bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding activity in Broca’s area predicts the occurrence of auditory hallucinations across subjects
Authors: Fovet Thomas , Yger Pierre , Lopes Renaud , de Pierrefeu Amicie , Duchesnay Edouard , Houenou Josselin , Thomas Pierre , Szaffarczyk Sébastien , Domenech Philippe , Jardri Renaud 
Published: May 2021

ABSTRACTBACKGROUNDFunctional magnetic resonance imaging (fMRI) capture aims at detecting auditory-verbal hallucinations (AVHs) from continuously recorded brain activity. Establishing efficient capture methods with low computational cost that easily generalize between patients remains a key objective in precision psychiatry. To address this issue, we developed a novel automatized fMRI-capture procedure for AVHs in schizophrenia patients.METHODSWe used a previously validated, but labor-intensive, personalized fMRI-capture method to train a linear classifier using machine-learning techniques. We benchmarked the performances of this classifier on 2320 AVH periods vs. resting-state periods obtained from schizophrenia patients with frequent symptoms (n=23). We characterized patterns of BOLD activity that were predictive of AVH both within- and between-subjects. Generalizability was assessed with a second independent sample gathering 2000 AVH labels (n=34 schizophrenia patients), while specificity was tested with a nonclinical control sample performing an auditory imagery task (840 labels, n=20).RESULTSOur between-subject classifier achieved high decoding accuracy (area-under-the-curve, AUC = 0.85) and discriminated AVH from rest and verbal imagery. Optimizing the parameters on the first schizophrenia dataset and testing its performance on the second dataset led to a 0.85 out-of-sample AUC (0.88 for the converse test). We showed that AVH detection critically depends on local BOLD activity patterns within Broca’s area.CONCLUSIONSOur results demonstrate that it is possible to reliably detect AVH-states from BOLD signals in schizophrenia patients using a multivariate decoder without performing complex regularization procedures. These findings constitute a crucial step toward brain-based treatments for severe drug-resistant hallucinations.
Polo-like kinase 2 inhibition reduces serine-129 phosphorylation of physiological nuclear alpha-synuclein but not of the aggregated alpha-synuclein
Authors: Elfarrash Sara , Jensen Nanna Møller , Ferreira Nelson , Schmidt Sissel Ida , Gregersen Emil , Vestergaard Marie Vibeke , Nabavi Sadegh , Meyer Morten , Jensen Poul Henning 
Published: May 2021

AbstractAccumulation of aggregated alpha-synuclein (α-syn) is believed to play a pivotal role in the pathophysiology of Parkinson’s disease (PD) and other synucleinopathies. α-Syn is a key constituent protein of Lewy pathology, and α-syn phosphorylated at serine-129 (pS129) constitutes more than 90% of α-syn in Lewy bodies and hence, it is used extensively as a pathological marker for the aggregated form of α-syn. However, the exact role of pS129 remains controversial as well as the kinase(s) responsible for the phosphorylation.In this study, we investigated the effect of Polo-like kinase 2 (PLK2) inhibition on formation of pS129 using ex-vivo organotypic brain slice model of synucleinopathy. Our data demonstrated that PLK2 inhibition has no effect on α-syn aggregation, pS129 or inter-neuronal spreading of the aggregated α-syn seen in the organotypic slices. Instead, PLK2 inhibition reduced the soluble nuclear pS129 level confined in the nuclei. The same finding was replicated in an in-vivo mouse models of templated α-syn aggregation and human dopaminergic neurons, suggesting that PLK2 is more likely to be involved in S129 phosphorylation of soluble non-pathology related fraction of α-syn. We also demonstrated that reduction of nuclear pS129 but not the aggregates specific pS129 following PLK2 inhibition for a short time before sample collection improves the signal to noise ratio when quantifying pS129 aggregate pathology.
Vegetation characteristics control sediment and nutrient retention on but not underneath vegetation in floodplain meadows
Authors: Kretz Lena , Bondar-Kunze Elisabeth , Hein Thomas , Richter Ronny , Schulz-Zunkel Christiane , Seele-Dilbat Carolin , van der Plas Fons , Vieweg Michael , Wirth Christian 
Published: May 2021

AbstractSediment and nutrient retention are essential ecosystem functions that floodplains provide and that improve river water quality. During floods, the floodplain vegetation retains sediment, which settles on plant surfaces and the soil underneath plants. Both sedimentation processes require that flow velocity is reduced, which may be caused by the topographic features and the vegetation structure of the floodplain. However, the relative importance of these two drivers and their key components have rarely been both quantified. In addition to topographic factors, we expect vegetation height and density, mean leaf size and pubescence, as well as species diversity of the floodplain vegetation to increase the floodplain’s capacity for sedimentation. To test this, we measured sediment and nutrients (carbon, nitrogen and phosphorus) both on the vegetation itself and on sediment traps underneath the vegetation after a flood at 24 sites along the River Mulde (Germany). Additionally, we measured biotic and topographic predictor variables. Sedimentation on the vegetation surface was positively driven by plant biomass and the height variation of the vegetation, and decreased with the hydrological distance (total R2=0.56). Sedimentation underneath the vegetation was not driven by any vegetation characteristics but decreased with hydrological distance (total R2=0.42). Carbon, nitrogen and phosphorus content in the sediment on the traps increased with the total amount of sediment (total R2=0.64, 0.62 and 0.84, respectively), while C, N and P on the vegetation additionally increased with hydrological distance (total R2=0.80, 0.79 and 0.92, respectively). This offers the potential to promote sediment and especially nutrient retention via vegetation management, such as adapted mowing. The pronounced signal of the hydrological distance to the river emphasises the importance of a laterally connected floodplain with abandoned meanders and morphological depressions. Our study improves our understanding of the locations where floodplain management has its most significant impact on sediment and nutrient retention to increase water purification processes.
Larval dispersal of Brachyura in the largest estuarine / marine system in the world
Authors: de Lima Francielly Alcântara , Butturi-Gomes Davi , das Neves Pantoja Marcela Helena , Martinelli-Lemos Jussara Moretto 
Published: May 2021

AbstractFor the first time, this study monitored six sites in a wide transect with approximately 240 km radius on the Amazon Continental Shelf (ACS) every three months. The objective was to analyze the larval composition of Brachyura, its abundance in shallow/subsurface and oblique hauls, the extent of larval dispersion related to the estuary/plume, and to predict the probability of occurrence and abundance for the temperature, salinity, and chlorophyll-aprofiles of the water column. A total of 17,759 identified larvae are distributed in 8 families and 25 taxa. The water salinity was the best predictor of larval distribution. The statistical models used indicated that Panopeidae and Portunidae larvae are more frequent and more likely to occur in shallow water layers, while Calappidae occur in deeper layers, and Grapsidae, Ocypodidae, Sesarmidae, Pinnotheridae and Leucosiidae occur similarly in both strata. The larval dispersion extent varies among families and throughout the year while the groups are distributed in different salinities along the platform. The probability of occurrence of Portunidae is higher in ocean water (> = 33.5); Grapsidae, Panopeidae, and Pinnotheridae is higher in intermediate and ocean salinity waters (25.5 to 33.5); Ocypodidae, Sesarmidae and Calappidae is higher in estuarine and intermediate salinity waters (5 to 25.5), whereas Leucosiidae, euryhaline, occur in all salinities (5 to 33.5). Furthermore, the Amazon River seasonal flow and plume movement throughout the year not only regulate the larval distribution and dispersion of estuarine species but are fundamental for the ACS species, providing the necessary nutrient input for larval development in the region plankton.
Analyzing Biomarker Discovery: Estimating the Reproducibility of Biomarker Sets
Authors: Forouzandeh Amir , Rutar Alex , Kalmady Sunil V , Greiner Russell 
Published: May 2021

ABSTRACTMany researchers try to understand a biological condition by identifying biomarkers. This is typically done using univariate hypothesis testing over a labeled dataset, declaring a feature to be a biomarker if there is a significant statistical difference between its values for the subjects with different outcomes. However, such sets of proposed biomarkers are often not reproducible – subsequent studies often fail to identify the same sets. Indeed, there is often a very small overlap between the biomarkers proposed in pairs of related studies that explore the same phenotypes over the same distribution of subjects. This paper first defines the Reproducibility Score for a labeled dataset as a measure (taking values between 0 and 1) of the reproducibility of the results produced by an arbitrary fixed biomarker discovery process for a given distribution of subjects. We then provide ways to reliably estimate this score by defining algorithms that produce an over-bound and an under-bound for this score for a given dataset and biomarker discovery process, for the case of univariate hypothesis testing on dichotomous groups. We confirm that these approximations are meaningful by providing empirical results on a large number of datasets and show that these predictions match known reproducibility results. We have also created a publicly available website, hosted at https://biomarker.shinyapps.io/BiomarkerReprod/, that produces these Reproducibility Score approximations for any given dataset (with continuous or discrete features and binary class labels).
Vascular epiphytes contribute disproportionately to global centres of plant diversity
Authors: Taylor Amanda , Zotz Gerhard , Weigelt Patrick , Cai Lirong , Karger Dirk Nikolaus , König Christian , Kreft Holger 
Published: May 2021

AbstractAimVascular epiphytes are ubiquitous features of wet tropical forests where they contribute substantially to local and regional plant diversity. While some basic epiphyte distribution patterns are relatively well studied, little effort has been made to understand the drivers responsible for constraining their global distribution. This study quantifies the substantial contribution of epiphytes to global gradients and centres of vascular plant diversity and explores whether epiphytes vary from terrestrial plants in relation to contemporary and historical environmental variables.LocationGlobal.Time periodPresent.Major taxa studiedVascular epiphytes.MethodsWe integrated EpiList 1.0, a comprehensive list comprising > 30,000 vascular epiphyte species, and species distributions derived from the GIFT database to describe the global biogeography of epiphytes. We used generalized linear mixed effects models to assess the relationship between epiphytic and terrestrial plant diversity, and contemporary and historical environmental predictors.ResultsWe find that epiphytes substantially contribute to global centres of vascular plant diversity, accounting for up to 39% of the vascular flora in the Neotropics. Epiphytes decrease in species numbers with increasing latitude at a rate three times faster than terrestrial plants, a trend that is driven mainly by the distribution of tropical forests and precipitation. Further, large regional differences emerge that are explained by several large endemic angiosperm families (e.g., Neotropical Bromeliaceae) that are absent in other tropical regions.Main conclusionsOur results show that epiphytes are disproportionately diverse in most global centres of plant diversity and play an important role in driving the global latitudinal diversity gradient for plants. The distribution of precipitation and tropical forests emerge as major drivers of the latitudinal diversity gradient in epiphyte species richness. Finally, our findings demonstrate how epiphyte floras in different biogeographical realms are composed of different families and higher taxa revealing an important signature of historical biogeography.
A dentate gyrus– CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation
Authors: Twarkowski Hannah , Steininger Victor , Kim Min Jae , Sahay Amar 
Published: May 2021

AbstractMemories encoded in the dentate gyrus (DG) – CA3 circuit of the hippocampus are routed from CA1 to anterior cingulate cortex (ACC) for consolidation. Although CA1 parvalbumin inhibitory neurons (PV INs) orchestrate hippocampal-cortical communication, we know less about CA3 PV INs or DG – CA3 principal neuron – IN circuit mechanisms that contribute to evolution of hippocampal-cortical ensembles during memory consolidation. Using viral genetics to selectively mimic and boost an endogenous learning-dependent circuit mechanism, DG cell recruitment of CA3 PV INs and feed-forward inhibition (FFI) in CA3, in combination with longitudinal in vivo calcium imaging, we demonstrate that FFI facilitates formation and maintenance of context-associated neuronal ensembles in CA1. Increasing FFI in DG – CA3 promoted context specificity of neuronal ensembles in ACC over time and enhanced long-term contextual fear memory. In vivo LFP recordings in mice with increased FFI in DG – CA3 identified enhanced CA1 sharp-wave ripple – ACC spindle coupling as a potential network mechanism facilitating memory consolidation. Our findings illuminate how FFI in DG – CA3 dictates evolution of ensemble properties in CA1 and ACC during memory consolidation and suggest a teacher-like function for hippocampal CA1 in stabilization and re-organization of cortical representations.
Missense variants in human ACE2 modify binding to SARS-CoV-2 Spike
Authors: MacGowan Stuart A. , Barton Michael I. , Kutuzov Mikhail , Dushek Omer , van der Merwe P. Anton , Barton Geoffrey J. 
Published: May 2021

AbstractSARS-CoV-2 infection begins with the interaction of the SARS-CoV-2 Spike (Spike) and human angiotensin-converting enzyme 2 (ACE2). To explore whether population variants in ACE2 might influence Spike binding and hence infection, we selected 10 ACE2 variants based on affinity predictions and prevalence in gnomAD and measured their affinities for Spike receptor binding domain through surface plasmon resonance (SPR). We discovered variants that enhance and reduce binding, including two variants with distinct population distributions that enhanced affinity for Spike. ACE2 p.Ser19Pro (ΔΔG = ± 0.59 0.08 kcal mol−1) is often seen in the gnomAD African cohort (AF = 0.003) whilst p.Lys26Arg (ΔΔG = 0.26 0.09 kcal mol−1) is predominant in the Ashkenazi Jewish (AF = 0.01) and European non-Finnish (AF = 0.006) cohorts. Carriers of these alleles may be more susceptible to infection or severe disease and these variants may influence the global epidemiology of Covid-19. We also identified three rare ACE2 variants that strongly inhibited (p.Glu37Lys, ΔΔG = −1.33 ± 0.15 kcal mol−1 and p.Gly352Val, predicted ΔΔG = −1.17 kcal mol−1) or abolished (p.Asp355Asn) Spike binding. These variants may confer resistance to infection. Finally, we calibrated the mCSM-PPI2 ΔΔG prediction algorithm against our SPR data, give new predictions for all possible ACE2 missense variants at the Spike interface and estimate the overall burden of ACE2 variants on Covid-19 phenotypes.
Probenecid Inhibits SARS-CoV-2 Replication In Vivo and In Vitro
Authors: Murray Jackelyn , Hogan Robert J. , Martin David E. , Blahunka Kathy , Sancillo Fred , Balyan Rajiv , Lovern Mark , Still Richard , Tripp Ralph A. 
Published: May 2021

AbstractEffective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC90 value are achievable for 24h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans.
A genetic switch for male UV-iridescence in an incipient species pair of sulphur butterflies
Authors: Ficarrotta Vincent , Hanly Joseph J. , Loh Ling S. , Francescutti Caroline M. , Ren Anna , Tunström Kalle , Wheat Christopher W. , Porter Adam H. , Counterman Brian A. , Martin Arnaud 
Published: May 2021

AbstractMating cues evolve rapidly and can contribute to species formation and maintenance. However, little is known about how sexual signals diverge and how this variation integrates with other barrier loci to shape the genomic landscape of reproductive isolation. Here, we elucidate the genetic basis of UV iridescence, a courtship signal that differentiates the males ofColias eurythemebutterflies from a sister species, allowing females to avoid costly heterospecific matings. Anthropogenic range expansion of the two incipient species established a large zone of secondary contact across the eastern US with strong signatures of genomic admixtures spanning all autosomes. In contrast, Z chromosomes are highly differentiated between the two species, supporting a disproportionate role of sex chromosomes in speciation known as the large-X (or large-Z) effect. Within this chromosome-wide reproductive barrier, linkage mapping indicates thatcis-regulatory variation ofbric a brac(bab) underlies the male UV-iridescence polymorphism between the two species. Bab is expressed in all non-UV scales, and butterflies of either species or sex acquire widespread ectopic iridescence following its CRISPR knock-out, demonstrating that Bab functions as a suppressor of UV-scale differentiation that potentiates mating cue divergence. These results highlight how a genetic switch can regulate a premating signal and integrate with other reproductive barriers during intermediate phases of speciation.Significance statementIncipient species are at an intermediate stage of speciation where reproductive isolation is counteracted by the homogenizing effects of gene flow. Human activity sometimes leads such species to reunite, as seen in the Orange Sulphur butterfly, which forms large hybridizing populations with the Clouded Sulphur in alfalfa fields. Here we show that the sex chromosome maintains these species as distinct, while the rest of their genome is admixed. Sex chromosomes notably determine which males display to females a bright, iridescent ultraviolet signal on their wings. Genetic mapping, antibody stainings, and CRISPR knock-outs collectively indicate that the genebric a braccontrols whether UV-iridescent nanostructures develop in each species, elucidating how a master switch gene modulates a male courtship signal.
Rapid evolution of seed dormancy during sunflower de-domestication
Authors: Hernández Fernando , Vercellino Roman B. , Pandolfo Claudio , Mandel Jennifer R. , Presotto Alejandro 
Published: May 2021

AbstractHybridization between crops and their wild relatives may promote the evolution of de-domesticated (feral) weeds. Wild sunflower (Helianthus annuus L.) is typically found in ruderal environments, but crop-wild hybridization may facilitate the evolution of weedy populations. Using one crop-specific mitochondrial marker (CMS-PET1) and 14 nuclear SSR markers, we studied the origin and genetic diversity of a recently discovered weedy population of sunflower (named BRW). Then, using a resurrection approach, we tested for rapid evolution of weedy traits (seed dormancy, herbicide resistance, and competitive ability) by sampling weedy and wild populations 10 years apart (2007 and 2017). All the weedy plants present the CMS-PET1 cytotype, confirming their feral origin. At the nuclear markers, BRW showed higher genetic diversity than the cultivated lines and low differentiation with one wild population, suggesting that wild hybridization increased their genetic diversity. We found support for rapid evolution towards higher seed dormancy, but not for higher competitive ability or herbicide resistance. Our results highlight the importance of seed dormancy during the earliest stages of adaptation and show that crop-wild hybrids can evolve quickly in agricultural environments.
Impact of Type II LRRK2 inhibitors on signalling and mitophagy
Authors: Tasegian Anna , Singh Francois , Ganley Ian G , Reith Alastair D , Alessi Dario R 
Published: May 2021

AbstractMuch effort has been devoted to the development of selective inhibitors of the LRRK2 as a potential treatment for LRRK2 driven Parkinson’s disease. In this study we first compare the properties of Type I (GSK3357679A and MLi-2) and Type II (GZD-824, Rebastinib and Ponatinib) kinase inhibitors that bind to the closed or open conformations of the LRRK2 kinase domain, respectively. We show that Type I and Type II inhibitors suppress phosphorylation of Rab10 and Rab12, key physiological substrates of LRRK2 and also promote mitophagy, a process suppressed by LRRK2. Type II inhibitors also display higher potency towards wild type LRRK2 compared to pathogenic mutants. Unexpectedly, we find that Type II inhibitors, in contrast to Type I compounds, fail to induce dephosphorylation of a set of well-studied LRRK2 biomarker phosphorylation sites at the N-terminal region of LRRK2, including Ser935. These findings emphasize that the biomarker phosphorylation sites on LRRK2 are likely reporting on the open vs closed conformation of LRRK2 kinase and that only inhibitors which stabilize the closed conformation induce dephosphorylation of these biomarker sites. Finally, we demonstrate that the LRRK2[A2016T] mutant which is resistant to MLi-2 Type 1 inhibitor, also induces resistance to GZD-824 and Rebastinib suggesting this mutation could be exploited to distinguish off target effects of Type II inhibitors. Our observations provide a framework of knowledge to aide with the development of more selective Type II LRRK2 inhibitors.
DJ-1 depletion slows down immunoaging in T-cell compartments
Authors: Zeng Ni , Capelle Christophe , Baron Alexandre , Cire Severine , Leonard Cathy , Coowar Djalil , Koseki Haruhiko , Westendorf Astrid M. , Buer Jan , Brenner Dirk , Krüger Rejko , Balling Rudi , Ollert Markus , Hefeng Feng Q. 
Published: May 2021

AbstractDecline in immune function during aging increases susceptibility to different aging related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson’s disease (PD), unexpectedly delayed immunoaging in both human and mice. Compared with two gender-matched unaffected sibling carriers of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled frequencies of non-senescent T cells. The observation of a ‘younger’ immune system in the index patient was further consolidated by the results in aged DJ-1 knockout mice. Our data from bone marrow chimera models and adoptive transfer experiments demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.