bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial dysfunction promotes alternative gasdermin D-mediated inflammatory cell death and susceptibility to infection
Authors: Weindel Chi G. , Zhao Xiao , Martinez Eduardo , Bell Samantha L. , Vail Krystal J. , Coleman Aja K. , VanPortfliet Jordyn J. , Zhao Baoyu , Mabry Cory J. , Li Pingwei , Phillip West A. , Karpac Jason , Patrick Kristin L. , Watson Robert O. 
Published: November 2021

SUMMARYHuman mutations in mitochondrial-associated genes are associated with inflammatory diseases and susceptibility to infection. However, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) promotes mitochondrial hyper-fission, depolarization, and oxidative stress in macrophages. In the presence of Lrrk2G2019S-dependent mitochondrial perturbations, AIM2 inflammasome activation promotes more cell death but not more pyroptotic IL-1b release. Instead, inflammasome activation in Lrrk2G2019S macrophages triggers gasdermin D (GSDMD)-mediated mitochondrial pores, driving up ROS-mediated RIPK1/RIPK3/MLKL dependent necroptosis. Consequently, infection of Lrrk2G2019S mice with Mycobacterium tuberculosis elicits hyperinflammation and immunopathology via enhanced neutrophil infiltration. By uncovering that GSDMD promotes non-pyroptotic cell death in Lrrk2G2019S macrophages, our findings demonstrate that altered mitochondrial function can reprogram cell death modalities to elicit distinct immune outcomes. This provides mechanistic insights into why mutations in LRRK2 are associated with susceptibility to chronic inflammatory and infectious diseases.HIGHLIGHTSAltered mitochondrial homeostasis reprograms cell death modalitiesGSDMD associates with and depolarizes mitochondrial membranes following AIM2 activationGSDMD initiates a shift from pyroptotic to necroptotic cell death in Lrrk2G2019S macrophagesLrrk2G2019S elicits hyperinflammation and susceptibility to infection in flies and mice
Prostaglandin PGE2 receptor EP4 regulates microglial phagocytosis and increases susceptibility to diet-induced obesity
Authors: Niraula Anzela , Fasnacht Rachael D. , Ness Kelly M. , Frey Jeremy M. , Dorfman Mauricio D. , Thaler Joshua P. 
Published: November 2021

AbstractBackgroundIn rodents, susceptibility to diet-induced obesity requires microglial activation, but the molecular components of this pathway remain incompletely defined. Prostaglandin E2 (PGE2) levels increase in the mediobasal hypothalamus during high fat diet (HFD) feeding, and the PGE2 receptor EP4 regulates microglial activation state and phagocytic activity, suggesting a potential role for microglial EP4 signaling in obesity pathogenesis.MethodMetabolic phenotyping, as assessed by body weight, energy expenditure, glucose, and insulin tolerance, was performed in microglia-specific EP4 knockout (MG-EP4 KO) mice and littermate controls on HFD. Morphological and gene expression analysis of microglia, and a histological survey of microglia-neuron interactions in the arcuate nucleus was performed. Phagocytosis was assessed using in vivo and in vitro pharmacological techniques.ResultsMicroglial EP4 deletion markedly reduced weight gain and food intake in response to HFD feeding. In correspondence with this lean phenotype, insulin sensitivity was also improved in the HFD-fed MG-EP4 KO mice though glucose tolerance remained surprisingly unaffected. Mechanistically, EP4-deficient microglia showed an attenuated phagocytic state marked by reduced CD68 expression and fewer contacts with POMC neuron soma and processes. These cellular changes observed in the microglial EP4 knockout mice corresponded with an increased density of POMC neurites extending into the paraventricular nucleus.ConclusionThese findings reveal that microglial EP4 signaling promotes body weight gain and insulin resistance during HFD feeding. Furthermore, the data suggest that curbing microglial phagocytic function may preserve POMC cytoarchitecture and PVN input to limit overconsumption during diet-induced obesity.
Multitrophic higher-order interactions modulate species persistence
Authors: Buche Lisa , Bartomeus Ignasi , Godoy Oscar 
Published: November 2021

AbstractThere is growing recognition that interactions between species pairs are modified in a multispecies context by the density of a third species. However, how these higher-order interactions (HOIs) affect species persistence remains poorly understood. To explore the effect of HOIs steaming from multiple trophic layers on plant persistence, we experimentally built a mutualistic system containing three plants and three pollinators species with two contrasting network structures. For both structures, we first estimated the statistically supported HOIs on plant species, in addition to the pairwise interactions among plants and plant-pollinators. Following a structuralist approach, we then assessed the effects of the supported HOIs on the persistence probability of each of the three competing plant species and their combinations. HOIs produced substantial effects on the strength and sign of per capita interactions between plant species to such an extent that predictions of species persistence differ from a non-HOIs scenario. Changes in network structure due to removing a plant-pollinator link further modulated the species persistence probabilities by reorganizing per capita interaction strengths of both pairwise interactions and HOIs. Our study provides empirical evidence of the joint importance of HOIs and network structure for determining the probability of species to persist within diverse communities.
Cytotoxicity mechanisms and composition of the glyphosate formulated herbicide RangerPro
Authors: Mesnage Robin , Ferguson Scarlett , Mazzacuva Francesca , Caldwell Anna , Halket John , Antoniou Michael N 
Published: November 2021

AbstractUnderstanding the nature of co-formulants and toxic effects of major glyphosate-based herbicide (GBH) formulations is considered a research priority. Indeed, the toxicity of the co-formulants present in GBHs have been widely discussed and the European Union recently banned the co-formulant polyoxyethylene tallow amine (POEA). We provide a foundation for the development of new environmental epidemiological studies by reporting the presence of the most commonly used POEA, known as POE-15 tallow amine, in the widely used US GBH RangerPro. In order to understand if POE-15 tallow amine is present in RangerPro at a concentration at which it can exert toxic effects, we also tested the cytotoxicity of this GBH compared to glyphosate and POE-15 tallow amine in the human epithelial cell line Caco-2, a representative of the human intestinal epithelium, and the first to be exposed from the human diet to glyphosate herbicides. The lethal concentration 50 for each of these substances was 125 μg/ml, 17200 μg/ml, and 5.7 μg/ml, for RangerPro, glyphosate and POE-15, respectively. The Caco-2 cell cytotoxicity assay indicated that RangerPro is more cytotoxic than glyphosate, suggesting that its toxicity can be due to the presence of the POE-15 surfactant. RangerPro and POE-15 tallow amine but not glyphosate exerted cell necrotic effects, but did not induce oxidative stress. We show that RangerPro contains POE-15 tallow amine at a concentration at which it could exert toxic effects, which offers a starting point for conducting surveys of co-formulant exposure in human populations.
Multiple adaptive solutions to face climatic constraints: novel insights in the debate over the role of convergence in local adaptation
Authors: Benjelloun Badr , Leempoel Kevin , Boyer Frédéric , Stucki Sylvie , Streeter Ian , Orozco-terWengel Pablo , Alberto Florian J. , Servin Bertrand , Biscarini Filippo , Alberti Adriana , Engelen Stefan , Stella Alessandra , Colli Licia , Coissac Eric , Bruford Michael W. , Ajmone-Marsan Paolo , Negrini Riccardo , Clarke Laura , Flicek Paul , Chikhi Abdelkader , Joost Stéphane , Taberlet Pierre , Pompanon François 
Published: November 2021

AbstractThe extent to which genomic convergence shapes locally adapted phenotypes in different species remains a fundamental question in evolutionary biology. To bring new insights to this debate we set up a framework which aimed to compare the adaptive trajectories of two domesticated mammal species co-distributed in diversified landscapes. We sequenced the genomes of 160 sheep and 161 goats extensively managed along environmental gradients, including temperature, rainfall, seasonality and altitude, to identify genes and biological processes shaping local adaptation. Allele frequencies at adaptive loci were rarely found to vary gradually along environmental gradients, but rather displayed a discontinuous shift at the extremities of environmental clines. Of the more than 430 adaptive genes identified, only 6 were orthologous between sheep and goats and those responded differently to environmental pressures, suggesting different adaptive mechanisms in these two closely related species. Such diversity of adaptive pathways may result from a high number of biological functions involved in adaptation to multiple eco-climatic gradients, and provides more arguments for the role of contingency and stochasticity in adaptation rather than repeatability.
STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci
Authors: Dashnow Harriet , Pedersen Brent S. , Hiatt Laurel , Brown Joe , Beecroft Sarah J. , Ravenscroft Gianina , LaCroix Amy J. , Lamont Phillipa , Roxburgh Richard H. , Rodrigues Miriam J. , Davis Mark , Mefford Heather C. , Laing Nigel G. , Quinlan Aaron R. 
Published: November 2021

AbstractExpansions of short tandem repeats (STRs) cause dozens of rare Mendelian diseases. However, STR expansions, especially those arising from repeats not present in the reference genome, are challenging to detect from short-read sequencing data. Such “novel” STRs include new repeat units occurring at known STR loci, or entirely new STR loci where the sequence is absent from the reference genome. A primary cause of difficulty detecting STR expansions is that reads arising from STR expansions are frequently mismapped or unmapped. To address this challenge, we have developed STRling, a new STR detection algorithm that counts k-mers (short DNA sequences of length k) in DNA sequencing reads, to efficiently recover reads that inform the presence and size of STR expansions. As a result, STRling can call expansions at both known and novel STR loci. STRling has a sensitivity of 83% for 14 known STR disease loci, including the novel STRs that cause CANVAS and DBQD2. It is the first method to resolve the position of novel STR expansions to base pair accuracy. Such accuracy is essential to interpreting the consequence of each expansion. STRling has an estimated 0.078 false discovery rate for known pathogenic loci in unaffected individuals and a 0.20 false discovery rate for genome-wide loci in unaffected individuals when using variants called from long-read data as truth. STRling is fast, scalable on cloud computing, open-source, and freely available athttps://github.com/quinlan-lab/STRling.
Evidence for the role of transcription factors in the co-transcriptional regulation of intron retention
Authors: Ullah Fahad , Salton Maayan , Reddy Anireddy SN , Ben-Hur Asa 
Published: November 2021

ABSTRACTAlternative splicing is a widespread regulatory phenomenon that enables a single gene to produce multiple transcripts. Among the different types of alternative splicing, intron retention is one of the least explored despite its high prevalence in both plants and animals. The recent discovery that the majority of splicing is co-transcriptional has led to the finding that chromatin state affects alternative splicing. Therefore it is plausible that transcription factors can regulate splicing outcomes. We provide evidence for this hypothesis by studying regions of open chromatin in retained and excised introns. Using deep learning models designed to distinguish between regions of open chromatin in retained introns and non-retained introns, we identified motifs enriched in IR events with significant hits to known human transcription factors. Our model predicts that the majority of transcription factors that affect intron retention come from the zinc finger family. We demonstrate the validity of these predictions using ChIP-seq data for multiple zinc finger transcription factors and find strong over-representation for their peaks in intron retention events.AvailabilitySource code available at https://github.com/fahadahaf/chromir
Passive Exposure Sparsifies Neural Activity in the Primary Visual Cortex
Authors: Homann Jan , Kim Hyewon , Tank David W. , Berry Michael J. 
Published: November 2021

AbstractA notable feature of neural activity is sparseness – namely, that only a small fraction of neurons in a local circuit have high activity at any moment. Not only is sparse neural activity observed experimentally in most areas of the brain, but sparseness has been proposed as an optimization or design principle for neural circuits. Sparseness can increase the energy efficiency of the neural code as well as allow for beneficial computations to be carried out. But how does the brain achieve sparse-ness? Here, we found that when neurons in the primary visual cortex were passively exposed to a set of images over several days, neural responses became more sparse. Sparsification was driven by a decrease in the response of neurons with low or moderate activity, while highly active neurons retained similar responses. We also observed a net decorrelation of neural activity. These changes sculpt neural activity for greater coding efficiency.
Indirect effects of parental conflict on conspecific offspring development
Authors: Coughlan J.M. 
Published: November 2021

AbstractHybrid Seed Inviability (HSI) is a common barrier in angiosperms. Recent work suggests that the rapid evolution of HSI may, in part, be due to conflict between maternal and paternal optima for resource allocation to developing offspring (i.e. parental conflict). However, parental conflict requires that paternally-derived resource acquiring alleles impose a maternal cost. I test this requirement using three closely related species in theMimulus guttatusspecies complex that exhibit significant HSI and differ in their inferred histories of parental conflict. I show that the presence of hybrid seeds significantly affects conspecific seed size for almost all crosses, such that conspecific seeds are smaller after developing with hybrids from fathers with a stronger history of conflict, and larger after developing with hybrids from fathers with a weaker history of conflict. This work demonstrates a cost of paternally-derived alleles, and also has implications for species fitness in secondary contact.
Label-free adaptive optics single-molecule localization microscopy for whole animals
Authors: Park Sanghyeon , Jo Yonghyeon , Kang Minsu , Hong Jin Hee , Ko Sangyoon , Kim Suhyun , Park Sangjun , Park Hae-Chul , Shim Sang-Hee , Choi Wonshik 
Published: November 2021

AbstractThe specimen-induced aberration has been a major factor limiting the imaging depth of single-molecule localization microscopy (SMLM). Here, we report the application of label-free wavefront sensing adaptive optics to SMLM for deep-tissue super-resolution imaging. The proposed system measures complex tissue aberrations from intrinsic reflectance rather than fluorescence emission and physically corrects the wavefront distortion more than three-fold stronger than the previous limit. This enables us to resolve sub-diffraction morphologies of cilia and oligodendrocytes in whole intact zebrafish as well as dendritic spines in thick mouse brain tissues at the depth of up to 102 μm with localization number enhancement by up to 37 times and localization precision comparable to aberration-free samples. The proposed approach can expand the application range of SMLM to intact animals that cause the loss of localization points owing to severe tissue aberrations.
Polygalacturonase production enhancement by Piriformospora indica from sugar beet pulp under submerged fermentation using surface methodology
Authors: Kiani Somayyeh , Rezaei Parisa Fathi , Jamalzadegan Sina 
Published: November 2021

AbstractThis study proposed a novel and cost-effective approach to enhance and optimize the polygalacturonase from P. indica. In current investigation, the impact of ammonium sulfate, sugar beet pulp (SBP) and glucose as variables on induction of polygalacturonase from P. indica was optimized using the central composite design (CCD) of response surface methodology (RSM) under SmF. Additionally, partial polygalacturonase purification and in situ analysis were performed. The optimal reaction conditions, which resulted in the highest enzyme activity were observed as the following conditions: ammonium sulfate (4 g/L), SBP (20 g/L), glucose (60 g/L). Under the optimized condition, the maximum enzyme activity reached to 19.4 U/ml (127 U/mg) which increased by 5.84 times compared to non-optimized conditions. The partial purified polygalacturonase molecular weight was estimated 60 KDa. In line with the bioinformatic analysis, exo-polygalacturonase sequence of P. indica showed similarity with Rhizoctonia solani’s and Thanateporus cucumeris. These results indicated that SBP act as a cheap and suitable inducer of polygalacturonase production by P. indica in a submerged cultivation. The outcome of this study will be useful for industries to decrease environmental pollution with cost-effective approaches.
Monitoring of SARS-CoV-2 Antibodies Using Dried Blood Spot for At-Home Collection
Authors: Miesse Peyton K. , Collier Bradley B. , Grant Russell P. 
Published: November 2021

AbstractThe utilization of vaccines to fight the spread of SARS-CoV-2 has led to a growing need for expansive serological testing. To address this, an EUA approved immunoassay for detection of antibodies to SARS-CoV-2 in venous serum samples was investigated for use with dried blood spot (DBS) samples. Results from self-collected DBS samples demonstrated a 98.1% categorical agreement to venous serum with a correlation (R) of 0.9600 while professionally collected DBS samples demonstrated a categorical agreement of 100.0% with a correlation of 0.9888 to venous serum. Additional studies were performed to stress aspects of at-home DBS collection, including shipping stability, interference effects, and other sample-specific robustness studies. These studies demonstrated a categorical agreement of at least 95.0% and a mean bias less than ±20.0%. Furthermore, the ability to track antibody levels following vaccination with the BioNTech/Pfizer vaccine was demonstrated with self-collected DBS samples from pre-dose (Day 0) out to 19 weeks.
A genome assembly of the Atlantic chub mackerel (Scomber colias): a valuable teleost fishing resource
Authors: Machado André M. , Gomes-dos-Santos André , Fonseca Miguel , da Fonseca Rute R. , Veríssimo Ana , Felício Mónica , Capela Ricardo , Alves Nélson , Santos Miguel , Salvador-Caramelo Filipe , Domingues Marcos , Ruivo Raquel , Froufe Elsa , Castro L. Filipe C. 
Published: November 2021

AbstractThe Atlantic chub mackerel, Scomber colias Gmelin, 1789, is a medium-size pelagic fish with substantial importance in the fisheries of the Atlantic Ocean and the Mediterranean Sea. Over the past decade, this species has gained special relevance being one of the main targets of pelagic fisheries in the NE Atlantic. Here, we sequenced and annotated the first high-quality draft genome assembly of S. colias, produced with Pacbio HiFi long reads and Illumina Paired-End short reads. The estimated genome size is 814 Mb distributed into 2,028 scaffolds and 2,093 contigs with an N50 length of 4,19 and 3,34 Mb, respectively. We annotated 27,675 protein-coding genes and the BUSCO analyses indicated high completeness, with 97.3 % of the single-copy orthologs in the Actinopterygii library profile. The present genome assembly represents a valuable resource to address the biology and management of this relevant fishery. Finally, this is the fourth high-quality genome assembly within the Order Scombriformes and the first in the genus Scomber.
Chemical Reversible Crosslinking Enables Measurement of RNA 3D Distances and Alternative Conformations in Cells
Authors: Van Damme Ryan , Li Kongpan , Zhang Minjie , Bai Jianhui , Lee Wilson H. , Yesselman Joseph D. , Lu Zhipeng , Velema Willem A. 
Published: November 2021

ABSTRACTThree-dimensional (3D) structures dictate the functions of RNA molecules in a wide variety of biological processes. However, direct determination of RNA 3D structures in vivo is difficult due to their large sizes, conformational heterogeneity, and dynamics. Here we present a new method, Spatial 2’-Hydroxyl Acylation Reversible Crosslinking (SHARC), which uses chemical crosslinkers of defined lengths to measure distances between nucleotides in cellular RNA. Integrating crosslinking, exonuclease (exo) trimming, proximity ligation, and high throughput sequencing, SHARC enables transcriptome-wide tertiary structure contact maps at high accuracy and precision, revealing heterogeneous RNA structures and interactions. SHARC data provide constraints that improves Rosetta-based RNA 3D structure modeling at near-nanometer resolution. Integrating SHARC-exo with other crosslinking-based methods, we discover compact folding of the 7SK RNA, a critical regulator of transcriptional elongation. These results establish a new strategy for measuring RNA 3D distances and alternative conformations in their native cellular context.
Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells
Authors: Kuo Yu-Yi , Chen Wei-Ting , Lin Guan-Bo , Lu Chueh-Hsuan , Chao Chih-Yu 
Published: November 2021

AbstractBackgroundPancreatic cancer is a deadly cancer around the world. To reduce side effects and enhance treatment efficacy, study on combination therapy for pancreatic cancer has gained much attention in recent years.MethodsIn this paper, we propose a novel triple treatment combining propolis and two physical stimuli‒thermal cycling-hyperthermia (TC-HT) and low-intensity ultrasound (US) on a human pancreatic cancer cell line PANC-1. MTT assay was used to determine the viability of PANC-1 cells. Flow cytometry was used to detect apoptosis, mitochondrial membrane potential (MMP) loss, and intracellular reactive oxygen species (ROS) levels. Western blot analysis was further performed to measure protein expression and phosphorylation.ResultsThe experiments found that, after the triple treatment, the cell viability of the PANC-1 cells decreased to a level 80% less than the control, without affecting the normal pancreatic cells. Another result was excessive accumulation of ROS after the triple treatment, leading to the amplification of apoptotic pathway through the mitogen-activated protein kinase (MAPK) family and mitochondrial dysfunction. Moreover, the combination of TC-HT and US also promotes the anticancer effect of the heat-sensitive chemotherapy drug cisplatin on PANC-1 cells.ConclusionThis study, to the best of our knowledge, is the first attempt to combine TC-HT, US and a nature compound in cancer treatment. We demonstrate that physical stimuli could augment the therapeutical effect of anticancer agents. It is expected that optimized parameters for different agents and different types of cancer will expand the methodology on oncological therapy in a safe manner.