Biology subjects

Sun, D.

Publications and source records attributed to Sun, D..

At least 127 records · Page 7Linked to original sources

bioRxiv2021

A MYB transcription factor, PlMYB308, plays an essential role in flower senescence of herbaceous peony

Herbaceous peony is an important cut-flower plant cultivated across the world, but its short vase life substantially restricts the economic value of this crop. It is well established that endogenous hormones regulate the senescing process, but the molecular mechanism of them in flower senescence is still unclear. Here, we isolated a MYB transcription factor gene PlMYB308 from herbaceous peony flowers. Transcript abundance of PlMYB308 was strongly up-regulated in senescing petals. Silencing of PlMYB308 resulted in delayed peony flower senescence, and dramatically increased gibberellin (GA) but reduced ethylene and abscisic acid (ABA) levels in petals. Ectopic overexpression of PlMYB308 in tobacco accelerated flower senescence, and reduced GA but increased ethylene and ABA accumulation. Correspondingly, biosynthetic genes of ethylene, ABA, and GA showed variable expression levels in petals after silencing or overexpression of PlMYB308. A dual-luciferase assay showed that PlMYB308 specifically bound to the PlACO1 promoter. High expression levels of PlMYB308 were accompanied by low petal anthocyanin accumulation in senescing petals. A further bimolecular fluorescence complementation assay revealed an interaction between PlMYB308 and PlbHLH33, which was supposed to inhibit the anthocyanin biosynthesis. Taken together, our results suggest that the PlMYB308-PlACO1 and PlMYB308-PlbHLH33 regulatory checkpoints perhaps positively and negatively operate the production of ethylene and anthocyanin, respectively, and thus contribute to the senescence with impaired pigmentation in herbaceous peony flowers.

biophysics↗

bioRxiv2021

Retinoschisin deficiency induces persistent aberrant waves of activity affecting neuroglial signaling in the retina

Genetic disorders which present during development make treatment strategies particularly challenging because there is a need to disentangle primary pathophysiology from downstream dysfunction caused at key developmental stages. To provide a deeper insight into this question, we studied a mouse model of X-linked juvenile retinoschisis (XLRS), an early onset inherited condition caused by mutations in the RS1 gene encoding retinoschisin (RS1) and characterized by cystic retinal lesions and early visual deficits. Using an unbiased approach in expressing the fast intracellular calcium indicator GCaMP6f in neuronal, glial, and vascular cells of the retina of mice lacking RS1, we found that initial cyst formation is paralleled by the appearance of aberrant spontaneous neuro-glial signals as early as postnatal day 13. These presented as glutamate-driven wavelets of neuronal activity and sporadic radial bursts of activity by Muller glia, spanning all retinal layers and disrupting light-induced signaling. This study highlights a critical role for RS1 in early retinal development with a potential to disrupt circuit formation to central targets. Additionally, it confers a functional role to RS1 beyond the scope of an adhesion molecule and identifies an early onset for dysfunction, a potential temporal target for therapeutic intervention and diagnosis. Significance Statement/ HighlightsO_LIPhotoreceptor inner segments express Rs1 at P5, after which RS1 protein is detected in the inner segments by P9 and throughout the retina at later ages, with structural abnormalities observed by optical coherence tomography at P13 in Rs1 mutant mouse models. C_LIO_LIAberrant glutamate-driven wavelets identified by GCaMP6f-based analyses are a novel pathophysiological feature of RS1 deficient mice that emerge after maximal RS1 expression. C_LIO_LIMuller glia display abnormal radial glutamate-driven coordinated and sporadic bursts of activity in RS1-deficient mice. C_LIO_LIThese data identify a novel pathophysiological feature of RS1-deficient mice and define a window where treatments might be most effective. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/457777v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@3f27eborg.highwire.dtl.DTLVardef@55e5a4org.highwire.dtl.DTLVardef@1577435org.highwire.dtl.DTLVardef@8e55b3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Epigenetic reprogramming of DCCs into dormancy suppresses metastasis via restored TGFβ-SMAD4 signaling.

Disseminated cancer cells (DCCs) identified in secondary organs, sometimes before the primary tumor becomes detectable and treated, can remain dormant for years to decades before manifesting. Microenvironmental and epigenetic mechanisms may control the onset and escape from dormancy, and here we reveal how a combination of the DNA methylation inhibitor 5-azacytidine (AZA) and retinoic acid receptor ligands all-trans retinoic acid (atRA), orchestrate a novel program of stable dormancy. Treatment of HNSCC tumor cells with AZA+atRA induced a SMAD2/3/4 dependent regulation of downstream transcriptional program that restored the anti-proliferative function of TGF{beta} signaling. Significantly, AZA+atRA or AZA+AM80, an RAR specific agonist, strongly suppresses lung metastasis formation. The metastatic suppression occurs via the induction and maintenance of phenotypically homogenous dormant SMAD4+/NR2F1+ non-proliferative DCCs. These findings suggest that strategies that maintain or induce dormancy programs may be a viable alternative strategy to improve patient outcomes by preventing or significantly delaying metastasis development.

cancer biology↗

bioRxiv2021

Genetic loci of the R. anatipestifer serotype discovered by Pan-GWAS and its application for the development of a multiplex PCR serotyping method

The disease caused by Riemerella anatipestifer (R. anatipestifer) causes large economic losses to the global duck industry every year. Serotype-related genomic variation (such as in O-antigen and capsular polysaccharide gene clusters) has been widely used for the serotyping in many gram-negative bacteria. To date, there have been few studies focused on genetic basis of serotypes in R. anatipestifer. Here, we used pan-genome-wide association studies (Pan-GWAS) to identify the serotype-specific genetic loci of 38 R. anatipestifers strain. Analyses of the loci of 11 serotypes showed that the loci could be well mapped with the serotypes of the corresponding strains. We constructed the knockout strain for the wzy gene at the locus, and the results showed that the mutant lost the agglutination characteristics to positive antisera. Based on the of Pan-GWAS results, we developed a multiple PCR method to identify serotypes 1, 2, and 11 of R. anatipestifer. Our study provides a precedent for systematically analysing the genetic basis of the R anatipestifer serotypes and establishing a complete serotyping system in the future. HighlightsO_LIR. anatipestifer serotype-specific locus was identified by Pan-GWAS for the first time. C_LIO_LIMolecular serotyping multiplex PCR was developed based on O-antigen biosynthesis gene clusters C_LI

genomics↗

bioRxiv2021

Cellular Pharmacology of Curcumin With and Without Piperine

Prior reports have suggested that piperine enhances curcumins anti-carcinogenesis. We tested the hypothesis that piperine increases the intracellular concentrations of curcumin by improving intracellular uptake or reducing curcumin efflux or metabolism in breast cells. We incubated SUM149, MCF10A, primary normal human breast cells, ALDH+, and ALDH-CD44+24- SUM149 cells with curcumin {+/-} piperine at concentrations 1 M to 15 M for time periods of 15 minutes to 24 hours. We assayed cell viability by MTT assay and proliferation by primary mammosphere assay. Curcumin and its metabolites were assayed using liquid chromatography mass spectroscopy. Curcumin, but not piperine, showed significantly higher effects on the viability of breast cancer SUM149 cells than in non-tumorigenic MCF10A cells. Curcumin + piperine synergistically reduced viability of SUM149 cells but had a concentration dependent effect upon MCF10A cell viability. Cellular uptake of curcumin in SUM149 is significantly higher, while the efflux in SUM149 is significantly lower than in MCF10A, which correlated with cell viability. Piperine did not alter curcumin cellular uptake, efflux, or metabolism in any of the cell models. The observed synergism of piperine+curcumin in reducing breast stem cell self renewal is likely due to independent anti-carcinogenesis effects rather than any effects upon intracellular curcumin concentrations.

pharmacology and toxicology↗

bioRxiv2021

Direct Observation of Electrically Conductive Pili Emanating from Geobacter sulfurreducens

Geobacter sulfurreducens is a model microbe for elucidating the mechanisms for extracellular electron transfer in several biogeochemical cycles, bioelectrochemical applications, and microbial metal corrosion. Multiple lines of evidence previously suggested that electrically conductive pili (e-pili) are an essential conduit for long-range extracellular electron transport in G. sulfurreducens. However, it has recently been reported that G. sulfurreducens does not express e-pili and that filaments comprised of multi-heme c-type cytochromes are responsible for long-range electron transport. This possibility was directly investigated by examining cells, rather than filament preparations, with atomic force microscopy. Approximately 90 % of the filaments emanating from wild-type cells had a diameter (3 nm) and conductance consistent with previous reports of e-pili harvested from G. sulfurreducens or heterologously expressed in E. coli from the G. sulfurreducens pilin gene. The remaining 10% of filaments had a morphology consistent with filaments comprised of the c-type cytochrome OmcS. A strain expressing a modified pilin gene designed to yield poorly conductive pili expressed 90 % filaments with a 3 nm diameter, but greatly reduced conductance, further indicating that the 3 nm diameter conductive filaments in the wild-type strain were e-pili. A strain in which genes for five of the most abundant outer-surface c-type cytochromes, including OmcS, was deleted yielded only 3 nm diameter filaments with the same conductance as in the wild-type. These results demonstrate that e-pili are the most abundant conductive filaments expressed by G. sulfurreducens, consistent with previous functional studies demonstrating the need for e-pili for long-range extracellular electron transfer. ImportanceElectroactive microbes have significant environmental impacts as well as applications in bioenergy and bioremediation. The composition, function, and even existence of electrically conductive pili (e-pili) has been one of the most contentious areas of investigation in electromicrobiology, in part because e-pili offer a mechanism for long-range electron transport that does not involve the metal co-factors common in much of biological electron transport. This study demonstrates that e-pili are abundant filaments emanating from Geobacter sulfurreducens, which serves as a model for long-range extracellular electron transfer in direct interspecies electron transfer, dissimilatory metal reduction, microbe-electrode exchange, and corrosion caused by direct electron uptake from Fe(0). The methods described in this study provide a simple strategy for evaluating the distribution of conductive filaments throughout the microbial world with an approach that avoids artifactual production and/or enrichment of filaments that may not be physiologically relevant.

microbiology↗

bioRxiv2021

Knowledge-based antibody repertoire simulation, a novel allele detection tool evaluation and application

Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel alleles using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the novel alleles detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.

bioinformatics↗

bioRxiv2021

Acquisition of alveolar fate and differentiation competence by human fetal lung epithelial progenitor cells

Variation in lung alveolar development is strongly linked to disease susceptibility. However, the cellular and molecular mechanisms underlying alveolar development are difficult to study in humans. Using primary human fetal lungs we have characterized a tip progenitor cell population with alveolar fate potential. These data allowed us to benchmark a self-organising organoid system which captures key aspects of lung lineage commitment and can be efficiently differentiated to alveolar type 2 cell fate. Our data show that Wnt and FGF signalling, and the downstream transcription factors NKX2.1 and TFAP2C, promote human alveolar or airway fate respectively. Moreover, we have functionally validated cell-cell interactions in human lung alveolar patterning. We show that Wnt signalling from differentiating fibroblasts promotes alveolar type 2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. Our organoid system recapitulates key aspects of human lung development allowing mechanistic experiments to determine the underpinning molecular regulation.

developmental biology↗

bioRxiv2021

Alcohol Use Disrupts Age-Appropriate Cortical Thinning in Adolescence: A Data Driven Approach

ObjectiveCortical thickness changes dramatically during development and is influenced by adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying heterogeneity from the effects of alcohol. MethodsAdolescents (n=657; 12-22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) who endorsed little to no alcohol use at baseline were assessed with structural MRI and followed longitudinally at four yearly intervals. Seven unique spatially covarying patterns of cortical thickness were obtained from the baseline scans by applying a novel data-driven method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness. ResultsIn most NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts, among moderate drinkers the decline was faster in the younger cohort and slower in the older cohort, among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort (FDR corrected p-values < 0.01). ConclusionsThe NMF method can delineate spatially coordinated patterns of cortical thickness at the vertex level that are unconstrained by anatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers.

neuroscience↗

bioRxiv2021

Mesenchymal Lineage Heterogeneity Underlies Non-Redundant Functions of Pancreatic Cancer-Associated Fibroblasts

Cancer-associated fibroblast (CAF) heterogeneity is increasingly appreciated, but the origins and functions of distinct CAF subtypes remain poorly understood. The abundant and transcriptionally diverse CAF population in pancreatic ductal adenocarcinoma (PDAC) is thought to arise from a common cell of origin, pancreatic stellate cells (PSCs), with diversification resulting from cytokine and growth factor gradients within the tumor microenvironment. Here we analyzed the differentiation and function of PSCs during tumor progression in vivo. Contrary to expectations, we found that PSCs give rise to a numerically minor subset of PDAC CAFs. Targeted ablation of PSC-derived CAFs within their host tissue revealed non-redundant functions for this defined CAF population in shaping the PDAC microenvironment, including production of specific components of the extracellular matrix. Together, these findings link stromal evolution from distinct cells of origin to transcriptional heterogeneity among PDAC CAFs, and demonstrate unique functions for CAFs of a defined cellular origin. Statement of significanceBy tracking and ablating a specific CAF population, we find that a numerically minor CAF subtype from a defined cell of origin plays unique roles in establishing the pancreatic tumor microenvironment. Together with prior studies, this work suggests that mesenchymal lineage heterogeneity as well as signaling gradients diversify PDAC CAFs.

cancer biology↗

bioRxiv2021

Design of time-delayed safety switches for CRISPR gene therapy

CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. Inspired by previously reported Cas9 self-elimination systems, time-delayed safety switches are designed in this work. Firstly, ultrasensitive relationship is constructed between Cas9-sgRNA (enzyme) and Cas9 plasmids (substrate), which generates the artificial time delay. Then intrinsic time delay in biomolecular activities is revealed by data fitting and utilized in constructing safety switches. The time-delayed safety switches function by separating the gene editing process and self-elimination process, and the tunable delay time may ensure a good balance between gene editing efficiency and side effect minimization. By addressing gene therapy efficiency, off-target effect, immune response and drug accumulation, we hope our safety switches may offer inspiration in realizing safe and efficient gene therapy in humans.

systems biology↗

bioRxiv2021

Structural Covariance Networks in Post-Traumatic Stress Disorder: A Multisite ENIGMA-PGC Study

IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subjects data from 29 cohorts in five countries (n=3439). MethodsUsing Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN. ResultsNotable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comorbid PTSD and MDD showed higher CT-based centrality in the right anterior cingulate gyrus, right parahippocampal gyrus and lower SA-based centrality in left insular gyrus. ConclusionUnlike previous studies with smaller sample sizes ([≤]318), our study found differences in centrality measures using a sample size of 3439 subjects. This is the first cross-sectional study to examine SCN interactions with age, sex, and comorbid MDD. Although limited to group level inferences, centrality measures offer insights into a nodes relationship to the entire functional connectome unlike approaches like seed-based connectivity or independent component analysis. Nodes having higher centrality have greater structural or functional connections, lending them invaluable for translational treatments like neuromodulation.

neuroscience↗

bioRxiv2021

Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes

There is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel aerosolization route to treat SARS-CoV-2 infections efficiently. However, it remains unknown if they possess broadly neutralizing activities against the prevalent circulating strains. We found that potent neutralizing Nbs are highly resistant to the convergent variants of concern that evade a large panel of neutralizing antibodies (Abs) and significantly reduce the activities of convalescent or vaccine-elicited sera. Subsequent determination of 9 high-resolution structures involving 6 potent neutralizing Nbs by cryoelectron microscopy reveals conserved and novel epitopes on virus spike inaccessible to Abs. Systematic structural comparison of neutralizing Abs and Nbs provides critical insights into how Nbs uniquely target the spike to achieve high-affinity and broadly neutralizing activity against the evolving virus. Our study will inform the rational design of novel pan-coronavirus vaccines and therapeutics.

biophysics↗

bioRxiv2021

Spatiotemporal organization of BamA governs the pattern of outer membrane protein distribution in growing Escherichia coli cells

The outer membrane (OM) of Gram-negative bacteria is a robust protective barrier that excludes major classes of antibiotics. The assembly, integrity and functioning of the OM is dependent on {beta}-barrel outer membrane proteins (OMPs), the insertion of which is catalyzed by BamA, the core component of the {beta}-barrel assembly machine (BAM) complex. Little is known about BamA in the context of its native OM environment. Here, using high-affinity fluorescently-labelled antibodies in combination with diffraction-limited and super-resolution fluorescence microscopy, we uncover the spatial and temporal organization of BamA in live Escherichia coli K-12 cells. BamA is clustered into ~150 nm diameter islands that contain an average of 10-11 BamA molecules, in addition to other OMPs, and are distributed throughout the OM and which migrate to the poles during growth. In stationary phase cells, BamA is largely confined to the poles. Emergence from stationary phase coincides with new BamA-containing islands appearing on the longitudinal axis of cells, suggesting they are not seeded by pre-existing BamAs but initiate spontaneously. Consistent with this interpretation, BamA-catalyzed OMP biogenesis is biased towards non-polar regions. Cells ensure the capacity for OMP biogenesis is uniformly distributed during exponential growth, even if the growth rate changes, by maintaining an invariant density of BamA-containing OMP islands (~9 islands/m2) that only diminishes as cells enter stationary phase, the latter change governing what OMPs predominate as cells become quiescent. We conclude that OMP distribution in E. coli is driven by the spatiotemporal organisation of BamA which varies with the different phases of growth. SignificanceThe integrity and functioning of the outer membrane (OM) of Gram-negative bacteria depends on the {beta}-barrel assembly machinery (BAM). Although the structure and the mechanism of the complex have been widely explored, little information exists about the organization of the BAM complex and how it dictates protein distribution in the OM. Here, we utilized highly specific monoclonal antibodies to study the spatiotemporal organization of BamA, the key component of this complex. We reveal that BAM organization is dynamic and tightly linked to the cells growth phase. We further discover that the rate of BAM facilitated OMP biogenesis is significantly reduced near the poles. In turn, these features govern the biogenesis patterns and the distribution of OMPs on the cell surface.

microbiology↗

bioRxiv2020

SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging

Since the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified recombinant viral components and inactivated viruses. However, investigation of the SARS-CoV-2 infection in the native cellular context is scarce, and there is a lack of comprehensive knowledge on SARS-CoV-2 replicative cycle. Understanding the genome replication, assembly and egress of SARS-CoV-2, a multistage process that involves different cellular compartments and the activity of many viral and cellular proteins, is critically important as it bears the means of medical intervention to stop infection. Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Our results reveal at the whole cell level profound cytopathic effects of SARS-CoV-2 infection, exemplified by a large amount of heterogeneous vesicles in the cytoplasm for RNA synthesis and virus assembly, formation of membrane tunnels through which viruses exit, and drastic cytoplasm invasion into nucleus. Furthermore, cryoET of cell lamellae reveals how viral RNAs are transported from double-membrane vesicles where they are synthesized to viral assembly sites; how viral spikes and RNPs assist in virus assembly and budding; and how fully assembled virus particles exit the cell, thus stablishing a model of SARS-CoV-2 genome replication, virus assembly and egress pathways.

microbiology↗

bioRxiv2020

CryoET structures of immature HIV Gag reveal a complete six-helix bundle and stabilizing small molecules distinct from IP6

Gag is the major HIV-1 structural polyprotein precursor. The Gag SP1 domain with the last residues of CA have been hypothesized to form a six-helix bundle necessary for particle assembly, but this bundle has not been fully resolved. Here, we determined the structures of complete CA-SP1 six-helix bundle connecting to the NC domain, from both in vitro Gag assemblies and viral-like particles (VLPs) carrying a T8I mutation in SP1, to near-atomic resolutions using cryoET and subtomogram averaging. The structures revealed novel densities, however distinct from IP6, inside the six-helix bundle of Gag assemblies, stabilizing the immature lattice. Interestingly, the T8I mutation impaired proteolytic cleavage of Gag at both SP1 boundaries. Our findings signify the involvement of small molecules in immature Gag assembly and provide the structural basis for development of small molecule inhibitors that stabilize SP1 helix, thus interfere with PR-mediated virus maturation.

microbiology↗

bioRxiv2020

Response of land use change and ecosystem services based on different functional scenarios: Case study of Nanjing

Land Use/Land Cover Change (LUCC) is one of the important reasons for the change of ecosystem services (ESs). Due to the uncertainty of future development policies and the complexity of LUCC, assessing the impact of future urban sprawl on ecosystem services remains challenging. We simulated the effect of urban land-use change on ESs on the basis of different functional scenarios, which is of important value to urban land-use planning and ESs protection. In our study, we designed three scenarios: Production function priority scenario (PFP scenario) Living function priority scenario (LFP scenario) Ecological function priority scenario (EFP Scenario). And we used the GeoSOS-FLUS software to realize visualization. Based on invest model, we evaluated five types of ESs: carbon storage, warter yield, habitat quality, water purification and soil conservation. Research showed that from 2000 to 2015, carbon storage, habitat quality and water production in Nanjing decreased significantly, soil conservation increased slightly, and the performance of the two indicators for water purification was not consistent. From different scenarios, carbon storage and habitat quality were the highest in EFP scenario, water yield was the highest in PFP scenario and soil conservation was the highest in LFP scenario. We analyzed the trade-offs among various ESs, found that the change of land-use types in cities does not fundamentally change the trade-offs among various ESs. We believed that the determination of the main function of LUCC was the first condition to judge the applicability of scenario, and the scenario simulation which integrated the main function of the city could provide more references for the related research.

ecology↗

bioRxiv2020

Divergent DNA methylation signatures underlying X chromosome regulation in marsupials and eutherians

X chromosome inactivation (XCI) mediated by differential DNA methylation between sexes is well characterized in eutherian mammals. Although XCI is shared between eutherians and marsupials, the role of DNA methylation in marsupial XCI remains contested. Here we examine genome-wide signatures of DNA methylation from methylation maps across fives tissues from a male and female koala (Phascolarctos cinereus) and present the first whole genome, multi-tissue marsupial "methylome atlas." Using these novel data, we elucidate divergent versus common features of marsupial and eutherian DNA methylation. First, tissue-specific differential DNA methylation in marsupials primarily occurs in gene bodies. Second, females show significant global reduction (hypomethylation) of X chromosome DNA methylation compared to males. We show that this pattern is also observed in eutherians. Third, on average, promoter DNA methylation shows little difference between male and female koala X chromosomes, a pattern distinct from that of eutherians. Fourth, the sex-specific DNA methylation landscape upstream of Rsx, the primary lncRNA associated with marsupial XCI, is consistent with the epigenetic regulation of female-(and presumably inactive X chromosome-) specific expression. Finally, we utilize the prominent female X chromosome hypomethylation and classify 98 previously unplaced scaffolds as X-linked, contributing an additional 14.6 Mb (21.5 %) to genomic data annotated as the koala X chromosome. Our work demonstrates evolutionarily divergent pathways leading to functionally conserved patterns of XCI in two deep branches of mammals.

evolutionary biology↗