bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin regulates glucose homeostasis via the canonical WNT pathway
Authors: Kamstra Kaj , Rizwan Mohammed Z. , Horsfield Julia A. , Pretz Dominik , Shepherd Peter R. , Grattan David R. , Tups Alexander
Published: February 2021

Leptin is a body weight regulatory hormone, but it is arguably even more potent at regulating blood glucose levels. To further our understanding of the molecular mechanisms by which leptin controls glucose homeostasis, we have used transgenic zebrafish models and conditional deletion of beta catenin in the mediobasal hypothalamus of adult mice to show that Wnt signalling in the brain mediates glucoregulatory effects of leptin. In zebrafish, under normal feeding conditions, leptin regulates glucose homeostasis but not adipostasis. In times of nutrient excess, we found that leptin also regulates body weight and size in this species. Using a Wnt signalling reporter fish, we show that leptin directly activates the canonical Wnt pathwayin vivo. Pharmacological inhibition of this pathway prevented the leptin-induced improvement in glucose tolerance. In adult mice, conditional deletion of the key Wnt effector molecule, β-catenin, in the mediobasal hypothalamus of male mice confirmed the essential role of the Wnt pathway in mediating leptin action and the neuroendocrine regulation of glucose homeostasis. Adult-onset β-catenin deletion in the mediobasal hypothalamus led to glucose intolerance, exacerbation of caloric intake and body weight gain under high fat diet, as well as resistance to exogenous leptin.
Integrating plant stoichiometry and feeding experiments: state-dependent forage choice and its implications on body mass
Authors: Balluffi-Fry Juliana , Leroux Shawn J. , Wiersma Yolanda F. , Richmond Isabella C. , Heckford Travis R. , Rizzuto Matteo , Kennah Joanie L. , Vander Wal Eric
Published: February 2021

Intraspecific feeding choices account for a large portion of herbivore foraging in many ecosystems. Plant resource quality is heterogeneously distributed, affected by nutrient availability and growing conditions. Herbivores navigate landscapes, making feeding decisions according to food qualities, but also energetic and nutritional demands. We test three non-exclusive foraging hypotheses using the snowshoe hare (Lepus americanus): 1) herbivores feeding choices and body conditions respond to intraspecific plant quality variation, 2) feeding responses are mitigated when energetic demands are high, and 3) feeding responses are inflated when nutritional demands are high. We measured black spruce (Picea mariana) nitrogen, phosphorus, and terpene compositions, as indicators of quality, within a snowshoe hare trapping grid and found plant growing conditions to explain spruce quality variation (R2< 0.36). We then offered two qualities of spruce (H1) from the trapping grid to hares in cafeteria-style experiments and measured their feeding and body condition responses (n = 75). We proxied energetic demands (H2) with ambient temperature and coat insulation (% white coat) and nutritional demands (H3) with the spruce quality (nitrogen and phosphorus content) in home ranges. Hares that preferred higher-quality spruce lost less weight during experiments (p = 0.018). The results supported our energetic predictions: hares in colder temperatures and with less-insulative coats (lower % white) consumed more spruce and were less selective towards high-quality spruce. Collectively, we found variation in plant growing conditions within herbivore home ranges substantial enough to affect herbivore body conditions, but any plant-herbivore interactions are also mediated by animal energetic states.
Robust clustering and interpretation of scRNA-seq data using reference component analysis
Authors: Schmidt Florian , Ranjan Bobby , Lin Quy Xiao Xuan , Krishnan Vaidehi , Joanito Ignasius , Honardoost Mohammad Amin , Nawaz Zahid , Venkatesh Prasanna Nori , Tan Joanna , Rayan Nirmala Arul , Ong S.Tiong , Prabhakar Shyam
Published: February 2021

Motivation

The transcriptomic diversity of the hundreds of cell types in the human body can be analysed in unprecedented detail using single cell (SC) technologies. Though clustering of cellular transcriptomes is the default technique for defining cell types and subtypes, single cell clustering can be strongly influenced by technical variation. In fact, the prevalent unsupervised clustering algorithms can cluster cells by technical, rather than biological, variation.

Results

Compared tode novo(unsupervised) clustering methods, we demonstrate using multiple benchmarks that supervised clustering, which uses reference transcriptomes as a guide, is robust to batch effects. To leverage the advantages of supervised clustering, we present RCA2, a new, scalable, and broadly applicable version of our RCA algorithm. RCA2 provides a user-friendly framework for supervised clustering and downstream analysis of large scRNA-seq data sets. RCA2 can be seamlessly incorporated into existing algorithmic pipelines. It incorporates various new reference panels for human and mouse, supports generation of custom panels and uses efficient graph-based clustering and sparse data structures to ensure scalability. We demonstrate the applicability of RCA2 on SC data from human bone marrow, healthy PBMCs and PBMCs from COVID-19 patients. Importantly, RCA2 facilitates cell-type-specific QC, which we show is essential for accurate clustering of SC data from heterogeneous tissues. In the era of cohort-scale SC analysis, supervised clustering methods such as RCA2 will facilitate unified analysis of diverse SC datasets.

Availability

RCA2 is implemented in R and is available atgithub.com/prabhakarlab/RCAv2
Simons Collaborative Marine Atlas Project (Simons CMAP): an open-source portal to share, visualize and analyze ocean data
Authors: Ashkezari Mohammad D. , Hagen Norland R. , Denholtz Michael , Neang Andrew , Burns Tansy C. , Morales Rhonda L. , Lee Charlotte P. , Hill Christopher N. , Armbrust E. Virginia
Published: February 2021

Simons Collaborative Marine Atlas Project (Simons CMAP) is an open-source data portal that interconnects large, complex, and diverse public data sets currently dispersed in different formats across different Oceanography discipline-specific databases. Simons CMAP is designed to streamline the retrieval of custom subsets of data, the generation of data visualizations, and the analyses of diverse data, thus expanding the power of these potentially underutilized data sets for cross-disciplinary studies of ocean processes. We describe a unified architecture that allows numerical model outputs, satellite products, and field observations to be readily shared, mined, and integrated regardless of data set size or resolution. A current focus of Simons CMAP is integration of physical, chemical, and biological data sets essential for characterizing the biogeography of key marine microbes across ocean basins and seasonal cycles. Using a practical example, we demonstrate how our unifying data harmonization plans significantly simplifies and allows for systematic data integration across all Simons CMAP data sets.
A test statistic to quantify treelikeness in phylogenetics
Authors: Cherryh Caitlin , Minh Bui Quang , Lanfear Rob
Published: February 2021

Most phylogenetic analyses assume that the evolutionary history of an alignment (either that of a single locus, or of multiple concatenated loci) can be described by a single bifurcating tree, the so-called the treelikeness assumption. Treelikeness can be violated by biological events such as recombination, introgression, or incomplete lineage sorting, and by systematic errors in phylogenetic analyses. The incorrect assumption of treelikeness may then mislead phylogenetic inferences. To quantify and test for treelikeness in alignments, we develop a test statistic which we call the tree proportion. This statistic quantifies the proportion of the edge weights in a phylogenetic network that are represented in a bifurcating phylogenetic tree of the same alignment. We extend this statistic to a statistical test of treelikeness using a parametric bootstrap. We use extensive simulations to compare tree proportion to a range of related approaches. We show that tree proportion successfully identifies non-treelikeness in a wide range of simulation scenarios, and discuss its strengths and weaknesses compared to other approaches. The power of the tree-proportion test to reject non-treelike alignments can be lower than some other approaches, but these approaches tend to be limited in their scope and/or the ease with which they can be interpreted. Our recommendation is to test treelikeness of sequence alignments with both tree proportion and mosaic methods such as 3Seq. The scripts necessary to replicate this study are available athttps://github.com/caitlinch/treelikeness
High-throughput and dosage-controlled intracellular delivery of large cargos by an acoustic-electric micro-vortices platform
Authors: Aghaamoo Mohammad , Chen Yu-Hsi , Li Xuan , Garg Neha , Jiang Ruoyu , Lee Abraham P.
Published: February 2021

Intracellular delivery of cargos for cell engineering plays a pivotal role in transforming medicine and biomedical discoveries. Recent advances in microfluidics and nanotechnology have opened up new avenues for efficient, safe, and controllable intracellular delivery, as they improve precision down to the single-cell level. Based on this capability, several promising micro- and nanotechnology approaches outperform viral and conventional non-viral techniques in offering dosage-controlled delivery and/or intracellular delivery of large cargos. However, to achieve this level of precision and effectiveness, they are either low in throughput, limited to specific cell types (e.g., adherent vs. suspension cells), or complicated to operate with. To address these challenges, here we introduce a versatile and simple-to-use intracellular delivery microfluidic platform, termed Acoustic-Electric Shear Orbiting Poration (AESOP). Hundreds of acoustic microstreaming vortices form the production line of the AESOP platform, wherein hundreds of thousands of cells are trapped, permeabilized, and mixed with exogenous cargos. Using AESOP, we show intracellular delivery of a wide range of molecules (from <1 kDa to 2 MDa) with high efficiency, cell viability, and dosage-controlled capability into both suspension and adherent cells and demonstrate throughput at 1 million cells/min per single chip. In addition, we demonstrate AESOP for two gene editing applications that require delivery of large plasmids: i) eGFP plasmid (6.1 kbp) transfection, and ii) CRISPR-Cas9-mediated gene knockout using a 9.3 kbp plasmid DNA encoding Cas9 protein and sgRNA. Compared to alternative platforms, AESOP not only offers dosage-controlled intracellular delivery of large plasmids (>6kbp) with viabilities over 80% and comparable delivery efficiencies, but also is an order of magnitude higher in throughput, compatible with both adherent and suspension cell lines, and simple to operate.
Can Carbon Nanofibers Affect Anurofauna? Study Involving NeotropicalPhysalaemus cuvieri(Fitzinger, 1826) Tadpoles
Authors: Guimarães Abraão Tiago Batista , Estrela Fernanda Neves , de Lima Rodrigues Aline Sueli , Nóbrega Rafael Henrique , Charlie-Silva Ives , Malafaia Guilherme
Published: February 2021

Although carbon nanotubes’ (CNTs) toxicity in different experimental systems (in vivoandin vitro) is known, little is known about the toxic effects of carbon nanofibers (CNFs) on aquatic vertebrates. We herein investigated the potential impact of CNFs (1 and 10 mg/L) by usingPhysalaemus cuvieritadpoles as experimental model. CNFs were able to induce nutritional deficit in animals after 48-h exposure to them, and this finding was inferred by reductions observed in body concentrations of total soluble carbohydrates, total proteins, and triglycerides. The increased production of hydrogen peroxide, reactive oxygen species and thiobarbituric acid reactive substances in tadpoles exposed to CNFs has suggested REDOX homeostasis change into oxidative stress. This process was correlated to the largest number of apoptotic and necrotic cells in the blood of these animals. On the other hand, the increased superoxide dismutase and catalase activity has suggested that the antioxidant system of animals exposed to CNFs was not enough to maintain REDOX balance. In addition, CNFs induced increase in acetylcholinesterase and butyrylcholinesterase activity, as well as changes in the number of neuromats evaluated on body surface (which is indicative of the neurotoxic effect of nanomaterials on the assessed model system). To the best of our knowledge, this is the first report on the impact of CNFs on amphibians; therefore, it broadened our understanding about ecotoxicological risks associated with their dispersion in freshwater ecosystems and possible contribution to the decline in the populations of anurofauna species.
Chromosome segregation fidelity is controlled by small changes in phospho-occupancy at the kinetochore-microtubule interface
Authors: Kucharski Thomas J. , Hards Rufus , Godek Kristina M. , Gerber Scott A. , Compton Duane A.
Published: February 2021

Kinetochore protein phosphorylation promotes the correction of erroneous microtubule attachments to ensure faithful chromosome segregation during cell division. Determining how phosphorylation executes error correction requires an understanding of whether kinetochore substrates are completely (i.e. all-or-none) or only fractionally phosphorylated. Using quantitative mass spectrometry (MS), we measured phospho-occupancy on the conserved kinetochore protein Hec1 (NDC80) that directly binds microtubules. None of the positions measured exceeded ∼50% phospho-occupancy, and the cumulative phospho-occupancy changed by only ∼20% in response to changes in microtubule attachment status. The narrow dynamic range of phospho-occupancy is maintained by ongoing phosphatase activity. Further, both Cdk1-Cyclin B1 and Aurora kinases phosphorylate Hec1 to enhance error correction in response to different types of microtubule attachment errors. Thus, networks of kinases and phosphatases maintain low inherent phospho-occupancy to promote microtubule attachment to kinetochores while providing for high sensitivity of kinetochore-microtubule attachments to very small changes in phospho-occupancy to ensure high mitotic fidelity.
Predicting Dengue Fever in Brazilian Cities
Authors: Roster Kirstin , Connaughton Colm , Rodrigues Francisco A.
Published: February 2021

Dengue Fever is an increasingly serious public health concern both in Brazil and globally. In the absence of a universal vaccine or specific treatments, prevention relies on vector control and disease surveillance. Accurate and early forecasts can help reduce the spread of the disease. In this study, we develop a model to predict the number of Dengue Fever cases in Brazilian cities one month ahead. We compare different machine learning approaches as well as different sets of input features based on epidemiological and meteorological data. We find that different models work best in different cities, and a random forests model trained on data of historical Dengue cases performs best overall. It produces lower aggregate errors than a seasonal naïve baseline model, Gradient Boosting Regression, feed-forward Neural Networks, and Support Vector Regression. Predictions on an unseen test set are on average within 11.5 cases for the median city. Mean absolute errors on the hold-out test set are reduced to 10.8 for the median city when selecting the optimal combination of algorithm and input features for each city individually.
Polyelectrolyte chain at thermal equilibrium: A comparison between the density functional theory framework (DFT) and the molecular dynamic simulations (MD)
Authors: Edwards Mike J.
Published: February 2021

By means of the density functional theory framework (DFT) as well as the molecular dynamic simulations (MD), a polyelectrolyte chain (PE) in the good solvent conditions at thermal equilibrium is studied. The strength of the electrostatic interactions is varied by the Bjerrum length of the solvent. It turns out that average extension of a PE scales with the degree of polymerization, very much similar to a neutral polymer chain in good solvent. Remarkably, the difference between a PE and a neutral chain appears to be solely in the correlations among monomers which are stored in the Virial coefficients. Interestingly, upon increasing the Bjerrum length of solvent, the chain shrinks. This outcome is confirmed by the DFT framework as well as the MD simulations.

SIGNIFICANCE

The significance of this study is that it strongly criticizes the idea (already mentioned in T. Kreer,Soft Matter,12, 3479 (2016)) that the PEs behave similar to a neutral ideal chain. This study could be useful in our understanding of biopolymers.
Predictive coding across the left fronto-temporal hierarchy during language comprehension
Authors: Wang Lin , Schoot Lotte , Brothers Trevor , Alexander Edward , Warnke Lena , Kim Minjae , Khan Sheraz , Hämäläinen Matti , Kuperberg Gina R.
Published: February 2021

We used MEG and ERPs to track the time-course and localization of evoked activity produced byexpected,unexpected plausibleandimplausiblewords during incremental language comprehension. We interpret the full pattern of evoked responses and functional connectivity within a hierarchical predictive coding framework in which evoked activity reflects residual information (error) that is passed up and down the cortical hierarchy. Between 300-500ms, the three conditions produced progressively larger responses within left temporal cortex (lexico-semantic prediction error), whileimplausibleinputs produced a selectively enhanced response within left inferior frontal cortex (event-level prediction error). Between 600-1000ms,unexpected plausiblewords activated left inferior frontal and middle temporal cortices (feedback activity that induced top-down shifts of event-level and lexico-semantic representations), while highlyimplausibleinputs activated posterior fusiform and medial temporal cortices, supporting orthographic reanalysis and new learning. Therefore, predictive coding may provide a unifying theory that links language comprehension to other domains of cognition.
SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys
Authors: Saunders Kevin O. , Lee Esther , Parks Robert , Martinez David R. , Li Dapeng , Chen Haiyan , Edwards Robert J. , Gobeil Sophie , Barr Maggie , Mansouri Katayoun , Alam S. Munir , Sutherland Laura L. , Cai Fangping , Sanzone Aja M. , Berry Madison , Manne Kartik , Kapingidza Anyway B. , Azoitei Mihai , Tse Longping V. , Scobey Trevor D. , Spreng Rachel L. , Rountree R. Wes , DeMarco C. Todd , Denny Thomas N. , Woods Christopher W. , Petzold Elizabeth W. , Oguin Thomas H. , Sempowski Gregory D. , Gagne Matthew , Douek Daniel C. , Tomai Mark A. , Fox Christopher B. , Seder Robert , Wiehe Kevin , Weissman Drew , Pardi Norbert , Acharya Priyamvada , Andersen Hanne , Lewis Mark G. , Moore Ian N. , Montefiori David C. , Baric Ralph S. , Haynes Barton F.
Published: February 2021

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.
The frequency and topology of pseudoorthologs
Authors: Smith Megan L. , Hahn Matthew W.
Published: February 2021

Phylogenetics has long relied on the use of orthologs, or genes related through speciation events, to infer species relationships. However, identifying orthologs is difficult because gene duplication can obscure relationships among genes. Researchers have been particularly concerned with the insidious effects of pseudoorthologs—duplicated genes that are mistaken for orthologs because they are present in a single copy in each sampled species. Because gene tree topologies of pseudoorthologs may differ from the species tree topology, they have often been invoked as the cause of counterintuitive results in phylogenetics. Despite these perceived problems, no previous work has calculated the probabilities of pseudoortholog topologies, or has been able to circumscribe the regions of parameter space in which pseudoorthologs are most likely to occur. Here, we introduce a model for calculating the probabilities and branch lengths of orthologs and pseudoorthologs, including concordant and discordant pseudoortholog topologies, on a rooted three-taxon species tree. We show that the probability of orthologs is high relative to the probability of pseudoorthologs across reasonable regions of parameter space. Furthermore, the probabilities of the two discordant topologies are equal and never exceed that of the concordant topology, generally being much lower. We describe the species tree topologies most prone to generating pseudoorthologs, finding that they are likely to present problems to phylogenetic inference irrespective of the presence of pseudoorthologs. Overall, our results suggest that pseudoorthologs are less of a problem for phylogenetics than currently believed, which should allow researchers to greatly increase the number of genes used in phylogenetic inference.

Significance Statement

Phylogenetics has long relied on the use of orthologs, or genes related through speciation events, to infer species relationships. However, filtering datasets to include only orthologs is both difficult and restrictive, drastically limiting the amount of data available for phylogenetic inference. Here, we introduce a model to study the probability and topologies of pseudoorthologs—duplicated genes that are mistaken for orthologs because they are present in a single copy in each sampled species. We show that pseudoorthologs are rare and that, even when they are present, they should not mislead phylogenetic inference. Our results suggest that strict filtering to remove pseudoorthologs unnecessarily limits the amount of data used in phylogenetic inference.
Discovery of a molecular glue that enhances UPRmtto restore proteostasisviaTRKA-GRB2-EVI1-CRLS1 axis
Authors: Qi Li-Feng-Rong , Qian Cheng , Liu Shuai , Peng Chao , Zhang Mu , Yang Peng , Wu Ping , Li Ping , Xu Xiaojun
Published: February 2021

Lowering proteotoxicity is a potentially powerful approach for the treatment of neurological disorders, such as Parkinson’s disease. The unfolded protein response (UPR) is a major mechanism that preserves the network maintaining cellular proteostasis. In the present study, we developed the screening strategy to discover compounds that significantly enhanced the activation of mitochondrial UPR (UPRmt) through increasing cardiolipin content. We identified that ginsenoside Rg3 (Rg3) increased cardiolipin depending on cardiolipin synthase 1 (CRLS1) in both worms and in human neural cells. Using LiP-SMap (limited proteolysis-mass spectrometry) strategy, we identified GRB2 (growth factor receptor bound protein 2) as a direct target of Rg3 in human neural cells. Rg3 enhances the binding between GRB2 and TRKA, that transduces signalsviaphosphrorylation of ERK. We provide bioinformatic and experimental evidence that EVI1, the critical oncogenic transcriptional regulator in leukemia, binds toCRLS1promoter region and stimulatedCRLS1expression and subsequently increased cardiolipin content in the presence of Rg3. In a Parkinson’s disease mouse model, Rg3 restores motor function by protecting nigral dopaminergic neurons dependent on Grb2. Our data recapitulate the TRKA-GRB2-EVI1-CRLS1 axis in maintaining proteostasis in Parkinson’s diseaseviaUPRmt.
Discovery of photosynthesis genes through whole-genome sequencing of acetate-requiring mutants ofChlamydomonas reinhardtii
Authors: Wakao Setsuko , Shih Patrick M. , Guan Katharine , Schackwitz Wendy , Ye Joshua , Shih Robert M. , Chovatia Mansi , Sharma Aditi , Martin Joel , Wei Chia-Lin , Niyogi Krishna K.
Published: February 2021

Large-scale mutant libraries have been indispensable for genetic studies, and the development of next-generation genome sequencing technologies has greatly advanced efforts to analyze mutants. In this work, we sequenced the genomes of 660Chlamydomonas reinhardtiiacetate-requiring mutants, part of a larger photosynthesis mutant collection previously generated by insertional mutagenesis with a linearized plasmid. We identified 554 insertion events from 509 mutants by mapping the plasmid insertion sites through paired-end sequences, in which one end aligned to the plasmid and the other to a chromosomal location. Nearly all (96%) of the events were associated with deletions, duplications, or more complex rearrangements of genomic DNA at the sites of plasmid insertion, and 1405 genes in total were affected. Functional annotations of these genes were enriched in those related to photosynthesis, signaling, and tetrapyrrole synthesis as would be expected from a library enriched for photosynthesis mutants. Systematic manual analysis of the disrupted genes for each mutant generated a list of 273 higher-confidence candidate photosynthesis genes, and we experimentally validated two genes that are essential for photoautotrophic growth,CrLPA3andCrPSBP4. The inventory of candidate genes includes 55 genes from a phylogenomically defined set of conserved genes in green algae and plants. Altogether, 68 candidate genes encode proteins with previously characterized functions in photosynthesis inChlamydomonas, land plants, and/or cyanobacteria, 15 genes encode proteins previously shown to have functions unrelated to photosynthesis, and 190 genes encode proteins without any functional annotation, signifying that our results connect a function related to photosynthesis to these previously unknown proteins. This mutant library, with genome sequences that reveal the molecular extent of the chromosomal lesions and resulting higher-confidence candidate genes, represents a rich resource for gene discovery and protein functional analysis in photosynthesis.
Testing hypotheses of marsupial brain size variation using phylogenetic multiple imputations and a Bayesian comparative framework
Authors: Todorov Orlin S. , Blomberg Simone P. , Goswami Anjali , Sears Karen , Drhlík Patrik , Peters James , Weisbecker Vera
Published: February 2021

Considerable controversy exists about which hypotheses and variables best explain mammalian brain size variation. We use a new, high-coverage dataset of marsupial brain and body sizes, and the first phylogenetically imputed full datasets of 16 predictor variables, to model the prevalent hypotheses explaining brain size evolution using phylogenetically corrected Bayesian generalised linear mixed-effects modelling. Despite this comprehensive analysis, litter size emerges as the only significant predictor. Marsupials differ from the more frequently studied placentals in displaying much lower diversity of reproductive traits, which are known to interact extensively with many behavioural and ecological predictors of brain size. Our results therefore suggest that studies of relative brain size evolution in placental mammals may require targeted co-analysis or adjustment of reproductive parameters like litter size, weaning age, or gestation length. This supports suggestions that significant associations between behavioural or ecological variables with relative brain size may be due to a confounding influence of the extensive reproductive diversity of placental mammals.
Phospholipid peroxidation fuels ExoU phospholipase-dependent cell necrosis and supportsPseudomonas aeruginosa-driven pathology
Authors: Bagayoko Salimata , Icaza Stephen Leon , Pinilla Miriam , Hessel Audrey , Santoni Karin , Bordignon Pierre-Jean , Moreau Flavie , Eren Elif , Boyancé Aurélien , Naser Emmanuelle , Lefèvre Lise , Berrone Céline , Iakobachvili Nino , Metais Arnaud , Rombouts Yoann , Coste Agnès , Attrée Ina , Frank Dara W. , Clevers Hans , Peters Peter J. , Cougoule Céline , Planès Rémi , Meunier Etienne
Published: February 2021

Regulated cell necrosis supports immune and anti-infectious strategies of the body; however, dysregulation of these processes drives pathological organ damage.Pseudomonas aeruginosaexpresses a phospholipase, ExoU that triggers pathological host cell necrosis through a poorly characterized pathway. Here, we investigated the molecular and cellular mechanisms of ExoU-mediated necrosis. We show that cellular peroxidised phospholipids enhance ExoU phospholipase activity, which drives necrosis of immune and non-immune cells. Conversely, both the endogenous lipid peroxidation regulator GPX4 and the pharmacological inhibition of lipid peroxidation delay ExoU-dependent cell necrosis and improve bacterial eliminationin vitroandin vivo. Our findings also pertain to the ExoU-related phospholipase from the bacterial pathogenBurkholderia thailandensis, suggesting that exploitation of peroxidised phospholipids might be a conserved virulence mechanism among various microbial phospholipases. Overall, our results identify an original lipid peroxidation-based virulence mechanism as a strong contributor of microbial phospholipase-driven pathology.
Skillful prediction of tropical Pacific fisheries provided by Atlantic Niños
Authors: Gómara Iñigo , Rodríguez-Fonseca Belén , Mohino Elsa , Losada Teresa , Polo Irene , Coll Marta
Published: February 2021

Tropical Pacific upwelling-dependent ecosystems are the most productive and variable worldwide, mainly due to the influence of El Niño Southern Oscillation (ENSO). ENSO can be forecasted seasons ahead thanks to assorted climate precursors (local-Pacific processes, pantropical interactions). However, owing to observational data scarcity and bias-related issues in earth system models, little is known about the importance of these precursors for marine ecosystem prediction. With recently released reanalysis-nudged global marine ecosystem simulations, these constraints can be sidestepped, allowing full examination of tropical Pacific ecosystem predictability. By complementing historical fishing records with marine ecosystem model data, we show herein that equatorial Atlantic Sea Surface Temperatures (SSTs) constitute a superlative predictability source for tropical Pacific marine yields, which can be forecasted over large-scale areas up to 2 years in advance. A detailed physical-biological mechanism is proposed whereby Atlantic SSTs modulate upwelling of nutrient-rich waters in the tropical Pacific, leading to a bottom-up propagation of the climate-related signal across the marine food web. Our results represent historical and near-future climate conditions and provide a useful springboard for implementing a marine ecosystem prediction system in the tropical Pacific.
Evidences for functional trans-acting eRNA-promoter R-loops at Alu sequences
Authors: Bai Xue , Li Feifei , Zhang Zhihua
Published: February 2021

Enhancers modulate gene expression by interacting with promoters. Models of enhancer-promoter interactions (EPIs) in the literature involve the activity of many components, including transcription factors and nucleic acid. However, the role that sequence similarity plays in EPIs, remains largely unexplored. Herein, we report that Alu-derived sequences dominate sequence similarity between enhancers and promoters. After rejecting the alternative DNA:DNA and DNA:RNA triplex models, we proposed that enhancer-associated RNAs, or eRNAs, may directly contact their targeted promoters by forming trans-acting R-loops at those Alu sequences. We showed how the characteristic distribution of functional genomic data, such as RNA-DNA proximate ligation reads, binding of transcription factors, and RNA-binding proteins, align with the Alu sequences of EPIs. We also showed that these aligned Alu sequences may be subject to the constraint of coevolution, further implying the functional significance of these R-loop hybrids. Finally, our results showed that eRNA and Alu elements associate in a manner previously unrecognized in the EPIs and the evolution of gene regulation networks in mammals.
Gene expression profiling of skeletal muscles
Authors: Alto Sarah I. , Chang Chih-Ning , Brown Kevin , Kioussi Chrissa , Filtz Theresa M.
Published: February 2021

Soleus and tibialis anterior are two well-characterized skeletal muscles commonly utilized in skeletal muscle-related studies. Next-generation sequencing provides an opportunity for an in-depth biocomputational analysis to identify the gene expression patterns between soleus and tibialis anterior and analyze those genes’ functions based on past literature. This study acquired the gene expression profiles from soleus and tibialis anterior murine skeletal muscle biopsies via RNA-sequencing. Read counts were processed through edgeR’s differential gene expression analysis. Differentially expressed genes were filtered down using a false discovery rate less than 0.05c, a fold-change value larger than twenty, and an association with overrepresented pathways based on the Reactome pathway over-representation analysis tool. Most of the differentially expressed genes associated with soleus encoded for components of lipid metabolism and unique contractile elements. Differentially expressed genes associated with tibialis anterior encoded mostly for glucose and glycogen metabolic pathways’ regulatory enzymes and calcium-sensitive contractile components. These gene expression distinctions partly explain the genetic basis for muscle specialization and may help to explain skeletal muscle susceptibility to disease and drugs and refine tissue engineering approaches.
Soil respiration variation along an altitudinal gradient in Italian Alps: Disentangling forest structure and temperature effects
Authors: Badraghi Aysan , Ventura Maurizio , Polo Andrea , Borruso Luigimaria , Montagnani Leonardo
Published: February 2021

To understand the main determinants of soil respiration (SR), we investigated the changes of soil respiration and soil physicochemical properties, including soil carbon (C) and nitrogen (N), root C and N, litter C and N, soil bulk densities and soil pH at five forest sites, along an elevation/temperature gradient (404 to 2101 m a.s.l) in Northern Italy, where confounding factors such as aspect and soil parent material are minimized, but an ample variation in forest structure and composition is present. Our result indicated that SR rates increased with temperature in all sites, and about 55% - 76% of SR was explained by temperature. Annual cumulative SR, ranging between 0.65 and 1.40 kg C m-2yr-1, declined along the elevation gradient, while temperature sensitivity (Q10) of SR increased with elevation. However, a high SR rate (1.27 kg C m-2yr-1) and low Q10 were recorded in the old conifer forest stand at 1731 m a.s.l., characterized by a complex structure and high productivity, introducing nonlinearity in the relations with elevation and temperature. Reference SR at the temperature of 10°C (SRref) was not related to elevation. A significant linear negative relationship was found for bulk density with elevation. On the contrary, soil C, soil N, root C, root N, pH and litter mass were better fitted by nonlinear relations with elevation. However, it was not possible to confirm a significant correlation of SR with these parameters once the effect of temperature has been removed (SRref). These results show how the main factor affecting SR in forest ecosystems along this Alpine elevation gradient is temperature, but its regulating role can be strongly influenced by site biological characteristics, particularly vegetation type and structure. This study also confirms that high elevation sites are rich in C stored in the soil and also more sensitive to climate change, being prone to high carbon losses as CO2. Conversely, forest ecosystems with a complex structure, with high SRrefand moderate Q10, can be more resilient.
Stink bugAgonoscelisspp. (Heteroptera: Pentatomidae)-An Emerging Threat for Seed Production in Alfalfa Crop (Medicago sativaL.) and Their Successful Management
Authors: Karar Haider , Bashir Muhammad Amjad , Khaliq Abdul , Ali Muhammad Jaffar , Alajmi Reem Atalla , Metwally Dina M.
Published: February 2021

Forages are vital constituent for sustainable agriculture because they provide feed for animals that ultimately converted into human food. Alfalfa is one of the most important forages that has highest feeding value for livestock, and seed production of alfalfa seriously affected by several factors, but seed yield loss due to stink bug attack is more as compared to other factors. Studies were conducted to control stink bug by different insecticides at Fodder Research Institute, Sargodha, Punjab-Pakistan during 2016-17. The efficacy of ten insecticides viz., acephate, dimethoate, malathion, chlorpyriphos, bifenthrin, lambdacyhalothrin, deltamethrin, acetamiprid, imidacloprid and carbosulfan were tested against stink bug,Agonoscelisspp. (Heteroptera Pentatomidae) on alfalfa,Medicago sativaL. variety SGD-2002. The mortality of stink bug was recorded one, three, five, seven, ten and fifteen days after spray. Similarly the population of pollinators was recorded before and one, three and five days after spray. From this study it had been observed that acetamiprid (81.14 %) and acephate (80.65%) had the higest mortality of stink bug and proved to be the most effective insecticides against stink bug. By spray of insecticides the population of pollinators declined one day after spray, but it had been rehabilitated three days after spray. By chemical treatment against stink bug, seed yield increased from 28.05 Kg/acre (during last four year without chemical control of stink bug) to 116 Kg/acre in 2016-17 (with chemical control). From this study it has been concluded that chemicals can be used in integrated management program of alfalfa seed production.
Time Trend, Social Vulnerability, and Identification of Risk Areas for Tuberculosis in Brazil: an Ecological Study
Authors: de Paiva João Paulo Silva , Magalhães Mônica Avelar Figueiredo Mafra , Leal Thiago Cavalcanti , da Silva Leonardo Feitosa , da Silva Lucas Gomes , do Carmo Rodrigo Feliciano , de Souza Carlos Dornels Freire
Published: February 2021

INTRODUCTION

Tuberculosis is one of the ten leading causes of death and the leading infectious cause worldwide. The disease represents a challenge to health systems around the world. In 2018, it is estimated that 10 million people were affected by tuberculosis, and approximately 1.5 million people died due to the disease worldwide, including 251,000 patients coinfected with HIV. In Brazil, the disease caused 4,490 deaths, with rate of 2.2 deaths per 100,000 inhabitants. The objective of this study was to analyze the time behavior, spatial distribution, and the effects of social vulnerability on the incidence of TB in Brazil during the period from 2001 to 2017.

METHODS

A spatial-temporal ecological study was conducted, including all new cases of tuberculosis registered in Brazil during the period from 2001 to 2017. The following variables were analyzed: incidence rate of tuberculosis, the Social Vulnerability Index, its subindices, its 16 indicators, and an additional 14 variables available on the Atlas of Social Vulnerability. The statistical treatment of the data consisted of the following three stages: a) time trend analysis with a joinpoint regression model; b) spatial analysis and identification of risk areas based on smoothing of the incidence rate by local empirical Bayesian model, application of global and local Moran statistics, and, finally, spatial-temporal scan statistics; and c) analysis of association between the incidence rate and the indicators of social vulnerability.

RESULTS

Brazil reduced the incidence of tuberculosis from 42.8 per 100,000 to 35.2 per 100,000 between 2001 and 2017. Only the state of Minas Gerais showed an increasing trend, whereas nine other states showed a stationary trend. A total of 326 Brazilian municipalities were classified as high priority, and 22 high-risk spatial clusters were identified. The overall Social Vulnerability Index and the subindices of Human Capital and Income and Work were associated with the incidence of tuberculosis. It was also observed that the incidence rates were greater in municipalities with greater social vulnerability.

CONCLUSIONS

This study identified spatial clusters with high risk of TB in Brazil. A significant association was observed between the incidence rate of TB and the indices of social vulnerability.
A parasite’s paradise: Biotrophic species prevail oomycete community composition in tree canopies
Authors: Jauss Robin-Tobias , Walden Susanne , Fiore-Donno Anna Maria , Schaffer Stefan , Wolf Ronny , Feng Kai , Bonkowski Michael , Schlegel Martin
Published: February 2021

Oomycetes (Stramenopiles, Protista) are among the most severe plant pathogens, comprising species with a high economic and ecologic impact on forest ecosystems. Their diversity and community structures are well studied in terrestrial habitats, but tree canopies as huge and diverse habitats have been widely neglected. A recent study highlighted distinct oomycete communities in the canopy region compared to forest soils when taking oomycete abundances into account, in contrast to the homogeneity at the incidence level. It remains however unknown if this homogeneity also leads to a functional homogenisation among microhabitats. In this study, we supplemented functional traits to oomycete canopy and ground communities, which were determined over a time period of two years with a metabarcoding approach. Our results showed that even though most oomycetes occurred in all habitats, a strong discrepancy between the strata and correspondingly the distribution of oomycete lifestyles could be observed, which was constant over time. Obligate biotrophic species, exclusively feeding on living host tissue, dominated the canopy region, implying tree canopies to be a hitherto neglected reservoir for parasitic protists. Parasites highly specialised on hosts that were not sampled could be determined in high abundances in the canopy and the surrounding air, challenging the strict host dependencies ruled for some oomycetes. Our findings further contribute to the understanding of oomycete ecosystem functioning in forest ecosystems.
Stony Coral Tissue Loss Disease biomarker bacteria identified in corals and overlying waters using a rapid field-based sequencing approach
Authors: Becker Cynthia C. , Brandt Marilyn , Miller Carolyn A. , Apprill Amy
Published: February 2021

Stony Coral Tissue Loss Disease (SCTLD) is a devastating disease. Since 2014, it has spread along the entire Florida Reef Tract, presumably via a water-borne vector, and into the greater Caribbean. It was first detected in the United States Virgin Islands (USVI) in January 2019. To more quickly identify disease biomarker microbes, we developed a rapid pipeline for microbiome sequencing. Over a span of 10 days we collected, processed, and sequenced coral tissue and near-coral seawater microbiomes from diseased and apparently healthyColpophyllia natans,Montastraea cavernosa,Meandrina meandritesandOrbicella franksi. Analysis of the resulting bacterial and archaeal 16S ribosomal RNA sequences revealed 25 biomarker amplicon sequence variants (ASVs) enriched in diseased tissue. These biomarker ASVs were additionally recovered in near-coral seawater (within 5 cm of coral surface), a potential recruitment zone for pathogens. Phylogenetic analysis of the biomarker ASVs belonging toVibrio, Arcobacter,Rhizobiaceae, and Rhodobacteraceae revealed relatedness to other coral disease-associated bacteria and lineages novel to corals. Additionally, four ASVs (Algicola,Cohaesibacter,ThalassobiusandVibrio) were exact sequence matches to microbes previously associated with SCTLD. This work represents the first rapid coral disease sequencing effort and identifies biomarkers of SCTLD that could be targets for future SCTLD research.
Multiple Sites on SARS-CoV-2 Spike Protein are Susceptible to Proteolysis by Cathepsins B, K, L, S, and V
Authors: Bollavaram Keval , Leeman Tiffanie H. , Lee Maggie W. , Kulkarni Akhil , Upshaw Sophia G. , Yang Jiabei , Song Hannah , Platt Manu O.
Published: February 2021

SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Proteases are central to the infection process of SARS-CoV-2. Cleavage of the spike protein on the virus’s capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein must be identified. We identified amino acid sequences in all regions of spike protein, including the S1/S2 region critical for activation and viral entry, that are susceptible to cleavage by furin and cathepsins B, K, L, S, and V using PACMANS, a computational platform that identifies and ranks preferred sites of proteolytic cleavage on substrates, and verified with molecular docking analysis and immunoblotting to determine if binding of these proteases can occur on the spike protein that were identified as possible cleavage sites. Together, this study highlights cathepsins B, K, L, S, and V for consideration in SARS-CoV-2 infection and presents methodologies by which other proteases can be screened to determine a role in viral entry. This highlights additional proteases to be considered in COVID-19 studies, particularly regarding exacerbated damage in inflammatory preconditions where these proteases are generally upregulated.
A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
Authors: Fatihi Saman , Rathore Surabhi , Pathak Ankit K. , Gahlot Deepanshi , Mukerji Mitali , Jatana Nidhi , Thukral Lipi
Published: February 2021

The recent release of SARS-CoV-2 genomic data from several countries has provided clues into the potential antigenic drift of the coronavirus population. In particular, the genomic instability observed in the spike protein necessitates immediate action and further exploration in the context of viralhost interactions. By temporally tracking 527,988 SARS-CoV-2 genomes, we identified invariant and hypervariable regions within the spike protein. We evaluated combination of mutations from SARS-CoV-2 lineages and found that maximum number of lineage-defining mutations were present in the N-terminal domain (NTD). Based on mutant 3D-structural models of known Variants of Concern (VOCs), we found that structural properties such as accessibility, secondary structural type, and intra-protein interactions at local mutation sites are greatly altered. Further, we observed significant differences between intra-protein networks of wild-type and Delta mutant, with the latter showing dense intra-protein contacts. Extensive molecular dynamics simulations of D614G mutant spike structure with hACE2 further revealed dynamic features with 47.7% of mutations mapping on flexible regions of spike protein. Thus, we propose that significant changes within spike protein structure have occurred that may impact SARS-CoV-2 pathogenesis, and repositioning of vaccine candidates is required to contain the spread of COVID-19 pathogen.