bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel computational pipeline forvargene expression augments the discovery of changes in thePlasmodium falciparumtranscriptome during transition fromin vivoto short-termin vitroculture
Authors: Andradi-Brown Clare , Wichers-Misterek Jan Stephan , von Thien Heidrun , Höppner Yannick D. , Scholz Judith A. M. , Hansson Helle , Hocke Emma Filtenborg , Gilberger Tim-Wolf , Duffy Michael F. , Lavstsen Thomas , Baum Jake , Otto Thomas D. , Cunnington Aubrey J. , Bachmann Anna 
Published: March 2023

AbstractThe pathogenesis of severePlasmodium falciparummalaria involves cytoadhesive microvascular sequestration of infected erythrocytes, mediated byP. falciparumerythrocyte membrane protein 1 (PfEMP1). PfEMP1 variants are encoded by the highly polymorphic family ofvargenes, the sequences of which are largely unknown in clinical samples. Previously, we published new approaches forvargene profiling and classification of predicted binding phenotypes in clinicalP. falciparumisolates (Wicherset al., 2021), which represented a major technical advance. Building on this, we report here a novel method forvargene assembly and multidimensional quantification from RNA-sequencing that outperforms the earlier approach of Wicherset al., 2021 on both laboratory and clinical isolates across a combination of metrics. Importantly, the tool can interrogate thevartranscriptome in context with the rest of the transcriptome and can be applied to enhance our understanding of the role ofvargenes in malaria pathogenesis. We applied this new method to investigate changes invargene expression through early transition of parasite isolates toin vitroculture, using paired sets ofex vivosamples from our previous study, cultured for up to three generations. In parallel, changes in non-polymorphic core gene expression were investigated. Modest but unpredictablevargene switching and convergence towardsvar2csawere observed in culture, along with differential expression of 19% of the core transcriptome between pairedex vivoand generation 1 samples. Our results cast doubt on the validity of the common practice of using short-term cultured parasites to make inferences aboutin vivophenotype and behaviour.
Microsaccades track location-based object rehearsal in visual working memory
Authors: de Vries Eelke , van Ede Freek 
Published: March 2023

ABSTRACTBesides controlling eye movements, the brain’s oculomotor system has been implicated in the control of covert spatial attention and the rehearsal of spatial information in working memory. We investigated whether the oculomotor system also contributes to rehearsing visual objects in working memory when object location is never asked about. To address this, we tracked the incidental use of locations for mnemonic rehearsal via directional biases in microsaccades while participants maintained two visual objects (coloured oriented gratings) in working memory. By varying the stimulus configuration (horizontal, diagonal, and vertical) at encoding, we could quantify whether microsaccades were more aligned with the configurational axis of the memory contents, as opposed to the orthogonal axis. Experiment 1 revealed that microsaccades continued to be biased along the axis of the memory content several seconds into the working-memory delay. In Experiment 2, we confirmed that this directional microsaccade bias was specific to memory demands, ruling out lingering effects from passive and attentive encoding of the same visual objects in the same configurations. Thus, by studying microsaccade directions, we uncover oculomotor-driven rehearsal of visual objects in working memory through their associated locations.SIGNIFICANCE STATEMENTHow humans rehearse information in working memory is a foundational question in psychology and neuroscience. To provide insight into the cognitive and neural bases of working-memory rehearsal, we turned to microsaccades – small eye-movements produced by the brain’s oculomotor system. We reveal how microsaccades track the locations of visual objects during memory rehearsal, even when object locations are never asked about. This brings three advances. From a psychology standpoint, it demonstrates how memory rehearsal automatically engages object locations. From a neuroscience standpoint, it demonstrates how such location-based rehearsal relies on brain circuitry that also controls our eyes. Finally, from a practical standpoint, it demonstrates how microsaccades can be utilised to track the properties of working-memory rehearsal across space and time.
Plastome-based Phylogenomic analyses provide insights into the germplasm resource diversity ofCibotiumin China
Authors: Jiang Ri-Hong , Liang Si-Qi , Wu Fei , Tang Li-Ming , Qin Bo , Chen Ying-Ying , Huang Yao-Heng , Li Kai-Xiang , Zhang Xian-Chun 
Published: March 2023

AbstractGermplasm resource is the source of herbal medicine production. Cultivation of superior germplasm resources helps to resolve the serious conflict between long-term population persistence and growing market demand by producing materials with high quality consistently.Cibotium barometzis the original plant of cibotii rhizoma (“Gouji”), a traditional Chinese medicine used in the therapy of pain, weakness, and numbness of lower extremity. Long-history use ofCibotiumhas rendered wild populations of this species declined seriously in China. Without sufficient understanding of species and lineage diversity ofCibotium, it is difficult to propose a targeted conservation scheme at present, let alone selecting high-quality germplasm resources. In order to fill such a knowledge gap, this study sampledC. barometzand relative species throughout their distribution in China, performed genome skimming to obtain plastome data, and conducted phylogenomic analyses. We constructed a well-supported plastome phylogeny of ChineseCibotium, which showed that three species with significant genetic difference distributed in China, namelyC. barometz,C. cumingii, andC. sino-burmaense, a cryptic species endemic to NW Yunnan and adjacent region of NE Myanmar. Moreover, our results revealed two differentiated lineages ofC. barometzdistributed in the east and west side of a classic phylogeographic boundary that probably shaped by monsoons and landforms in China. We also evaluated the resolution of nine traditional barcode loci, and designed five new DNA barcodes based on the plastome data which can discriminate all these species and lineages of ChineseCibotiumaccurately. These novel findings integrated genetic basis will guide conservation planners and medicinal plant breeders to build systematic conservation plans and exploit germplasm resources ofCibotiumin China.
Guidelines for Evaluating the Comparability of Down-Sampled GWAS Summary Statistics
Authors: Williams Camille M. , Poore Holly , Tanksley Peter T. , Kweon Hyeokmoon , Courchesne-Krak Natasia S. , Londono-Correa Diego , Mallard Travis T. , Barr Peter , Koellinger Philipp D. , Waldman Irwin D. , Sanchez-Roige Sandra , Harden K. Paige , Palmer Abraham A , Dick Danielle M. , Linnér Richard Karlsson 
Published: March 2023

AbstractProprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might change the genetic etiology of the phenotype being studied. These problems are further complicated when using multivariate GWAS methods, such as genomic structural equation modeling (Genomic SEM), that model genetic correlations across multiple traits. Here, we propose a systematic approach to assess the comparability of GWAS summary statistics that include versus exclude restricted data. Illustrating this approach with a multivariate GWAS of an externalizing factor, we assessed the impact of down-sampling on (1) the strength of the genetic signal in univariate GWASs, (2) the factor loadings and model fit in multivariate Genomic SEM, (3) the strength of the genetic signal at the factor level, (4) insights from gene-property analyses, (5) the pattern of genetic correlations with other traits, and (6) polygenic score analyses in independent samples. For the externalizing GWAS, down-sampling resulted in a loss of genetic signal and fewer genome-wide significant loci, while the factor loadings and model fit, gene-property analyses, genetic correlations, and polygenic score analyses are robust. Given the importance of data sharing for the advancement of open science, we recommend that investigators who share down-sampled summary statistics report these analyses as accompanying documentation to support other researchers’ use of the summary statistics.
A mechanistic-statistical approach to infer dispersal and demography from invasion dynamics, applied to a plant pathogen
Authors: Saubin Méline , Coville Jérome , Xhaard Constance , Frey Pascal , Soubeyrand Samuel , Halkett Fabien , Fabre Frédéric 
Published: March 2023

AbstractDispersal, and in particular the frequency of long-distance dispersal (LDD) events, has strong implications for population dynamics with possibly the acceleration of the colonisation front, and for evolution with possibly the conservation of genetic diversity along the colonised domain. However, accurately inferring LDD is challenging as it requires both large-scale data and a methodology that encompasses the redistribution of individuals in time and space. Here, we propose a mechanistic-statistical framework to estimate dispersal from one-dimensional invasions. The mechanistic model takes into account population growth and grasps the diversity in dispersal processes by using either diffusion, leading to a reaction-diffusion (R.D.) formalism, or kernels, leading to an integro-differential (I.D.) formalism. The latter considers different dispersal kernels (e.g. Gaussian, Exponential, and Exponential-power) differing in their frequency of LDD events. The statistical model relies on dedicated observation laws that describe two types of samples, clumped or not. As such, we take into account the variability in both habitat suitability and occupancy perception. We first check the identifiability of the parameters and the confidence in the selection of the dispersal process. We observed good identifiability for all parameters (correlation coefficient>0.9 between true and fitted values). The dispersal process that is the most confidently identified is Exponential-Power (i.e. fat-tailed) kernel. We then applied our framework to data describing an annual invasion of the poplar rust disease along the Durance River valley over nearly 200 km. This spatio-temporal survey consisted of 12 study sites examined at seven time points. We confidently estimated that the dispersal of poplar rust is best described by an Exponential-power kernel with a mean dispersal distance of 1.94 km and an exponent parameter of 0.24 characterising a fat-tailed kernel with frequent LDD events. By considering the whole range of possible dispersal processes our method forms a robust inference framework. It can be employed for a variety of organisms, provided they are monitored in time and space along a one-dimension invasion.
An improved rhythmicity analysis method using Gaussian Processes detects cell-density dependent circadian oscillations in stem cells
Authors: Sahay Shabnam , Adhikari Shishir , Hormoz Sahand , Chakrabarti Shaon 
Published: March 2023

AbstractDetecting oscillations in time series remains a challenging problem even after decades of research. In chronobiology, rhythms in time series (for instance gene expression, eclosion, egg-laying and feeding) datasets tend to be low amplitude, display large variations amongst replicates, and often exhibit varying peak-to-peak distances (non-stationarity). Most currently available rhythm detection methods are not specifically designed to handle such datasets. Here we introduce a new method, ODeGP (OscillationDetection usingGaussianProcesses), which combines Gaussian Process (GP) regression with Bayesian inference to provide a flexible approach to the problem. Besides naturally incorporating measurement errors and non-uniformly sampled data, ODeGP uses a recently developed kernel to improve detection of non-stationary waveforms. An additional advantage is that by using Bayes factors instead of p-values, ODeGP models both the null (non-rhythmic) and the alternative (rhythmic) hypotheses. Using a variety of synthetic datasets we first demonstrate that ODeGP almost always outperforms eight commonly used methods in detecting stationary as well as non-stationary oscillations. Next, on analyzing existing qPCR datasets that exhibit low amplitude and noisy oscillations, we demonstrate that our method is more sensitive compared to the existing methods at detecting weak oscillations. Finally, we generate new qPCR time-series datasets on pluripotent mouse embryonic stem cells, which are expected to exhibit no oscillations of the core circadian clock genes. Surprisingly, we discover using ODeGP that increasing cell density can result in the rapid generation of oscillations in theBmal1gene, thus highlighting our method’s ability to discover unexpected patterns. In its current implementation, ODeGP (available as an R package) is meant only for analyzing single or a few time-trajectories, not genome-wide datasets.
Brain functional characterization of response-code conflict in dual-tasking and its modulation by age
Authors: Paas Oliveros Lya K. , Cieslik Edna C. , Pieczykolan Aleks , Pläschke Rachel N. , Eickhoff Simon B. , Langner Robert 
Published: March 2023

AbstractCrosstalk between conflicting response codes contributes to interference in dual-tasking, an effect exacerbated in advanced age. Here, we investigated (1) brain activity correlates of such response-code conflicts, (2) activity modulations by individual dual-task performance and related cognitive abilities, (3) task-modulated connectivity within the task network, and (4)age-related differences in all these aspects. Young and older adults underwent fMRI while responding to the pitch of tones through spatially mapped speeded button presses with one or two hands concurrently. Using opposing stimulus–response mappings between hands, we induced conflict between simultaneously activated response codes. These response-code conflicts elicited activation in key regions of the multiple-demand network. Older adults showed non-compensatory hyperactivity in left superior frontal gyrus, and higher left intraparietal sulcus activity associated with lower attentional performance. While motor and parietal areas of the conflict-related network were modulated by attentional and task-switching abilities, efficient conflict resolution in dual-tasking was linked to suppressing visual cortex activity. Finally, connectivity between premotor or parietal seed regions and the conflict-sensitive network was neither conflict-specific nor age-sensitive. Overall, resolving dual-task response-code conflict recruited substantial parts of the multiple-demand network, whose activity and coupling, however, were only little affected by individual differences in task performance or age.
Evolution of intracellular free radical load in colon adenocarcinoma cells over the course of butyrate-induced redifferentiation
Authors: Sigaeva Alina , Zijlema Eline , Zhang Yue , Schirhagl Romana 
Published: March 2023

AbstractFluorescent nanodiamonds have exceptional optical properties and are highly biocompatible, which allows to use them as labels for long-term tracking of the cells. The research fields that make use of this application of nanodiamonds include stem cell biology and cancer biology, where quiescent and differentiating cells can be tracedin vitroandin vivo. However, these studies focus on using nanodiamonds as simple labels, whereas they can serve as highly sensitive intracellular sensors for free radical species. In this study, we aimed to bring the two approaches together and to assess the free radical production in the cells over the course of their differentiation.We report on the successful enterocytic differentiation of HT-29 colon adenocarcinoma cells, pre-loaded with fluorescent nanodiamonds. The cells were cultured in butyrate-free or butyrate-supplemented medium for 13 days. Butyrate-treated cells developed the morphological and molecular traits, characteristic for normal enterocytes. Fluorescent nanodiamonds did not have a negative effect on the process of differentiation. Moreover, the particles could be found in the cytoplasm of both undifferentiated and re-differentiated cells even after 13 days of culture. The internalized nanodiamonds were used to assess the free radical load in the undifferentiated and re-differentiated HT-29 cells at different stages of the experiment. Consistently with previous findings, re-differentiated HT-29 cells showed higher free radical load than undifferentiated ones.
Role of membrane estrogen receptor alpha on the positive feedback of estrogens on LH secretion
Authors: Faure Mélanie C. , Corona Rebeca , de Bournonville Catherine , Lenfant Françoise , Foidart Jean-Michel , Cornil Charlotte A. 
Published: March 2023

ABSTRACTEstrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling is unclear. To address this question, we used two complementary approaches: estetrol (E4) a natural estrogen described to act as an agonist of nuclear ERα and a mERα antagonist and the C451A-ERα mouse lacking mERα. E4dose-dependently blocks ovulation in female rats, but the mechanism underlying this effect is unknown. To determine whether E4acts centrally to control ovulation, we tested its effect on the positive feedback of estradiol (E2) on LH secretion. In ovariectomized females chronically exposed to a low dose of E2, estradiol benzoate (EB) alone or combined with progesterone (P) induced a LH surge and the associated increase in the number of activated kisspeptin (Kp) and gonadotropin-releasing hormone (GnRH) neurons. However, E4blocked these effects of EB when provided alone, but not when combined to P. These results indicate that E4blocked the induction of the positive feedback and the associated neuronal activation in the absence of P, suggesting an antagonistic effect of E4on mERα as shown in peripheral tissues. In parallel, C451A-ERα females do not show a pre-ovulatory LH surge and the associated activation of Kp and GnRH neurons in response to EB unless they are treated with P. The similarity of the responses of C451A-ERα mice and wild-type females treated with E4 supports a role for membrane-initiated estrogen signaling in the EB-induced LH surge.
Understanding the Divergent Evolution and Epidemiology of H3N8 Influenza Viruses in Dogs and Horses
Authors: Wasik Brian R. , Rothschild Evin , Voorhees Ian E.H. , Reedy Stephanie E. , Murcia Pablo R. , Pusterla Nicola , Chambers Thomas M. , Goodman Laura B. , Holmes Edward C. , Kile James C. , Parrish Colin R. 
Published: March 2023

ABSTRACTCross-species virus transmission events can lead to dire public health emergencies in the form of epidemics and pandemics. One example in animals is the emergence of the H3N8 equine influenza virus (EIV), first isolated in 1963 in Miami, Florida, USA, after emerging among horses in South America. In the early 21stcentury the American lineage of EIV diverged into two ‘Florida’ clades that persist today, while an EIV transferred to dogs around 1999 and gave rise to the H3N8 canine influenza virus (CIV), first reported in 2004. Here, we compare CIV in dogs and EIV in horses to reveal their host-specific evolution, to determine the sources and connections between significant outbreaks, and to gain insight into the factors controlling their different evolutionary fates. H3N8 CIV only circulated in North America, was geographically restricted after the first few years, and went extinct in 2016. Of the two EIV Florida clades, clade 1 circulates widely and shows frequent transfers between the USA and South America, Europe and elsewhere, while clade 2 was globally distributed early after it emerged, but since about 2018 has only been detected in Central Asia. Any potential zoonotic threat of these viruses to humans can only be determined with an understanding of its natural history and evolution. Our comparative analysis of these three viral lineages reveals distinct patterns and rates of sequence variation yet with similar overall evolution between clades, suggesting epidemiological intervention strategies for possible eradication of H3N8 EIV. (242 words)IMPORTANCEThe emergence of viruses in new hosts is a threat to human and animal health. The H3N8 equine influenza virus (EIV) emerged in 1963 by transfer of an avian influenza virus, and the H3N8 canine influenza virus (CIV) subsequently emerged in 1999 when EIV transferred to dogs. H3N8 CIV persistently circulated in only a few locations in the USA, and has not been detected since 2016. In the same period H3N8 EIV has circulated as two separate clades, one in North America and other regions of the world, while the other currently appears to be found only in Central Asia. By comparing the hosts, epidemiology, and evolution of these influenza viruses we explain how these lineages had different evolutionary fates, and show why elucidating these evolutionary processes is key to understanding zoonotic disease and viral emergence. (137 words)
Spinal control of locomotion before and after spinal cord injury
Authors: Danner Simon M. , Shepard Courtney T. , Hainline Casey , Shevtsova Natalia A. , Rybak Ilya A. , Magnuson David S.K. 
Published: March 2023

AbstractThoracic spinal cord injury affects long propriospinal neurons that interconnect the cervical and lumbar enlargements. These neurons are crucial for coordinating forelimb and hindlimb locomotor movements in a speed-dependent manner. However, recovery from spinal cord injury is usually studied over a very limited range of speeds that may not fully expose circuitry dysfunction. To overcome this limitation, we investigated overground locomotion in rats trained to move over an extended distance with a wide range of speeds both pre-injury and after recovery from thoracic hemisection or contusion injuries. In this experimental context, intact rats expressed a speed-dependent continuum of alternating (walk and trot) and non-alternating (canter, gallop, half-bound gallop, and bound) gaits. After a lateral hemisection injury, rats recovered the ability to locomote over a wide range of speeds but lost the ability to use the highest-speed gaits (half-bound gallop and bound) and predominantly used the limb contralateral to the injury as lead during canter and gallop. A moderate contusion injury caused a greater reduction in maximal speed, loss of all non-alternating gaits, and emergence of novel alternating gaits. These changes resulted from weak fore–hind coupling together with appropriate control of left–right alternation. After hemisection, animals expressed a subset of intact gaits with appropriate interlimb coordination even on the side of the injury, where the long propriospinal connections were severed. These observations highlight how investigating locomotion over the full range of speeds can reveal otherwise hidden aspects of spinal locomotor control and post-injury recovery.