bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses
Authors: Ryan Feargal J. , Norton Todd S. , McCafferty Conor , Blake Stephen J. , Stevens Natalie E. , James Jane , Eden Georgina L. , Tee Yee C. , Benson Saoirse C. , Masavuli Makutiro G. , Yeow Arthur EL , Abayasingam Arunasingam , Agapiou David , Stevens Hannah , Zecha Jana , Messina Nicole L. , Curtis Nigel , Ignjatovic Vera , Monagle Paul , Tran Huyen , McFadyen James D. , Bull Rowena A. , Grubor-Bauk Branka , Lynn Miriam A. , Botten Rochelle , Barry Simone E. , Lynn David J. 
Published: September 2022

AbstractWe longitudinally profiled immune responses in 102 adults who received BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) as their primary vaccinations. Bloods were collected pre-vaccination, 1-7 days after the 1st, 2ndand 3rddoses (BNT162b2 or mRNA-1273) to assess innate and early adaptive responses, and ∼28 days after the 2ndand 3rddoses to assess immunogenicity. Using a multi-omics approach including RNAseq, cytokine multiplex assay, proteomics, lipidomics, and flow cytometry we identified key differences in the immune responses induced by the ChAdOx1-S and BNT162b2 vaccines that were correlated with subsequent antigen-specific antibody and T cell responses or vaccine reactogenicity. We observed that vaccination with ChAdOx1-S but not BNT162b2 induced a memory-like response after the first dose, which was correlated with the expression of several proteins involved in complement and coagulation. The COVID-19 Vaccine Immune Responses Study (COVIRS) thus represents a major resource to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.
Glutamatergic Supramammillary Nucleus Neurons Respond to Threatening Stressors and Promote Active Coping
Authors: Escobedo Abraham , Holloway Salli-Ann , Votoupal Megan , Cone Aaron L , Skelton Hannah E , Legaria Alex A. , Ndiokho Imeh , Floyd Tasheia , Kravitz Alexxai V. , Bruchas Michael R. , Norris Aaron J. 
Published: September 2022

AbstractThreat-response neural circuits are conserved across species and play roles in normal behavior and psychiatric diseases. Maladaptive changes in these neural circuits contribute to stress, mood, and anxiety disorders. Active coping in response to stressors is a psychosocial factor associated with resilience against stress-induced mood and anxiety disorders. The neural circuitry underlying active coping is poorly understood, but the functioning of these circuits could be key for overcoming anxiety and related disorders. The supramammillary nucleus (SuM) has been suggested to be engaged by threat. SuM has many projections and contains a poorly understood diversity of populations. We identified a unique population of glutamatergic SuM neurons (SuMVGLUT2+::POA) based on projection to the preoptic area of the hypothalamus (POA) and found SuMVGLUT2+::POA neurons have extensive arborizations. SuMVGLUT2+::POA neurons project to brain areas that mediate various features of the stress and threat responses including the paraventricular nucleus thalamus (PVT), periaqueductal gray (PAG), and the habenula (Hb). Thus, SuMVGLUT2+::POA neurons are positioned as a hub, connecting to areas implicated in regulating stress responses. Here we report SuMVGLUT2+::POA neurons are recruited by diverse threatening stressors, and recruitment of SuMVGLUT2+::POA neurons correlated with active coping behaviors. We found that selective photoactivation of the SuMVGLUT2+::POA population drove aversion but not anxiety like behaviors. Activation of SuMVGLUT2+::POA neurons in the absence of acute stressors evoked active coping like behaviors and drove instrumental behavior (selective port activations) (Figure 6). Also, activation of SuMVGLUT2+::POA neurons was sufficient to convert passive coping strategies to active behaviors during acute stress. In contrast, we found activation of GABAergic (VGAT+) SuM neurons (SuMVGAT+) neurons did not alter drive aversion or active coping, but termination of photostimulation was followed by increased mobility in the forced swim test. These findings establish a new node in stress response circuitry that has projections to many brain areas, evokes flexible active coping behaviors, and offers new opportunities for furthering our neurobiological understanding of stress.
Phytohormones enhance heavy metal responses inEuglena gracilis: evidence from uptake of Ni, Pb and Cd and linkages to hormonomic and metabolomic dynamics
Authors: Nguyen Hai Ngoc , Nguyen Quoc Thien , Dang Duc Huy , R. J. Neil Emery 
Published: September 2022

AbstractOver the last decade, significant effort has been made to understand phytohormonal functions (e.g. cytokinins (CKs) and abscisic acid (ABA)) in metal stress responses of higher plants and algae. Despite the potential for these phytohormones to improve industrial remediation byEuglena gracilis(Euglenophyceae), no such roles have been elucidated for this highly adaptive species and its response to heavy metals. This study demonstrates that toxic metals (nickel, lead, cadmium) modify hormonal activity profiles (i.e., CK forms and their concentrations) inE. gracilis. Furthermore, exogenous ABA or CK (tZ) enabled higher metal uptake efficiency and alleviated metal toxicity through the regulation of endogenous CKs and gibberellins (GAs) levels. These responses suggest thatE. gracilisregulates multiple phytohormone signals during metal stress acclimation. A deeper approach, using untargeted metabolomic analyses, gave more detailed insight into phytohormone-controlled pathways and associated modified metabolites, which were frequently related to metal accumulation and the physiological acclimation to metal presence. Significant changes in the levels of cellular metabolites, especially those involved in acclimation to metal stress, were under the influence of phytohormones in algal cells. When grown under metal stress conditions, the presence of exogenous ABA or CKs, caused changes in cellular metabolites which included those from: lipid pathways, riboflavin metabolism, the biosynthesis of cofactors/vitamins, and carbohydrate metabolism. Also, bioactive secondary metabolites (e.g., terpenoids, alkaloids, flavonoids, carotenoids) were modified in algal cells treated with phytohormones. Thus, the study gives a detailed view on the regulatory functions of ABA and CKs in algal metal bioremediation strategies, which are attributed to enhanced metal uptake and in the fine-tuning of plant hormone levels during metal stress response. The results can guide efforts to develop efficient, low-cost and environmentally friendly methods for bioremediation.HighlightsMetal stress produces phytohormone-specific responses inEuglena gracilis.Phytohormones (ABA and CK) enhance metal accumulation rates.Phytohormone-controlled metal uptake reflects enhanced CK activity profiles.Modified hormonal crosstalk is involved in phytohormone-induced metal uptake.Metabolomic responses to phytohormones-involve metal stress mitigation compounds.
Altered MAM function shifts mitochondrial metabolism in SOD1-mutant models of ALS
Authors: Larrea Delfina , Tamucci Kirstin A. , Kabra Khushbu , Velasco Kevin R. , Yun Taekyung D. , Pera Marta , Montesinos Jorge , Agrawal Rishi R. , Smerdon John W. , Lowry Emily R. , Stepanova Anna , Yoval-Sanchez Belem , Galkin Alexander , Wichterle Hynek , Area-Gomez Estela 
Published: September 2022

AbstractMitochondrial defects are a common hallmark of familial and sporadic forms of amyotrophic lateral sclerosis (ALS). However, the origin of these defects, including reduced pyruvate metabolism and reduced oxygen consumption, is poorly understood. These metabolic functions are regulated in specialized endoplasmic reticulum (ER) domains in close contact with mitochondria, called mitochondrial-associated ER membranes (MAM). Recently it has been shown that MAM domains are disrupted in ALS, but the connection between MAM dysregulation and mitochondrial defects in ALS cells remains unclear. Using human embryonic stem cell (ESC)-derived motor neurons (hMNs) and mouse models with ALS-pathogenic mutations in superoxide dismutase 1 (SOD1), we found that the glycolytic deficiency in ALS is a direct consequence of the progressive disruption of MAM structure and function that hinders the use of glucose-derived pyruvate as a mitochondrial fuel and triggers a shift in mitochondrial substrates from pyruvate to fatty acids. This glycolytic deficiency, over time, induces significant alterations in mitochondrial electron flow and in the active/dormant (A/D) status of complex I in spinal cord, but not in brain. These data agree with a role for MAM in the maintenance and regulation of cellular glucose metabolism and suggest that MAM disruption in ALS could be the underlying cause of the bioenergetic deficits observed in the disease.
Environmental, social, and morphological drivers of fission-fusion dynamics in a social ungulate
Authors: Goff Morgane Le , Hendrix Jack G. , Webber Quinn M. R. , Robitaille Alec L. , Wal Eric Vander 
Published: September 2022

AbstractSocial groups exist because individuals within the group accrue a net benefit from sharing space. The profitability of sociality, however, varies with ecological context. As ecological context varies, tension emerges among the costs and benefits of social grouping. Fission-fusion societies are fluid in their group dynamics across spatial and temporal contexts, permitting insights into how context affects whether animals choose to join or depart a group. We tested four non-mutually exclusive hypotheses driving variation in fission and fusion in caribou: the risky places, environment heterogeneity, activity budget, and social familiarity hypotheses. The risky places hypothesis predicts animals are unlikely to diffuse when habitats are open and risk of predation is elevated. The habitat heterogeneity hypothesis predicts that fission is more likely in a heterogeneous landscape due to the rising conflicts of interest between group members. The activity budget hypothesis predicts dyads associate by body size due to similar food passage rates. The social cohesion hypothesis predicts that familiar individuals are less likely to fission. We tested the hypotheses using time-to-event (time before fission) analyses and a linear model that assesses spatial, social, and body size relationships among female caribou (n = 22) on Fogo Island, Newfoundland, Canada. Contrary to our prediction for risky places, probability of fission was not influenced by habitat openness. The hypothesis of environmental heterogeneity was partially supported, as caribou remained less cohesive in environments with a higher richness of habitats. No direct evidence emerged to support the activity budget hypothesis. However, it appears that caribou maintain the strongest social bonds among variably sized individuals and these social bonds do decrease the propensity to split. Collectively, our findings showed that social interactions may depend not only on individual identity and characteristics, but also the spatial context in which these interactions occur.
Tumoroscope: a probabilistic model for mapping cancer clones in tumor tissues
Authors: Shafighi Shadi Darvish , Geras Agnieszka , Jurzysta Barbara , Naeini Alireza Sahaf , Filipiuk Igor , Rączkowski Łukasz , Toosi Hosein , Koperski Łukasz , Thrane Kim , Engblom Camilla , Mold Jeff , Chen Xinsong , Hartman Johan , Nowis Dominika , Carbone Alessandra , Lagergren Jens , Szczurek Ewa 
Published: September 2022

AbstractSpatial and genomic heterogeneity of tumors is the key for cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic model that accurately infers cancer clones and their high-resolution localization by integrating pathological images, whole exome sequencing, and spatial transcriptomics data. In contrast to previous methods, Tumoroscope explicitly addresses the problem of deconvoluting the proportions of clones in spatial transcriptomics spots. Applied to a reference prostate cancer dataset and a newly generated breast cancer dataset, Tumoroscope reveals spatial patterns of clone colocalization and mutual exclusion in sub-areas of the tumor tissue. We further infer clone-specific gene expression levels and the most highly expressed genes for each clone. In summary, Tumoroscope enables an integrated study of the spatial, genomic, and phenotypic organization of tumors.
Dopaminergic innervation at the central nucleus of the amygdala reveals distinct topographically and functionally segregated regions
Authors: Casey Eric , Avale María Elena , Kravitz Alexxai , Rubinstein Marcelo 
Published: September 2022

AbstractThe central nucleus of the amygdala (CeA) is involved in the expression of fear and has been implicated in several anxiety disorders. Anatomically, it is divided in a medial (CeM), a lateral (CeL) and a capsular division (CeC). The CeA is densely innervated by dopaminergic projections that originate in the ventral periaqueductal gray/dorsal raphe (vPAG/DR) and the ventral tegmental area/substantia nigra compacta (VTA/SNc). However, it is unknown if DA exerts a homogenous control over the CeA or, conversely, if different parts of the CeA are regulated in a distinct manner. Here, we performed a neuroanatomical and functional analysis of the mouse CeA and revealed that dopaminergic innervations arriving from the PAG/DR and the VTA/SNc constitute distinct, non-overlapping pathways that differ in their expression of dopamine transporter. By quantifying the distribution of DAergic fibers and the origin of the innervation, we identified two regions in the CeL: a frontal region innervated by both the VTA/SNc and the vPAG/DR, and a caudal region innervated only by the vPAG/DR; and three regions in the CeC: a fronto-dorsal region innervated only by the VTA/SNc, a fronto-ventral region with sparse DAergic innervation, and a caudal region with low innervation from the vPAG/DR. In addition, we found that each region displays a unique pattern of cFos activation after the administration of cocaine, SKF 38393, quinpirole or haloperidol, demonstrating that the regions identified here are functionally distinct from each other. In summary, this analysis reveals unique properties of the DAergic pathways innervating the CeA, and distinguishes six topographically segregated and functionally distinct regions in the CeA. This unanticipated level of functional heterogeneity calls for more precise anatomical specificity in future functional studies of the CeA.
Meta-analysis of (single-cell method) benchmarks reveals the need for extensibility and interoperability
Authors: Sonrel Anthony , Luetge Almut , Soneson Charlotte , Mallona Izaskun , Germain Pierre-Luc , Knyazev Sergey , Gilis Jeroen , Gerber Reto , Seurinck Ruth , Paul Dominique , Sonder Emanuel , Crowell Helena L. , Fanaswala Imran , Al-Ajami Ahmad , Heidari Elyas , Schmeing Stephan , Milosavljevic Stefan , Saeys Yvan , Mangul Serghei , Robinson Mark D. 
Published: September 2022

AbstractComputational methods represent the lifeblood of modern molecular biology. Benchmarking is important for all methods, but with a focus here on computational methods, benchmarking is critical to dissect important steps of analysis pipelines, formally assess performance across common situations as well as edge cases, and ultimately guide users on what tools to use. Benchmarking can also be important for community building and advancing methods in a principled way. We conducted a meta-analysis of recent single-cell benchmarks to summarize the scope, extensibility, neutrality, as well as technical features and whether best practices in open data and reproducible research were followed. The results highlight that while benchmarks often make code available and are in principle reproducible, they remain difficult to extend, for example, as new methods and new ways to assess methods emerge. In addition, embracing containerization and workflow systems would enhance reusability of intermediate benchmarking results, thus also driving wider adoption.
Anticodon-like loop-mediated dimerization in the crystal structures of HDV-like CPEB3 ribozymes
Authors: Przytula-Mally Anna Ilaria , Engilberge Sylvain , Johannsen Silke , Olieric Vincent , Masquida Benoît , Sigel Roland K.O. 
Published: September 2022

ABSTRACTCytoplasmic polyadenylation element-binding (CPEB) proteins are involved in many cellular processes, including cell division, synaptic plasticity, learning, and memory. A highly conserved, short mammalian ribozyme has been found within the second intron of the CPEB3 gene. Based on its cleavage mechanism and structural features, this ribozyme belongs to the hepatitis delta virus (HDV)-like ribozyme family. Here, we present the first crystallographic structures of human and chimpanzee CPEB3 ribozymes, both confirming the general topology of the HDV ribozyme with two parallel coaxial helical stacks. However, the residues involved in forming the P1.1 mini-helix, which is an integral part of the characteristic nested double pseudoknot involving P1, P2, and P3, instead participate in a seven nucleotides loop with a conformation similar to the one from the anticodon (AC) loop of tRNAs when interacting with the mRNA codon. The conformation of the loop supports the formation of a four-base pair helix by interacting with the AC-like loop from a symmetry-related ribozyme leading to ribozyme dimer formation. The present crystal structures link for the first time the sequence specificities of the CPEB3 and the HDV (genomic and antigenomic) ribozymes to their different structural features. This work corroborates the hypothesis made by Szostak that HDV ribozymes may have evolved from the CPEB3 ribozyme.
Accurate genotype-based demultiplexing of single cell RNA sequencing samples from non-human animals
Authors: Cardiello Joseph F. , Araus Alberto Joven , Giatrellis Sarantis , Simon András , Leigh Nicholas D. 
Published: September 2022

AbstractSingle cell sequencing technologies (scRNA-seq, scATAC-seq, etc.) have revolutionized the study of complex tissues and unique organisms, providing researchers with a much needed species agnostic tool to study biological processes at the cellular level. To date, scRNA-seq technologies are expensive, require sufficient cell quantities, and need biological replicates to avoid batch effects or artifactual results. Pooling cells from multiple individuals into a single scRNA-seq library can address these problems. However, sample labeling protocols for facilitating the computational separation of pooled scRNA-seq samples, termed demultiplexing, have undesirable limitations, particularly in resource-limited organisms. One promising solution developed for use in humans exploits the genetic diversity between individuals (i.e., single nucleotide polymorphisms (SNP)) to demultiplex pooled scRNA-seq samples. The use of SNP-based demultiplexing methods has not been validated for use in non-human species, but the widespread use of SNP-based demuxers would greatly facilitate research in commonly used, emerging, and more obscure species. In this study we applied SNP-based demultiplexing algorithms to pooled scRNA-seq datasets from numerous species and applied diverse ground truth confirmation assays to validate genetic demultiplexing results. SNP-based demultiplexers were found to accurately demultiplex pooled scRNA-seq data from species including zebrafish, African green monkey, Xenopus laevis, axolotl, Pleurodeles waltl, and Notophthalmus viridescens. Our results demonstrate that SNP-based demultiplexing of unlabeled, pooled scRNA-seq samples can be used with confidence in all of the species studied in this work. Further, we show that the only genomic resource required for this approach is the single-cell sequencing data and a de novo transcriptome. The incorporation of pooling and SNP-demultiplexing into scRNA-seq study designs will greatly increase the reproducibility and experimental options for studying species previously limited by technical uncertainties, computational hurdles, or limited cell quantities.
Designing a Minimal Artificial Glycolytic Pathway
Authors: Yang Yiqun , Liu Yuwan , Zhang Jie , Yang Qiaoyu , Cheng Jian , Chu Huanyu , Zhao Haodong , Luo Mengting , Lu Xiaoyun , Liu Dingyu , Sheng Xiang , Zhang Yi-Heng P. J. , Jiang Huifeng , Ma Yanhe 
Published: September 2022

AbstractThe canonical glycolysis generates two molecules of acetyl-coenzyme A (acetyl-CoA) from one glucose through eleven cascade biochemical reactions. Here, we designed and constructed a Minimal Artificial Glycolytic (MAG) pathway consisting of only three types of biochemical reactions, with phosphoketolase as the core, combined with phosphatase and isomerase as auxiliary enzymes. It could theoretically achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating one-carbon condensation reaction. We tested the MAG pathway in vitro and in vivo, demonstrating the catabolism of typical C1-C6 carbohydrates to acetyl-CoA with yields from 82% to 95%. This novel glycolytic pathway provides a promising route for biomanufacturing with stoichiometric productivity from multiple carbon sources in the future.
A formula for calculating 30-item Geriatric Depression Scale (GDS-30) scores from the 15-item version (GDS-15)
Authors: Zhang Yuge , Hoozemans Marco , Pijnappels Mirjam , Bruijn Sjoerd M. 
Published: September 2022

AbstractThe Geriatric Depression Scale with 30 items (GDS-30) and with 15 items (GDS-15) are both valid tools for assessing depression in older adults, but their absolute values are not directly comparable. Here, we used a dataset (n=431) with GDS-30 scores from a project concerning fall-risk assessment in older adults (FARAO) to develop and validate a formula which can be used to convert GDS-15 scores into GDS-30 scores. We found that the GDS-15 score cannot simply be multiplied by 2 to obtain the GDS-30 scores and that estimations of GDS-30 from GDS-15 are not affected by age, sex and MMSE. Therefore, the optimal formula to estimate the GDS-30 score from the GDS-15 score was: GDS-30_estimated = 1.57 + 1.95 × GDS-15. This formula yielded an estimate of GDS-30 with an explained variance of 79%, compared to 63% when GDS-15 was simply multiplied by 2. Researchers that have used the GDS-15 and want to compare their outcomes to other studies that reported only the GDS-30 are advised to use this formula.