bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genomic basis of the plant island syndrome in Darwin’s giant daisies
Authors: Cerca José , Petersen Bent , Lazaro Guevara José Miguel , Rivera-Colón Angel , Birkeland Siri , Vizueta Joel , Li Siyu , Loureiro João , Kosawang Chatchai , Díaz Patricia Jaramillo , Rivas-Torres Gonzalo , Fernández-Mazuecos Mario , Vargas Pablo , McCauley Ross , Petersen Gitte , Santos-Bay Luisa , Wales Nathan , Catchen Julian , Machado Daniel , Nowak Michael D. , Suh Alexander , Sinha Neelima , Nielsen Lene R. , Seberg Ole , Gilbert M. Thomas P. , Leebens-Mack James H. , Rieseberg Loren , Martin Michael D. 
Published: January 2022

AbstractOceanic archipelagos comprise multiple disparate environments over small geographic areas and are isolated from other biotas. These conditions have led to some of the most spectacular adaptive radiations, which have been key to our understanding of evolution, and offer a unique chance to characterise the genomic basis underlying rapid and pronounced phenotypic changes. Repeated patterns of evolutionary change in plants on oceanic archipelagos, i.e. the plant island syndrome, include changes in leaf morphology, acquisition of perennial life-style, and change of ploidy. Here, we describe the genome of the critically endangered and Galápagos endemicScalesia atractyloidesArnot., obtaining a chromosome-resolved 3.2-Gbp assembly with 43,093 candidate gene models. Using a combination of fossil transposable elements,k-mer spectra analyses and orthologue assignment, we identify the two ancestral subgenomes and date their divergence and the polyploidization event, concluding that the ancestor of allScalesiaspecies on the Galápagos was an allotetraploid. There are a comparable number of genes and transposable elements across the two subgenomes, and while their synteny has been mostly conserved, we find multiple inversions that may have facilitated adaptation. We identify clear signatures of selection across genes associated with vascular development, life-growth, adaptation to salinity and changes in flowering time, thus finding compelling evidence for a genomic basis of island syndrome in Darwin’s giant daisy radiation. This work advances understanding of factors influencing subgenome divergence in polyploid genomes, and characterizes the quick and pronounced genomic changes in a specular and diverse radiation of an iconic island plant radiation.
Evolutionary convergence of a neural mechanism in the cavefish lateral line system
Authors: Lunsford Elias T. , Paz Alexandra , Keene Alex C. , Liao James C. 
Published: January 2022

AbstractAnimals can evolve dramatic sensory functions in response to environmental constraints, but little is known about the neural mechanisms underlying these changes. The Mexican tetra, Astyanax mexicanus, is a leading model to study genetic, behavioral, and physiological evolution by comparing eyed surface populations and blind cave populations. We compared neurophysiological responses of posterior lateral line afferent neurons and motor neurons across A. mexicanus populations to reveal how shifts in sensory function may shape behavioral diversity. These studies indicate differences in intrinsic afferent signaling and gain control across populations. Elevated endogenous afferent activity identified a lower response threshold in the lateral line of blind cavefish relative to surface fish. We next measured the effect of inhibitory corollary discharges from hindbrain efferent neurons onto afferents during locomotion. We discovered that three independently-derived cavefish populations have evolved persistent afferent activity during locomotion, suggesting for the first time that regression of the efferent system can be an evolutionary mechanism for neural adaptation of a vertebrate sensory system.
Cognitive Deficits and Altered Cholinergic Innervation in Young Adult Mice Carrying a Parkinson’s Disease LRRK2-G2019S Knockin Mutation
Authors: Hussein Ayan , Tielemans Alexander , Baxter Mark G. , Benson Deanna L. , Huntley George W. 
Published: January 2022

ABSTRACTImpaired executive function is a common and debilitating non-motor symptom of idiopathic and hereditary Parkinson’s disease (PD), but there is little understanding of the underlying pathophysiological mechanisms and circuits. The G2019S mutation in the kinase domain of leucine-rich repeat kinase 2 (LRRK2) greatly increases risk for late-onset PD, and non-manifesting LRRK2-G2019S carriers also exhibit early and significant cognitive impairment. Here, we subjected young adult mice carrying a Lrrk2-G2019S knockin mutation to touchscreen-based operant tasks that measure attention, goal-directed learning and cognitive flexibility, all of which rely on prefrontal-striatal connectivity and are strongly modulated by cholinergic innervation. In a visuospatial attention task, mutant mice exhibited significantly more omissions and longer response latencies than controls that could not be attributed to deficits in motivation, visual sensory perception per se or locomotion, thereby suggesting impairment in divided attention and slower information processing speed. Pretreating mice with the acetylcholinesterase inhibitor donepezil normalized both higher omission rates and longer reward latencies in the mutants, but did not affect any performance metric in controls. Strikingly, cholinergic fiber density in mPFC and dorsomedial striatum was significantly sparser in mutants than in controls, while further behavioral interrogation of the mutants revealed significant impairments in action-outcome associations but preserved cognitive flexibility. These data suggest that the G2019S mutation impacts cholinergic innervation and impairs corticostriatal network function in young adulthood that may contribute to early PD-associated cognitive deficits.STATEMENT OF SIGNIFICANCEThe LRRK2-G2019S mutation causes hereditary Parkinson’s disease and is found in some idiopathic cases. Early cognitive impairment is a common symptom of hereditary and idiopathic PD, yet there is little mechanistic understanding of such impairment. Here, we tested young adult Lrrk2-G2019S knockin mice in a series of touchscreen-based visuospatial tasks. We found that mutants exhibited significant deficits in attention and goal-directed learning, and had significantly slower information processing speed. Treatment with an acetylcholinesterase inhibitor reversed some of these behavioral deficits, while anatomical analyses showed significantly sparser cholinergic innervation of brain structures important for executive function. These findings suggest the G2019S mutation alters cholinergic signaling in young adulthood, and thus may contribute to early PD-associated impairment in several cognitive domains.
Direct type I Interferon signaling in hepatocytes control malaria
Authors: Marques-da-Silva Camila , Peissig Kristen , Walker Michael P. , Shiau Justine , Kyle Dennis E. , Vijay Rahul , Lindner Scott E. , Kurup Samarchith P. 
Published: January 2022

SummaryMalaria is a devastating disease impacting over half of the world’s population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, preventing the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a novel transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary and sufficient to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire new anti-malarial drugs and vaccine strategies.
Genetic Regulation of Circular RNA Expression in Human Aortic Smooth Muscle Cells and Vascular Traits
Authors: Aherrahrou Redouane , Lue Dillon , Civelek Mete 
Published: January 2022

ABSTRACTBackgroundCircular RNAs (circRNAs) are a class of non-coding RNAs that have cell-type specific expression and are relevant in cardiovascular disease. Aortic smooth muscle cells (SMCs) play a crucial role in cardiovascular disease by differentiating from a quiescent to proliferative phenotype. The role of circRNAs in SMCs and their relevance to cardiovascular disease is largely unexplored.ResultsIn this study, we employ a systems genetics approach to identify circRNA transcripts at a genome wide level and their relevance in cardiovascular traits. We quantified circRNA expression across 151 quiescent and proliferative human aortic SMCs from multiethnic donors. We identified 1,589 expressed circRNAs. Between quiescent and proliferative SMCs, we identified 173 circRNAs which were differentially expressed. To characterize the genetic regulation of circRNA expression, we associated the genotypes of 6.3 million single nucleotide polymorphisms (SNPs) with circRNA abundance and found 96 circRNAs which were associated with genetic loci. Three SNPs were associated with circRNA expression in proliferative SMCs but not in quiescent SMCs. We identified 6 SNPs which had distinct association directions with circRNA isoforms from the same gene. Lastly, to identify the relevance of circRNAs in cardiovascular disease, we overlapped genetic loci associated with circRNA expression with vascular disease related GWAS loci. We identified 7 blood pressure, 1 myocardial infarction, and 3 coronary artery disease loci which were associated with a circRNA transcript (circZKSCAN1, circFOXK2, circANKRD36, circLARP4, circCEP85L, circGTF3C2, circPDS5A, circSLC4A7, and chr17:42610108|42659552) but not mRNA transcript.ConclusionsOverall, our results provide mechanistic insight into the regulation of circRNA expression and the genetic basis of cardiovascular disease.
Permethylation of ribonucleosides provides enhanced mass spectrometry quantification of post-transcriptional modifications
Authors: Xie Yixuan , Janssen Kevin A. , Scacchetti Alessandro , Bonasio Roberto , Garcia Benjamin A 
Published: January 2022

AbstractChemical modifications of RNA are associated with fundamental biological processes such as RNA splicing, export, translation, degradation, as well as human disease states such as cancer. However, the analysis of ribonucleoside modifications is impeded due to the hydrophilicity of the ribonucleoside molecules. In this research, we used solid-phase permethylation to derivatize the ribonucleosides, and the permethylated ribonucleosides, which were then quantitively analyzed using a liquid chromatography−tandem mass spectrometry (LC−MS/MS)-based method. The solid-phase permethylation efficiently derivatized the ribonucleosides, and more than 60 RNA modifications were simultaneously monitored using ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS) performed in the dynamic multiple reaction monitoring (dMRM) mode. Because of the increased hydrophobicity of permethylated ribonucleosides, this method enhanced retention, separation, and ionization efficiency, resulting in improved detection and quantification when compared to existing analytical strategies of RNA modifications. We applied this new approach to measure the extent of cytosine methylation and hydroxymethylation in RNA obtained from mouse embryonic stem cells with genetic deficiencies in ten-eleven translocation (TET) enzymes. The results matched previously performed analyses and highlighted the sensitivity, efficacy, and robustness of the new method. The advantage of this method enables comprehensive analysis of RNA modifications in biological samples.Abstract Figure
Determinants of SARS-CoV-2 nasopharyngeal testing in a rural community sample susceptible of first infection: the CHRIS COVID-19 study
Authors: Giardiello Daniele , Melotti Roberto , Barbieri Giulia , Gögele Martin , Weichenberger Christian X. , Foco Luisa , Bottigliengo Daniele , Barin Laura , Lundin Rebecca , Pramstaller Peter P. , Pattaro Cristian 
Published: January 2022

AbstractTo characterize COVID-19 epidemiology, numerous population-based studies have been undertaken to model the risk of SARS-CoV-2 infection. Less is known about what may drive the probability to undergo testing. Understanding how much testing is driven by contextual or individual conditions is important to delineate the role of individual behavior and to shape public health interventions and resource allocation. In the Val Venosta/Vinschgau district (South Tyrol, Italy), we conducted a population-representative longitudinal study on 697 individuals susceptible to first infection who completed 4,512 repeated online questionnaires at four week intervals between September 2020 and May 2021. Mixed-effects logistic regression models were fitted to investigate associations of self-reported SARS-CoV-2 testing with individual characteristics (social, demographic, and biological) and contextual determinants. Testing was associated with month of reporting, reflecting the timing of both the pandemic intensity and public health interventions, COVID-19-related symptoms (odds ratio, OR:8.26; 95% confidence interval, CI:6.04–11.31), contacts with infected individuals within home (OR:7.47, 95%CI:3.81–14.62) or outside home (OR:9.87, 95%CI:5.78–16.85), and being retired (OR:0.50, 95%CI:0.34-0.73). Symptoms and next within- and outside-home contacts were the leading determinants of swab testing predisposition in the most acute phase of the pandemics. Testing was not associated with age, sex, education, comorbidities, or lifestyle factors. In the study area, contextual determinants reflecting the course of the pandemic were predominant compared to individual sociodemographic characteristics in explaining the SARS-CoV-2 probability of testing. Decision makers should evaluate whether the intended target groups were correctly prioritized by the testing campaign.
Deletion of Sod1 in motor neurons exacerbates age-related changes in axons and NMJs associated with premature muscle atrophy in aging mice
Authors: Pollock N , Macpherson PC , Staunton CA , Hemmings K , Davis CS , Owen ED , Vasilaki A , Van Remmen H , Richardson A , McArdle A , Brooks SV , Jackson MJ 
Published: January 2022

AbstractWhole body knock out of Cu, Zn superoxide dismutase1 (Sod1KO) results in accelerated, age-related loss of muscle mass and function associated with a breakdown of neuromuscular junctions (NMJ) similar to sarcopenia. In order to determine whether altered redox in motor neurons is integral to this phenotype, an inducible neuron specific deletion of Sod1 (i-mnSod1KO) was compared with wild type (WT) mice of different ages (adult, mid-age and old) and whole body Sod1KO mice. Nerve oxidative damage, motor neuron numbers and structural changes to neurons and NMJ were examined.Deletion of neuronal Sod1 (induced by tamoxifen injection at 6 months of age) caused the exaggerated, age-associated loss of muscle mass and force generation previously reported. No effect of age or lack of neuronal Sod1 was seen on oxidation in the sciatic nerve assessed by electron paramagnetic resonance of the in vivo spin probe 1-hydroxy-3-carboxy-2,2,5,5 tetramethylpyrrolidine (CPH), analysis of protein 3-nitrotyrosines or carbonyl content. i-mnSod1KO mice showed increased numbers of denervated NMJs, a reduced number of large axons and increased number of small axons compared with age-matched old WT mice. A large proportion of the remaining innervated NMJs in i-mnSod1KO mice also displayed a much simpler structure than that seen in WT mice.Thus, while Sod1KO mice recapitulate substantially the neuromuscular phenotypes of old WT mice, deletion of Sod1 specifically in neurons induces exaggerated loss of muscle mass and force only in old (24-29 month) mice indicating that significant muscle declines require the accumulation of age-related changes such that a threshold is reached past which maintenance of structure and function is not possible.Significance statementSarcopenia is the age-related loss of muscle mass and function. It is a significant contributor to frailty and to increased falls in the elderly. While multifactorial, changes in redox status have been shown to have significant influence over neuromuscular aging, recent work suggests that changes in motor neurons may be the driving factor in muscle atrophy. The current study confirmed that a specific lack of Sod1 in the motor neuron causes significant alteration in axonal architecture and the neuromuscular junctions which can drive reduced muscle mass and function. Pinpointing early changes in motor neurons may provide therapeutic targets critical for maintaining muscle in the elderly.
Microdynamics of lamin A Ig-fold domain regulates higher order assembly of the protein
Authors: Mukherjee Chandrayee , Sengupta Duhita , Maganti Lakshmi , Mahendar M. , Bhattacharyya Dhananjay , Sengupta Kaushik 
Published: January 2022

AbstractLamins maintain the shape and rigidity of the nucleus in the form of a proteinaceous scaffold underneath the inner nuclear membrane (INM) and provide anchorage to chromatin and other nuclear proteins. Mutations in the human LMNA gene encoding lamin A/C cause about 16 different diseases with distinct phenotypes collectively termed as laminopathies which affect primarily the muscle tissues as well as adipose tissues, neuromuscular junctions and multiple other organs in progeroid syndromes. Lamins contain several domains of which Ig-fold is one of the well characterized and structured domains that harbours many mutations leading to deleterious interactions with other nuclear proteins. In this work, we have elucidated the effects of 3 such mutations namely R453W, W498C and W498R on the dynamics and flexibility of the Ig-fold domain and the consequent effect on the assembly into lamina by live cell imaging, fluorescence correlation spectroscopy (FCS) and molecular dynamics (MD) simulations. From our experimental observations, we concluded that R453W has somewhat increased flexibility compared to the other mutants but lower than that of the wild type. This might be attributed due to an alteration of the salt bridges in the Ig fold domain of the mutant. This is the first report where such an alteration in the full length has been documented by gross changes in diffusional properties as a sequel to a mutation in the Ig fold domain
Life history speed, population disappearances and noise-induced ratchet effects
Authors: Greyson-Gaito Christopher J. , Gellner Gabriel , McCann Kevin S. 
Published: January 2022

AbstractNature is replete with variation in the body sizes, reproductive output, and generation times of species that produce life history responses known to vary from small and fast to large and slow. Although researchers recognize that life history speed likely dictates fundamental processes in consumer-resource interactions like productivity and stability, theoretical work remains incomplete in this critical area. Here, we examine the role of life history speed on consumer-resource interactions by using a well used mathematical approach that manipulates the speed of the consumer’s growth rate in a consumer-resource interaction. Importantly, this approach holds the isocline geometry intact allowing us to assess the impacts of altered life history speed on stability (coefficient of variation, CV) without changing the underlying qualitative dynamics. Although slowing life history can be initially stabilizing, we find that in stochastic settings slowing ultimately drives highly destabilizing population disappearances, especially under reddened noise. Our results suggest that human-driven reddening of noise may decrease species stability because the autocorrelation of red noise enlarges the period and magnitude of perturbations, overwhelming a species’ natural compensatory responses via a ratchet-like effect. This ratchet-like effect then pushes species’ population dynamics far away from equilibria that can lead to precipitous local extinction.
Experimental disruption of social structure reveals totipotency in the orchid bee, Euglossa dilemma
Authors: Saleh Nicholas W. , Henske Jonas , Ramírez Santiago R. 
Published: January 2022

AbstractEusociality has evolved multiple times across the insect phylogeny. Social insects with greater levels of social complexity tend to exhibit specialized castes with low levels of individual phenotypic plasticity. In contrast, species with small, simple social groups may consist of totipotent individuals that can transition among behavioral and reproductive states as the social hierarchy shifts. However, recent work has shown that in some simple social groups, there can still be constraint on individual plasticity, caused by differences in maternal nourishment or initial social interaction. It is not well understood how and when these constraints arise during social evolution, ultimately leading to the evolution of nonreproductive workers. Some species of orchid bees can form social groups of a dominant and 1-2 subordinate helpers where all individuals are reproductive. Females can also disperse on emergence to start their own nest as a solitary foundress, which includes a nonreproductive nest guarding phase not typically expressed by subordinates. Little data exist to characterize the flexibility of orchid bees across these trajectories. Here, using the orchid bee Euglossa dilemma, we conduct an experiment assessing the plasticity of subordinate helpers, finding that they are highly flexible and capable of the behavioral, physiological, transcriptomic, and chemical changes seen in foundresses. Furthermore, we identify genes and gene networks associated with reproductive changes in E. dilemma that overlap with genes associated with worker physiology in eusocial species. Our results provide evidence that the lack of nonreproductive workers in E. dilemma is not due to a lack of subordinate plasticity.