bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leg choice for volitional goal-directed stepping is primarily influenced by effort rather than success: A preliminary investigation in neurotypical adults
Authors: Charalambous Charalambos C. , Espinoza-Wade Eric R. , Cesar Guilherme M. , Gerger Michaela , Lai Yi-Hsuan , Winstein Carolee J. 
Published: April 2024

AbstractDuring reaching, arm choice depends on success and motor effort. Whether these factors influence leg choice for stepping behavior is unknown. Here, we conducted two experiments (1: proof-of-principle; 2: kinematic analysis) to explore whether limb selection for goal-directed stepping depends on success and/or effort under twoChoiceconditions:Free(choose either leg) andConstrained(no choice – only left leg). For both experiments, in which Free trials always preceded Constrained trials, we adapted the classic center-out target array in which right-leg dominant neurotypical adults stood in the middle of the array and stepped to pre-cued targets as accurately as possible. TheFreecondition reflected the preferred limb choice. We compared success, effort, and self-perceived difficulty betweenFreeandConstrainedtrials, separately for three (Experiment 1) and two (Experiment 2) regions. Overall, inFreecondition, participants uniformly selected the limb ipsilateral to lateral left and right targets and with slight leg dominance-based bias for central targets. Success (step accuracy and consistency/precision) did not depend on Choice condition, rather, performance improved over repeated trials. Effort (peak vertical foot lift and step path ratio) depended on Choice condition. Finally, independent of Choice condition, participants perceived posterior targets (particularly far targets) as the most difficult during non-dominant left steps. Present findings suggest that effort may influence leg choice to a greater degree than success for goal-directed stepping. Future work that probes these findings’ robustness in patients with unilateral paresis (intrinsic constraint) may advance our understanding of the motor decision processes for goal-directed mobility behaviors.
Controlled Noise: Evidence of Epigenetic Regulation of Single-Cell Expression Variability
Authors: Zhong Yan , Cui Siwei , Yang Yongjian , Cai James J. 
Published: April 2024

AbstractMotivationUnderstanding single-cell expression variability (scEV) or gene expression noise among cells of the same type and state is crucial for delineating population-level cellular function. While epigenetic mechanisms are widely implicated in gene expression regulation, a definitive link between chromatin accessibility and scEV remains elusive. Advances in single-cell techniques now enable simultaneous measurement of scATAC-seq and scRNA-seq within individual cells, presenting an unprecedented opportunity to address this gap.ResultsThis paper introduces an innovative testing pipeline to investigate the association between chromatin accessibility and scEV. The pipeline hinges on comparing the prediction performance of scATAC-seq data on gene expression levels between highly variable genes (HVGs) and non-highly variable genes (non-HVGs). Applying this pipeline to paired scATAC-seq and scRNA-seq data from human hematopoietic stem and progenitor cells, we observed a significantly superior prediction performance of scATAC-seq data for HVGs compared to non-HVGs. Notably, there was substantial overlap between well-predicted genes and HVGs. The gene pathways enriched from well-predicted genes are highly pertinent to cell type-specific functions. Our findings support the notion that scEV largely stems from cell-to-cell variability in chromatin accessibility, providing compelling evidence for the epigenetic regulation of scEV and offering promising avenues for investigating gene regulation mechanisms at the single-cell level.Availability and implementationThe source code and data used in this paper can be found athttps://github.com/SiweiCui/EpigeneticControlOfSingle-CellExpressionVariability.
Optimising crown-of-thorns starfish control effort on the Great Barrier Reef
Authors: Agarwal Kanupriya , Bode Michael , Helmstedt Kate J. 
Published: April 2024

AbstractOutbreaks of crown-of-thorns starfishAcanthaster planci(COTS), a disruptive coral-eating predator, are responsible for almost half of total coral cover loss on Australia’s Great Barrier Reef. As the pressures of climate change continue to intensify the frequency and severity of disturbance events such as cyclones and coral bleaching, efficiently managing COTS outbreaks is essential for reef protection. We aim to understand how the spatial distribution and intensity of crown-of-thorns starfish control – specifically manual culling of COTS by human divers – can impact coral cover on the GBR. We construct a metapopulation model based on a predator-prey model with larval dispersal and removal of crown-of-thorns starfish to simulate and compare spatial control strategies. When outbreaks begin on reefs between Cairns and Cooktown, we found the best strategy is to target those reefs at the source of the COTS outbreak. Increasing the spatial spread of control results in a larger spatial area protected across the GBR, but a lower total coral cover on the GBR. Our findings suggest that carefully targeting future control by considering larval connectivity patterns and spatial control strategies could lead to more efficient crown-of-thorns management. With the increasing pressures of climate change, any efficiency gains in reef management will prove beneficial for the Great Barrier Reef.
A fast fish swimming protocol that provides similar insights as critical sustained swimming speed
Authors: Bamford Stephanie M. , Seebacher Frank 
Published: April 2024

AbstractPerformance measures are an important tool to assess the impact of environmental change on animals. In fish, performance is often measured as critical sustained swimming speed (Ucrit), which reflects individual physiological capacities. A drawback of Ucritis that trials are relatively long (∼30-75 min). Ucritis therefore not suitable for repeated measurements because of the potential for training effects, long recovery periods, and low throughput. Here we test a shorter (∼4-5 min) protocol, “Ucritfast” (UCfast) in zebrafish (Danio rerio). We show that UCfastand Ucrithave similar, significant repeatabilities within individuals. Unlike Ucrit, repeated UCfasttrials do not elicit a training effect. Both UCfastand Ucritprovide the same insights into thermal acclimation, and both provide similar estimates of individual acclimation capacity in doubly acclimated fish. We propose that UCfastis a valid substitute for Ucritparticularly when higher throughput and repeated measures are necessary.
Drp1-JNKknockdown mitigates Scribble loss induced cell proliferation, metastasis and lethality phenotypes inDrosophila
Authors: Singh Jyotsna , Srikrishna Saripella 
Published: April 2024

AbstractMitochondrial dynamics are emerging as master regulators for targeting several types of cancers, including breast cancer, cervical cancer, and hepatocellular carcinoma, for therapeutic intervention. Mitochondrial morphology, size, position and activity within cells is regulated by dynamic fission and fusion events. Dynamin-related protein 1 (Drp1) promotes mitochondrial fission and maintains mitochondrial homeostasis. Loss ofScribis implicated in several human cancers wherein mitochondrial dysfunction leads to excessive cell proliferation and metastasis. However, the exact molecular mechanisms behind theScribloss induced dysregulation of mitochondrial dynamics in cancer progression remains obscure. Although the role of mitochondrial dynamics are being investigated in several types of cancers, but the role ofDrp1- mediated fission event in regulating the maintenance of polarity of cells upon loss ofScribfunction is elusive. In this study, for the first time, we blocked the function ofDrp1activity inScribknockdown induced metastasis cancer model by two ways, firstly, through genetic ablation ofDrp1,and secondly by using mdivi-1, aDrp1specific inhibitor. Genetic depletion ofDrp1expression (Drp1RNAi) inScribknockdown cells inhibits MetalloproteinaseMMP1, reduces ROS production, restores apico-basal (A/B) cell polarity and enhances ATP production. Further to confirm role of Drp1 in regulation of cell polarity, we employed mdivi, a Drp1 specific inhibitor which has dose dependent effect in cell polarity regulation. This study also reveals thatJNKinhibition (JNKRNAi) inScribabrogated cells mitigates theDrp1expression and controls cell proliferation leading to restoration of mitochondrial morphology and epithelial cellpolarity. Our results highlightDrp1as a key regulator in maintaining the apico-basal polarity of cells which gets affected upon loss ofScribbutDrp1-JNKdownregulation effectively mitigatesScribRNAiassociated cell proliferation, metastasis and pupal lethality phenotypes.
Copy number normalization distinguishes differential signals driven by copy number differences in ATAC-seq and ChIP-seq
Authors: Su Dingwen , Peters Moritz , Soltys Volker , Chan Yingguang Frank 
Published: April 2024

AbstractA common objective across ATAC-seq and ChIP-seq analyses is to identify differential signals across contrasted conditions. However, in differential analyses, the impact of copy number variation is often overlooked. Here, we demonstrated copy number differences among samples could drive, if not dominate, differential signals. To address this, we propose a pipeline featuring copy number normalization. By comparing the averaged signal per gene copy, it effectively segregates differential signals driven by copy number differences from other factors. Further applying it to Down syndrome, we unveiled distinct dosage-dependent and -independent changes on chromosome 21. Thus, we recommend normalization as a general approach.
An intestinal Sir2-HSF1-ATGL1 pathway regulates lipolysis inC. elegans
Authors: Somogyvári Milán , Khatatneh Saba , Hajdú Gábor , Sotil Bar , Murányi József , Sőti Csaba 
Published: April 2024

AbstractProteostasis maintenance and lipid metabolism are critical for survival and promote longevity, however, their coordination is largely unclear. Here we show that the heat shock factor HSF-1 and the proteostasis state regulates lipolysis inC. elegans. We find that in response to starvation, the sirtuin 1 ortholog SIR-2.1 activates lipolysis by upregulation of the adipose triglyceride lipase ATGL-1. In feeding worms, intestinal HSF-1 represses ATGL-1 expression and lipolysis via the microRNA system. In starving worms, SIR-2.1 suspends amiR-53-mediated suppression of lipolysis by inhibiting its HSF-1-dependent expression. The apparent antagonism of SIR-2.1 and HSF-1, distinct from their synergism at heat shock promoters suggests a context-specific regulation of HSF-1 by SIR-2.1. We demonstrate that the SIR-2.1 and protein kinase A pathways are both indispensable, and independently converge on ATGL- 1 for lipolysis. HSF-1 activation by proteostasis disturbances inhibits starvation-induced lipid mobilization, whereas its age-related decline limits fat deposition throughatgl-1. Our findings reveal a crosstalk between proteostasis and lipid/energy metabolism, which may modulate stress resilience and aging.
Longevity hinders evolutionary rescue through slower growth but not necessarily slower adaptation
Authors: Nordstrom Scott W. , Melbourne Brett A. 
Published: April 2024

Abstract“Evolutionary rescue” is the process by which a population experiencing severe environmental change avoids extinction through adaptation. Theory and empirical work typically focus on short life histories with non-overlapping generations, leaving longevity’s effects on rescue relatively understudied. Recent models demonstrate that longevity can inhibit rescue through slower phenotypic evolution but have assumptions that may not generalize across life histories. We built a model integrating evolutionary rescue with concepts from life-history theory, particularly the fast-slow pace-of-life continuum. Longevity is modeled by the balance of survival and reproduction with selection acting on survival, allowing for multiple selection episodes throughout the lifespan. We used this model to simulate three life-history strategies along the fast-slow continuum responding to sudden environmental change. Under nearly all simulated conditions, higher longevities (slower pace of life) resulted in more time at low density and increased extinctions. With perfect trait heritability, rates of adaptation were nearly identical across longevities. But at lower heritabilities, longevity allowed for repeated selection and decoupling of mean genotypes and phenotypes, producing a transient phase of rapid phenotypic change. Our results demonstrate that prior findings that longevity slows adaptation do not hold in all cases and are relevant to long-lived conservation targets.
Current genomic deep learning architectures generalize across grass species but not alleles
Authors: Wrightsman Travis , Ferebee Taylor H. , Romay M. Cinta , Seetharam Arun S. , AuBuchon-Elder Taylor , Phillips Alyssa R. , Syring Michael , Hufford Matthew B. , Kellogg Elizabeth A. , Buckler Edward S. 
Published: April 2024

AbstractNon-coding regions of the genome are just as important as coding regions for understanding the mapping from genotype to phenotype. Interpreting deep learning models trained on RNA-seq is an emerging method to highlight functional sites within non-coding regions. Most of the work on RNA abundance models has been done within humans and mice, with little attention paid to plants. Here, we benchmark four genomic deep learning model architectures with genomes and RNA-seq data from 18 species closely related to maize and sorghum within the Andropogoneae. The Andropogoneae are a tribe of C4 grasses that have adapted to a wide range of environments worldwide since diverging 18 million years ago. Hundreds of millions of years of evolution across these species has produced a large, diverse pool of training alleles across species sharing a common physiology. As model input, we extracted 1,026 base pairs upstream of each gene’s translation start site. We held out maize as our test set and two closely related species as our validation set, training each architecture on the remaining Andropogoneae genomes. Within a panel of 26 maize lines, all architectures predict expression across genes moderately well but poorly across alleles. DanQ consistently ranked highest or second highest among all architectures yet performance was generally very similar across architectures despite orders of magnitude differences in size. This suggests that state-of-the-art supervised genomic deep learning models are able to generalize moderately well across related species but not sensitively separate alleles within species, the latter of which agrees with recent work within humans. We are releasing the preprocessed data and code for this work as a community benchmark to evaluate new architectures on our across-species and across-allele tasks.
Infanticide is driven by unfamiliarity with offspring location and associated with androgenic shifts in mimic poison frogs
Authors: Lewis Amaris R. , Goolsby Billie C. , Juarez Bryan H. , Lacey Madison P. , O’Connell Lauren A. 
Published: April 2024

AbstractInfanticide is widespread across the animal kingdom, but the physiological drivers of infanticide versus care or neglect are relatively unexplored. Here, we identified salient environmental and physiological antecedents of infanticide in the mimic poison frog (Ranitomeya imitator), a biparental amphibian in which female parents feed their tadpoles unfertilized eggs. Specifically, we explored potential environmental cues influencing infant- directed behavior by evaluating changes in the frequency of food provisioning and tadpole mortality after either cross-fostering tadpoles between family units or displacing tadpoles within the terraria of their parents. We found that changes in offspring location reduce care and increase infanticide. Specifically, parents fed their displaced offspring less and, in some instances, tadpole mortality increased. We also investigated whether care and infanticide were related to changes in steroid hormone concentrations in an unfamiliar setting. Infanticide of fertilized eggs and hatchlings in the new territory included cannibalism and was associated with lower testosterone concentrations, but not with changes in corticosterone. Overall, our results support earlier findings that familiarity with offspring location drives parental investment in poison frogs, while indicating an association between low androgen levels and infanticidal behavior in an amphibian.HighlightsOffspring location drives parental decisions of care vs. infanticide.In novel territories, adults cannibalize conspecific, unrelated young.Lower circulating testosterone in novel territory is associated with infanticide.
Interstitial telomeric sequences promote gross chromosomal rearrangement via multiple mechanisms
Authors: Rosas Bringas Fernando R. , Yin Ziqing , Yao Yue , Boudeman Jonathan , Ollivaud Sandra , Chang Michael 
Published: April 2024

AbstractTelomeric DNA sequences are difficult to replicate. Replication forks frequently pause or stall at telomeres, which can lead to telomere truncation and dysfunction. In addition to being at chromosome ends, telomere repeats are also present at internal locations within chromosomes, known as interstitial telomeric sequences (ITSs). These sequences are unstable and prone to triggering gross chromosomal rearrangements (GCRs). In this study, we quantitatively examined the effect of ITSs on GCR rate inSaccharomyces cerevisiaeusing a genetic assay. We find that GCR rate increases exponentially with ITS length. This increase can be attributed to the telomere repeat binding protein Rap1 impeding DNA replication and a bias of repairing DNA breaks at or distal to the ITS via de novo telomere addition. Additionally, we performed a genome-wide screen for genes that modulate the rate of ITS-induced GCRs. We find that mutation of core components of the DNA replication machinery leads to an increase in GCRs, but many mutants known to increase GCR rate in the absence of an ITS do not significantly affect GCR rate when an ITS is present. We also identified genes that promote the formation of ITS-induced GCRs, including genes with roles in telomere maintenance, nucleotide excision repair, and transcription. Our work thus uncovers multiple mechanisms by which an ITS promotes GCR.Significance statementTelomeric DNA repeats are found at the ends of linear chromosomes where they, together with specialized proteins that bind to them, protect chromosome ends from degradation and unwanted DNA repair activities. Telomeric repeats can also be found at internal locations in the genome, where they are called interstitial telomeric sequences (ITSs). ITSs are prone to breakage and are associated with human diseases. In this study, using baker’s yeast as a model organism, we show that instability at ITSs is driven by multiple factors, and identify genes that either promote or suppress gross chromosomal rearrangements induced by the presence of an ITS.
Revisiting the role of the spindle assembly checkpoint in the formation of gross chromosomal rearrangements inSaccharomyces cerevisiae
Authors: Yao Yue , Yin Ziqing , Rosas Bringas Fernando R. , Boudeman Jonathan , Novarina Daniele , Chang Michael 
Published: April 2024

AbstractMultiple pathways are known to suppress the formation of gross chromosomal rearrangements (GCRs), which can cause human diseases including cancer. In contrast, much less is known about pathways that promote their formation. The spindle assembly checkpoint (SAC), which ensures the proper separation of chromosomes during mitosis, has been reported to promote GCR, possibly by delaying mitosis to allow GCR-inducing DNA repair to occur. Here we show that this conclusion is the result of an experimental artifact arising from the synthetic lethality caused by disruption of the SAC and loss of theCIN8gene, which is often lost in the genetic assay used to select for GCRs. After correcting for this artifact, we find no role of the SAC in promoting GCR.Significance statementA gross chromosomal rearrangement (GCR) is an abnormal structural change of a native chromosome. Examples of GCRs include deletions, duplications, inversions, and translocations. GCRs can lead to genetic diseases such as cancer. A previous study implicated the spindle assembly checkpoint (SAC), which ensures the proper separation of chromosomes during cell division, in facilitating the formation of GCRs. In this study, we show that this is not the case; the SAC does not promote GCR.
Quantitative tests of albendazole resistance in beta-tubulin mutants
Authors: Collins J.B. , Stone Skyler A. , Koury Emily J. , Paredes Anna G. , Shao Fiona , Lovato Crystal , Chen Michael , Shi Richelle , Li Anwyn Y. , Candal Isa , Moutaa Khadija Al , Moya Nicolas , Andersen Erik C. 
Published: April 2024

AbstractBenzimidazole (BZ) anthelmintics are among the most important treatments for parasitic nematode infections in the developing world. Widespread BZ resistance in veterinary parasites and emerging resistance in human parasites raise major concerns for the continued use of BZs. Knowledge of the mechanisms of resistance is necessary to make informed treatment decisions and circumvent resistance. Benzimidazole resistance has traditionally been associated with mutations and natural variants in theC. elegansbeta-tubulin geneben-1and orthologs in parasitic species. However, variants inben-1alone do not explain the differences in BZ responses across parasite populations. Here, we examine the roles of fiveC. elegansbeta-tubulin genes (tbb-1,mec-7,tbb-4,ben-1, andtbb-6) to identify the role each gene plays in BZ response. We generatedC. elegansstrains with a loss of each beta-tubulin gene, as well as strains with a loss oftbb-1,mec-7,tbb-4, ortbb-6in a genetic background that also lacksben-1to test beta-tubulin redundancy in BZ response. We found that only the individual loss ofben-1conferred a substantial level of BZ resistance, although the loss oftbb-1was found to confer a small benefit in the presence of albendazole (ABZ). The loss ofben-1was found to confer an almost complete rescue of animal development in the presence of 30 µM ABZ, likely explaining why no additive effects caused by the loss of a second beta-tubulin were observed. We demonstrate thatben-1is the only beta-tubulin gene inC. eleganswhere loss confers substantial BZ resistance.Highlights-Loss ofben-1provides almost complete rescue of development in albendazole (ABZ)-Loss of different beta-tubulin genes does not confer ABZ resistance-Loss ofben-1and a second beta-tubulin does not enhance theben-1level of ABZ resistance