bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harmonization of SARS CoV-2 antibodies determination. Is it really possible?
Authors: Dittadi Ruggero 
Published: December 2021

AbstractThe WHO standard was prepared with the aim of harmonizing assays detecting antibodies against SARS CoV-2. The aspect of the harmonization of the assays is to date under debate. We re-evaluated a previously studied set of cases (108 specimens of 48 patients and 60 specimens of 20 vaccinated subjects, collected after 14 days from the first dose, 14 days and 3 months after a second dose of the Comirnaty BNT162b2 vaccine), calculating the ratios between the results of two methods (SARS-CoV-2 IgG anti-RBD, SNIBE and anti-SARS-CoV-2 QuantiVac ELISA IgG, Euroimmun).In the vaccinated subjects the ratios of the results between methods according to the WHO standard were relatively dispersed, but the harmonization results good. On the other hand, in patient samples the variability between tests was very high and the harmonization was unsatisfactory (median ratios between methods 2.23, 10th-90th percentile: 1.1-5.6).Interestingly, in patient samples the harmonization depends on the time from the onset of symptoms, and greatly improves after 6 months from the diagnosis. 40 patient specimens and 31 of vaccinated subjects after the second dose were evaluated also with a third method (Access SARS-CoV-2 IgG (1st IS), Beckman Coulter), obtaining a similar trend.We can conclude that the actual effectiveness of harmonization between methods may vary depending on the scenario in which they will be used.
Both Prey and Predator Features Determine Predation Risk and Survival of Schooling Prey
Authors: Jolles Jolle W. , Sosna Matthew M. G. , Mazué Geoffrey P. F. , Twomey Colin R. , Bak-Coleman Joseph , Rubenstein Daniel I. , Couzin Iain D. 
Published: December 2021

SummaryPredation is one of the main evolutionary drivers of social grouping. While it is well appreciated that predation risk is likely not shared equally among individuals within groups, its detailed quantification has remained difficult due to the speed of attacks and the highly-dynamic nature of collective prey response. Here, using high-resolution tracking of solitary predators (Northern pike) hunting schooling fish (golden shiners), we not only provide detailed insights into predator decision-making but show which key spatial and kinematic features of predator and prey influence individual’s risk to be targeted and survive attacks. Pike tended to stealthily approach the largest groups, and were often already inside the school when launching their attack, making prey in this frontal “strike zone” the most vulnerable to be targeted. From the prey’s perspective, those fish in central locations, but relatively far from, and less aligned with, neighbours, were most likely to be targeted. While the majority of attacks (70%) were successful, targeted individuals that did manage to avoid capture exhibited a higher maximum acceleration response just before the attack and were further away from the pike‘s head. Our results highlight the crucial interplay between predators’ attack strategy and response of prey in determining predation risk in mobile animal groups.
Mucosal and systemic responses to SARS-CoV-2 vaccination in infection naïve and experienced individuals
Authors: Sajadi Mohammad M. , Myers Amber , Logue James , Saadat Saman , Shokatpour Narjes , Quinn James , Newman Michelle , Deming Megan , Tehrani Zahra Rikhtegaran , Karimi Maryam , Abbasi Abdolrahim , Shlyak Mike , Frieman Matthew B. , Crotty Shane , Harris Anthony D. 
Published: December 2021

ABSTRACTWith much of the world infected with or vaccinated against SARS-CoV-2, understanding the immune responses to the SARS-CoV-2 spike (S) protein in different situations is crucial to controlling the pandemic. We studied the clinical, systemic, mucosal, and cellular responses to two doses of SARS-CoV-2 mRNA vaccines in 62 individuals with and without prior SARS-CoV-2 exposure that were divided into three groups based on serostatus and/or degree of symptoms: Antibody negative, Asymptomatic, and Symptomatic. In the previously SARS-CoV-2-infected (SARS2-infected) Asymptomatic and Symptomatic groups, symptoms related to a recall response were elicited after the first vaccination. Anti-S trimer IgA and IgG levels peaked after 1st vaccination in the SARS2-infected groups, and were higher that the in the SARS2-naive group in the plasma and nasal samples at all time points. Neutralizing antibodies titers were also higher against the WA-1 and B.1.617.2 (Delta) variants of SARS-CoV-2 in the SARS2-infected compared to SARS2-naïve vaccinees. After the first vaccination, differences in cellular immunity were not evident between groups, but the AIM+ CD4+ cell response correlated with durability of humoral immunity against the SARS-CoV-2 S protein. In those SARS2-infected, the number of vaccinations needed for protection, the durability, and need for boosters are unknown. However, the lingering differences between the SARS2-infected and SARS2-naïve up to 10 months post-vaccination could explain the decreased reinfection rates in the SARS2-infected vaccinees recently reported and suggests that additional strategies (such as boosting of the SARS2-naïve vaccinees) are needed to narrow the differences observed between these groups.
Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior
Authors: Farinha-Ferreira Miguel , Rei Nádia , Fonseca-Gomes João , Miranda-Lourenço Catarina , Serrão Paula , Vaz Sandra H. , Gomes Joana I. , Martins Valéria , de Alves Pereira Beatriz , Sebastião Ana M. 
Published: December 2021

ABSTRACTChronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely Δ9-tetrahydrocannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct outcomes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious- or depressive-like behaviors. We then tested whether chronic adolescent HU-210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treatment simultaneously induced marked antidepressant- and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both.Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.
The anti-angiogenic compound dimethyl fumarate inhibits the serine synthesis pathway and increases glycolysis in endothelial cells
Authors: Ocaña Maria Carmen , Yang Chendong , Bernal Manuel , Martínez-Poveda Beatriz , Vu Hieu S. , Cárdenas Casimiro , DeBerardinis Ralph J. , Quesada Ana R. , Medina Miguel Ángel 
Published: December 2021

AbstractA pathological and persistent angiogenesis is observed in several diseases like retinopathies, diabetes, psoriasis and cancer. Dimethyl fumarate, an ester from the Krebs cycle intermediate fumarate, is approved as a drug for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity has been reported in vitro and in vivo. However, it is not known whether dimethyl fumarate is able to modulate endothelial cell metabolism, considered an essential feature for the angiogenic switch. By means of different experimental approximations, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in endothelial cells. This new target can open a new field of study regarding the mechanism of action of dimethyl fumarate.
Modeling Synaptic Effects of Anesthesia and its Cortical Cholinergic Reversal
Authors: Eniwaye Bolaji P. , Booth Victoria , Hudetz Anthony G. , Zochowski Michal 
Published: December 2021

AbstractGeneral anesthetics work through a variety of molecular mechanisms while resulting in the common end point of sedation and loss of consciousness. Generally, the administration of common inhalation anesthetics induces decreases in synaptic excitation while promoting synaptic inhibition. Animal studies have shown that, during anesthesia, exogenously induced increases in acetylcholine-mediated effects in the brain can elicit wakeful-like behavior despite the continued presence of the anesthetic. Less investigated, however, is the question of whether the brain’s electrophysiological activity is also restored to pre-anesthetic levels and quality by such interventions. Here we apply a computational model of a network composed of excitatory and inhibitory neurons to simulate the network effects of changes in synaptic inhibition and excitation due to anesthesia and its reversal by muscarinic receptor-mediated cholinergic effects. We use a differential evolution algorithm to fit model parameters to match measures of spiking activity, neuronal connectivity, and network dynamics recorded in the visual cortex of rodents during anesthesia with desflurane in vivo. We find that facilitating muscarinic receptor effects of acetylcholine on top of anesthetic-induced synaptic changes predicts reversal of the neurons’ spiking activity, functional connectivity, as well as pairwise and population interactions. Thus, our model results predict a possible neuronal mechanism for the induced reversal of the effects of anesthesia on post synaptic potentials, consistent with experimental behavioral observations.Author SummaryHere, we apply a computational model of a network composed of excitatory and inhibitory neurons to simulate the network effects of changes in synaptic inhibition and excitation due to anesthesia and we investigate the possibility of its reversal by muscarinic receptor-mediated cholinergic effects. Specifically, we use a differential evolution algorithm to fit model parameters to match dynamics recorded in the visual cortex of rodents during anesthesia with desflurane in vivo. We find that changes of the fitted synaptic parameters in response to the increasing desflurane concentration matched those established by neurophysiology. Further, our results demonstrate that the cellular effects induced by anesthesia can be mitigated by the changes in cellular excitability due to acetylcholine.
A convergent malignant phenotype in B-cell acute lymphoblastic leukemia involving the splicing factor SRRM1
Authors: Closa Adria , Reixachs-Solé Marina , Fuentes-Fayos Antonio C. , Hayer Katharina E. , Melero Juan Luis , Adriaanse Fabienne R. S. , Bos Romy S. , Torres-Diz Manuel , Hunger Stephen , Roberts Kathryn G. , Mullighan Charles , Stam Ronald W. , Thomas-Tikhonenko Andrei , Castaño Justo P. , Luque Raúl M. , Eyras Eduardo 
Published: December 2021

AbstractA significant proportion of infant B-cell acute lymphoblastic leukemia (B-ALL) patients remains with a dismal prognosis due to yet undetermined mechanisms. We performed a comprehensive multicohort analysis of gene expression, gene fusions, and RNA splicing alterations to uncover molecular signatures potentially linked to the observed poor outcome. We identified 87 fusions with significant allele frequency across patients and shared functional impacts, suggesting common mechanisms across fusions. We further identified a gene expression signature that predicts high risk independently of the gene fusion background and includes the upregulation of the splicing factorSRRM1. Experiments in B-ALL cell lines provided further evidence for the role of SRRM1 on cell survival, proliferation, and invasion. Supplementary analysis revealed that SRRM1 potentially modulates splicing events associated with poor outcomes through protein-protein interactions with other splicing factors. Our findings reveal a potential convergent mechanism of aberrant RNA processing that sustains a malignant phenotype independently of the underlying gene fusion, and that could potentially complement current clinical strategies in infant B-ALL.
A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A
Authors: Simon Matthew , Yang Jiping , Gigas Jonathan , Earley Eric J. , Schaff Tory M. , Zhang Lei , Zagorulya Maria , Tombline Greg , Gilbert Michael , Yuen Samantha L. , Pope Alexis , Meter Michael Van , Emmrich Stephan , Han Jeehae , Ryu Seungjin , Tare Archana , Zhu Yizhou , Hudgins Adam , Atzmon Gil , Barzilai Nir , Wolfe Aaron , Moody Kelsey , Garcia Benjamin A. , Thomas David D. , Robbins Paul D. , Vijg Jan , Seluanov Andrei , Suh Yousin , Gorbunova Vera 
Published: December 2021

SUMMARYSirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in the regulation of aging and metabolism. Targeted sequencing identified a SIRT6 allele containing two linked substitutions (N308K/A313S) as enriched in Ashkenazi Jewish (AJ) centenarians as compared to AJ control individuals. Characterization of this SIRT6 (centSIRT6) allele demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double strand break repair, and more robust cancer cell killing compared to the wild type. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.
Metabolic properties of murine kidney mitochondria
Authors: Panov Alexander V. , Mayorov Vladimir I. , Dikalov Sergey I. 
Published: December 2021

AbstractWe show that mitochondria from the kidney of mice (MKM), rat brain (RBM), and heart (RHM) oxidize long-chain fatty acids at high rates in all metabolic states only in the presence of any other mitochondrial metabolites: succinate, glutamate, or pyruvate. All supporting substrates increased several folds the respiration rates in State 4 and State 3. The stimulations of the State 3 respiration with palmitoyl-carnitine + malate oxidation (100%) were: with succinate in MKM 340%, RBM 370%, and RHM 340%; with glutamate - MKM 200%, RBM 270%, and RHM 270%; and with pyruvate - MKM 150%, RBM 260%, and RHM 280%. The increases in O2 consumption in State 4 were due to increased leakage of electrons to produce superoxide radicals (O2•). Earlier, we have shown that the brain and heart mitochondria possess a strong intrinsic inhibition of succinate oxidation to prevent the excessive O2• production at diminished functional loads. We show that kidney mitochondria lack the intrinsic inhibition of SDH. The new methodology to study β-oxidation of LCFAs opens the opportunity to study energy metabolism under normal and pathological conditions, particularly in the organs that utilize LCFAs as the main energy source.
Single cell genome sequencing of laboratory mouse microbiota improves taxonomic and functional resolution of this model microbial community
Authors: Lyalina Svetlana , Stepanauskas Ramunas , Wu Frank , Sanjabi Shomyseh , Pollard Katherine S. 
Published: December 2021

AbstractLaboratory mice are widely studied as models of mammalian biology, including the microbiota. However, much of the taxonomic and functional diversity of the mouse gut microbiome is missed in current metagenomic studies, because genome databases have not achieved a balanced representation of the diverse members of this ecosystem. Towards solving this problem, we used flow cytometry and low-coverage sequencing to capture the genomes of 764 single cells from the stool of three laboratory mice. From these, we generated 298 high-coverage microbial genome assemblies, which we annotated for open reading frames and phylogenetic placement. These genomes increase the gene catalog and phylogenetic breadth of the mouse microbiota, adding 135 novel species with the greatest increase in diversity to the Muribaculaceae and Bacteroidaceae families. This new diversity also improves the read mapping rate, taxonomic classifier performance, and gene detection rate of mouse stool metagenomes. The novel microbial functions revealed through our single-cell genomes highlight previously invisible pathways that may be important for life in the murine gastrointestinal tract.
Comparison of biological features of wild European rabbit mesenchymal stem cells derived from different tissues
Authors: Calle Alexandra , Zamora-Ceballos María , Bárcena Juan , Blanco Esther , Ramírez Miguel Ángel 
Published: December 2021

AbstractAlthough the European rabbit is an “endangered” species and a notorious biological model, the analysis and comparative characterization of new tissue sources of rabbit mesenchymal stem cells (rMSCs) has not been well studied. Here we report for the first time the isolation and characterization of rMSCs derived from an animal belonging to a natural rabbit population within the species native region. New rMSC lines were isolated from different tissues: oral mucosa (rOM-MSC), dermal skin (rDS-MSC), subcutaneous adipose tissue (rSCA-MSC), ovarian adipose tissue (rOA-MSC), oviduct (rO-MSC), and mammary gland (rMG-MSC). The six rMSC lines showed plastic adhesion with fibroblast-like morphology and were all shown to be positive for CD44 and CD29 expression (characteristic markers of MSCs), and negative for CD34 or CD45 expression. In terms of pluripotency features, all rMSC lines expressed NANOG, OCT4, and SOX2. Furthermore, all rMSC lines cultured under osteogenic, chondrogenic, and adipogenic conditions showed differentiation capacity. In conclusion, this study describes the isolation and characterization of new rabbit cell lines from different tissue origins, with a clear mesenchymal pattern. We show that rMSC do not exhibit differences in terms of morphological features, expression of the cell surface, and intracellular markers of pluripotency and in vitro differentiation capacities, attributable to their tissue of origin.
Gross anatomy of the gluteal and posterior thigh muscles in koalas based on their innervations
Authors: Tojima Sayaka , Anetai Hidaka , Koike Kaito , Anetai Saori , Tokita Kounosuke , Leigh Chris , Kumaratilake Jaliya 
Published: December 2021

AbstractThere are not many descriptions of the muscle morphology of marsupials, despite the fact that they should show diversity according to the adaptation and dispersal to a variety of environments. Most of the previous studies regarding the gross anatomy of marsupials were conducted in the 1800 - 1900’s, and many issues still remain that need to be reexamined. For instance, the muscle identification had been performed based only on their attachments and thus, muscle descriptions are often inconsistent among the studies. These classic studies often do not include figures or photographs, so the discrepancies in the descriptions of the muscles could only be verified by performing the muscle identification again with a more reliable method. This problem can be solved by performing muscle identification by innervation. This method, which focuses on the ontogenic origin of the muscle as opposed to the attachment site, is prone to individual and interspecies variation and is a common technique in recent anatomical research. This technique is more reliable than previous methods and is suitable for comparison with other taxa (i.e., eutherians). In this study, we first conducted muscle identification based on innervation in the gluteal and posterior thighs of koalas in order to reorganize the anatomical knowledge of marsupials. This is because the gluteus and posterior thighs of koalas are the areas where previous studies have been particularly inconsistent. We dissected five individual koalas and clarified discrepancies in previous studies, as well as investigated the unique muscle morphology and their function in koalas. Specifically, the koala’s gluteal muscle group is suitable for abduction, while the posterior thigh muscles are particularly suitable for flexion. In the future, we will update the anatomical findings of marsupials in the same way to clarify the adaptive dissipation process of marsupials, as well as to contribute to the understanding of the evolutionary morphology of mammals.
Genome edited colorectal cancer organoid models reveal distinct microRNA activity patterns across different mutation profiles
Authors: Villanueva Jonathan W. , Kwong Lawrence , Han Teng , Martinez Salvador Alonso , Shanahan Michael T. , Kanke Matt , Dow Lukas E. , Danko Charles G. , Sethupathy Praveen 
Published: December 2021

AbstractSomatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify 12 different modules of microRNA expression patterns across distinct combinations of mutations common in CRC. We also show that miR-24-3p is aberrantly upregulated in genetically-modified mouse enteroids irrespective of mutational context. Furthermore, we identify an enrichment of miR-24-3p predicted targets in downregulated gene lists from various mutational contexts compared to WT. In follow-up experiments, we demonstrate that miR-24-3p promotes CRC cell survival in multiple cell contexts. Our novel characterization of genotype-specific patterns of miRNA expression offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.