bioRxiv : the preprint server for biology最新文献

{"title":"A Narrow Range of Transcript-error Rates Across the Tree of Life.","authors":"Weiyi Li, Stephan Baehr, Michelle Marasco, Lauren Reyes, Danielle Brister, Craig S Pikaard, Jean-Francois Gout, Marc Vermulst, Michael Lynch","doi":"10.1101/2023.05.02.538944","DOIUrl":"10.1101/2023.05.02.538944","url":null,"abstract":"<p><p>The expression of genomically-encoded information is not error-free. Transcript-error rates are dramatically higher than DNA-level mutation rates, and despite their transient nature, the steady-state load of such errors must impose some burden on cellular performance. However, a broad perspective on the degree to which transcript-error rates are constrained by natural selection and diverge among lineages remains to be developed. Here, we present a genome-wide analysis of transcript-error rates across the Tree of Life using a modified rolling-circle sequencing method, revealing that the range in error rates is remarkably narrow across diverse species. Transcript errors tend to be randomly distributed, with little evidence supporting local control of error rates associated with gene-expression levels. A majority of transcript errors result in missense errors if translated, and as with a fraction of nonsense transcript errors, these are underrepresented relative to random expectations, suggesting the existence of mechanisms for purging some such errors. To quantitatively understand how natural selection and random genetic drift might shape transcript-error rates across species, we present a model based on cell biology and population genetics, incorporating information on cell volume, proteome size, average degree of exposure of individual errors, and effective population size. However, while this model provides a framework for understanding the evolution of this highly conserved trait, as currently structured it explains only 20% of the variation in the data, suggesting a need for further theoretical work in this area.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81289250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury.","authors":"Tony Marchand, Kemi E Akinnola, Shoichiro Takeishi, Maria Maryanovich, Sandra Pinho, Julien Saint-Vanne, Alexander Birbrair, Thierry Lamy, Karin Tarte, Paul S Frenette, Kira Gritsman","doi":"10.1101/2023.01.12.523842","DOIUrl":"10.1101/2023.01.12.523842","url":null,"abstract":"<p><p>Skeletal stem cells have been isolated from various tissues, including periosteum and bone marrow, where they exhibit key functions in bone biology and hematopoiesis, respectively. The role of periosteal skeletal stem cells in bone regeneration and healing has been extensively studied, but their ability to contribute to the bone marrow stroma is still under debate. In the present study, we characterized a whole bone transplantation model that mimics the initial bone marrow necrosis and fatty infiltration seen after injury. Using this model and a lineage tracing approach, we observed the migration of periosteal skeletal stem cells into the bone marrow after transplantation. Once in the bone marrow, periosteal skeletal stem cells are phenotypically and functionally reprogrammed into bone marrow mesenchymal stem cells that express high levels of hematopoietic stem cell niche factors such as Cxcl12 and Kitl. In addition, using <i>ex vivo</i> and <i>in vivo</i> approaches, we found that periosteal skeletal stem cells are more resistant to acute stress than bone marrow mesenchymal stem cells. These results highlight the plasticity of periosteal skeletal stem cells and their potential role in bone marrow regeneration after bone marrow injury.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9333505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain using 7 Tesla fMRI.","authors":"Jiahe Zhang, Danlei Chen, Philip Deming, Tara Srirangarajan, Jordan Theriault, Philip A Kragel, Ludger Hartley, Kent M Lee, Kieran McVeigh, Tor D Wager, Lawrence L Wald, Ajay B Satpute, Karen S Quigley, Susan Whitfield-Gabrieli, Lisa Feldman Barrett, Marta Bianciardi","doi":"10.1101/2023.07.20.548178","DOIUrl":"10.1101/2023.07.20.548178","url":null,"abstract":"<p><p>The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, called allostasis. In support of allostasis, the brain continually models the sensory state of the body, called interoception. We replicated and extended a large-scale system supporting allostasis and interoception in the human brain using ultra-high precision 7 Tesla functional magnetic resonance imaging (fMRI) (<i>N</i> = 90), improving the precision of subgenual and pregenual anterior cingulate topography combined with extensive brainstem nuclei mapping. We observed over 90% of the anatomical connections published in tract-tracing studies in non-human animals. The system also included regions of dense intrinsic connectivity broadly throughout the system, some of which were identified previously as part of the backbone of neural communication across the brain. These results strengthen previous evidence for a whole-brain system supporting the modeling and regulation of the internal milieu of the body.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/d3/nihpp-2023.07.20.548178v1.PMC10401932.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vectorized instructive signals in cortical dendrites during a brain-computer interface task.","authors":"Valerio Francioni, Vincent D Tang, Enrique H S Toloza, Norma J Brown, Mark T Harnett","doi":"10.1101/2023.11.03.565534","DOIUrl":"10.1101/2023.11.03.565534","url":null,"abstract":"<p><p>Vectorization of teaching signals is a key element of virtually all modern machine learning algorithms, including backpropagation, target propagation and reinforcement learning. Vectorization allows a scalable and computationally efficient solution to the credit assignment problem by tailoring instructive signals to individual neurons. Recent theoretical models have suggested that neural circuits could implement single-phase vectorized learning at the cellular level by processing feedforward and feedback information streams in separate dendritic compartments^1-5. This presents a compelling, but untested, hypothesis for how cortical circuits could solve credit assignment in the brain. We leveraged a neurofeedback brain-computer interface (BCI) task with an experimenter-defined reward function to test for vectorized instructive signals in dendrites. We trained mice to modulate the activity of two spatially intermingled populations (4 or 5 neurons each) of layer 5 pyramidal neurons in the retrosplenial cortex to rotate a visual grating towards a target orientation while we recorded GCaMP activity from somas and corresponding distal apical dendrites. We observed that the relative magnitudes of somatic versus dendritic signals could be predicted using the activity of the surrounding network and contained information about task-related variables that could serve as instructive signals, including reward and error. The signs of these putative teaching signals both depended on the causal role of individual neurons in the task and predicted changes in overall activity over the course of learning. Furthermore, targeted optogenetic perturbation of these signals disrupted learning. These results provide the first biological evidence of a vectorized instructive signal in the brain, implemented via semi-independent computation in cortical dendrites, unveiling a potential mechanism for solving credit assignment in the brain.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10635122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92158003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic RNA G-quadruplex Accumulation in Aging and Alzheimer's Disease.","authors":"Lena Kallweit, Eric D Hamlett, Hannah Saternos, Anah Gilmore, Ann-Charlotte Granholm, Scott Horowitz","doi":"10.1101/2023.10.02.560545","DOIUrl":"10.1101/2023.10.02.560545","url":null,"abstract":"<p><strong>Introduction: </strong>As the world population ages, new molecular targets in aging and Alzheimer's Disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored. METHODS: In this study, we examined human hippocampal <i>postmortem</i> tissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD.</p><p><strong>Results: </strong>We found that rG4 immunostaining strongly increased in the hippocampus with both age and with AD severity. We further found that neurons with accumulation of phospho-tau immunostaining contained rG4s, that rG4 structure can drive tau aggregation, and that rG4 staining density depended on APOE genotype in the human tissue examined.</p><p><strong>Discussion: </strong>Combined with previous studies showing the dependence of rG4 structure on stress and the extreme power of rG4s at oligomerizing proteins, we propose a model of neurodegeneration in which chronic rG4 formation is linked to proteostasis collapse. These morphological findings suggest that further investigation of RNA structure in neurodegeneration is a critical avenue for future treatments and diagnoses.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592952/pdf/nihpp-2023.10.02.560545v1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.","authors":"Ching-Chieh Chou, Ryan Vest, Miguel A Prado, Joshua Wilson-Grady, Joao A Paulo, Yohei Shibuya, Patricia Moran-Losada, Ting-Ting Lee, Jian Luo, Steven P Gygi, Jeffery W Kelly, Daniel Finley, Marius Wernig, Tony Wyss-Coray, Judith Frydman","doi":"10.1101/2023.03.27.534444","DOIUrl":"10.1101/2023.03.27.534444","url":null,"abstract":"<p><p>Aging is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in AD brains remain elusive. Here, we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains aging hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-Tau and Aβ, resembling those in AD patient and APP mouse brains. Quantitative tNeuron proteomics identify aging and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome-lysosomal components. Lysosomal deficits in aged tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Supporting lysosomal deficits' centrality in AD, compounds ameliorating lysosomal function reduce Aβ deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of aging and AD.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9265432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automatic multisensory integration follows subjective confidence rather than objective performance.","authors":"Yi Gao, Kai Xue, Brian Odegaard, Dobromir Rahnev","doi":"10.1101/2023.06.07.544029","DOIUrl":"10.1101/2023.06.07.544029","url":null,"abstract":"<p><p>It is well known that sensory information from one modality can automatically affect judgments from a different sensory modality. However, it remains unclear what determines the strength of the influence of an irrelevant sensory cue from one modality on a perceptual judgment for a different modality. Here we test whether the strength of multisensory impact by an irrelevant sensory cue depends on participants' objective accuracy or subjective confidence for that cue. We created visual motion stimuli with low vs. high overall motion energy, where high-energy stimuli yielded higher confidence but lower accuracy in a visual-only task. We then tested the impact of the low- and high-energy visual stimuli on auditory motion perception. We found that the high-energy visual stimuli influenced the auditory motion judgments more strongly than the low-energy visual stimuli, consistent with their higher confidence but contrary to their lower accuracy. A computational model assuming common principles underlying confidence reports and multisensory integration captured these effects. Our findings show that automatic multisensory integration follows subjective confidence rather than objective performance and suggest the existence of common computations across vastly different stages of perceptual decision making.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9666325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDZ Domains from the Junctional Proteins Afadin and ZO-1 Act as Mechanosensors.","authors":"Vipul T Vachharajani, Matthew P DeJong, Soumya Dutta, Jonathan Chapman, Eashani Ghosh, Abhishek Singharoy, Alexander R Dunn","doi":"10.1101/2023.09.24.559210","DOIUrl":"10.1101/2023.09.24.559210","url":null,"abstract":"<p><p>Intercellular adhesion complexes must withstand mechanical forces to maintain tissue cohesion while also retaining the capacity for dynamic remodeling during tissue morphogenesis and repair. Many cell-cell adhesion complexes contain at least one PSD95/Dlg/ZO-1 (PDZ) domain situated between the adhesion molecule and the actin cytoskeleton. However, PDZ-mediated interactions are characteristically nonspecific, weak, and transient, with multiple binding partners per PDZ domain, micromolar dissociation constants, and bond lifetimes of seconds or less. Here, we demonstrate that the bonds between the PDZ domain of the cytoskeletal adaptor protein afadin and the intracellular domains of the adhesion molecules nectin-1 and JAM-A form molecular catch bonds that reinforce in response to mechanical load. In contrast, the bond between the PDZ3-SH3-GUK (PSG) domain of the cytoskeletal adaptor ZO-1 and the JAM-A intracellular domain becomes dramatically weaker in response to ∼2 pN of load, the amount generated by single molecules of the cytoskeletal motor protein myosin II. Thus, physiologically relevant forces can exert dramatic and opposite effects on the stability of two of the major linkages between cell-cell adhesion proteins and the F-actin cytoskeleton. Our data demonstrate that that PDZ domains can serve as force-responsive mechanical anchors at cell-cell adhesion complexes. More broadly, our findings suggest that mechanical force may serve as a previously unsuspected regulator of the hundreds of PDZ-ligand interactions present in animal cells.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BIBSNet: A Deep Learning Baby Image Brain Segmentation Network for MRI Scans.","authors":"Timothy J Hendrickson, Paul Reiners, Lucille A Moore, Jacob T Lundquist, Begim Fayzullobekova, Anders J Perrone, Erik G Lee, Julia Moser, Trevor K M Day, Dimitrios Alexopoulos, Martin Styner, Omid Kardan, Taylor A Chamberlain, Anurima Mummaneni, Henrique A Caldas, Brad Bower, Sally Stoyell, Tabitha Martin, Sooyeon Sung, Ermias A Fair, Kenevan Carter, Jonathan Uriarte-Lopez, Amanda R Rueter, Essa Yacoub, Monica D Rosenberg, Christopher D Smyser, Jed T Elison, Alice Graham, Damien A Fair, Eric Feczko","doi":"10.1101/2023.03.22.533696","DOIUrl":"10.1101/2023.03.22.533696","url":null,"abstract":"<p><strong>Objectives: </strong>Brain segmentation of infant magnetic resonance (MR) images is vitally important for studying typical and atypical brain development. The infant brain undergoes many changes throughout the first years of postnatal life, making tissue segmentation difficult for most existing algorithms. Here we introduce a deep neural network BIBSNet ( <b>B</b> aby and <b>I</b> nfant <b>B</b> rain <b>S</b> egmentation Neural <b>Net</b> work), an open-source, community-driven model for robust and generalizable brain segmentation leveraging data augmentation and a large sample size of manually annotated images.</p><p><strong>Experimental design: </strong>Included in model training and testing were MR brain images from 90 participants with an age range of 0-8 months (median age 4.6 months). Using the BOBs repository of manually annotated real images along with synthetic segmentation images produced using SynthSeg, the model was trained using a 10-fold procedure. Model performance of segmentations was assessed by comparing BIBSNet, joint label fusion (JLF) inferred segmentation to ground truth segmentations using Dice Similarity Coefficient (DSC). Additionally, MR data along with the FreeSurfer compatible segmentations were processed with the DCAN labs infant-ABCD-BIDS processing pipeline from ground truth, JLF, and BIBSNet to further assess model performance on derivative data, including cortical thickness, resting state connectivity and brain region volumes.</p><p><strong>Principal observations: </strong>BIBSNet segmentations outperforms JLF across all regions based on DSC comparisons. Additionally, with processed derived metrics, BIBSNet segmentations outperforms JLF segmentations across nearly all metrics.</p><p><strong>Conclusions: </strong>BIBSNet segmentation shows marked improvement over JLF across all age groups analyzed. The BIBSNet model is 600x faster compared to JLF, produces FreeSurfer-compatible segmentation labels, and can be easily included in other processing pipelines. BIBSNet provides a viable alternative for segmenting the brain in the earliest stages of development.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of bidirectional network cores in the brain with perceptual awareness and cognition.","authors":"Tomoya Taguchi, Jun Kitazono, Shuntaro Sasai, Masafumi Oizumi","doi":"10.1101/2024.04.30.591001","DOIUrl":"10.1101/2024.04.30.591001","url":null,"abstract":"<p><p>The brain comprises a complex network of interacting regions. To understand the roles and mechanisms of this intricate network, it is crucial to elucidate its structural features related to cognitive functions. Recent empirical evidence suggests that both feedforward and feedback signals are necessary for conscious perception, emphasizing the importance of subnetworks with bidirectional interactions. However, the link between such subnetworks and conscious perception remains unclear due to the complexity of brain networks. In this study, we propose a framework for extracting subnetworks with strong bidirectional interactions-termed the \"cores\" of a network-from brain activity. We applied this framework to resting-state and task-based human fMRI data from participants of both sexes to identify regions forming strongly bidirectional cores. We then explored the association of these cores with conscious perception and cognitive functions. We found that the extracted central cores predominantly included cerebral cortical regions rather than subcortical regions. Additionally, regarding their relation to conscious perception, we demonstrated that the cores tend to include regions previously reported to be affected by electrical stimulation that altered conscious perception, although the results are not statistically robust due to the small sample size. Furthermore, in relation to cognitive functions, based on a meta-analysis and comparison of the core structure with a cortical functional connectivity gradient, we found that the central cores were related to unimodal sensorimotor functions. The proposed framework provides novel insights into the roles of network cores with strong bidirectional interactions in conscious perception and unimodal sensorimotor functions.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}