bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dynamic generative model can extract interpretable oscillatory components from multichannel neurophysiological recordings
Authors: Das Proloy , He Mingjian , Purdon Patrick L. 
Published: July 2023

AbstractModern neurophysiological recordings are performed using multichannel sensor arrays that are able to record activity in an increasingly high number of channels numbering in the 100’s to 1000’s. Often, underlying lower-dimensional patterns of activity are responsible for the observed dynamics, but these representations are difficult to reliably identify using existing methods that attempt to summarize multivariate relationships in a post-hoc manner from univariate analyses, or using current blind source separation methods. While such methods can reveal appealing patterns of activity, determining the number of components to include, assessing their statistical significance, and interpreting them requires extensive manual intervention and subjective judgement in practice. These difficulties with component selection and interpretation occur in large part because these methods lack a generative model for the underlying spatio-temporal dynamics. Here we describe a novel component analysis method anchored by a generative model where each source is described by a bio-physically inspired state space representation. The parameters governing this representation readily capture the oscillatory temporal dynamics of the components, so we refer to it as Oscillation Component Analysis (OCA). These parameters – the oscillatory properties, the component mixing weights at the sensors, and the number of oscillations – all are inferred in a data-driven fashion within a Bayesian framework employing an instance of the expectation maximization algorithm. We analyze high-dimensional electroencephalography and magnetoencephalography recordings from human studies to illustrate the potential utility of this method for neuroscience data.Significance StatementNeuroscience studies often involve simultaneous recordings in a large number of sensors in which a smaller number of dynamic components generate the complex spatio-temporal patterns observed in the data. Current blind source separation techniques produce sub-optimal results and are difficult to interpret because these methods lack an appropriate generative model that can guide both statistical inference and interpretation. Here we describe a novel component analysis method employing a dynamic generative model that can decompose high-dimensional multivariate data into a smaller set of oscillatory components are learned in a data-driven way, with parameters that are immediately interpretable. We show how this method can be applied to neurophysiological recordings with millisecond precision that exhibit oscillatory activity such as electroencephalography and magnetoencephalography.
CAVE: Connectome Annotation Versioning Engine
Authors: Dorkenwald Sven , Schneider-Mizell Casey M. , Brittain Derrick , Halageri Akhilesh , Jordan Chris , Kemnitz Nico , Castro Manual A. , Silversmith William , Maitin-Shephard Jeremy , Troidl Jakob , Pfister Hanspeter , Gillet Valentin , Xenes Daniel , Bae J. Alexander , Bodor Agnes L. , Buchanan JoAnn , Bumbarger Daniel J. , Elabbady Leila , Jia Zhen , Kapner Daniel , Kinn Sam , Lee Kisuk , Li Kai , Lu Ran , Macrina Thomas , Mahalingam Gayathri , Mitchell Eric , Mondal Shanka Subhra , Mu Shang , Nehoran Barak , Popovych Sergiy , Takeno Marc , Torres Russel , Turner Nicholas L. , Wong William , Wu Jingpeng , Yin Wenjing , Yu Szi-chieh , Reid R. Clay , da Costa Nuno Maçarico , Seung H. Sebastian , Collman Forrest 
Published: July 2023

AbstractAdvances in Electron Microscopy, image segmentation and computational infrastructure have given rise to large-scale and richly annotated connectomic datasets which are increasingly shared across communities. To enable collaboration, users need to be able to concurrently create new annotations and correct errors in the automated segmentation by proofreading. In large datasets, every proofreading edit relabels cell identities of millions of voxels and thousands of annotations like synapses. For analysis, users require immediate and reproducible access to this constantly changing and expanding data landscape. Here, we present the Connectome Annotation Versioning Engine (CAVE), a computational infrastructure for immediate and reproducible connectome analysis in up-to petascale datasets (∼1mm3) while proofreading and annotating is ongoing. For segmentation, CAVE provides a distributed proofreading infrastructure for continuous versioning of large reconstructions. Annotations in CAVE are defined by locations such that they can be quickly assigned to the underlying segment which enables fast analysis queries of CAVE’s data for arbitrary time points. CAVE supports schematized, extensible annotations, so that researchers can readily design novel annotation types. CAVE is already used for many connectomics datasets, including the largest datasets available to date.
KCNQ5 controls perivascular adipose tissue-mediated vasodilation
Authors: Tsvetkov Dmitry , Schleifenbaum Johanna , Wang Yibin , Kassmann Mario , Polovitskaya Maya M , Schütze Sebastian , Rothe Michael , Luft Friedrich C , Jentsch Thomas J , Gollasch Maik 
Published: July 2023

AbstractBackgroundSmall arteries exhibit resting tone, a partially contracted state that maintains arterial blood pressure. In arterial smooth muscle cells (SMCs), potassium channels control contraction and relaxation. Perivascular adipose tissue (PVAT) has been shown to exert anticontractile effects on the blood vessels. However, the mechanisms by which PVAT signals small arteries, and their relevance, remain largely unknown. We aimed to uncover key molecular components in adipose-vascular coupling.MethodsA wide-spectrum of genetic mouse models targetingKcnq3, Kcnq4andKcnq5genes (Kcnq3−/−,Kcnq4−/−,Kcnq5−/−,Kcnq5dn/dn,Kcnq4−/−/Kcnq5dn/dn,Kcnq4−/−/Kcnq5−/−), telemetry blood pressure measurements, targeted lipidomics, and RNA-Seq profiling, wire-myography, patch-clamp, and sharp-electrode membrane potential measurements were used.ResultsWe show that PVAT causes SMC KCNQ5 (KV7.5) channels to hyperpolarize the membrane potential. This effect relaxes small arteries and regulates blood pressure. Oxygenation of polyunsaturated fats generates oxylipins, a superclass of lipid mediators. We identified numerous oxylipins released by PVAT that potentiate vasodilatory action in small arteries by opening SMC KCNQ5 channels.ConclusionsOur results reveal a key molecular function of KCNQ5 channels in adipose-vascular coupling, translating PVAT signals, particularly oxylipins, to the central physiological function of vasoregulation. This novel pathway opens new therapeutic perspectives.
Artificial Intelligence Enables the Label-Free Identification of Chronic Myeloid Leukemia Cells with Mitochondrial Morphological Alterations
Authors: Suzuki Kohjin , Watanabe Naoki , Torii Satoru , Arakawa Satoko , Ochi Kiyosumi , Tsuchiya Shun , Yamada Kazuhiro , Kawamura Yoko , Ota Sadao , Komatsu Norio , Shimizu Shigeomi , Ando Miki , Takaku Tomoiku 
Published: July 2023

AbstractLong-term tyrosine kinase inhibitor (TKI) treatment for patients with chronic myeloid leukemia (CML) causes various adverse events. Achieving a deep molecular response (DMR) is necessary for discontinuing TKIs and attaining treatment-free remission. Thus, early diagnosis is crucial as a lower DMR achievement rate has been reported in high-risk patients. Therefore, we attempted to identify CML cells using a novel technology that combines artificial intelligence (AI) with flow cytometry and investigated the basis for AI- mediated identification. Our findings indicate thatBCR-ABL1-transduced cells and leukocytes from patients with CML showed significantly fragmented mitochondria and decreased mitochondrial membrane potential. Additionally,BCR-ABL1enhanced the phosphorylation of Drp1 via the mitogen-activated protein kinase pathway, inducing mitochondrial fragmentation. Finally, the AI identified cell line models and patient leukocytes that showed mitochondrial morphological changes. Our study suggested that this AI- based technology enables the highly sensitive detection ofBCR-ABL1-positive cells and early diagnosis of CML.
When Maturation is Not Linear: Brain Oscillatory Activity in the Process of Aging as Measured by Electrophysiology
Authors: Doval Sandra , López-Sanz David , Bruña Ricardo , Cuesta Pablo , Antón-Toro Luis , Taguas Ignacio , Torres-Simón Lucía , Chino Brenda , Maestú Fernando 
Published: July 2023

AbstractChanges in brain oscillatory activity are commonly used as biomarkers both in cognitive neuroscience and in neuropsychiatric conditions. However, little is known about how its profile changes across maturation. Here we use regression models to characterize magnetoencephalography power changes within classical frequency bands in a sample of 792 healthy participants, covering the range 13 to 80 years old.Our results reveal complex, non-linear trajectories of power changes that challenge the linear model traditionally reported. Moreover, these trajectories also exhibit variations across cortical regions. Remarkably, we observed that increases in slow wave activity are associated with a better cognitive performance across the lifespan, as well as with larger gray matter volume for elderlies, while fast wave activity decreases with adulthood.These results suggest that elevated power in low-frequency resting-state activity during aging may reflect a proxy for deterioration, rather than serving as a compensatory mechanism, as usually interpreted. In addition, it enhances our comprehension of both neurodevelopment and the aging process by highlighting the complexity and regional specificity of changes in brain rhythms. Furthermore, our findings have potential implications for understanding cognitive performance and structural integrity.
Enforcing local DNA kinks by sequence-selective trisintercalating oligopeptides of a tricationic porphyrin. A polarizable Molecular Dynamics study
Authors: Gresh Nohad , Hage Krystel El , Lagardère Louis , Brégier Frédérique , Godard Jérémy , Piquemal Jean-Philip , Perrée-Fauvet Martine , Sol Vincent 
Published: July 2023

SummaryBisacridinyl-bisarginyl porphyrin (BABAP) is a trisintercalating derivative of a tricationic porphyrin, formerly designed and synthesized in order to selectively target and photosensitize the ten-base pair palindromic sequence d(CGGGCGCCCG)2. We resorted to the previously derived (Far et al., 2004) lowest energy-minimized (EM) structure of the BABAP complex with this sequence as a starting point. We performed polarizable molecular dynamics (MD) on this complex. It showed, over a 150 ns duration, the persistent binding of the Arg side-chain on each BABAP arm to the two G bases upstream from the central porphyrin intercalation site. We subsequently performed progressive shortenings of the connector chain linking the Arg-Gly backbone to the acridine, from n=6 methylenes to 4, followed by removal of the Gly backbone and further connector shortenings, from n=4 to n=1. These resulted into progressive deformations (‘kinks’) of the DNA backbone. In its most accented kinked structure, the DNA backbone was found to have a close overlap with that of DNA bound toCrerecombinase, with, at the level of one acridine intercalation site, negative roll and positive tilt values consistent with those experimentally found for this DNA at its own kinked dinucleotide sequence. Thus, in addition to their photosensitizing properties, some BABAP derivatives could induce sequence-selective, controlled DNA deformations, which are targets for cleavage by endonucleases or for repair enzymes.
Unravelling vulture avoidance tactic of wind turbines combining empirical and simulation data
Authors: Yohan Sassi , Noémie Ziletti , Olivier Duriez , Benjamin Robira 
Published: July 2023

AbstractThe increase of wind turbine installations to limit climate change may affect bird populations because of collisions with rotor blades. Birds may respond to wind turbine presence along a gradient of behavioural changes: avoiding the wind farm (macro-scale) or only the wind turbines either by anticipating wind turbine locations (meso-scale) or engaging into last-minute flee attempts after late perception (micro-scale). We investigated the flight response at these three spatial scales of 25 adult griffon vultures (Gyps fulvus) equipped with GPS tags over three years when flying in an area including ten wind farms in the Causses, France. At macro-scale, the population foraging range and habitat use revealed that vultures did not avoid wind farms. To investigate avoidance at meso- and micro-scales we focused on the four mostly visited wind farms. We compared vulture flights to null movement models, based on a method allowing us to keep the correlation between flights and topography while creating movement independent of wind turbine locations. At most sites, vultures did not show avoidance behaviour. Yet, simulations from our agent-based model highlighted that the avoidance pattern detected at one wind farm matched with an anticipated avoidance of turbines, probably linked to the presence of a ridge nearby. Overall, our results suggest wind farm-specific responses by soaring birds as a function of the landscape topography. Thus, stakeholders should carefully consider the wind farm location for siting and designing preventive measures (e.g. improve detection of species not able to avoid turbines in switching off on-demand technologies) to reduce collision risk of soaring birds.
Interaction of SCoV-2NSP7orNSP8alone withNSP12causes constriction of the RNA entry channel: Implications for novel RdRp inhibitor drug discovery
Authors: Singh Deepa , Kushwaha Tushar , Kulandaisamy Rajkumar , Kumar Vikas , Baswal Kamal , Tiwari Saras H , Ghorai Arkadyuti , Kumar Manoj , Kumar Saroj , Polamarasetty Aparoy , Sehgal Deepak , Katika Madhumohan R , Gadde Suresh , Côté Marceline , Kayampeta Sarala R , Appaiahgari Mohan B , Inampudi Krishna K 
Published: July 2023

ABSTRACTRNA-dependent RNA polymerase (RdRP) is a critical component of the RNA virus life cycle, including SCoV-2. Among the Coronavirus-encoded proteins, non-structural protein 12 (NSP12) exhibits polymerase activity in collaboration with one unit ofNSP7and two units ofNSP8, constituting the RdRp holoenzyme. While there is abundant information on SCoV-2 RdRp-mediated RNA replication, the influence of interplay amongNSP12, NSP7, andNSP8on template RNA binding and primer extension activity remains relatively unexplored and poorly understood. Here, we recreated a functional RdRp holoenzymein vitrousing recombinant SCoV-2NSP12, NSP7, andNSP8, and established its functional activity. Subsequently, molecular interactions among theNSPs in the presence of a variety of templates and their effects on polymerase activity were studied, wherein we found thatNSP12alone exhibited notable polymerase activity that increased significantly in the presence ofNSP7andNSP8. However, this activity was completely shut down, and the template RNA-primer complex was detached fromNSP12when one of the two cofactors was present. Through computational analysis, we found that the template RNA entry channel was more constricted in the presence of one of the two cofactors, which was relatively more constricted in the presence ofNSP8compared to that in the presence ofNSP7. In conclusion, we report thatNSP7andNSP8together synergise to enhance the activity ofNSP12, but antagonise when present alone. Our findings have implications for novel drug development, and compounds that obstruct the binding ofNSP7orNSP8toNSP12can have lethal effects on viral RNA replication.
Four Individually Identified Paired Dopamine Neurons Signal Taste Punishment in LarvalDrosophila
Authors: Weber Denise , Vogt Katrin , Miroschnikow Anton , Pankratz Michael , Thum Andreas S. 
Published: July 2023

AbstractDopaminergic neurons (DANs) carry out multiple tasks in the brain, including the transmission of information related to rewards and punishments across various animal species. They are responsible for evaluating sensory input, storing resulting associations as memory, and continuously updating them based on their relevance and reliability. Accurate comprehension of the dopaminergic system’s operation necessitates an understanding of the specific functions mediated by individual DANs. To this end, our research employsDrosophilalarvae, which possess approximately 12,000 neurons in their brains, of which only around 1% (approximately 120) are DANs.The presynaptic projections to the mushroom body (MB) - a brain region pivotal for associative olfactory learning in insects - are limited to only eight larval dopaminergic neurons. These DANs are further subdivided into two clusters: the primary protocerebral anterior medial cluster (pPAM) comprises four cells, and the dorsolateral 1 cluster (DL1) comprises the remaining four cells. Our findings confirm previous research that demonstrates that the pPAM DANs innervating the MB’s medial lobe encode for a gustatory sugar reward signal. Furthermore, we have identified four DANs in the DL1 cluster - DAN-c1, DAN-d1, DAN-f1, and DAN-g1 - each of which innervates distinct compartments of the MB peduncle, lateral appendix, and vertical lobe. Optogenetic activation of DAN-f1 and DAN-g1 alone suffices to substitute for punishment. Furthermore, optogenetic inhibition, calcium imaging results and electron microscopy-based reconstruction of all sensory input circuits to the four DL1 DANs demonstrate that each DAN encodes a different aspect of punishment, with DAN-g1 being of central importance for the salt dependent teaching signal.To summarize, our investigation has revealed the existence of a cellular division of labor among larval DANs concerning the transmission of dopaminergic reward (pPAM cluster) and punishment signals (DL1 cluster). Individual DANs in each cluster encode for distinct but partially overlapping aspects of the teaching signal. The striking resemblance in the organizing principle of larval DANs with that of its adult counterpart and the mammalian basal ganglion suggests that there may be a limited number of efficient neural circuit solutions available to address more complex cognitive challenges in nature.
Functional analysis of Cdc20 reveals a critical role of CRY box in mitotic checkpoint signaling
Authors: Zhang Yuqing , Young Rose , Garvanska Dimitriya H , Song Chunlin , Zhai Yujing , Wang Ying , Jiang Hongfei , Fang Jing , Nilsson Jakob , Alfieri Claudio , Zhang Gang 
Published: July 2023

AbstractAccurate chromosome segregation is coordinated by the spindle assembly checkpoint (SAC) through its effector the mitotic checkpoint complex (MCC), to inhibit the anaphase-promoting complex or cyclosome (APC/C). Cdc20 is an essential mitotic regulator since it promotes mitotic exit through activating the APC/C and monitors kinetochore-microtubule attachment through activating the SAC. The proper functioning of Cdc20 requires multiple interactions with APC/C and MCC subunits. To functionally assess each of these interactions within cells requires efficient depletion of endogenous Cdc20, which is highly difficult to achieve by RNAi. Here we generated Cdc20 RNAi sensitive cell lines by CRISPR/Cas9 which display a penetrant metaphase arrest phenotype by a single RNAi treatment. In this null background, we accurately measured the contribution of each known motif of Cdc20 on APC/C and SAC activation. The CRY box, a previously identified degron was found to be critical for the SAC by promoting the MCC formation and stabilizing the interaction between the MCC and APC/C. These data reveal additional regulatory components within the SAC and establish a novel method to interrogate Cdc20 function.
Coordination of rhythmic RNA synthesis and degradation orchestrates 24-hour and 12-hour RNA expression patterns in mouse fibroblasts
Authors: Unruh Benjamin A. , Weidemann Douglas E. , Kojima Shihoko 
Published: July 2023

AbstractCircadian RNA expression is essential to ultimately regulate a plethora of downstream rhythmic biochemical, physiological, and behavioral processes. Both transcriptional and post transcriptional mechanisms are considered important to drive rhythmic RNA expression, however, the extent to which each regulatory process contributes to the rhythmic RNA expression remains controversial. To systematically address this, we monitored RNA dynamics using metabolic RNA labeling technology during a circadian cycle in mouse fibroblasts. We find that rhythmic RNA synthesis is the primary contributor of 24 hr RNA rhythms, while rhythmic degradation is more important for 12 hr RNA rhythms. These rhythms were predominantly regulated byBmal1and/or the core clock mechanism, and interplay between rhythmic synthesis and degradation has a significant impact in shaping rhythmic RNA expression patterns. Interestingly, core clock RNAs are regulated by multiple rhythmic processes and have the highest amplitude of synthesis and degradation, presumably critical to sustain robust rhythmicity of cell-autonomous circadian rhythms. Our study yields invaluable insights into the temporal dynamics of both 24 hr and 12 hr RNA rhythms in mouse fibroblasts.
Sexual coordination in a whole-brain map of prairie vole pair bonding
Authors: Gustison Morgan L. , Muñoz-Castañeda Rodrigo , Osten Pavel , Phelps Steven M. 
Published: July 2023

AbstractSexual bonds are central to the social lives of many species, including humans, and monogamous prairie voles have become the predominant model for investigating such attachments. We developed an automated whole-brain mapping pipeline to identify brain circuits underlying pair-bonding behavior. We identified bonding-related c-Fos induction in 68 brain regions clustered in seven major brain-wide neuronal circuits. These circuits include known regulators of bonding, such as the bed nucleus of the stria terminalis, paraventricular hypothalamus, ventral pallidum, and prefrontal cortex. They also include brain regions previously unknown to shape bonding, such as ventromedial hypothalamus, medial preoptic area and the medial amygdala, but that play essential roles in bonding-relevant processes, such as sexual behavior, social reward and territorial aggression. Contrary to some hypotheses, we found that circuits active during mating and bonding were largely sexually monomorphic. Moreover, c-Fos induction across regions was strikingly consistent between members of a pair, with activity best predicted by rates of ejaculation. A novel cluster of regions centered in the amygdala remained coordinated after bonds had formed, suggesting novel substrates for bond maintenance. Our tools and results provide an unprecedented resource for elucidating the networks that translate sexual experience into an enduring bond.