bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulus-Locked Responses on Human Upper Limb Muscles and Corrective Reaches are Preferentially Evoked by Low Spatial Frequencies
Authors: Kozak Rebecca A. , Kreyenmeier Philipp , Gu Chao , Johnston Kevin , Corneil Brian D. 
Published: July 2019

AbstractIn situations requiring immediate action, humans can generate visually-guided responses at remarkably short latencies. Here, to better understand the visual attributes that best evoke such rapid responses, we recorded upper limb muscle activity while participants performed visually-guided reaches towards Gabor patches composed of differing spatial frequencies. We studied reaches initiated from a stable posture (experiment 1, a static condition), or during on-line reach corrections to an abruptly displaced target (experiment 2, a dynamic condition). In both experiments, we detail the latency and prevalence of stimulus-locked responses (SLRs), which are brief bursts of EMG activity that are time-locked to target presentation rather than movement onset. SLRs represent the first wave of EMG recruitment influenced by target presentation, and enable quantification of rapid visuomotor transformations. In both experiments, reach targets composed of low spatial frequencies elicited the shortest latency and most prevalent SLRs, with SLR latency increasing and SLR prevalence decreasing for reach targets composed of progressively higher spatial frequencies. SLRs could be evoked in either the static or dynamic condition, and when present in experiment 2, were associated with shorter latency and larger magnitude corrections. Furthermore, SLRs evolved at shorter latencies (~20 ms) when the arm was already in motion. These results demonstrate that stimuli composed of low spatial frequencies preferentially evoke the most rapid visuomotor responses which, in the context of rapidly correcting an on-going reaching movement, are associated with earlier and larger on-line reach corrections.Significance StatementHumans have a remarkable capacity to respond quickly to changes in our visual environment. Although our visual world is composed of a range of spatial frequencies, surprisingly little is known about which frequencies preferentially evoke rapid reaching responses. Here, we systematically varied the spatial frequency of peripheral reach targets while measuring EMG activity on an upper limb muscle. We found that visual stimuli composed of low-spatial frequencies elicit the most rapid and robust EMG responses and corrective reaches. Thus, when time is of the essence, low spatial frequencies preferentially drive fast visuomotor responses.
Molecular Profiling to Infer Neuronal Cell Identity: Lessons from small ganglia of the Crab Cancer borealis
Authors: Northcutt Adam J. , Kick Daniel R. , Otopalik Adriane G. , Goetz Benjamin M. , Harris Rayna M. , Santin Joseph M. , Hofmann Hans A. , Marder Eve , Schulz David J. 
Published: July 2019

ABSTRACTUnderstanding circuit organization depends on identification of cell types. Recent advances in transcriptional profiling methods have enabled classification of cell types by their gene expression. While exceptionally powerful and high throughput, the ground-truth validation of these methods is difficult: if cell type is unknown, how does one assess whether a given analysis accurately captures neuronal identity? To shed light on the capabilities and limitations of solely using transcriptional profiling for cell type classification, we performed two forms of transcriptional profiling – RNA-seq and quantitative RT-PCR, in single, unambiguously identified neurons from two small crustacean networks: the stomatogastric and cardiac ganglia. We then combined our knowledge of cell type with unbiased clustering analyses and supervised machine learning to determine how accurately functionally-defined neuron types can be classified by expression profile alone. Our results demonstrate that expression profile is able to capture neuronal identity most accurately when combined with multimodal information that allows for post-hoc grouping so analysis can proceed from a supervised perspective. Solely unsupervised clustering can lead to misidentification and an inability to distinguish between two or more cell types. Therefore, our study supports the general utility of cell identification by transcriptional profiling, but adds a caution: it is difficult or impossible to know under what conditions transcriptional profiling alone is capable of assigning cell identity. Only by combining multiple modalities of information such as physiology, morphology or innervation target can neuronal identity be unambiguously determined.SIGNIFICANCE STATEMENTSingle cell transcriptional profiling has become a widespread tool in cell identification, particularly in the nervous system, based on the notion that genomic information determines cell identity. However, many cell type classification studies are unconstrained by other cellular attributes (e.g., morphology, physiology). Here, we systematically test how accurately transcriptional profiling can assign cell identity to well-studied anatomically- and functionally-identified neurons in two small neuronal networks. While these neurons clearly possess distinct patterns of gene expression across cell types, their expression profiles are not sufficient to unambiguously confirm their identity. We suggest that true cell identity can only be determined by combining gene expression data with other cellular attributes such as innervation pattern, morphology, or physiology.
Altitude and life-history shape the evolution ofHeliconiuswings
Authors: Montejo-Kovacevich Gabriela , Smith Jennifer E. , Meier Joana I. , Bacquet Caroline N. , Whiltshire-Romero Eva , Nadeau Nicola J. , Jiggins Chris D. 
Published: July 2019

AbstractPhenotypic divergence between closely related species has long interested biologists. Taxa that inhabit a range of environments and have known and diverse, natural histories, can help understand how different selection pressures shape diverging traits. In butterflies, wing colour patterns have been extensively studied, whereas wing shape diversity is less well understood despite its importance for flight. Here we study a measure of wing shape, aspect ratio, and wing size in a large dataset of over 3200 individuals, representing 13Heliconiusspecies, from across the Neotropics. We assess the relative importance of phylogenetic relatedness, natural history and habitat in determining wing shape and size. We find that both larval and adult behavioural ecology affect patterns of adult size dimorphisms. On one hand, species with solitary larvae have larger adult males, in contrast to gregariousHeliconiusspecies, and indeed most Lepidoptera. On the other hand, species in the pupal-mating clade are smaller overall than those in the adult-mating clade. Interestingly, while controlling for phylogeny, sex ratios and allometry, we find that species inhabiting higher altitudes have rounder wings and, in one of the two majorHeliconiusclades, are also bigger in size than their lowland relatives. Thus, we reveal novel adaptive wing morphological divergence amongHeliconiusspecies beyond that imposed by natural selection on aposematic wing colouration. Our study highlights the value of phylogenetic comparative methods in study systems that have diverse and well-studied natural histories to disentangle the selection pressures shaping adaptive phenotypes.
Loss of cyclin A2 in murine colonic epithelial cells disrupts colon homeostasis by triggering DNA damage and dysplasia and high cyclin A2 expression is a good-prognosis factor in patients with colorectal cancer
Authors: Guo Yuchen , Gabola Monica , Lattanzio Rossano , Paul Conception , Pinet Valérie , Tang Ruizhi , Tulari Hulya , Bremond Julie , Maurizy Chloé , Da Costa Quentin , Finetti Pascal , Boissière-Michot Florence , Lemmers Céline , Garnier Séverine , Bertucci François , Azar Rania , Blanchard Jean-Marie , Sicinski Piotr , Mamessier Emilie , Lemmers Bénédicte , Hahne Michael 
Published: July 2019

AbstractTo clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC) we generated mice deficient for cyclin A2 in colonic epithelial cells (CEC). Colons of those mice displayed architectural changes in the mucosa, and signs of inflammation as well as an increased proliferation of CEC associated with the appearance of low- and high-grade dysplasia. The main initial events triggering those alterations in cyclin A2 deficient CEC appear to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CEC promoted the development of dysplasia and adenocarcinomas in the murine colitis-associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein level and found higher expression in tumors of stage I and II patients compared to those of stage III and IV. A meta-analysis of 11 transcriptome datasets comprising 2,239 primary CRC tumors displayed differentCCNA2(the mRNA coding for cyclin A2) expression levels among the CRC tumor subtypes with highest in CMS1 and lowest in CMS4. Moreover, high expression ofCCNA2was found to be a good prognosis factor independently from other prognostic factors for the CMS1, CMS3 and CMS4 subtypes.
Histone H2AK119 Mono-Ubiquitination is Essential for Polycomb-Mediated Transcriptional Repression
Authors: Tamburri Simone , Lavarone Elisa , Fernández-Pérez Daniel , Zanotti Marika , Manganaro Daria , Conway Eric , Pasini Diego 
Published: July 2019

ABSTRACTThe major function of Polycomb group proteins (PcG) is to maintain transcriptional repression to preserve cellular identity. This is exerted by two distinct repressive complexes, PRC1 and PRC2, that modify histones by depositing H2AK119ub1 and H3K27me3, respectively. Both complexes are essential for development and are deregulated in several types of human tumors. PRC1 and PRC2 exist in different variants and show a complex regulatory cross-talk. However, the contribution that H2AK119ub1 plays in mediating PcG repressive functions remains largely controversial. Coupling an inducible system with the expression of a fully catalytic inactive RING1B mutant, we demonstrated that H2AK119ub1 deposition is essential to maintain PcG-target genes repressed in ESC. Loss of H2AK119ub1 induced a rapid displacement of PRC2 activity and a loss of H3K27me3 deposition. This affected both PRC2.1 and PRC2.2 variants and further correlated with a strong displacement and destabilization of canonical PRC1. Finally, we find that variant PRC1 forms can sense H2AK119ub1 deposition, which contributes to their stabilization specifically at sites where this modification is highly enriched. Overall our data place H2AK119ub1 deposition as central hub that mount PcG repressive machineries to preserve cell transcriptional identity.
Leveraging genome-enabled growth models to study shoot growth responses to water deficit in rice
Authors: Campbell Malachy , Grondin Alexandre , Walia Harkamal , Morota Gota 
Published: July 2019

AbstractElucidating genotype-by-environment interactions (G×E) and partitioning its contribution to the phenotypic variation remains a long standing challenge for plant scientists. Recent quantitative genetic frameworks have improved predictions of G× E responses. However, these models do not explicitly consider the processes that give rise to G×E. To overcome this limitation, we propose a novel framework to elucidate the genetic basis of dynamic shoot growth trajectories under contrasting water regimes using genome-wide markers to model genotype-specific shoot growth trajectories as a function of soil water availability. A rice diversity panel was phenotyped daily over a period of twenty-one days during the early vegetative stage using an automated, high-throughput image-based, phenotyping platform that enabled us to estimate daily shoot biomass and soil water content. Using these data, we modeled shoot growth as a function of time and soil water content, and were able to determine the soil water content and/or time point where an inflection in the growth trajectory occurred. We found that larger, more vigorous plants tend to exhibit an earlier repression in growth compared to smaller, slow growing plants, indicating a potential trade off between early vigor and tolerance to prolonged water deficits. We integrated the growth model within a hierarchical Bayesian framework and used marker information to estimate model parameters and the associated loci through genome-wide association analysis. Genomic inference for model parameters and time of inflection (TOI) identified several candidate genes. Among them an aquaporin,OsPIP1;1was identified as a candidate for time of inflection under drought and showed significantly lower expression in accessions exhibiting later TOI in drought. This study is the first to utilize a genome-enabled growth model to study drought responses in rice, and presents a new approach to jointly model dynamic morpho-physiological responses and environmental covariates.
Generalist Eimeria species in rodents: multilocus analyses indicate inadequate resolution of established markers
Authors: Jarquín-Díaz Víctor Hugo , Balard Alice , Mácová Anna , Jost Jenny , Roth von Szepesbéla Tabea , Berktold Karin , Tank Steffen , Kvičerová Jana , Heitlinger Emanuel 
Published: July 2019

AbstractIntracellular parasites of the genus Eimeria are described as tissue/host specific. Phylogenetic classification of rodent Eimeria suggested that some species have a broader host range than previously assumed. We explore if Eimeria spp. infecting house mice are misclassified by the most widely used molecular markers due to a lack of resolution, or if, instead, these parasite species are indeed infecting multiple host species.With the commonly used markers (18S/COI), we recovered monophyletic clades of E. falciformis and E. vermiformis from Mus that included E. apionodes identified in other rodent host species (Apodemus spp., Myodes glareolus, and Microtus arvalis). A lack of internal resolution in these clades could suggest the existence of a species complex with a wide host range infecting murid and cricetid rodents. We question, however, the power of COI and 18S markers to provide adequate resolution for assessing host specificity. In addition to the rarely used marker ORF470 from the apicoplast genome, we present multilocus genotyping as an alternative approach. Phylogenetic analysis of 35 nuclear markers differentiated E. falciformis from house mice from isolates from Apodemus hosts. Isolates of E. vermiformis from Mus are still found in clusters interleaved with non-Mus isolates, even with this high resolution data.In conclusion, we show that species-level resolution should not be assumed for COI and 18S markers in Coccidia. Host-parasite co-speciation at shallow phylogenetic nodes, as well as contemporary coccidian host ranges more generally, are still open questions that need to be addressed using novel genetic markers with higher resolution.
Steady-state responses in the somatosensory system interact with endogenous beta activity
Authors: Wälti Michel J. , Bächinger Marc , Ruddy Kathy L. , Wenderoth Nicole 
Published: July 2019

AbstractBrain oscillations have been related to many aspects of human behavior. To understand a potential causal relationship, it is of great importance to develop methods for modulating ongoing neural activity. It has been shown that external rhythmic stimulation leads to an oscillatory brain response that follows the temporal structure of the presented stimulus and is assumed to reflect the synchronization of ongoing neural oscillations with the stimulation rhythm. This interaction between individual brain activity and so called steady-state evoked potentials (SSEPs) is the fundamental requirement of neural entrainment. Here, we investigate whether neural responses to rhythmic vibrotactile stimulation, measured with EEG, are dependent on ongoing individual brain oscillations, and therefore reflect entrained oscillatory activity. For this, we measured phase synchronization in response to rhythmic stimulation across various frequencies in the alpha and beta band. Three different stimulation intensities were applied for each frequency relative to the individual sensory threshold. We found that a higher stimulation intensity, compared to lower intensities, resulted in a more pronounced phase synchronization with the stimulation signal. Moreover, EEG responses to low stimulation frequencies closer to individual beta peak frequencies revealed a higher degree of entrainment, compared to stimulation conditions with frequencies that were more distant to endogenous oscillations. Our findings provide evidence that the efficacy of vibrotactile rhythmic beta stimulation to evoke a SSEPs is dependent on ongoing brain oscillations.
Phagocytic predation by the fungivorous amoebaProtostelium aurantiumtargets metal ion and redox homeostasis
Authors: Radosa Silvia , Sprague Jakob L. , Tóth Renáta , Wolf Thomas , Sprenger Marcel , Brunke Sascha , Panagiotou Gianni , Linde Jörg , Gácser Attila , Hillmann Falk 
Published: July 2019

SummaryPredatory interactions among microbes are considered to be a major evolutionary driving force for biodiversity and the defense against phagocytic killing. The fungivorous amoebaProtostelium aurantiumhas a wide fungal food spectrum but strongly discriminates among major pathogenic members of theSaccharomycotina. WhileC. albicansis not recognized,C. glabratais rapidly internalized, but remains undigested. Phagocytic killing and feeding byP. aurantiumis highly effective for the third major fungal pathogen,C. parapsilosis.Here we show that the different prey patterns of the three yeasts were reflected by distinct transcriptional responses, indicating fungal copper and redox homeostasis as primary targets during intracellular killing ofC. parapsilosis. Gene deletions in this fungus for the highly expressed copper exporter Crp1 and the peroxiredoxin Prx1 confirmed their role in copper and redox homeostasis, respectively and identified methionine biosynthesis as a ROS sensitive metabolic target during predation. Both, intact Cu export and redox homeostasis contributed to the survival ofC. parapsilosisnot only when encounteringP. aurantium, but also in the presence of human macrophages. As both genes were found to be widely conserved within the entireCandidaclade, our results suggest that they could be part of a basic tool-kit to survive phagocytic attacks by environmental predators.
High-throughput transposon sequencing highlights the cell wall as an important barrier for osmotic stress in methicillin resistantStaphylococcus aureusand underlines a tailored response to different osmotic stressors
Authors: Schuster Christopher F. , Wiedemann David M. , Kirsebom Freja C. M. , Santiago Marina , Walker Suzanne , Gründling Angelika 
Published: July 2019

SummaryStaphylococcus aureusis an opportunistic pathogen that can cause soft tissue infections but is also a frequent cause of foodborne illnesses. One contributing factor for this food association is its high salt tolerance allowing this organism to survive commonly used food preservation methods. How this resistance is mediated is poorly understood, particularly during long-term exposure. In this study, we used TN-seq to understand how the responses to osmotic stressors differ. Our results revealed distinctly different long-term responses to NaCl, KCl and sucrose stresses. In addition, we identified the DUF2538 domain containing geneSAUSA300_0957(gene957) as essential under salt stress. Interestingly, a957mutant was less susceptible to oxacillin and showed increased peptidoglycan crosslinking. The salt sensitivity phenotype could be suppressed by amino acid substitutions in the transglycosylase domain of the penicillin binding protein Pbp2, and these changes restored the peptidoglycan crosslinking to WT levels. These results indicate that increased crosslinking of the peptidoglycan polymer can be detrimental and highlight a critical role of the bacterial cell wall for osmotic stress resistance. This study will serve as a starting point for future research on osmotic stress response and help develop better strategies to tackle foodborne staphylococcal infections.
Genetic contributions to variation in human stature in prehistoric Europe
Authors: Cox Samantha L. , Ruff Christopher B. , Maier Robert M. , Mathieson Iain 
Published: July 2019

AbstractThe relative contributions of genetics and environment to temporal and geographic variation in human height remain largely unknown. Ancient DNA has identified changes in genetic ancestry over time, but it is not clear whether those changes in ancestry are associated with changes in height. Here, we directly test whether changes over the past 38,000 years in European height predicted using DNA from 1071 ancient individuals are consistent with changes observed in 1159 skeletal remains from comparable populations. We show that the observed decrease in height between the Early Upper Paleolithic and the Mesolithic is qualitatively predicted by genetics. Similarly, both skeletal and genetic height remained constant between the Mesolithic and Neolithic and increased between the Neolithic and Bronze Age. Sitting height changes much less than standing height–consistent with genetic predictions–although genetics predicts a small Bronze Age increase that is not observed in skeletal remains. Geographic variation in stature is also qualitatively consistent with genetic predictions, particularly with respect to latitude. Finally, we hypothesize that an observed decrease in genetic heel bone mineral density in the Neolithic reflects adaptation to the decreased mobility indicated by decreased femoral bending strength. This study provides a model for interpreting phenotypic changes predicted from ancient DNA and demonstrates how they can be combined with phenotypic measurements to understand the relative contribution of genetic and developmentally plastic responses to environmental change.SignificanceMeasurements of prehistoric human skeletal remains provide a record of changes in height and other anthropometric traits, over time. Often, these changes are interpreted in terms of plastic developmental response to shifts in diet, climate or other environmental factors. These changes can also be genetic in origin but, until recently, it has been impossible to separate the effects of genetics and environment. Here we use ancient DNA to directly estimate genetic changes in phenotypes and to identify changes driven not by genetics, but by environment. We show that changes over the past 35,000 years are largely predicted by genetics, but also identify specific shifts that are more likely to be environmentally driven.
Developmental exposure to pesticide contaminated food impedes bumblebee brain growth predisposing adults to become poorer learners
Authors: Smith Dylan B. , Arce Andres N. , Rodrigues Ana Ramos , Bischoff Philipp H. , Burris Daisy , Ahmed Farah , Gill Richard J. 
Published: July 2019

AbstractUnderstanding the risk to biodiversity from pesticide exposure is a global priority. For bees, an understudied step in evaluating pesticide risk is understanding how pesticide contaminated foraged food brought back to the colony can affect developing individuals. Provisioning bumblebee colonies with pesticide (neonicotinoid) treated food, we investigated how exposure during two key developmental phases (brood and/or early-adult), impacted brain growth and assessed the consequent effects on adult learning behaviour. Using micro-computed tomography (µCT) scanning and 3D image analysis, we compared brain development for multiple neuropils in workers 3 and 12-days post-emergence. Mushroom body calyces were the neuropils most affected by exposure during either of the developmental phases, with both age cohorts showing smaller structural volumes. Critically, reduced calyces’ growth in pesticide exposed workers was associated with lower responsiveness to a sucrose reward and impaired learning performance. Furthermore, the impact from brood exposure appeared irrecoverable despite no exposure during adulthood.