency, leading to faster plant growth and elevated biomass production. One lead transgenic event accumulated 53% more above-ground dry biomass over a five month growth period in a controlled environment. Pilot projects with photosynthesis-enhanced trees in the field are in progress. Our results provide a proof-of-concept for engineering trees to help combat climate change.
Spatiotemporally Mapping Thermodynamics of Lysosomes and Mitochondria using Cascade Organelle-Targeting Upconversion Nanoparticles
Authors: Di Xiangjun , Su Qian Peter , Wang Dejiang , Liu Yongtao , Maddahfar Mahnaz , Zhou Jiajia , Jin Dayong 
Published: February 2022

AbstractThe intracellular metabolism of organelles, like lysosomes and mitochondria, are highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of ATP generation during active metabolism. Here, we develop temperature-sensitive LysoDots and MitoDots to monitor the in situ thermodynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K-1 and accuracy of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the intracellular ion concentrations- and pH values. With Ca2+ ion shock, the temperatures of both lysosomes and mitochondria increased by 2∼4 °C. Intriguingly, with Chloroquine treatment, the lysosomal temperature was observed to decrease by up to ∼3 °C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed a 3∼7 °C thermal increase and transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multi-modality functional imaging of subcellular organelles and interactions with high spatial, temporal and thermal dynamics resolutions.Graphical AbstractCascade organelle-targeted nano-thermometers based on upconversion LysoDots and MitoDots.