Biology subjects

Yu, Q.

Publications and source records attributed to Yu, Q..

187 records · Page 11Linked to original sources

bioRxiv2018

Adopting Literature-based Discovery on Rehabilitation Therapy Repositioning for Stroke

Stroke is a common disabling disease severely affecting the daily life of the patients. There is evidence that rehabilitation therapy can improve the movement function. However, there are no clear guidelines that identify specific, effective rehabilitation therapy schemes, and the development of new rehabilitation techniques has been fairly slow. One informatics translational approach, called ABC model in Literature-based Discovery, was used to mine an existing rehabilitation candidate which is most likely to be repositioned for stroke. As in the classic ABC model originated from Don Swanson, we built the internal links of stroke (A), assessment scales (B), rehabilitation therapies (C) in PubMed relating to upper limb function measurements for stroke patients. In the first step, with E-utility we retrieved both stroke related assessment scales and rehabilitation therapies records, and complied two datasets called Stroke_Scales and Stroke_Therapies, respectively. In the next step, we crawled all rehabilitation therapies co-occurred with the Stroke_Theapies, named as All_Therapies. Therapies that were already included in Stroke_Therapies were deleted from All_Therapies, so that the remaining therapies were the potential rehabilitation therapies, which could be repositioned for stroke after subsequent filtration by manual check. We identified the top ranked repositioning rehabilitation therapy following by subsequent clinical validation. Hand-arm bimanual intensive training (HABIT) ranked the first in our repositioning rehabilitation therapies list, with the most interaction links with Stroke_Scales. HABIT showed a significant improvement in clinical scores on assessment scales of Fugl-Meyer Assessment and Action Research Arm Test in the clinical validation on upper limb function for acute stroke patients. Based on the ABC model and clinical validation of the results, we put forward that HABIT as a promising rehabilitation therapy for stroke, which shows that the ABC model is an effective text mining approach for rehabilitation therapy repositioning. The results seem to be promoted in clinical knowledge discovery.\n\nAuthor SummaryIn the present study, we proposed a text mining approach to mining terms related to disease, rehabilitation therapy, and assessment scale from literature, with a subsequent ABC inference analysis to identify relationships of these terms across publications. The clinical validation demonstrated that our approach can be used to identify potential repositioning rehabilitation therapy strategies for stroke. Specifically, we identified a promising rehabilitation method called HABIT previously used in pediatric congenital hemiplegia. A subsequent clinical trial confirmed this as a highly promising rehabilitation therapy for stroke.

bioinformatics↗

bioRxiv2018

CryoEM structures of MDA5-dsRNA filaments at different stages of ATP hydrolysis

Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type-I-interferon signaling platform. Here, we determined cryoEM structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs, at resolutions sufficient to build and refine atomic models. The structures identify the filament forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.\n\neTOCStructures of MDA5 bound to double-stranded RNA reveal a flexible, predominantly hydrophobic filament forming interface. The filaments have variable helical twist. Structures determined with ATP and transition state analogs show how the ATPase cycle is coupled to changes in helical twist, the mode of RNA binding and the length of the RNA footprint of MDA5.\n\nHighlightsO_LICryoEM structures of MDA5-dsRNA filaments determined for three catalytic states\nC_LIO_LIFilament forming interfaces are flexible and predominantly hydrophobic\nC_LIO_LIMutation of filament-forming residues can cause loss or gain of IFN-{beta} signaling\nC_LIO_LIATPase cycle is coupled to changes in filament twist and size of the RNA footprint\nC_LI

immunology↗

bioRxiv2018

The Role of Location-Context Binding in Nonspatial Visual Working Memory

Successful retrieval of an item from visual working memory (VWM) often requires an associated representation of the trial-unique context in which that item was presented. We dissociated the effects on fMRI signal of memory load versus context binding by comparing nonspatial VWM for one oriented bar vs. three bars individuated by their location on the screen vs. three items drawn from different categories (orientation, color, and luminance), for which location context was superfluous. Delay-period fMRI signal in frontal and parietal cortex was sensitive to stimulus homogeneity rather than to memory load per se. Behavioral performance revealed a broad range in swap errors, an index of the efficacy of context binding, and subjects were classified as high swap error or low swap error. During the delay period, the strength of the representation of stimulus location in parietal cortex predicted individual differences in swap errors. During recall, activity in occipital cortex revealed two dissociable neural correlates of context binding: high swap-error subjects allocated less spatial attention to the location of the probed item and more spatial attention the location of non-probed items; high swap-error subjects also represented the orientation of the probed item more weakly and the orientation of nonprobed items more strongly. Our results suggest context binding is a computation that influences all stages of VWM processing.\n\nSignificance StatementAlthough we often think of the contents of visual working memory (VWM) as representations of the items that need to be remembered, each items trial-unique context is also critical for successful performance. For example, if one observes a red, then a black, then a blue car passing through an intersection, vivid memory for the colors, alone, wouldnt allow one to execute the instruction \"Follow the first of the three cars that just drove by.\" Although manipulating load is commonly assumed to isolate storage functions, requiring memory for multiple items drawn from the same category also increases demands on the context binding needed to individuate these items. This experiment tracked the influence of context binding on VWM stimulus processing.

neuroscience↗

bioRxiv2018

Different states of priority recruit different neural codes in visual working memory

We tracked the neural representation of the orientation and the location of stimuli held in working memory at different levels of priority (\"attended\" and \"unattended\" memory items -- AMI and UMI), using multivariate inverted encoding models of human fMRI. Although representation of the orientation of the AMI and of the UMI could be reconstructed in several brain regions, including in early visual and parietal regions, the identity of the UMI was actively represented in early visual cortex in a distinct \"reversed\" code, suggesting this region as a site of the focus of attention to nonspatial stimulus information. The location of stimuli was also broadly represented, although only in parietal cortex was the location of the UMI represented in a reversed code. Our results suggest that a common recoding operation may be engaged, across stimulus dimensions and brain areas, to retain information in working memory while outside the focus of attention.

neuroscience↗

bioRxiv2018

Construction of high-density genetic maps and detection of QTLs associated with Huanglongbing infection in citrus

No true resistance to Huanglongbing (HLB), a citrus disease associated with infection of Candidatus Liberibacter asiaticus (CLas), is found within commercial citrus cultivars, though trifoliate orange (Poncirus trifoliata) has been described as resistant or tolerant. Through genotyping an intergeneric F1 population by Genotyping-by-Sequencing, high-density SNP-based genetic maps were constructed separately for trifoliate orange and sweet orange (Citrus sinensis). Both genetic maps exhibited high synteny and high coverage of citrus genome. After exposure to intense HLB pressure for two years, Ct value of qPCR for CLas detection in leaves throughout ten time points during the next three years was above 35 in trifoliate oranges, under 28 in sweet oranges, and ranged from 24 to 38 and exhibited obvious segregation among progenies. Phenotypic data of percentage of healthy trees showed high correlation with the Ct value. By mapping the two traits at all time points, a total of nine clusters of QTLs were detected, of which five, respectively located on LG-t7 and LG-t8 of trifoliate orange map and LG-s3, LG-s5 and LG-s9 of sweet orange map, collectively explained a major part of the phenotypic variation. This study provides a starting point for citrus breeding to support long-term control of this devastating disease.\n\nHighlight1). Constructed the first high-density genetic map for trifoliate orange (Poncirus trifoliata)\n\n2). The first report on identification of QTLs related to Huanglongbing in citrus.\n\nAbbreviations

genetics↗

bioRxiv2017

Endodermal differentiation is reconstructed by coordination of two parallel signaling systems derived from the stele in roots

The plant roots represent the exquisitely controlled cell fate map in which different cell types undergo a complete status transition from stem cell division and initial fate specification, to the terminal differentiation. The endodermis is initially specified in meristem but further differentiates to form Casparian strips (CSs), the apoplastic barrier in the mature zone for the selective transport between stele and outer tissues, and thus is regarded as plant inner skin. In the Arabidopsis thaliana root the transcription factors SHORTROOT (SHR) regulate asymmetric cell division in cortical initials to separate endodermal and cortex cell layer. In this paper, we utilized synthetic approach to examine the reconstruction of fully functional Casparian strips in plant roots. Our results revealed that SHR serves as a master regulator of a hierarchical signaling cascade that, combined with stele-derived small peptides, is sufficient to rebuild the functional CS in non-endodermal cells. This is a demonstration of the deployment of two parallel signaling systems, in which both apoplastic and symplastic communication were employed, for coordinately specifying the endodermal cell fate.

plant biology↗

bioRxiv2017

Identification of functional modules relevant to human neuron maturation and generation of neuron maturity index

BackgroundNeuron maturation is a critical process in neurogenesis, during which neurons gain their morphological, electrophysiological and molecular characteristics for their functions as the central components of the nervous system.\n\nResultsTo better understand the molecular changes during this process, we combined the protein-protein interaction network and public single cell RNA-seq data of mature and immature neurons to identify functional modules relevant to the neuron maturation process in humans. The analysis resulted in 33 discriminable modules which participate in varied functions including energy consumption, synaptic functions and housekeeping functions such as translation and splicing. Based on the identified modules, we trained a neuron maturity index (NMI) model for the quantification of maturation states of single neurons or purified bulk neurons. Applied to multiple single neuron transcriptome data sets of neuron development in humans and mice, the NMI model made estimation of neuron maturity states which were significantly correlated with the neuron maturation trajectories in both species, implying the reproducibility and conservation of the identified transcriptome transition.\n\nConclusionWe identified 33 functional modules whose activities were significantly correlated with single neuron maturity states, which may play important roles in the neuron maturation process.

bioinformatics↗