bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceiving Depth from Texture and Disparity Cues: Evidence for a Non-Probabilistic Account of Cue Integration
Authors: Kemp Jovan T. , Cesanek Evan , Domini Fulvio 
Published: October 2022

AbstractThe fundamental question of how the brain derives 3D information from the inherently ambiguous visual input has been approached during the last two decades with probabilistic theories of 3D perception. Probabilistic models, such as the Maximum Likelihood Estimation (MLE) model, derive from multiple independent depth cues the most probable 3D interpretations. These estimates are then combined by weighing them according to their uncertainty to obtain the most accurate and least noisy estimate. In three experiments we tested an alternative theory of cue integration termed the Intrinsic Constraint (IC) theory. This theory postulates that the visual system does not derive the most probable interpretation of the visual input, but the most stable interpretation amid variations in viewing conditions. This goal is achieved with the Vector Sum model, that represents individual cue estimates as components of a multidimensional vector whose norm determines the combined output. In contrast with the MLE model, individual cue estimates are not accurate, but linearly related to distal 3D properties through a deterministic mapping. In Experiment 1, we measured the cue-specific biases that arise when viewing single-cue stimuli of various simulated depths and show that the Vector Sum model accurately predicts an increase in perceived depth when the same cues are presented together in a combined-cue stimulus. In Experiment 2, we show how Just Noticeable Differences (JNDs) are accounted for by the IC theory and demonstrate that the Vector Sum model predicts the classic finding of smaller JNDs for combined-cue versus single-cue stimuli. Most importantly, this prediction is made through a radical re-interpretation of the JND, a hallmark measure of stimulus discriminability previously thought to estimate perceptual uncertainty. In Experiment 3, we show that biases found in cue-integration experiments cannot be attributed to flatness cues, as assumed by the MLE model. Instead, we show that flatness cues produce no measurable difference in perceived depth for monocular (3A) or binocular viewing (3B), as predicted by the Vector Sum model.
Structural elements facilitate extreme long-range gene regulation at a human disease locus
Authors: Chen Liang-Fu , Long Hannah Katherine , Park Minhee , Swigut Tomek , Boettiger Alistair Nicol , Wysocka Joanna 
Published: October 2022

SummaryEnhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulateSOX9expression at genomic distances over 1.25 megabases. We applied optical reconstruction of chromatin architecture (ORCA) imaging to trace 3D locus topology during PRS-enhancer activation. While we observed pronounced changes in locus topology between cell-types, analysis of single chromatin fiber traces revealed that these ensemble-average differences arise not from the presence of cell-type unique conformations, but through changes in frequency of commonly sampled topologies. We further identified two CTCF-bound elements, internal to theSOX9topologically associating domain, which are positioned near its 3D geometric center and bridge enhancer-promoter contacts in a series of chromatin loops. Ablation of these elements results in diminishedSOX9expression and altered domain-wide contacts. Polymer models with uniform loading across the domain and frequent cohesin collisions recapitulate this multiloop, centrally clustered geometry, suggesting a mechanism for gene regulation over ultralong ranges.Four short bullet points that convey the key message of the paperSOX9domain topology dynamically changes during a developmental transitionStructural elements promote TAD-wide interactions, stripe formation and transcriptionStructural elements are CTCF-dependent and situated centrally in the 3D TAD structurePolymer simulations of multi-loop model best recapitulate topological features
Some Mendelian Disorders could be fixed with a pill? A Structural Bioinformatic investigation
Authors: Bongini Pietro , Iovinelli Daniele , Trezza Alfonso , Bianchini Monica , Spiga Ottavia , Gardini Simone , Niccolai Neri 
Published: October 2022

AbstractIt has been recently suggested that amino acid replacements with Gly can modify the shape of protein surfaces and, hence, protein dynamics and functions. We have browsed ClinVar, the database of all the reported variants of clinical relevance, to identify all the proteins having missense X/Gly mutations that determine Mendelian disorders. We have found 959 benign and 875 pathogenic X/Gly substitutions. Pathogenicity origins were initially searched in the distribution profiles of replaced amino acids. These profiles indicate that Mendelian disorders including Gly-replacements arise mainly from substitutions of amino acids bearing bulky hydrophobic side chains, thus reducing protein core stability. In the case mutated proteins were structurally defined, we could give a deeper insight into pathogenicity mechanisms, checking whether Gly-mutations altered protein shapes, modifying water surface dynamics and, hence, the physiological protein-protein interaction processes. In several cases, indeed, we have found that pathological Gly-mutants present additional surface pockets, suggesting that the new pockets could be the target of a pharmacological strategy for Mendelian disorder remediation.HighlightsClinVar has been scanned to find signals for pathogenicity due to X/Gly mutationsPathogenicity origins of X/Gly replacements have been structurally analyzedX/Gly mutations can create protein surface pockets with binding capabilitiesGly-formed new protein binding sites can be the target for Mendelian disorder curesAI procedures will expand the search for structural damages due to X/Gly mutationsGraphical abstract
Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and non-users
Authors: Taylor Caitlin M. , Furman Daniella J. , Berry Anne S. , White Robert L. , Jagust William J. , D’Esposito Mark , Jacobs Emily G. 
Published: October 2022

AbstractIn rodents and nonhuman primates, sex hormones are powerful modulators of dopamine neurotransmission. Yet little is known about hormonal regulation of the dopamine system in the human brain. Using Positron Emission Tomography (PET), we address this gap by comparing hormonal contraceptive users and non-users across multiple aspects of dopamine function: dopamine synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and dopamine release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n=21 naturally cycling; n=15 hormonal contraceptive users), and men (n=20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater dopamine synthesis capacity than naturally cycling participants, particularly in dorsal caudate, and greater cognitive flexibility. Further, across individuals the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or dopamine release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women’s hormone status. Hormonal contraception (in the form of pill, shot, implant, ring or IUD) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the dopamine system. Findings from this study begin to address this critical gap in women’s health.
Decoy Receptor Fine-tunes Cytokinin Signaling
Authors: Králová Michaela , Kubalová Ivona , Hajný Jakub , Kubiasová Karolina , Gallei Michelle , Semerádová Hana , Novák Ondřej , Benková Eva , Ikeda Yoshihisa , Zalabák David 
Published: October 2022

AbstractHormone perception and signaling pathways play a fundamental regulatory function in cell growth, developmental, and physiological processes in both plant and animal systems. Those pathways are activated by hormone binding to the receptor to trigger cellular responses. Equally important are mechanisms that suppress activated transduction cascades to reset the system. Different mechanisms at the level of hormone biosynthesis and deactivation through degradation, conjugation, and production of repressors that attenuate transduction cascades downstream of receptors are known. In animal systems, decoy receptors have been identified as another important mechanism for fine-tuning the activity of the signaling pathways in processes like inflammatory responses, apoptosis, and blood vessel formation. Decoy receptors recognize and bind specific signaling molecules, but they cannot activate downstream signaling pathways thus providing competitive inhibition. Here we describe the first decoy receptor in plants. We show that the splicing variant ofCRE1/AHK4receptor of cytokinin, a hormone with a key role in the regulation of cell division and meristem maintenance in plants, acts as a decoy receptor to attenuate cytokinin signaling. We propose that this novel mechanism of signaling control applies in processes when modulation of CK signaling is needed.
Negative Mem-Capacitance and Warburg Ionic Filtering in Asymmetric Nanopores
Authors: Farajpour Nasim , Nuwan Y. M. , Bandara D. Y. , Sharma Vinay , Lastra Lauren , Freedman Kevin J. 
Published: October 2022

AbstractThe pervasive model for a solvated, ion-filled nanopore is often a resistor in parallel with a capacitor. However, for conical nanopore geometries, we propose the inclusion of a Warburg-like element which is necessary to explain otherwise anomalous observations such as negative capacitance and lowpass filtering of translocation events (i.e.,a phenomenon we term Warburg filtering). The negative capacitance observed here is characterized as having long equilibration times and memory (i.e.,mem-capacitance) at negative voltages. Next, we used the transient occlusion of the pore using λ-DNA and 10-kbp DNA to test whether events are being attenuated by purely ionic phenomena even when there is sufficient amplifier bandwidth. The inclusion of the Warburg-like element is mechanistically linked to concentration polarization and the activation energy to generate and maintain localized concentration gradients. We conclude the study with a new interpretation of molecular translocations which is not simply based on the pulse-like resistance changes but rather a complex and non-linear storage of ions that changes during molecular transit.
Consolidation-dependent behavioral integration of sequences related to mPFC neural overlap and hippocampal-cortical connectivity
Authors: Tompary Alexa , Davachi Lila 
Published: October 2022

AbstractSystems consolidation theories propose two mechanisms that enable the behavioral integration of related memories: coordinated reactivation between hippocampus and cortex, and the emergence of cortical traces that reflect overlap across memories. However, there is limited empirical evidence that links these mechanisms to the emergence of behavioral integration over time. In two experiments, participants implicitly encoded sequences of objects with overlapping structure. Assessment of behavioral integration showed that response times during a recognition task reflected behavioral priming between objects that never occurred together in time but belonged to overlapping sequences. This priming was consolidation-dependent and only emerged for sequences learned 24 hours prior to the test. Critically, behavioral integration was related to changes in neural pattern similarity in the medial prefrontal cortex and increases in post-learning rest connectivity between the posterior hippocampus and lateral occipital cortex. These findings suggest that memories with a shared predictive structure become behaviorally and neurally integrated through a consolidation-related restructuring of the learned sequences, providing insight into the relationship between different consolidation mechanisms that support behavioral integration.
Non-invasive muscle biopsy: estimation of muscle fibre size from a neuromuscular interface
Authors: Casolo Andrea , Maeo Sumiaki , Balshaw Thomas G. , Lanza Marcel B. , Martin Neil R. W. , Nuccio Stefano , Moro Tatiana , Paoli Antonio , Felici Francesco , Maffulli Nicola , Eskofier Bjoern , Kinfe Thomas M. , Folland Jonathan P. , Farina Dario , Del Vecchio Alessandro 
Published: October 2022

ABSTRACTBecause of the biophysical relation between muscle fibre diameter and the propagation velocity of action potentials along the muscle fibres, motor unit conduction velocity (MUCV) could be a non-invasive index of muscle fibre size in humans. However, the relation between MUCV and fibre size has been only assessed indirectly in animal models and in human patients with invasive intramuscular EMG recordings, or it has been mathematically derived from computer simulations. By combining advanced non-invasive techniques to record motor unit activity in vivo, i.e., high-density surface EMG, with the gold standard technique for muscle tissue sampling, i.e., muscle biopsy, here we investigated the relation between the conduction velocity of populations of motor units identified from the biceps brachii muscle, and muscle fibre diameter. Moreover, we demonstrate the possibility to predict muscle fibre diameter (R2= 0.66) and cross-sectional area (R2= 0.65) from conduction velocity estimates with low systematic bias (~2% and ~4% respectively) and a relatively low margin of individual error (~8% and ~16%, respectively). The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling. The non-invasive nature of high-density surface EMG for the assessment of muscle fibre size may be useful in studies monitoring child development, aging, space and exercise physiology.SIGNIFICANCE STATEMENTOur study explored the relation between the conduction velocity of populations of motor units and muscle fibre size in healthy humans. Our results provide in vivo evidence that a high-density surface EMG-derived physiological parameter, i.e. motor unit conduction velocity, can be adopted to estimate muscle fibre size, without the need of surgical biopsy sampling. Here we propose a neuromuscular interface that opens new perspectives not only in the study of neuromuscular disorders, but also in other fields where the non-invasive and painless determination of muscle fibre and motor unit size becomes a priority, such as in aging, space and exercise physiology.
Molecular Basis for Interferon-mediated Pathogen Restriction in Human Cells
Authors: Matta Sumit K. , Kohio Hinissan P. , Chandra Pallavi , Brown Adam , Doench John G. , Philips Jennifer A. , Ding Siyuan , Sibley L. David 
Published: October 2022

AbstractTo define novel mechanisms for cellular immunity to the intracellular pathogenToxoplasma gondii, we performed a genome-wide CRISPR loss-of-function screen to provide an unbiased assessment of genes important for IFN-γ-dependent growth restriction. We revealed a previously unknown role for the tumor suppressor NF2/Merlin for maximum induction of Interferon Stimulated Genes (ISG), which are positively regulated by the transcription factor IRF-1. We then performed an additional focused ISG-targeted CRISPR screen that identified the host E3 ubiquitin ligase RNF213 as essential for IFN-γ mediated control ofT. gondii. RNF213 mediated ubiquitination of targets on the parasite-containing vacuole and growth restriction in response to IFN-γ in a variety of cell types, thus identifying a conserved factor that plays a prominent role in human cells. Surprisingly, growth inhibition did not require the autophagy protein ATG5, indicating that RNF213 initiates restriction independent of a non-canonical autophagy pathway that has previously been implicated in control ofT. gondii. RNF213 was also important for control of unrelated intracellular pathogens in human cells treated with IFN, as shown here forMycobacterium tuberculosisand Vesicular Stomatitis Virus. Collectively, our findings establish RNF213 as a critical component of cell-autonomous immunity to a broad spectrum of intracellular pathogens in human cells.
The genetic architecture of cerebellar lobules: Insights from the UK Biobank
Authors: Carriόn-Castillo Amaia , Boeckx Cedric 
Published: October 2022

ABSTRACTIn this work we take advantage of opportunities afforded by the UK Biobank, and complement recent studies examining the genetics of cerebellar volume from that vantage point. We examine the genetic underpinnings of the different cerebellar lob(ul)es, possible reflexes of their evolutionary history, and their genetic relation to psychiatric disorders, cognitive performance and the cortical language network as well as to subcortical regions. Overall, our results show that the cerebellum is a heritable structure, not only globally but also at the regional level. However, our analysis also reveals significant variability across different substructures, justifying the need for a more detailed analysis affording greater structural resolution. Aspects of the “neo-cerebellum”, especially lobule VI/Crus I and, to a lesser extent, Crus II, stand out in our analysis.
Hippocampal inactivation during rearing on hind legs impairs spatial memory
Authors: Layfied D.M. , Sidell N. , Blankenberger K. , Newman E.L. 
Published: October 2022

AbstractSpatial memory requires an intact hippocampus. Hippocampal function during epochs of locomotion and quiet rest (e.g., grooming and reward consumption) have been the target of extensive study. However, during navigation rats frequently rear up on to their hind legs and the importance of hippocampal activity during these periods of attentive sampling for spatial memory is unknown. To address this, we tested the necessity of dorsal hippocampal activity during rearing epochs in the study phase of a delayed win-shift task for memory performance in the subsequent test phase. Hippocampal activity was manipulated with closed-loop, bilateral, optogenetic inactivation. Spatial memory accuracy was significantly and selectively reduced when the dorsal hippocampus was inactivated during rearing epochs at encoding. These data show that hippocampal activity during periods of rearing can be important for spatial memory, revealing a novel link between hippocampal function during epochs of rearing and spatial memory.
RALF peptides modulate immune response in the mossPhyscomitrium patens
Authors: Mamaeva Anna , Lyapina Irina , Knyazev Andrey , Golub Nina , Mollaev Timur , Chudinova Elena , Elansky Sergey , Babenko Vladislav V. , Veselovsky Vladimir A. , Klimina Ksenia M. , Gribova Tatiana , Kharlampieva Daria , Lazarev Vassili , Fesenko Igor 
Published: October 2022

AbstractRAPID ALKALINIZATION FACTOR (RALFs) are cysteine-rich peptides that regulate multiple physiological processes in plants. This peptide family has considerably expanded during land plant evolution, but the role of ancient RALFs in modulating stress response is unknown. Here, we used the mossPhyscomitrium patensas a model to gain insight into the role of RALF peptides in coordination of plant growth and stress response in non-vascular plants. The quantitative proteomic analysis revealed concerted downregulation of M6 metalloproteases and some membrane proteins, including those involved in stress response, inPpRALF1, 2and3knockout (KO) lines. We found that knockout ofPpRALF2andPpRALF3genes resulted in increased resistance to bacterial and fungal phytopathogens -Pectobacterium carotovorumandFusarium solani, suggesting the role of these peptides in negative regulation of immune response inP. patens. The comparative transcriptome analysis ofPpRALF3KO and wild type plants underFusarium solaniinfection showed the clear difference in regulation of genes belonging to phenylpropanoid pathway and associated with cell wall modification and biogenesis between these genotypes. The follow-up analysis revealed the role of PpRALF3 in growth regulation under abiotic and biotic stress regulation, which suggests the role of RALFs in responses to different adverse conditions. Thus, our study sheds light on the function of the previously uncharacterized PpRALF3 peptide and gives a clue to ancestral functions of RALF peptides in plant stress response.
Extracellular matrix flow guides in-vitro epithelial morphogenesis
Authors: Fattah Abdel Rahman Abdel , Sgualdino Francesca , Poovathingal Suresh , Davie Kristofer , Baatsen Pieter , Vints Katlijn , Gunko Natalia , Ranga Adrian 
Published: October 2022

AbstractChanges in spatial localization of the extracellular matrix (ECM) are necessary for establishing morphogenesis in multiple developmental contexts. Both ECM motion and tissue deformation require multicellular scale coordination, however the interplay between them remain largely unexplored. Here, we reveal a novel mechanism coupling morphogenetic events and epithelia-driven ECM flowin vitro. We show that exposure to ECM components triggers periodic morphogenesis of dome-shaped structures in human pluripotent stem cell (hPSC) monolayers, driven by directional ECM flow. We show that this flow is initiated by local symmetry breaking events, is driven by microvilli and requires unperturbed flow conditions, microvilli function, and cytoskeletal contractility. Anin silicomodel shows that a reaction-diffusion-like mechanism is responsible for organizing local morphogenesis into global tissue-wide events. We validate this model by predicting changes in cell patterning landscape during mesoderm differentiation, and demonstrate changes in cellular identity by immunohistochemistry and scRNAseq. These results demonstrate that transport of ECM over epithelia, termed ECM flow, is a major contributor in sustaining morphogenesis and differentiation. Ourin vitroapproach suggests that ECM flow may be a broadly conserved mechanism guiding multi-cellular morphogenesis and may be further explored to investigate the role of ECM transport in other model systems.