bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beacon-based sleep status and physical activity monitoring in humans
Authors: Kikusui Takefumi , Yagisawa Mizuho , Koyama Kahori , Fujiwara Koichi , Kume Kazuhiko , Nomoto Kensaku , Nagasawa Miho 
Published: November 2023

AbstractOne out of every five people in Japan is dissatisfied with their sleep and various diseases caused by lack of exercise have been pointed out, but there are few effective remedies for these problems. In this study, we aimed to develop a simple method for measuring behavioral sleep patterns and physical activity using a beacon accelerometer wirelessly connected with a smartphone. A sleep prediction model was created comparing the data obtained from the accelerometer with the sleep status data obtained by a previously validated sleep monitoring system. The Random Forest model was able to classify sleep and wakefulness with a 97.4% and 85.4% precision, respectively, which were comparable to those of conventional acceleration-based sleep monitoring devices. Additionally, the same data acquisition method was used to classify exercise intensity into seven levels and a high correlation (r=0.813, p<0.0001) was found when comparing the classified exercise intensity to metabolic equivalent (MET) values. This suggests that the proposed method can be used for accurate measurement of both behavioral sleep and physical activity classifying over a long period of time.
Non-canonical ORFs are an important source of tumor-specific antigens in a liver cancer meta-cohort
Authors: Camarena Marta E. , Theunissen Patrick , Ruiz Marta , Ruiz-Orera Jorge , Calvo-Serra Beatriz , Castelo Robert , Sarobe Pablo , Fortes Puri , Perera-Bel Júlia , Albà M. Mar 
Published: November 2023

ABSTRACTThe expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Antigens that have been used as cancer vaccines are those originated by non- synonymous mutations and those derived from cancer/testis antigens. However, the first class is predominantly patient-specific, preventing the development of therapies than can benefit multiple patients, and the second one offers a limited set of actionable targets. A possible alternative is the use of peptides derived from non-canonical ORFs (ncORFs). While many ncORFs have been shown to be translated in cancer cells, their tumor-specificity and patient distribution remains to be determined. Here we analyze RNA sequencing data 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue, together with ribosome profiling data from an additional 10 HCC tumors, to answer these open questions. Combining HLA-epitope binding predictions and experimental validation experiments we conclude that around 40% of the tumor-specific antigens in HCC are likely to be derived from ncORFs in lncRNAs, including two peptides that can trigger an immune response in mice. We identify a subset of 33 tumor-specific lncRNAs expressing novel cancer antigens shared by more than 10% of the HCC analyzed, which could be combined to target a large proportion of the patients. The results of the study open new avenues for extending the range of anti-cancer vaccines.
A Computational Model of Coarctation of the Aorta in Rabbits: Ventricular and Ascending Aortic Remodeling
Authors: Hiebing Ashley A. , Culver Matthew A. , LaDisa John F. , Witzenburg Colleen M. 
Published: November 2023

ABSTRACTCoarctation of the aorta (CoA) is a common congenital cardiovascular lesion that typically presents as a localized narrowing of the proximal descending thoracic aorta just distal to the left subclavian artery. While improvements in surgical and catheter-based techniques have increased short-term survival, there is a high long-term risk of hypertension after CoA correction and a reduced average lifespan despite treatment. Computational models can be used to estimate ventricular and arterial remodeling, potentially serving as key tools in developing a mechanistic understanding of the interplay between pre-correction hemodynamics, post-correction recovery, and long-term hypertension risk. In this study, we developed a lumped parameter model of the heart and circulation to simulate aortic coarctation. We then used the model to estimate changes in ventricular thickness and ascending aortic compliance from imaging and catheterization data collected in rabbits with untreated and corrected CoA that used the current putative clinical treatment threshold (≥20 mmHg). Model outputs were compared to reported stroke volume, ejection fraction, systolic and diastolic ascending aortic pressures, peak ascending aortic flow, mean and peak aortic blood pressure gradients, and upper-to-lower body flow split, with all results falling within one standard deviation of the data for control, untreated CoA, and corrected CoA groups. In the untreated CoA and corrected simulations, a decrease in ascending aortic compliance was necessary to match reported hemodynamics, suggesting the rabbits exposed to CoA ≥20 mmHg underwent vascular remodeling that persisted after repair.
Interactive visualization of whole eukaryote genome alignments using NCBI’s Comparative Genome Viewer (CGV)
Authors: Rangwala Sanjida H , Rudnev Dmitry V , Ananiev Victor V , Asztalos Andrea , Benica Barrett , Borodin Evgeny A , Bouk Nathan , Evgeniev Vladislav I , Kodali Vamsi K , Lotov Vadim , Mozes Eyal , Oh Dong-Ha , Omelchenko Marina V , Savkina Sofya , Sukharnikov Ekaterina , Virothaisakun Joël , Murphy Terence D. , Pruitt Kim D , Schneider Valerie A. 
Published: November 2023

AbstractWe report a new visualization tool for analysis of whole genome assembly-assembly alignments, the Comparative Genome Viewer (CGV) (https://ncbi.nlm.nih.gov/genome/cgv/). CGV visualizes pairwise same-species and cross-species alignments provided by NCBI using assembly alignment algorithms developed by us and others. Researchers can examine the alignments between the two assemblies using two alternate views: a chromosome ideogram- based view or a 2D genome dotplot. Whole genome alignment views expose large structural differences spanning chromosomes, such as inversions or translocations. Users can also navigate to regions of interest, where they can detect and analyze smaller-scale deletions and rearrangements within specific chromosome or gene regions. RefSeq or user-provided gene annotation is displayed in the ideogram view where available. CGV currently provides approximately 700 alignments from over 300 animal, plant, and fungal species. CGV and related NCBI viewers are undergoing active development to further meet needs of the research community in comparative genome visualization.
Salience-dependent disruption of sustained auditory attention can be inferred from evoked pupil responses and neural tracking of task-irrelevant sounds
Authors: Fiedler Lorenz , Johnsrude Ingrid , Wendt Dorothea 
Published: November 2023

AbstractStimulus-driven attention allows us to react to relevant stimuli (and imminent danger!) outside our current focus of attention. But irrelevant stimuli can also disrupt attention; for example, during listening to speech. The degree to which sound captures attention is called salience, which can be estimated by existing, behaviorally validated, computational models (Huang & Elhilali, 2017). Here we examined whether neurophysiological responses to task-irrelevant sounds indicate the degree of distraction during a sustained-listening task and how much this depends on individual hearing thresholds. N = 47 Danish-speaking adults (28/19 female/male; mean age: 60.1, SD: 15.9 years) with heterogenous hearing thresholds (PTA; mean: 25.5, SD: 18.0 dbHL) listened to continuous speech while one-second-long, task-irrelevant natural sounds (distractors) of varying computed salience were presented at unpredictable times and locations. Eye tracking and electroencephalography were used to estimate pupil response and neural tracking, respectively. The task-irrelevant sounds evoked a consistent pupil response (PR), distractor-tracking (DT) and a drop of target-tracking (ΔTT), and statistical modelling of these three measures within subjects showed that all three are enhanced for sounds with higher computed salience. Participants with larger PR showed a stronger drop in target tracking (ΔTT) and performed worse in target speech comprehension. We conclude that distraction can be inferred from neurophysiological responses to task-irrelevant stimuli. These results are a first step towards neurophysiological assessment of attention dynamics during continuous listening, with potential applications in hearing-care diagnostics.Significance statementSuccessful speech-in-noise comprehension in daily life does not only depend on the acuity of the auditory input, but also cognitive factors like attentional control. Being able to measure distraction-dependent neurophysiological responses to peripheral, task-irrelevant stimuli would enable monitoring the extent to which the attentional focus is instantaneously captured away from a target under sustained attention. Here we show that especially pupil response and neural tracking of distractor sounds reflect the degree to which people with both normal and elevated hearing thresholds are distracted. Such a measure could be used to non-invasively track the focus of attention and thus could find application in hearing care diagnostics, where cognitive factors like attentional control are being increasingly recognized as important.
Spatial and single-cell transcriptomics illuminate bat immunity and barrier tissue evolution
Authors: Levinger Roy , Tussia-Cohen Dafna , Friedman Sivan , Lender Yan , Nissan Yomiran , Fraimovitch Evgeny , Gavriel Yuval , Tearle Jacqueline , Kolodziejczyk Aleksandra A. , Gomes Tomás , Kunowska Natalia , Weinberg Maya , Donati Giacomo , James Kylie R , Yovel Yossi , Hagai Tzachi 
Published: November 2023

AbstractThe Egyptian fruit bat displays tolerance to lethal viruses and unique dietary adaptations, but the molecular basis for this is poorly understood. To this end, we generated detailed maps of bat gut, lung and blood cells using spatial and single-cell transcriptomics. We compared bat with mouse and human cells to reveal divergence in genetic programs associated with environmental interactions and immune responses. Complement system genes are transcriptionally divergent, uniquely expressed in bat lung and gut epithelium, and undergo rapid coding-sequence evolution. Specifically in the tip of the gut villus, bat enterocytes express evolutionarily young genes while lacking expression of genes related to specific nutrient absorption. Profiling immune stimulation of PBMCs revealed a monocyte subset with conserved cross-species interferon expression, suggesting strong constraints to avoid an excessive immune response. Our study thus uncovers conserved and divergent immune pathways in bat tissues, providing a unique resource to study bat immunity and evolution.
Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes
Authors: Xue Feng , Li Fei , Zhang Ke-ming , Ding Lufeng , Wang Yang , Zhao Xingtao , Xu Fang , Zhang Danke , Sun Mingzhai , Lau Pak-Ming , Zhu Qingyuan , Zhou Pengcheng , Bi Guo-Qiang 
Published: November 2023

ABSTRACTTo investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of equipment. Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice. Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.
Shifted levels of sleep and activity under darkness as mechanisms underlying ectoparasite resistance
Authors: Benoit Joshua B. , Ajayi Oluwaseun M. , Webster Ashley , Grieshop Karl , Lewis David , Talbott Hailie , Bose Joy , Polak Michal 
Published: November 2023

AbstractParasites harm host fitness and are pervasive agents of natural selection capable of driving the evolution of host resistance traits. Indeed, host resistance in natural populations typically shows ample genetic variation, which may be maintained when parasite resistance imposes fitness costs on the host in the absence of parasites. Previously we demonstrated significant evolutionary responses to artificial selection for increasing behavioral immunity toGamasodes queenslandicusmites in replicate lines ofDrosophila melanogaster. Here, we report transcriptional shifts in metabolic processes between selected and control fly lines based on RNA-seq analyses. We also show decreased starvation resistance and increased use of nutrient reserves in flies from mite-resistant lines. Additionally, resistant lines exhibited increased behavioral activity, reduced sleep and elevated oxygen consumption under conditions of darkness. Using an independent panel ofD. melanogastergenetic lines exhibiting variable sleep durations, we found a positive correlation between mite resistance and reduced sleep, providing additional support for a link between resistance and sleep. Experimentally restraining the activity of artificially selected mite-resistant flies during exposure to parasites under dark conditions reduced their resistance advantage relative to control flies. The results suggest that ectoparasite resistance in this system involves increased dark-condition activity and metabolic gene expression at the expense of nutrient reserves and starvation resistance.Significance statementParasites are potent agents of selection, yet resistance may often be constrained evolutionarily because of trade-offs involving other fitness-related traits. Using artificial selection, we show that resistance to ectoparasites directly increases metabolism and decreases starvation resistance, predominantly through altered sleep and activity patterns at night. These studies highlight that active-resting patterns of the host are a significant driving force in ectoparasite resistance, but may have a negative impact on fitness during periods of low food availability. Our strongly integrative work suggests that parasite pressure may influence the evolution of host sleep and activity patterns.
The brittle star genome illuminates the genetic basis of animal appendage regeneration
Authors: Parey Elise , Ortega-Martinez Olga , Delroisse Jérôme , Piovani Laura , Czarkwiani Anna , Dylus David , Arya Srishti , Dupont Samuel , Thorndyke Michael , Larsson Tomas , Johannesson Kerstin , Buckley Katherine M. , Martinez Pedro , Oliveri Paola , Marlétaz Ferdinand 
Published: November 2023

AbstractSpecies within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited genomic resources. Here, we report a chromosome-scale genome assembly for the brittle starAmphiura filiformis.We show that the brittle star genome is the most rearranged amongst echinoderms sequenced to date, featuring a reorganised Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression during brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, particularly during the proliferative phase of regeneration. Our findings emphasise the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems.
A new family of statistical tests for neuronal spiking and autocorrelated timeseries data
Authors: Montijn Jorrit S. , Meijer Guido T. , Heimel J. Alexander 
Published: November 2023

AbstractQuantifying whether and when signals are modulated by autonomous or external events is ubiquitous in the field of neuroscience. Existing statistical approaches, however, are not ideally suited to do this, especially when the signals under scrutiny show temporal autocorrelations. For example, a standard approach in the analysis of calcium imaging data is to use a t-test on predetermined time-windows to quantify whether neurons respond (differently) to an event of interest. While this is attractive because of its simplicity, only average signal differences can be detected. In practice, neurons often show complex response dynamics which are missed by conventional statistical tests. More advanced methods, such as bin-wise ANOVAs, do not share this drawback, but can suffer from high false-positive rates or “ghost correlations” when applied to temporally autocorrelated data. To solve this issue, we have developed three novel statistical tests extending the original ZETA-test to other use cases: 1) a test for time-series data; 2) a two-sample test to detect differences in neural responses between two conditions; and 3) a two-sample test to detect differences in time-series data between two conditions. In addition, we have improved upon the original ZETA-test. We show that our methods have a statistical sensitivity superior to t-tests and ANOVAs and work well with temporally autocorrelated data where other approaches fail. Our methods are widely applicable and we present example applications to Neuropixels data, two-photon GCaMP imaging data, and human electrocorticogram data. Open-source code for implementations in MATLAB and Python is available on GitHub and PyPi.Significance StatementNeurophysiology involves the detection of weak signals in a noisy background. Often these signals, as well as the background, are temporally autocorrelated. This means that many statistical methods, such as the ANOVA, are inappropriate. In some cases, these statistical tests produce “ghost” signals that mislead researchers into thinking there is an effect of their experiment, when in reality there is none. We have therefore developed a new family of statistical tests, the ZETA-tests, that are not negatively impacted by temporal autocorrelations. They do not use arbitrary (hyper)parameters, like bin size, and show superior statistical sensitivity compared to other methods like t-tests and ANOVAs. We provide easy-to-use implementations and expect our methods to be useful for many neuroscientists from various disciplines.
Different complex regulatory phenotypes underlie hybrid male sterility in divergent rodent crosses
Authors: Hunnicutt Kelsie E. , Callahan Colin , Keeble Sara , Moore Emily C. , Good Jeffrey M. , Larson Erica L. 
Published: November 2023

ABSTRACTHybrid incompatibilities are a critical component of species barriers and may arise due to negative interactions between divergent regulatory elements in parental species. We used a comparative approach to identify common themes in the regulatory phenotypes associated with hybrid male sterility in two divergent rodent crosses, dwarf hamsters and house mice. We investigated three potential characteristic gene expression phenotypes in hybrids including the propensity of transgressive differentially expressed genes towards over or underexpression, the influence of developmental stage on patterns of misexpression, and the role of the sex chromosomes on misexpression phenotypes. In contrast to near pervasive overexpression in hybrid house mice, we found that misexpression in hybrid dwarf hamsters was dependent on developmental stage. In both house mouse and dwarf hamster hybrids, however, misexpression increased with the progression of spermatogenesis, although to varying extents and with potentially different consequences. In both systems, we detected sex-chromosome specific overexpression in stages of spermatogenesis where inactivated X chromosome expression was expected, but the hybrid overexpression phenotypes were fundamentally different. Importantly, misexpression phenotypes support the presence of multiple developmental blocks to spermatogenesis in dwarf hamster hybrids, including a potential role of meiotic stalling or breakdown early in spermatogenesis. Collectively, we demonstrate that while there are some similarities in hybrid expression phenotypes of house mice and dwarf hamsters, there are also clear differences that point towards unique mechanisms underlying hybrid male sterility. Our results highlight the potential of comparative approaches in helping to understand the causes and consequences of disrupted gene expression in speciation.
Cerebellar deep brain stimulation as a dual-function therapeutic for restoring movement and sleep in dystonic mice
Authors: Leon Luis E. Salazar , Kim Linda H. , Sillitoe Roy V. 
Published: November 2023

AbstractDystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor (sleep-related) symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect of cerebellar DBS in two genetic mouse models with dystonia that exhibit sleep defects—Ptf1aCre;Vglut2fx/fxandPdx1Cre;Vglut2fx/fx—which have overlapping cerebellar circuit miswiring defects but differing severity in motor phenotypes. By targeting DBS to the cerebellar fastigial and interposed nuclei, we modulated sleep dysfunction by enhancing sleep quality and timing in both models. This DBS paradigm improved wakefulness (decreased) and rapid eye movement (REM) sleep (increased) in both mutants. Additionally, the latency to reach REM sleep, a deficit observed in human dystonia patients, was reduced in both models. Cerebellar DBS also induced alterations in the electrocorticogram (ECoG) patterns that define sleep states. As expected, DBS reduced the severe dystonic twisting motor symptoms that are observed in thePtf1aCre;Vglut2fx/fxmutant mice. These findings highlight the potential for using cerebellar DBS to improve sleep and reduce motor dysfunction in dystonia and uncover its potential as a dual-effectin vivotherapeutic strategy.