Biology subjects

Ye, Q.

Publications and source records attributed to Ye, Q..

10 recordsLinked to original sources

bioRxiv2018

Individual susceptibility to TMS affirms the precuneual role in meta-memory upon recollection

BackgroundA recent virtual-lesion study using inhibitory repetitive transcranial magnetic stimulation (rTMS) confirmed the causal behavioral relevance of the precuneus in the evaluation of ones own memory performance (aka mnemonic metacognition).\n\nObjectiveThis studys goal is to elucidate how these TMS-induced neuromodulatory effects might relate to the neural correlates and be modulated by individual anatomical profiles in relation to meta-memory.\n\nMethodsIn a within-subjects design, we assessed the impact of 20-min rTMS over the precuneus, compared to the vertex, across three magnetic resonance imaging (MRI) neuro-profiles on 18 healthy subjects during a memory versus a perceptual task.\n\nResultsTask-based functional MRI revealed that BOLD signal magnitude in the precuneus is associated with variation in individual meta-memory efficiency, and such correlation diminished significantly following TMS targeted at the precuneus. Moreover, individuals with higher resting-state functional connectivity (rs-fcMRI) between the precuneus and the hippocampus, or smaller grey matter volume in the stimulated precuneal region exhibit considerably higher vulnerability to the TMS effect. These effects were not observed in the perceptual domain.\n\nConclusionWe provide compelling evidence in outlining a possible circuit encompassing the precuneus and its mnemonic midbrain neighbor the hippocampus at the service of realizing our meta-awareness during memory recollection of episodic details.\n\nHighlightsO_LITMS on precuneus reduces meta-memory ability during memory retrieval.\nC_LIO_LITMS disrupts the correlation between BOLD activity and meta-memory ability.\nC_LIO_LITMS effect is modulated by rs-fcMRI between precuneus and hippocampus.\nC_LIO_LIIndividuals with greater precuneal grey matter volume more immune to TMS effect.\nC_LI

neuroscience↗

bioRxiv2018

A conserved mechanism for meiotic chromosome organization through self-assembly of a filamentous chromosome axis core

The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that \"axis core proteins\" from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify motifs in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core complexes form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture and role in axis assembly and recombination control. We propose that the meiotic chromosome axis self-assembles through cooperative interactions between dynamic DNA loop-extruding cohesin complexes and the filamentous axis core, then serves as a platform for chromosome organization, recombination, and synaptonemal complex assembly.

biochemistry↗

bioRxiv2018

Extensive Expansion of the Speedy gene Family in Homininae and Functional Differentiation in Humans

BackgroundThe cell cycle plays important roles in physiology and disease. The Speedy/RINGO family of atypical cyclins regulates the cell cycle. However, the origin, evolution and function of the Speedy family are not completely understood. Understanding the origins and evolution of Speedy family would shed lights on the evolution of complexity of cell cycles in eukaryotes.\n\nResultsHere, we performed a comprehensive identification of Speedy genes in 258 eukaryotic species and found that the Speedy subfamily E was extensively expanded in Homininae, characterized by emergence of a low-Spy1-identify domain. Furthermore, the Speedy gene family show functional differentiation in humans and have a distinct expression pattern, different regulation network and co-expressed gene networks associated with cell cycle and various signaling pathways. Expression levels of the Speedy gene family are prognostic biomarkers among different cancer types.\n\nConclusionsOverall, we present a comprehensive view of the Speedy genes and highlight their potential function.

evolutionary biology↗

bioRxiv2018

Sense-antisense gene overlap causes evolutionary retention of the few introns in Giardia genome and the implications

BackgroundIt is widely accepted that the last eukaryotic common ancestor (LECA) and early eukaryotes were intron-rich and intron loss dominated subsequent evolution, thus the presence of only very few introns in some modern eukaryotes must be the consequence of massive loss. But it is striking that few eukaryotes were found to have completely lost introns. Despite extensive research, the causes of massive intron losses remain elusive, and actually the reverse question - how the few introns are retained under the pressure of loss is equally significant but was rarely studied, except that it was conjectured that the essential functions of some introns prevent their loss. The extremely few (eight) spliceosome-mediated cis-spliced introns in the relatively simple genome of Giardia lamblia provide an excellent opportunity to explore this question.\n\nResultsOur investigation of the intron-containing genes and introns in Giardia found three types of intron distribution patterns: ancient intron in ancient gene, relatively new intron in ancient gene, and relatively new intron in relatively new gene, which can reflect to some extent the dynamic evolution of introns in Giardia. Not finding any special features or functional importance of these introns responsible for the retention, we noticed and experimentally verified that some intron-containing genes form sense-antisense gene pairs with functional genes on their complementary strands, and that the introns just reside in the overlapping regions.\n\nConclusionsIn Giardias evolution, despite constant pressure of intron loss, intron gain can still occur in both ancient and newly-evolved genes, but only a few introns have been retained; the evolutionary retention of introns is most likely not due to the functional constraint of the introns themselves but the causes outside of introns, such as the constraints imposed by other genomic functional elements overlapping with the introns. These findings can not only provide some clues to find new genomic functional elements -- in the areas overlapping with introngs, but suggest that \"functional constraint\" of introns may not be necessarily directly associated with intron loss and gain, or that the real functions or the way of functioning of introns are probably still outside of our current knowledge.

genomics↗

bioRxiv2018

Reduced but not Enhanced Default Mode Network Functional Connectivity in Major Depressive Disorder: Evidence from 25 Cohorts in the REST-meta-MDD Project

Major Depressive Disorder (MDD) is common and disabling, but its neural pathophysiology remains unclear. Functional brain network studies in MDD have largely had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. The 25 research groups in China composing the REST-meta-MDD Project contributed R-fMRI data of 1,300 patients with MDD and 1,128 normal controls (NCs). The data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to show increased FC in MDD. We found decreased instead of increased DMN FC when comparing 848 MDDs with 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naive MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDDs. Exploratory analyses also revealed alterations of local intrinsic activity in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates treatment response. This manuscript announces the publicly available resting-state fMRI indices of the REST-meta-MDD consortium shared via the R-fMRI Maps Project.\n\nSIGNIFICANCE STATEMENTFunctional connectivity within the default mode network in major depressive disorder patients has been frequently reported abnormal but with contradicting directions in previous small sample size studies. By creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments.

neuroscience↗

bioRxiv2018

Enhancement of Macrophage Function by the Antimicrobial Peptide Sublancin Protects Mice from Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen responsible for community and hospital bacterial infections. Sublancin, a glocosylated antimicrobial peptide isolated from Bacillus subtilis 168, possesses anti-bacterial infective effects. In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1{beta}, IL-6, TNF- and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophages activation by sublancin was found to be mediated through the TLR4 and the NF-{kappa}B and MAPK signaling pathways. Moreover, oral administration of sublancin increased the frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes. The protective activity of sublancin was associated with in vivo augmenting phagocytotic activity of peritoneal macrophages and partly improving T cell-mediated immunity. Macrophages thus represent a potentially pivotal and novel target for future development of innate defense regulator therapeutics againt S. aureus infection.

immunology↗

bioRxiv2018

Deciphering signaling specificity with interpretable deep neural networks

Protein kinase phosphorylation is a prevalent post-translational modification (PTM) regulating protein function and transmitting signals throughout the cell. Defective signal transductions, which are associated with protein phosphorylation, have been revealed to link to many human diseases, such as cancer. Defining the organization of the phosphorylation-based signaling network and, in particular, identifying kinase-specific substrates can help reveal the molecular mechanism of the signaling network. Here, we present DeepSignal, a deep learning framework for predicting the substrate specificity for kinase/SH2 sequences with or without mutations. Empowered by the memory and selection mechanism of recurrent neural network, DeepSignal can identify important specificity-defining residues to predict kinase specificity and changes upon mutations. Evaluated on several public benchmark datasets, DeepSignal significantly outperforms current methods on predicting substrate specificity on both kinase and SH2 domains. Further analysis in The Cancer Genome Atlas (TCGA) demonstrated that DeepSignal is able to aggregate mutations on both kinase/SH2 domains and substrates to quantify binding specificity changes, predict cancer genes related to signaling transduction, and identify novel perturbed pathways.\n\nAvailabilityImplementation of DeepSignal is at https://github.com/luoyunan/DeepSignal

bioinformatics↗

bioRxiv2018

Causal evidence for mnemonic metacognition in human precuneus

Metacognition is the capacity to introspectively monitor and control ones own cognitive processes. Previous anatomical and functional neuroimaging findings implicated the important role of precuneus in metacognition processing, especially during mnemonic tasks. However, the issue of whether this medial parietal cortex is a domain-specific region that supports mnemonic metacognition remains controversial. Here, we focally disrupted this parietal area with repetitive transcranial magnetic stimulation in healthy participants of both sexes, seeking to ascertain its functional necessity for metacognition for memory versus perceptual decisions. Perturbing the precuneal activity impaired the metacognitive efficiency selectively in the memory judgment of temporal-order, but not in perceptual discrimination. Moreover, the correlation in individuals metacognitive efficiency between the domains disappeared when the precuneus was perturbed. Together with the previous finding that lesion to the anterior prefrontal cortex impairs perceptual but not mnemonic metacognition, we double dissociated the macro-anatomical underpinnings for the two kinds of metacognitive capacity in an interconnected network of brain regions.\n\nSIGNIFICANCE STATEMENTTheories on the neural basis of metacognition have thus far largely centered on the role of prefrontal cortex. Here we refined the theoretical framework through characterizing a unique precuneal involvement in mnemonic metacognition with a noninvasive but inferentially powerful method: transcranial magnetic stimulation. By quantifying meta-cognitive efficiency across two distinct domains (memory vs. perception) that are matched for stimulus characteristics, we reveal an instrumental - and highly selective - role of the precuneus in mnemonic metacognition. These causal evidence corroborate ample clinical reports that parietal lobe lesions often produce inaccurate self-reports of confidence in memory recollection and establish that the precuneus as a nexus for the introspective ability to evaluate the success of memory judgment in humans.

neuroscience↗

bioRxiv2018

Locally distributed abstraction of temporal distance in human parietal cortex

An enduring puzzle in the neuroscience of memory is how the brain parsimoniously situates past events by their order in relation to time. By combining functional MRI, and representational similarity analysis, we reveal a multivoxel representation of time intervals separating pairs of episodic event-moments in the posterior medial memory system, especially when the events were experienced within a similar temporal context. We further show such multivoxel representations to be vulnerable to disruption through targeted repetitive transcranial magnetic stimulation and that perturbation to the mnemonic abstraction alters the neural--behavior relationship across the wider parietal memory network. Our findings establish a mnemonic \"pattern-based\" code of temporal distances in the human brain, a fundamental neural mechanism for supporting the temporal structure of past events, assigning the precuneus as a locus of flexibly effecting the manipulation of physical time during episodic memory retrieval.

neuroscience↗

bioRxiv2017

Learning Structural Motif Representations For Efficient Protein Structure Search

MotivationUnderstanding the relationship between protein structure and function is a fundamental problem in protein science. Given a protein of unknown function, fast identification of similar protein structures from the Protein Data Bank (PDB) is a critical step for inferring its biological function. Such structural neighbors can provide evolutionary insights into protein conformation, interfaces and binding sites that are not detectable from sequence similarity. However, the computational cost of performing pairwise structural alignment against all structures in PDB is prohibitively expensive. Alignment-free approaches have been introduced to enable fast but coarse comparisons by representing each protein as a vector of structure features or fingerprints and only computing similarity between vectors. As a notable example, FragBag represents each protein by a \"bag of fragments\", which is a vector of frequencies of contiguous short backbone fragments from a predetermined library.\n\nResultsHere we present a new approach to learning effective structural motif presentations using deep learning. We develop DeepFold, a deep convolutional neural network model to extract structural motif features of a protein structure. Similar to FragBag, DeepFold represents each protein structure or fold using a vector of learned structural motif features. We demonstrate that DeepFold substantially outperforms FragBag on protein structural search on a non-redundant protein structure database and a set of newly released structures. Remarkably, DeepFold not only extracts meaningful backbone segments but also finds important long-range interacting motifs for structural comparison. We expect that DeepFold will provide new insights into the evolution and hierarchical organization of protein structural motifs.\n\nAvailabilityhttps://github.com/largelymfs/DeepFold\n\nContactjianpeng@illinois.edu

bioinformatics↗