Biology subjects

Dong, L.

Publications and source records attributed to Dong, L..

7 recordsLinked to original sources

bioRxiv2026

Cortical Hierarchy Dynamically Organizes Large-Scale Neural Propagation

Flexible behaviour depends on the continuous coordination of sensory-driven and internally guided processing, yet whether the cortical hierarchy spanning lower-order sensory to higher-order association systems dynamically organizes large-scale cortical propagation over time remains unclear. Here we combined source-resolved magnetoencephalography with Riemannian cortical-flow modelling to derive hierarchy consistency, a moment-to-moment measure of the alignment between cortical propagation and the principal sensory-to-association functional gradient. We found that large-scale cortical propagation was dynamically organized by the cortical hierarchy. Hierarchy consistency exhibited a reproducible low-frequency periodic component that defined a characteristic timescale for the continuous updating of propagation direction. This dynamic organization was coordinated by a distributed cortical switchboard spanning the default-mode, salience, control and limbic systems, and was constrained by structural connectivity and network-control architecture. It flexibly adapted to behavioural demands, with hierarchy consistency increasing across both sensorimotor and working-memory states, while its characteristic periodicity shifted in a task-dependent manner. Moreover, hierarchy-related propagation dynamics were systematically reorganized across ageing and associated with higher-order cognitive function. Together, these findings establish the cortical hierarchy as a dynamic organizing principle that continuously shapes the direction and temporal evolution of large-scale cortical propagation to support adaptive behaviour.

neuroscience↗

bioRxiv2018

Composition and consistence of the bacterial microbiome in upper, middle and lower esophagus before and after Lugol’s iodine staining

Esophageal bacteria, as the integral composition of human ecosystem, have been reported to be associated with esophageal lesions. However, few studies focus on microbial compositions in different esophageal segments, especially after Lugols iodine staining (LIS) in the endoscopic examination for the screening of esophageal cancer. To investigate the composition of the bacterial microbiome in upper, middle and lower esophagus and if LIS would affect the detection of bacteria, 141 fasting samples including the upper, middle and lower esophagus from 27 participants were collected by brushing the mucosal surface of the esophagus before (Eso) and after (Lug) LIS. Bacterial V3-V4 region of 16S rRNA gene was amplified and sequenced by Illuminas sequencing platform and analyzed using LEfSe system to identify specific microbiota. The top six abundant bacterial phyla taxa among three locations from both Eso and Lug groups were Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and TM7. In terms of genera, the bacterium in three locations from two groups was all characterized by a highest relative abundance of Streptococcus. Bacteria diversity and the relative abundance between Eso and Lug were comparable (P > 0.05). Bacteria diversity was consistent in different esophageal locations for an individual, but it was significantly distinguishing in different subjects (P < 0.05). In Conclusion, the bacterial microbiome in healthy esophagus are highly diverse and consistent even among three physiological stenosis at all clades. Lugols iodine staining would not change local microenvironment in term of microbial composition. These finding provide an essential baseline for future studies investigating local and systemic bacterial microbiome and esophageal diseases.

epidemiology↗

bioRxiv2018

Genome-wide scan and fine-mapping of rare nonsynonymous associations implicates intracellular lipolysis genes in fat distribution and cardio-metabolic risk

Difficulties in identifying causal variants and genes underlying genetic associations have limited the translational potential of genetic studies of body fat distribution, an important, partly-heritable risk factor for cardio-metabolic disease. Rare variant associations facilitate fine-mapping of causal alleles, but their contribution to fat distribution is understudied. We performed a genome-wide scan of rare nonsynonymous variants for body mass index-adjusted waist-to-hip-ratio (BMI-adjusted WHR; a widely-used measure of fat distribution) in 450,562 European ancestry individuals, followed by systematic Bayesian fine-mapping at six genome-wide (p<5x10-08; main-analysis) and two subthreshold signals (significant at a Bonferroni-corrected p<1.3x10-06). We found strong statistical evidence of causal association for nonsynonymous alleles in CALCRL (p.L87P, pconditional=5.9x10-12; posterior-probability of association [PPA]=52%), PLIN1 (p.L90P, pconditional=5.5x10-13; PPA>99%), PDE3B (p.R783X, pconditional=6.2x10-15; PPA>99%), ACVR1C (p.I195T; pconditional=5.4x10-12; PPA>99%), and FGF1 (p.G21E, pconditional=1.6x10-07; PPA=98%). Alleles at the four likely-causal main-analysis genes affected fat distribution primarily via larger hip-rather than smaller waist-circumference and six of nine conditionally-independent WHR-lowering index-variants were associated with protection from cardiovascular or metabolic disease. All four genes are expressed in adipose tissue and have been linked with the regulation of intracellular lipolysis, which controls fat retention in mature cells. Targeted follow-up analyses of key intracellular-lipolysis genes revealed associations for a variant in the initiator of intracellular lipolysis PNPLA2 (p.N252K) with higher BMI-adjusted-WHR and higher cardio-metabolic risk. This study provides human genetic evidence of a link between intracellular lipolysis, fat-distribution and its cardio-metabolic complications in the general population.

genetics↗

bioRxiv2018

The first set of universal nuclear protein-coding loci markers for avian phylogenetic and population genetic studies

Multiple nuclear markers provide genetic polymorphism data for molecular systematics and population genetic studies. They are especially required for the coalescent-based analyses that can be used to accurately estimate species trees and infer population demographic histories. However, in avian evolutionary studies, these powerful coalescent-based methods are hindered by the lack of a sufficient number of markers. In this study, we designed PCR primers to amplify 136 nuclear protein-coding loci (NPCLs) by scanning the published Red Junglefowl (Gallus gallus) and Zebra Finch (Taeniopygia guttata) genomes. To test their utility, we amplified these loci in 41 bird species representing 23 Aves orders. The sixty-three best-performing NPCLs, based on high PCR success rates, were selected which had various mutation rates and were evenly distributed across 17 avian autosomal chromosomes and the Z chromosome. To test phylogenetic resolving power of these markers, we conducted a Neoavian phylogenies analysis using 63 concatenated NPCL markers derived from 48 whole genomes of birds. The resulting phylogenetic topology, to a large extent, is congruence with results resolved by previous whole genome data. To test the level of intraspecific polymorphism in these makers, we examined the genetic diversity in four populations of the Kentish Plover (Charadrius alexandrinus) at 17 of NPCL markers chosen at random. Our results showed that these NPCL markers exhibited a level of polymorphism comparable with mitochondrial loci. Therefore, this set of pan-avian nuclear protein-coding loci has great potential to facilitate studies in avian phylogenetics and population genetics.

evolutionary biology↗

bioRxiv2017

In the absence of apoptosis, myeloid cells arrest when deprived of growth factor, but remain viable without ATG5-dependent autophagy or uptake of glucose or glutamine.

Withdrawal of the growth factor interleukin 3 from IL3-dependent myeloid cells causes them to undergo Bax/Bak1-dependent apoptosis, whereas factor-deprived Bax-/-Bak1-/- cells remain viable, but arrest and shrink. It was reported that withdrawal of IL3 from Bax-/-Bak1-/- cells caused decreased expression of the glucose transporter Glut1, leading to reduced glucose uptake, so that arrested cells required Atg5-dependent autophagy for long-term survival. In other cell types, a decrease in Glut1 is mediated by the thioredoxin-interacting protein Txnip, which is induced in IL3-dependent myeloid cells when growth factor is removed. We mutated Atg5 and Txnip by CRISPR/Cas9 and found that Atg5-dependent autophagy was not necessary for the long-term viability of cycling or arrested Bax-/-Bak1-/- cells, and that Txnip was not required for the decrease in Glut1 expression in response to IL3 withdrawal. Surprisingly, Atg5-deficient Bax/Bak1 double mutant cells survived for several weeks in medium supplemented with 10% fetal bovine serum (FBS), without high concentrations of added glucose or glutamine. When serum was withdrawn, the provision of an equivalent amount of glucose present in 10% FBS (~0.5 mM) was sufficient to support cell survival for more than a week, in the presence or absence of IL3. Thus, Bax-/-Bak1-/- myeloid cells deprived of growth factor consume extracellular glucose to maintain long-term viability, without a requirement for Atg5-dependent autophagy.

cell biology↗

bioRxiv2017

Contextual Tumor Suppressor Function Of T Cell Death-Associated Gene 8 (TDAG8) In Hematological Malignancies

Key points1. TDAG8 (GPR65) gene expression is down-regulated in hematological malignancies.\n\n2. Restoration of TDAG8 gene expression in blood cancer cells suppresses tumor growth and metastasis.\n\nAbstractExtracellular acidosis is a condition found within the tumor microenvironment due to inadequate blood perfusion, hypoxia, and altered tumor cell metabolism. Acidosis has pleiotropic effects on malignant progression; therefore it is essential to understand how acidosis exerts its diverse effects. In this study a bioinformatics analysis revealed the expression of the proton sensing G-protein-coupled receptor TDAG8 is significantly reduced in human blood cancers in comparison to normal blood cells. To understand how TDAG8 functions in hematological malignancies, TDAG8 expression was restored in U937 acute myeloid leukemia cells and other blood cancer cells. It was discovered that severe acidosis, pH 6.4, inhibited U937 cell proliferation while mild acidosis, pH 6.9, stimulated cell proliferation. However, restoring TDAG8 gene expression modulated the U937 cell response to mild extracellular acidosis and physiological pH by reducing cell proliferation. Tumor xenograft experiments further revealed that restoring TDAG8 expression in U937 and Ramos cancer cells reduced tumor growth. It was also shown U937 cells with restored TDAG8 expression attached less to Matrigel, migrated slower toward a chemoattractant, and metastasized less in severe combined immunodeficient mice. These effects correlated with a reduction in c-myc oncogene expression. The mechanistic investigation indicated that G13/RhoA signaling arbitrated the TDAG8-mediated c-myc oncogene repression in response to acidosis. Overall, this study provides compelling data to support the concept that TDAG8 functions as a contextual tumor suppressor in hematological malignancies and sensitizes blood cancer cells to acidotic stress.

cancer biology↗

bioRxiv2017

Inoculation Of Biocontrol Bacteria Alleviated Panax ginseng Replanting Problem

Replanting problem is a common and serious issue hindering the continuous cultivation of Panax plants. Changes in soil microbial community driven by plant species of different ages and developmental stages are speculated to cause this problem. Inoculation of microbial antagonists is proposed to alleviate replanting issues efficiently.\n\nHigh-throughput sequencing revealed that bacterial diversity evidently decreased, and fungal diversity markedly increased in soils of adult ginseng plants in the root growth stage. Relatively few beneficial microbe agents, such as Luteolibacter, Cytophagaceae, Luteibacter, Sphingomonas, Sphingomonadaceae, and Zygomycota, were observed. On the contrary, the relative abundance of harmful microorganism agents, namely, Brevundimonas, Enterobacteriaceae, Pandoraea, Cantharellales, Dendryphion, Fusarium, and Chytridiomycota, increased with pant age. Furthermore, Bacillus subtilis 50-1 was isolated and served as microbial antagonists against pathogenic Fusarium oxysporum of ginseng root-rot, and its biocontrol efficacy was 67.8% using a dual culture assay. The ginseng death rate and relative abundance of Fusarium decreased by 63.3% and 46.1%, respectively, after inoculation with 50-1 in replanting soils. Data revealed that changes in the diversity and composition of rhizospheric microbial communities driven by ginseng of different ages and developmental stages could cause microecological degradation. Biocontrol using microbial antagonists was an effective method for alleviating the replanting problem.\n\nHighlightChanges in rhizospheric microbial communities driven by ginseng plants 13 of different ages and developmental stages could cause microecological degradation. 14 Biocontrol using microbial antagonists effectively alleviated the replanting problem.

microbiology↗