Biology subjects

Liu, Q.

Publications and source records attributed to Liu, Q..

41 records · Page 3Linked to original sources

bioRxiv2017

De novo mutations involved in post-transcriptional dysregulation contribute to six neuropsychiatric disorders

While deleterious de novo mutations (DNMs) in coding region conferring risk in neuropsychiatric disorders have been revealed by next-generation sequencing, the role of DNMs involved in post-transcriptional regulation in pathogenesis of these disorders remains to be elucidated. Here, we identified 1,736 post-transcriptionally impaired DNMs (piDNMs), and prioritized 1,482 candidate genes in four neuropsychiatric disorders from 7,748 families. Our results revealed higher prevalence of piDNMs in the probands than in controls (P = 8.19x10-17), and piDNM-harboring genes were enriched for epigenetic modifications and neuronal or synaptic functions. Moreover, we identified 86 piDNM-containing genes forming convergent co-expression modules and intensive protein-protein interactions in at least two neuropsychiatric disorders. These cross-disorder genes carrying piDNMs could form interaction network centered on RNA binding proteins, suggesting a shared post-transcriptional etiology underlying these disorders. Our findings illustrate the significant contribution of piDNMs to four neuropsychiatric disorders, and lay emphasis on combining functional and network-based evidences to identify regulatory causes of genetic disorders.

genomics↗

bioRxiv2017

Structure-based analysis of CysZ-mediated cellular uptake of sulfate

Sulfur, most abundantly found in the environment as sulfate (SO42-), is an essential element in metabolites required by all living cells, including amino acids, co-factors and vitamins. Current understanding of the cellular delivery of SO42- at the molecular level is limited however. CysZ has been described as a SO42- permease, but its sequence family is without known structural precedent. Based on crystallographic structure information, SO42- binding and uptake experiments in cells and proteoliposomes, and single-channel conductance measurements, we provide insight into the molecular mechanism of CysZ-mediated translocation of SO42- across membranes. CysZ properties differ markedly from those of known transporters and ion channels. The structures display a hitherto unknown fold with dual topology, assembling in CysZ from Pseudomonas denitrificans as a trimer of antiparallel dimers in the membrane. CysZ structures from two other species recapitulate dimers from this assembly. Mutational studies highlight the functional relevance of conserved CysZ residues.

biophysics↗

bioRxiv2017

Concurrent tACS-fMRI Reveals Causal Influence Of Power Synchronized Neural Activity On Resting State fMRI Connectivity

Resting state fMRI (rs-fMRI) is commonly used to study the brains intrinsic neural coupling, which reveals specific spatiotemporal patterns in the form of resting state networks (RSN). It has been hypothesized that slow rs-fMRI oscillations (<0.1 Hz) are driven by underlying electrophysiological rhythms that typically occur at much faster timescales (>5 Hz); however, causal evidence for this relationship is currently lacking. Here we measured rs-fMRI in humans while applying transcranial alternating current stimulation (tACS) to entrain brain rhythms in left and right sensorimotor cortices.\n\nThe two driving tACS signals were tailored to the individuals alpha rhythm (8-12 Hz) and fluctuated in amplitude according to a 1 Hz power envelope. We entrained the left versus right hemisphere in accordance to two different coupling modes where either alpha oscillations were synchronized between hemispheres (phase-synchronized tACS) or the slower oscillating power envelopes (power-synchronized tACS).\n\nPower-synchronized tACS significantly increased rs-fMRI connectivity within the stimulated RSN compared to phase-synchronized or no tACS. This effect outlasted the stimulation period and tended to be more effective in individuals who exhibited a naturally weak interhemispheric coupling. Using this novel approach, our data provide causal evidence that synchronized power fluctuations contribute to the formation of fMRI-based RSNs. Moreover, our findings demonstrate that the brains intrinsic coupling at rest can be selectively modulated by choosing appropriate tACS signals, which could lead to new interventions for patients with altered rs-fMRI connectivity.\n\nSignificance StatementResting state fMRI has become an important tool to estimate brain connectivity. However, relatively little is known about how slow hemodynamic oscillations measured with fMRI relate to electrophysiological processes.\n\nIt was suggested that slowly fluctuating power envelopes of electrophysiological signals synchronize across brain areas and that the topography of this activity is spatially correlated to resting state networks derived from rs-fMRI. Here we take a novel approach to address this problem and establish a causal link between the power fluctuations of electrophysiological signals and rs-fMRI via a new neuromodulation paradigm, which exploits these power-synchronization mechanisms.\n\nThese novel mechanistic insights bridge different scientific domains and are of broad interest to researchers in the fields of Medical Imaging, Neuroscience, Physiology and Psychology.

neuroscience↗

bioRxiv2016

Incidental identification of maternal malignancies in two Asian women underwent noninvasive prenatal test

Noninvasive prenatal test (NIPT) has been widely used as a screening test for trisomy 13, 18 and 21 worldwide. Recently, coexistence of maternal malignancy and pregnancy has drawn increasing attention in NIPT studies. Malignancy in pregnant women potentially affected NIPT results, which may cause false positive results or failed tests. However, no such case has ever been reported in Asian population. In this study, for the first time, we reported a stage III dysgerminoma and advanced gastric cancer during pregnancy accidentally identified during NIPT tests. These two women showed aberrant chromosome aneuploidies in NIPT results and concordant pattern of genome disruption found in tumor samples. The findings in this study further validate the effect of maternal malignancy on NIPT results and strengthen the possibility of detecting malignant tumors through NIPT in the future.

cancer biology↗

bioRxiv2016

Chimeric Genes Revealed in the Polyploidy Fish Hybrids of Carassius cuvieri (Female) x Megalobrama amblycephala (Male)

The genomes of newly formed natural or artificial polyploids may experience rapid gene loss and genome restructuring. In this study, we obtained tetraploid hybrids (4n=148, 4nJB) and triploid hybrids (3n=124, 3nJB) derived from the hybridization of two different subfamily species Carassius cuvieri ([female], 2n = 100, JCC) and Megalobrama amblycephala ([male], 2n = 48, BSB). Some significant morphological and physiological differences were detected in the polyploidy hybrids compared with their parents. To reveal the molecular traits of the polyploids, we compared the liver transcriptomes of 4nJB, 3nJB and their parents. The results indicated high proportion chimeric genes (31 > %) and mutated orthologous genes (17 > %) both in 4nJB and 3nJB. We classified 10 gene patterns within three categories in 4nJB and 3nJB orthologous gene, and characterized 30 randomly chosen genes using genomic DNA to confirm the chimera or mutant. Moreover, we mapped chimeric genes involved pathways and discussed that the phenotypic novelty of the hybrids may relate to some chimeric genes. For example, we found there is an intragenic insertion in the K+ channel kcnk5b, which may be related to the novel presence of the barbels in 4nJB. Our results indicated that the genomes of newly formed polyploids experienced rapid restructuring post-polyploidization, which may results in the phenotypic and phenotypic changes among the polyploidy hybrid offspring. The formation of the 4nJB and 3nJB provided new insights into the genotypic and phenotypic diversity of hybrid fish resulting from distant hybridization between subfamilies.

developmental biology↗