Biology subjects

Nie, S.

Publications and source records attributed to Nie, S..

34 records · Page 2Linked to original sources

bioRxiv2023

Differentiated genomic footprints and connections inferred from 440 Hmong-Mien genomes suggest their isolation and long-distance migration

BackgroundThe underrepresentation of Hmong-Mien (HM) people in Asian genomic studies has hindered our comprehensive understanding of population history and human health. South China is an ethnolinguistically diverse region and indigenously settled by ethnolinguistically diverse HM, Austroasiatic (AA), Tai-Kadai (TK), Austronesian (AN), and Sino-Tibetan (ST) people, which is regarded as East Asias initial cradle of biodiversity. However, previous fragmented genetic studies have only presented a fraction of the landscape of genetic diversity in this region, especially the lack of haplotype-based genomic resources. The deep characterization of demographic history and natural-selection-relevant architecture in HM people was necessary. ResultsWe comprehensively reported the population-specific genomic resources and explored the fine-scale genetic structure and adaptative features inferred from the high-density SNP data in 440 individuals from 34 ethnolinguistic populations, including previously unreported She. We identified solid genetic differentiation between inland (Miao/Yao) and coastal (She) southern Chinese HM people, and the latter obtained more gene flow from northern East Asians. Multiple admixture models further confirmed that extensive gene flow from surrounding ST, TK, and AN people entangled in forming the gene pool of coastal southeastern East Asian HM people. Population genetic findings of isolated shared unique ancestral components based on the sharing alleles and haplotypes deconstructed that HM people from Yungui Plateau carried the breadth of genomic diversity and previously unknown genetic features. We identified a direct and recent genetic connection between Chinese and Southeast Asian HM people as they shared the most extended IBD fragments, supporting the long-distance migration hypothesis. Uniparental phylogenetic topology and Network relationship reconstruction found ancient uniparental lineages in southwestern HM people. Finally, the population-specific biological adaptation study identified the shared and differentiated natural-selection signatures among inland and coastal HM people associated with physical features and immune function. The allele frequency spectrum (AFS) of clinical cancer susceptibility alleles and pharmacogenomic genes showed significant differences between HM and northern Chinese people. ConclusionsOur extensive genetic evidence combined with the historic documents supported the view that ancient HM people originated in Yungui regions associated with ancient Three-Miao tribes descended from the ancient Daxi-Qujialing-Shijiahe people. And then, some recently rapidly migrated to Southeast Asia, and some culturally dispersed eastward and mixed respectively with Southeast Asian indigenes, coastal Liangzhu-related ancient populations, and incoming southward Sino-Tibetan people. Generally, complex population migration, admixture, and adaptation history contributed to their specific patterns of non-coding or disease-related genetic variations.

genetics↗

bioRxiv2022

Lipid remodeling by hypoxia aggravates migratory potential in pancreatic cancer while maintaining membrane homeostasis

Membranes are crucial cell components underlying optimal cellular functioning under diverse conditions including cancer. The membrane physiology requires acute maintenance of biophysical properties and a regulation of cellular lipidome. Homeostatic adaptation of membranes to temperature, pressure and anti-cancer drugs is a well-recognized. However, how the same is regulated under the influence of oxygen deprivation in pancreatic cancers-highly hypoxic cancer- is not known. Here, we report robust lipidomic remodelling in response to HIF-1 induction in pancreatic cancer cells and significant accumulation of lipid droplets. The lipidome rewiring span changes across various lipid classes, levels of unsaturation and acyl chain lengths. Interestingly, despite extensive lipidome alteration, cellular membrane homeostatic response ensures no major modulation of membrane biophysical properties underlying enhanced migratory potential. The correlation of lipidome changes, with pathway analysis and proteomics provide the basis for mutually exclusive regulation of lipidome and membrane properties. These findings help to understand the hypoxic regulation of pancreatic membrane homeostasis.

biophysics↗

bioRxiv2022

Coordinated Regulation of Cdc42ep1, Actin, and Septin Filaments during Neural Crest Cell Migration

The septin cytoskeleton has been demonstrated to interact with other cytoskeletal components to regulate various cellular processes, including cell migration. However, the mechanisms of how septin regulates cell migration are not fully understood. In this study, we use the highly migratory neural crest cells of frog embryos to examine the role of septin filaments in cell migration. We found that septin filaments are required for proper migration of neural crest cells by controlling both the speed and the direction of cell migration. We further determined that septin filaments regulate these features of cell migration by interacting with actin stress fibers. In neural crest cells, septin filaments co-align with actin stress fibers, and the loss of septin filaments leads to impaired stability and contractility of actin stress fibers. In addition, we showed that a partial loss of septin filaments leads to drastic changes in the orientations of newly formed actin stress fibers, suggesting that septin filaments help maintain the persistent orientation of actin stress fibers during directed cell migration. Lastly, our study revealed that these activities of septin filaments depend on Cdc42ep1, which co-localizes with septin filaments in the center of neural crest cells. Cdc42ep1 interacts with septin filaments in a reciprocal manner, with septin filaments recruiting Cdc42ep1 to the cell center and Cdc42ep1 supporting the formation of septin filaments.

cell biology↗

bioRxiv2022

Remodelled Ribosomes Synthesise a Specific Proteome in Proliferating Plant Tissue during Cold

Plant acclimation to low temperatures occurs through system-wide mechanisms that include proteome shifts, some of which occur at the level of protein synthesis. All proteins are synthesised by ribosomes. Rather than being monolithic, transcript-to-protein translation machines, ribosomes can be selective and cause effective proteome shifts required for successful temperature acclimation. Here, we use apical root meristems of germinating seedlings of the monocotyledonous plant barley as a model to study changes in protein abundance and synthesis rates during cold acclimation. We measure metabolic and physiological parameters that allow us to compare protein synthesis rates in different physiological states, e.g., in cold acclimation compared to the optimal temperature state. We show that ribosomal proteins are independently synthesised and assembled into ribosomal complexes in root proliferative tissue, and assess how the ribo-proteome shifts during cold may be associated with changes in synthesis and accumulation of macromolecular complexes. We demonstrate that translation initiation is the limiting step during cold acclimation and based on our data propose a model of a ribosomal code that depends on a reconfigured ribosome population, where as a mode of cold acclimation, specific ribosomal protein compositions may confer selective association capabilities between 60S subunits and 48S initiation complexes.

plant biology↗

bioRxiv2022

Effects of chitin and chitosan on root growth, biochemical defense response and exudate proteome of Cannabis sativa

Fungal pathogens pose a major threat to Cannabis sativa production, requiring safe and effective management procedures to control disease. Chitin and chitosan are natural molecules that elicit plant defense responses. Investigation of their effects on C. sativa will advance understanding of plant responses towards elicitors and provide a potential pathway to enhance plant resistance against diseases. Plants were grown in the in vitro Root-TRAPR system and treated with colloidal chitin and chitosan. Plant morphology was monitored, then plant tissues and exudates were collected for enzymatic activity assays, phytohormone quantification, qPCR analysis and proteomics profiling. Chitosan treatments showed increased total chitinase activity and expression of pathogenesis-related (PR) genes by 3-5 times in the root tissues. In the exudates, total peroxidase and chitinase activities and levels of defense proteins such as PR protein 1 and endochitinase 2 were increased. Shoot development was unaffected, but root development was inhibited after chitosan exposure. No significant effects on plant defense were observed upon chitin treatment. These results indicate that colloidal chitosan significantly promoted production and secretion of plant defense proteins in C. sativa root system and could be used as a potential elicitor, particularly in hydroponic scenarios to manage crop diseases. HighlightChitosan induces defense protein productions and secretions in the root tissues and exudates of C. sativa, offering a potential pathway to enhance plant resistance against fungal attack.

plant biology↗

bioRxiv2022

Respiratory strategy at birth initiates distinct lung injury phenotypes in the preterm lamb lung

Bronchopulmonary disease is the chronic manifestation of the acute injury that may accompany ventilation following preterm birth. A lack of clear trial evidence often hampers clinical decision-making during support of the preterm lung at birth. Protein biomarkers have been used to define acute lung injury phenotypes and improve patient selection for specific interventions in adult respiratory distress syndrome. Here we present a mass spectrometry-based approach to profile the protein phenotype associated with three different aeration strategies known to cause different pathophysiological responses when applied at birth to preterm lambs. We were able to identify pathway enrichments specific to both ventilation strategy and lung regions based upon gravity-dependency. Ventilation strategy-specific phenotypes were further delineated by applying partial least square modelling to identify associations between specific proteins and clinical, physiological and morphological outcomes. This work highlights the specificity of lung injury responses to routinely applied birth interventions such as different respiratory support approaches and identified the molecular events associated with each. Furthermore, we demonstrate the capacity to subdivide preterm infants by the direct aetiology and response to lung injury; the first step towards true precision medicine in neonatology.

systems biology↗

bioRxiv2022

Accurate and efficient protein sequence designthrough learning concise local environment of residues

Protein sequence design has been widely applied in rational protein engineering and increasing the design accuracy and efficiency is highly desired. Here we present ProDESIGN-LE, an accurate and efficient design approach, which adopts a concise but informative representation of residues local environment and trains a transformer to select an appropriate residue at a position from its local environment. ProDESIGN-LE iteratively applies the transformer on the positions in the target structure, eventually acquiring a designed sequence with all residues fitting well with their local environments. ProDESIGN-LE designed sequences for 68 naturally occurring and 129 hallucinated proteins within 20 seconds per protein on average, and the predicted structures from the designed sequences perfectly resemble the target structures with state-of-the-art average TM-score exceeding 0.80. We further experimentally validated ProDESIGN-LE by designing five sequences for an enzyme, chloramphenicol O-acetyltransferase type III (CAT III), and recombinantly expressing the proteins in E. coli. Of these proteins, three exhibited excellent solubility, and one yielded monomeric species with circular dichroism spectra consistent with the natural CAT III protein.

bioinformatics↗

bioRxiv2022

Lipidomic change in Aedes aegypti female following blood feeding reveals similar changes in functionally related lipids

We conducted a lipidomic analysis of the whole body of female Aedes aegypti mosquitoes at different time points over the course of feeding and reproduction. There were temporal biphasic increases of more than 80% of lipids identified at the time of feeding and from 16 h to 30 h post blood meal. During these two increases, the abundance of many lipids dropped while body weight remained stable, probably reflecting blood lipid digestion and the synthesis of vitellogenin in this period. A concerted temporal pattern was particularly strong at the second peak for membrane and signalling lipids such as PE, PI, CL, HexCer and LPA. Lyso-glycerophospholipids showed three distinct change patterns which are functionally related: LPE and LPC, which are membrane lipids, showed little change; LPA, a signalling lipid, showed a dramatic increase from 16 to 30 h PBM; LPI, a bioactive lipid, and both LPG and LPS which are bacterial membrane lipids, showed one significant increase from the time of feeding to 16 hours post blood meal. The result of our study on the anautogenous insect Ae. aegypti point to specific lipids likely to be important in the reproductive process with a role in the formation and growth of ovarian follicles.

biochemistry↗

bioRxiv2021

Architecture of the cytoplasmic face of the nuclear pore

The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating the NPC symmetric core architecture, the asymmetrically decorated cytoplasmic face, essential for mRNA export and a hotspot for nucleoporin-associated diseases, has remained elusive. Here, we report a composite structure of the entire human cytoplasmic face obtained by combining biochemical reconstitution, crystal structure determination, docking into cryo-electron tomographic reconstructions, and physiological validation, accounting for a third of the NPCs mass. Whereas an evolutionarily conserved [~]540 kDa hetero-hexameric cytoplasmic filament nucleoporin complex is anchored by species-specific motifs above the central transport channel, attachment of the pentameric NUP358 bundles depends on the double-ring arrangement of the coat nucleoporin complex. Our results and the predictive power of our composite structure provide a rich foundation for elucidating the molecular basis of mRNA export and nucleoporin diseases. One sentence summaryAn interdisciplinary analysis established the near-atomic molecular architecture of the cytoplasmic face of the human nuclear pore complex.

biochemistry↗

bioRxiv2021

Architecture of the linker-scaffold in the nuclear pore

The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating the arrangement of the structured scaffold building blocks in the NPC symmetric core, their cohesion by multivalent unstructured linker proteins remained elusive. Combining biochemical reconstitution, high resolution structure determination, docking into cryo-electron tomographic reconstructions, and physiological validation, we elucidated the architecture of the entire linker-scaffold, yielding a near-atomic composite structure of the symmetric core accounting for [~]77 MDa of the human NPC. Whereas linkers generally play a rigidifying role, the linker-scaffold of the NPC provides the plasticity and robustness necessary for the reversible constriction and dilation of its central transport channel. Our results complete the structural characterization of the NPC symmetric core, providing a rich foundation for future functional studies. One sentence summaryAn interdisciplinary analysis established the near-atomic molecular architecture and evolutionary conservation of the linker-scaffold of the human nuclear pore complex.

biochemistry↗

bioRxiv2021

Getting more out of co-immunoprecipitation mass spectrometry experiments by reducing interference using FAIMS.

Co-immunoprecipitation of proteins coupled to mass spectrometry is critical for the understanding of protein interaction networks. In instances where a suitable antibody is not available, it is common to graft synthetic tags onto target protein sequences and allowing the use of commercially available antibodies for affinity purification. A common approach is through FLAG-Tag co-immunoprecipitation. To allow the selective elution of protein complexes, competitive displacement using a large molar excess of the tag peptides is often carried out. Yet, this creates downstream challenges for the mass spectrometry analysis due to the presence of large quantities of these peptides. Here, we demonstrate that Field Asymmetric Ion Mobility Spectrometry (FAIMS), a gas phase ion separation device prior to mass spectrometry analysis can be applied to FLAG-Tag co-immunoprecipitation experiment to increase the depth of protein coverage. By excluding these abundant tag peptides, we were able to observe deeper coverage of interacting proteins and as a result, deeper biological insights, without the need for additional sample handling or altering sample preparation protocols.

biochemistry↗

bioRxiv2020

Impacts of Crenarchaeota and Halobacterota on sulfate reduction in the subtropical mangrove ecosystem as revealed by SMDB analysis

Sulfate reduction is an important process in the sulfur cycle. However, the relationship between this process and the genotype of microorganisms involved in subtropical mangrove ecosystems is poorly understood. A dedicated and efficient gene integration database of sulfur metabolism has not been established yet. In this study, a sulfur metabolism gene integrative database (SMDB) had been constructed successfully. The database achieved high coverage, fast retrieval, and low false positives. Then the sulfate reduction by microorganisms in subtropical mangroves ecosystem had been evaluated quickly and accurately with SMDB database. Due to the environmental factors, dissimilatory sulfite reductase was significantly high in mangrove samples. Sulfide, Fe, and available sulfur were found to be the key environmental factors that influence the dissimilatory sulfate reduction, in which sulfur compounds could be utilized as potential energy sources for microorganism. Taxonomic assignment of dissimilatory sulfate-reduction genes revealed that Desulfobacterales and Chromatiales are completely responsible for this process. Sulfite reductase can help the community cope with the toxic sulfite produced by these Bacteria order. Collectively, these findings demonstrated that Desulfobacterales and Chromatiales play essential roles in dissimilatory sulfate reduction.

bioinformatics↗

bioRxiv2020

What are we missing by using hydrophilic enrichment? Improving bacterial glycoproteome coverage using total proteome and FAIMS analysis.

Hydrophilic Interaction Liquid Chromatography (HILIC) glycopeptide enrichment is an indispensable tool for the high-throughput characterisation of glycoproteomes. Despite its utility, HILIC enrichment is associated with a number of short comings including requiring large amounts of starting material, potentially introducing chemical artefacts such as formylation, and biasing/under-sampling specific classes of glycopeptides. Here we investigate HILIC enrichment independent approaches for the study of bacterial glycoproteomes. Using three Burkholderia species (B. cenocepacia, B. dolosa and B. ubonensis) we demonstrate that short aliphatic O-linked glycopeptides are typically absent from HILIC enrichments yet are readily identified in whole proteome samples. Using Field Asymmetric Waveform IMS (FAIMS) fractionation we show that at low compensation voltages (CVs) short aliphatic glycopeptides can be enriched from complex samples providing an alternative means to identify glycopeptides recalcitrant to hydrophilic based enrichment. Combining whole proteome and FAIMS analysis we show that the observable glycoproteome of these Burkholderia species is at least 30% larger than initially thought. Excitingly, the ability to enrich glycopeptides using FAIMS appears generally applicable, with the N-linked glycopeptides of Campylobacter fetus subsp. fetus also enrichable at low FAIMS CVs. Taken together, these results demonstrate that FAIMS provides an alternative means to access glycopeptides and is a valuable tool for glycoproteomic analysis.

microbiology↗

bioRxiv2019

Single-Cell RNA-Seq Reveals Endocardial Defect in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is one of the most challenging forms of congenital heart diseases. Previous studies were mainly focused on intrinsic defects in myocardium. However, this does not sufficiently explain the abnormal development of the cardiac valve, septum, and vasculature, known to originate from the endocardium. Here, using single-cell RNA profiling, induced pluripotent stem cells, and human fetal heart tissue with an underdeveloped left ventricle, we identified a developmentally impaired endocardial population in HLHS. The intrinsic endocardial deficits contributed to abnormal endothelial to mesenchymal transition, NOTCH signaling, and extracellular matrix organization, all of which are key factors in valve formation. Consequently, endocardial abnormalities conferred reduced proliferation and maturation of cardiomyocytes through a disrupted fibronectin-integrin interaction. Several recently described HLHS de novo mutations were associated with abnormal endocardial gene and FN1 regulation and expression. Our studies provide a rationale for considering endocardial function in future regenerative strategies for HLHS.

developmental biology↗

bioRxiv2019

Widespread remodelling of proteome solubility in response to different protein homeostasis stresses

The accumulation of protein deposits in neurodegenerative diseases involves the presence of a metastable subproteome vulnerable to aggregation. To investigate this subproteome and the mechanisms that regulates it, we measured the proteome solubility of the Neuro2a cell line under protein homeostasis stresses induced by Huntington Disease proteotoxicity; Hsp70, Hsp90, proteasome and ER-mediated folding inhibition; and oxidative stress. We found one-quarter of the proteome extensively changed solubility. Remarkably, almost all the increases in insolubility were counteracted by increases in solubility of other proteins. Each stress directed a highly specific pattern of change, which reflected the remodelling of protein complexes involved in adaptation to perturbation, most notably stress granule proteins, which responded differently to different stresses. These results indicate that the robustness of protein homeostasis relies on the absence of proteins highly vulnerable to aggregation and on large changes in aggregation state of regulatory mechanisms that restore protein solubility upon specific perturbations.

biochemistry↗

bioRxiv2018

Enterovirus 71 structural viral protein 1 promotes mouse Schwann cell autophagy via endoplasmic reticulum stress-mediated peripheral myelin protein 22 upregulation

Enterovirus 71 (EV71) accounts for the majority of hand, foot and mouth disease-related deaths due to fatal neurological complications. The clinical observations and animal models found the early invasion of nervous system, and the demyelinating phenomenon was observed. As one of the receptors of EV71 structural viral protein 1 (VP1), SCARB2 mainly exists on the myelin sheath. EV71 VP1 can promote viral replication through inducing autophagy in neuron cells. This study aims to investigate the role and mechanism of VP1 in autophagy of mouse Schwann cells (MSCs). An EV71 VP1-expressing vector (pEGFP-C3-VP1) was generated and transfected into MSCs. Transmission electron microscopy (TEM) and Western blot analysis of the autophagy marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) were used to assess autophagy in the cells. Real-time PCR and immunofluorescent staining were performed to determine the expression of PMP22. Small interfering RNA against PMP22 was employed to investigate the role of PMP22 in MSCs autophagy. Selective endoplasmic reticulum (ER) stress inhibitor salubrinal (SAL) was employed to determine whether PMP22 is mediated by ER stress. Our results demonstrated that VP1 played a promotive role in MSC autophagy. Overexpression of VP1 upregulated PMP22. PMP22 deficiency downregulated LC3B and thus inhibited autophagy. Furthermore, PMP22 expression was significantly suppressed by SAL. VP1 promotes MSC autophagy through upregulating ER stress-mediated PMP22 expression. VP1/ER stress/ PMP22 axis in autophagy may be a potential therapeutic target for EV71 infection-induced fatal neuronal damage.

cell biology↗