Biology subjects

Liu, Y.

Publications and source records attributed to Liu, Y..

At least 1,567 records · Page 87Linked to original sources

bioRxiv2023

Individualized network analysis reveals a link between the gut microbiome, diet intervention and Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM), a serious complication during pregnancy which is defined by abnormal glucose regulation, is commonly treated by diabetic diet and lifestyle changes. While recent findings place the microbiome as a natural mediator between diet interventions and diverse disease states, its role in GDM is still unknown. Here, based on observation data from healthy pregnant control group and GDM patients, we developed a new network approach using patterns of co-abundance of microorganism to construct microbial networks that represent human-specific information about gut microbiota in different groups. By calculating network similarity in different groups, we analyze the gut microbiome from 27 GDM subjects collected before and after two weeks of diet therapy compared with 30 control subjects to identify the health condition of microbial community balance in GDM subjects. Although the microbial communities remain similar after the diet phase, we find that the structure of their inter-species co-abundance network is significantly altered, which is reflected in that the ecological balance of GDM patients was not "healthier" after the diet intervention. In addition, we devised a method for individualized network analysis of the microbiome, thereby a pattern is found that individuals with large deviations in microbial networks are usually accompanied by their abnormal glucose regulation. This approach may help the development of individualized diagnosis strategies and microbiome-based therapies in the future. Author SummaryIn this study, we aimed to investigate the role of the gut microbiome in gestational diabetes mellitus (GDM), a condition that affects pregnant women and is characterized by abnormal glucose regulation. Specifically, we asked whether and how the gut microbiome is affected by diabetic diet which is commonly used to treat GDM patients. We developed a new network approach to analyze patterns of co-abundance of microorganisms in the gut microbiota of GDM patients and healthy pregnant women. Our findings show that although the microbial communities remained similar after the diet phase, the structure of their inter-species co-abundance network was significantly altered, indicating that the ecological balance of GDM patients was not "healthier" after the diet intervention. Furthermore, we suggest that abnormal glucose regulation is associated with large network deviations, which could lead to the development of individualized microbiome-based therapies in the future. Our work highlights the importance of studying the microbiome from a network perspective to better understand the dynamic interactions among microorganisms in the community balance of the microbiome.

systems biology↗

bioRxiv2023

Detection of interactions between genetic marker sets and environment in a genome-wide study of hypertension

As human complex diseases are influenced by the interplay of genes and environment, detecting gene-environment interactions (G x E) can shed light on biological mechanisms of diseases and play an important role in disease risk prediction. Development of powerful quantitative tools to incorporate G x E in complex diseases has potential to facilitate the accurate curation and analysis of large genetic epidemiological studies. However, most of existing methods that interrogate G x E focus on the interaction effects of an environmental factor and genetic variants, exclusively for common or rare variants. In this study, we proposed two tests, MAGEIT_RAN and MAGEIT_FIX, to detect interaction effects of an environmental factor and a set of genetic markers containing both rare and common variants, based on the MinQue for Summary statistics. The genetic main effects in MAGEIT_RAN and MAGEIT_FIX are modeled as random or fixed, respectively. Through simulation studies, we illustrated that both tests had type I error under control and MAGEIT_RAN was overall the most powerful test. We applied MAGEIT to a genome-wide analysis of gene-alcohol interactions on hypertension in the Multi-Ethnic Study of Atherosclerosis. We detected two genes, CCNDBP1 and EPB42, that interact with alcohol usage to influence blood pressure. Pathway analysis identified sixteen significant pathways related to signal transduction and development that were associated with hypertension, and several of them were reported to have an interactive effect with alcohol intake. Our results demonstrated that MAGEIT can detect biologically relevant genes that interact with environmental factors to influence complex traits.

genetics↗

bioRxiv2023

Lymphoid tissues contribute to viral clonotypes present in plasma at early post-ATI in SIV-infected rhesus macaques

The rebound-competent viral reservoir (RCVR), comprised of virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after antiretroviral therapy interruption (ATI), remains the biggest obstacle to the eradication of HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop targeted therapeutic strategies for reducing the RCVR. In this study, barcoded SIVmac239M was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood, lymphoid tissues (LTs, spleen, mesenteric and inguinal lymph nodes), and non-lymphoid tissues (NLTs, colon, ileum, lung, liver, and brain) were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX/RNAscope/in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy although plasma viral RNA remained < 22 copies/mL. Among the tissues studied, mesenteric and inguinal lymph nodes, and spleen contained viral barcodes detected in plasma, and trended to have higher cell-associated viral loads, higher intact provirus levels, and greater diversity of viral barcodes. CD4+ T cells were the main cell type harboring viral RNA (vRNA) after ATI. Further, T cell zones in LTs showed higher vRNA levels than B cell zones for most animals. These findings are consistent with LTs contributing to virus present in plasma early after ATI. One Sentence SummaryThe reemerging of SIV clonotypes at early post-ATI are likely from the secondary lymphoid tissues.

immunology↗

bioRxiv2023

Urinary protein changes during the short-term growth and development of rats

Can the urine proteome reflect short-term changes in the growth and development of animals? Do short-term developmental effects on urinary protein need to be considered when performing urine marker studies using model animals with faster growing periods? In this study, urine samples were collected from 10 Wistar rats aged 6-8 weeks 3 and 6 days apart. The results showed that the urine proteome could sensitively reflect short-term growth and development in rats. For example, comparing the urine proteome of Day 0 and Day 6, 195 differential proteins were identified after screening (FC [≥] 1.5 or [≤] 0.67, P < 0.05), and verified by randomization, the average number of randomly generated differential proteins was 17.99. At least 90.77% of the differential proteins were not randomly generated. This finding demonstrates that the differential proteins identified in the samples collected at different time points were not randomly generated. A large number of biological processes and pathways related to growth and development were enriched, which shows that the urine proteome reflects the short-term growth and development of rats, and provides a means for in-depth and meticulous study of growth and development. Moreover, an interfering factor in animal experiments using 6-to 8-week-old rats to construct models was identified. The results of this study demonstrated that there were differences in the urinary proteome in rats aged 6-8 weeks only 3-6 days apart, which suggests that the sensitivity of urinary proteomics is high and shows the sensitive and precise response of the urinary proteome to body changes.

biochemistry↗

bioRxiv2023

TPR domain assigns versatility of BcTir/Tpr system against viral infection

NAD+-derived signal produced by TIR domain triggered the host immune responses. The ubiquitous TPR domain involved in signal recognition and effector activation were found widely assembled with the TIR domain. However, the immune roles of these assemblies remain elusive. Here, a two-gene operon, one containing a TIR domain, designated as BcTir, and the other, BcTpr, from Bacillus cereus, exhibited anti-phage immunity. BcTpr, but not BcTir, exhibited NADase activity to produce the cyclic ADPR (cADPR) isomer and mediate NAD+ depletion. Noticeably, the truncated N terminus of BcTpr only depleted NAD+ unless at the presence of TPR domain to generate cADPR isomer unveiling its role played for glycosite selection. In addition, the BcTir/Tpr system significantly repressed viral proliferation and increased oxidation resistance by scavenging excessive reactive oxygen species (ROS) upon phage infection. These findings unraveled a multifunctional role of the BcTir/Tpr system during immune responses. In BriefThe bacterial BcTir/Tpr system was identified with the ability to protect against phage infection via NAD+ depletion, viral replication repression, and ROS homeostasis, in which BcTpr played a dual role in NAD+-derived signal production and NAD+ depletion. HighlightsO_LIThe BcTir/Tpr system works as a BcTir-BcTpr complex against phage infection. C_LIO_LIBcTpr, instead of BcTir, generates the NAD+-derived cADPR isomer through its glycosidase domain at N terminus. C_LIO_LIThe amount of cADPR isomer production is regulated by the helix numbers of the TPR domain at C terminus of BcTpr. C_LIO_LIThe BcTir/Tpr system can depress phage proliferation and decrease ROS production upon phage infection. C_LI

microbiology↗

bioRxiv2023

Theoretical framework and experimental solution for the air-water interface adsorption problem in cryoEM

As cryogenic electron microscopy (cryoEM) gains traction in the structural biology community as a method of choice for determining atomic structures of biological complexes, it has been increasingly recognized that many complexes that behave well under conventional negative-stain electron microscopy tend to have preferential orientation, aggregate or simply mysteriously "disappear" on cryoEM grids, but the reasons for such misbehavior are not well understood, limiting systematic approaches to solving the problem. Here, we have developed a theoretical formulation that explains these observations. Our formulation predicts that all particles migrate to the air-water interface (AWI) to lower the total potential surface energy -- rationalizing the use of surfactant, which is a direct solution to reducing the surface tension of the aqueous solution. By conducting cryogenic electron tomography (cryoET) with the widely-tested sample, GroEL, we demonstrate that, in a standard buffer solution, nearly all particles migrate to the AWI. Gradual reduction of the surface tension by introducing surfactants decreased the percentage of particles exposed to the surface. By conducting single-particle cryoEM, we confirm that applicable surfactants do not damage the biological complex, thus suggesting that they might offer a practical, simple, and general solution to the problem for high-resolution cryoEM. Application of this solution to a real-world AWI adsorption problem with a more challenging membrane protein, namely, the ClC-1 channel, has led to its first near-atomic structure using cryoEM.

biophysics↗

bioRxiv2023

Spp1 secreted by macrophages impairs osteogenic ability of Ctsk+Fmod+ periosteal cells in jaw bone

Periosteum, which covers the surface of most bones, mediates bone regeneration through endochondral ossification during fracture repair and intramembranous ossification under steady state. Periosteal cells (PCs) of jaw bones are different from those of long bones in phenotypic characteristics and functions. So far, the role of periosteum in jaw bones during bone grafting remain unclarified. Here we propose a subperiosteal bone grafting model based on the clinical procedures. By integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic (ST), we found a functional Ctsk+Fmod+ subset of PCs in jaw bones. The Ctsk+Fmod+ PCs had the potential of multi-directional differentiation. Furthermore, Spp1 secreted by macrophages could impair the osteogenic capacity of Ctsk+Fmod+ PCs, which could be partly rescued by blocking Spp1. The identification of this Ctsk+Fmod+ subclusters, which shows osteoprogenitor characteristics and close interaction with macrophages, reveals the heterogeneity of periosteal cells in jaw bones, and may provide target of intervention to improve osteogenesis during bone augmentation surgery.

cell biology↗

bioRxiv2023

Data Efficiency Semi-Supervised Meta-Learning Elucidates Understudied Interspecies Molecular Interactions

Many biological problems are understudied due to experimental limitations and human biases. Although deep learning is promising in accelerating scientific discovery, its power compromises when applied to problems with scarcely labeled data and data distribution shifts. We developed a semi-supervised meta learning framework Meta Model Agnostic Pseudo Label Learning (MMAPLE) to address these challenges by effectively exploring out-of-distribution (OOD) unlabeled data when transfer learning fails. The power of MMAPLE is demonstrated in multiple applications: predicting OOD drug-target interactions, hidden human metabolite-enzyme interactions, and understudied interspecies microbiome metabolite-human receptor interactions, where chemicals or proteins in unseen data are dramatically different from those in training data. MMAPLE achieves 11% to 242% improvement in the prediction-recall on multiple OOD benchmarks over baseline models. Using MMAPLE, we reveal novel interspecies metaboliteprotein interactions that are validated by bioactivity assays and fill in missing links in microbiome-human interactions. MMAPLE is a general framework to explore previously unrecognized biological domains beyond the reach of present experimental and computational techniques.

systems biology↗

bioRxiv2023

Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide

The eukaryotic cytosolic Fe-S protein assembly (CIA) machinery inserts iron-sulfur (Fe-S) clusters into cytosolic and nuclear proteins. In the final maturation step, the Fe-S cluster is transferred to the apo-proteins by the CIA-targeting complex (CTC). However, the molecular recognition determinants of client proteins are unknown. We show that a conserved [LIM]-[DES]-[WF]-COO- tripeptide present at the C-terminus of clients is necessary and sufficient for binding to the CTC in vitro and directing Fe-S cluster delivery in vivo. Remarkably, fusion of this TCR (target complex recognition) signal enables engineering of cluster maturation on a non-native protein via recruitment of the CIA machinery. Our study significantly advances our understanding of Fe-S protein maturation and paves the way for bioengineering applications. One-Sentence SummaryA C-terminal tripeptide guides eukaryotic iron-sulfur cluster insertion into cytosolic and nuclear proteins.

biochemistry↗

bioRxiv2023

Tumor Cytokine-Induced Hepatic Gluconeogenesis Contributes to Cancer Cachexia: Insights from Full Body Single Nuclei Sequencing

SummaryA primary cause of death in cancer patients is cachexia, a wasting syndrome attributed to tumor-induced metabolic dysregulation. Despite the major impact of cachexia on the treatment, quality of life, and survival of cancer patients, relatively little is known about the underlying pathogenic mechanisms. Hyperglycemia detected in glucose tolerance test is one of the earliest metabolic abnormalities observed in cancer patients; however, the pathogenesis by which tumors influence blood sugar levels remains poorly understood. Here, utilizing a Drosophila model, we demonstrate that the tumor secreted interleukin-like cytokine Upd3 induces fat body expression of Pepck1 and Pdk, two key regulatory enzymes of gluconeogenesis, contributing to hyperglycemia. Our data further indicate a conserved regulation of these genes by IL-6/JAK STAT signaling in mouse models. Importantly, in both fly and mouse cancer cachexia models, elevated gluconeogenesis gene levels are associated with poor prognosis. Altogether, our study uncovers a conserved role of Upd3/IL-6/JAK-STAT signaling in inducing tumor-associated hyperglycemia, which provides insights into the pathogenesis of IL-6 signaling in cancer cachexia. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=162 HEIGHT=200 SRC="FIGDIR/small/540823v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@508c1aorg.highwire.dtl.DTLVardef@1e1eecorg.highwire.dtl.DTLVardef@1802559org.highwire.dtl.DTLVardef@140e6c_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2023

GbyE: A New Genome Wide Association and Prediction Model based on Genetic by Environmental Interaction

Nowadays, studies on genetic by environment interactions (GxE) are receiving increasing attention because of its theoretical and practical importance in explaining individual behavioral traits. Use information from different environments to improve the statistical power of genome-wide association and prediction in the hope of obtaining individuals with better breeding value is the most expedient way. However, there are significant challenges when performing genome-wide association studies (GWAS) and genomic selection (GS) using multiple environments or traits, mainly because most diseases and quantitative traits have numerous associated loci with minimal effects. Therefore, this study constructed a new genotype design model program (GbyE) for genome-wide association and prediction using Kronecker product, which can enhance the statistical power of GWAS and GS by utilizing the interaction effects of multiple environments or traits. The data of 282 maize, 354 yaks and 255 peaches were used to evaluate the power of the model at different levels of heritability and genetic correlation. The results show that GbyE can provide higher statistical power for the traditional GWAS and GS models in any heritability and genetic correlation, and can detect more real loci. In addition, GbyE has increased statistical power to three Bayesian models (BRR, BayesA, and BayesCpi). GbyE can make full use of multiple environment or trait informations to increase the statistical power of the model, which can help us understand the GxE and provide a method for predicting association loci for complex traits.

bioinformatics↗

bioRxiv2023

DeSide: A unified deep learning approach for cellular decomposition of bulk tumors based on limited scRNA-seq data

Cellular decomposition employing bulk RNA-sequencing (RNA-seq) has been consistently under investigation due to its high fidelity, ease of use, and cost-effectiveness compared to single cell RNA-sequencing (scRNA-seq). However, the intricate nature of the tumor microenvironment, and the significant heterogeneity among patients and cells have made it challenging to precisely evaluate the cellular composition of solid tumors using a unified model. In this work, we developed DeSide, a deep learning and single-cell decomposition method for solid tumors, to estimate proportions of cell types presented in tumor samples. Our new deep neural network (DNN) architecture considers only non-cancerous cells during the training process, indirectly calculating the proportion of cancerous cells. This approach avoids directly handling the often more variable heterogeneity of cancerous cells, and instead leverages scRNA-seq data from three different cancer types to empower the DNN model with a robust generalization capability across diverse cancers. Additionally, we used a new sampling method and filtering strategies to simulate the gene expression profiles (GEPs) of solid tumors, creating a carefully controlled training set that could be compared to the bulk RNA-seq data from The Cancer Genome Atlas (TCGA), a database of bulk RNA-seq data collected from cancer patients. Relying on limited yet diverse scRNA-seq data, our approach outperformed current methods in accurately predicting the celluar composition of samples from TCGA and an additional validation set. Furthermore, we demonstrated that the predicted cellular composition can be utilized to stratify cancer patients into different groups with varying overall survival rates. With increased availability of scRNA-seq data for various types of tumors, DeSide holds the potential for a more precise cellular decomposition model using bulk RNA-seq.

bioinformatics↗

bioRxiv2023

The Host Adapted Fungal Pathogens of Pneumocystis Genus Utilize Genic Regional Centromeres

Centromeres are constricted chromosomal regions that are essential for cell division. In eukaryotes, centromeres display a remarkable architectural and genetic diversity. The basis of centromere accelerated evolution remains elusive. Here we focused on Pneumocystis species, a group of Mammalian-specific fungal pathogens that form a sister taxon with that of the Schizosaccharomyces pombe, an important genetic model for centromere biology research. Methods allowing reliable continuous culture of Pneumocystis species do not currently exist, precluding genetic manipulation. CENP-A, a variant of histone H3, is the epigenetic marker that defines centromeres in most eukaryotes. Using heterologous complementation, we show that the Pneumocystis CENP-A ortholog is functionally equivalent to CENP-ACnp1 of Schizosaccharomyces pombe. Using organisms from a short-term in vitro culture or infected animal models and ChIP-Seq, we identified CENP-A bound regions in two Pneumocystis species that diverged [~]35 million years ago. Each species has a unique short regional centromere (< 10kb) flanked by heterochromatin in 16-17 monocentric chromosomes. They span active genes and lack conserved DNA sequence motifs and repeats. These features suggest an epigenetic specification of centromere function. Analysis of centromeric DNA across multiple Pneumocystis species suggest a vertical transmission at least 100 million years ago. Common ancestry of Pneumocystis and S. pombe centromeres is untraceable at the DNA level but the overall architectural similarity could be the result of functional constraint for successful chromosomal segregation. Significance StatementPneumocystis species offer a suitable genetic system to study centromere evolution in pathogens because of their phylogenetic proximity with the nonpathogenic yeast Schizosaccharomyces pombe, a popular model for cell biology. We used this system to explore how centromeres have evolved after divergence of the two clades [~]460 million years ago. To address this question, we established a protocol combining short-term culture and ChIP-Seq to characterize centromeres in multiple Pneumocystis species. We show that Pneumocystis have short epigenetic centromeres that function differently from those in S. pombe. One sentence summaryInsights into the formation of genic centromeres in fungal pathogens.

genomics↗

bioRxiv2023

Transcript errors generate a continuous stream of amyloid and prion-like proteins in human cells

Aging is characterized by the accumulation of amyloid and prion-like proteins. However, the molecular mechanisms by which these proteins arise remain unclear. Here, we demonstrate that transcript errors generate amyloid and prion-like proteins in a wide variety of human cell types, including stem cells, brain organoids, and fully differentiated neurons. Intriguingly, some of these proteins are identical to proteins previously implicated in familial cases of amyloid diseases, raising the possibility that both familial and non-familial cases are caused by identical mutant proteins. However, transcript errors also generate amyloid proteins that have not been observed before, suggesting that aging cells are exposed to a second class of pathogenic proteins we are currently unaware of. Finally, we show that transcript errors are readily generated by DNA damage, a hallmark of human aging and a staple of multiple proteotoxic diseases, including Alzheimers disease. Together, these observations greatly expand our understanding of mutagenesis in human aging and disease and suggest a new mechanism by which amyloid diseases can develop.

molecular biology↗

bioRxiv2023

Regulatory mechanisms in multiple vascular diseases locus LRP1 involve repression by SNAIL and extracellular matrix remodeling

BackgroundGenome-wide association studies (GWAS) implicate common genetic variations in the low-density lipoprotein receptor-related protein 1 locus (LRP1) in risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown. MethodsFine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells (iPSC) were genome-edited using CRISPR-Cas9 to delete or modify candidate enhancer regions, and generate LRP1 knockout cell lines (KO). Cells were differentiated into smooth muscle cells (SMCs) through a mesodermal lineage. Transcription regulation was assessed using luciferase reporter assay, transcription factor knockdown and chromatin immunoprecipitation. Phenotype changes in cells were conducted using cellular assays, bulk RNA-sequencing and mass spectrometry. ResultsMulti-trait co-localization analyses pointed at rs11172113 as the most likely causal variant in LRP1 for fibromuscular dysplasia, migraine, pulse pressure and pulmonary function trait. We found rs11172113-T allele to associate with higher LRP1 expression. Genomic deletion in iPSC-derived SMCs supported rs11172113 to locate in an enhancer region regulating LRP1 expression. We found transcription factors MECP2 and SNAIL to repress LRP1 expression through an allele-specific mechanism, involving SNAIL interaction with disease risk allele. LRP1 KO decreased iPSC-derived SMCs proliferation and migration. Differentially expressed genes were enriched for collagen-containing extracellular matrix, connective tissue and lung development. LRP1 KO showed potentiated canonical TGF-{beta} signaling through enhanced phosphorylation of SMAD2/3. Analyses of protein content of decellularized extracts indicated partial extracellular matrix (ECM) remodeling involving enhanced secretion of CYR61, a known LRP1 ligand involved in vascular integrity and TIMP3, implicated in extracellular matrix maintenance and also known to interact with LRP1. ConclusionsOur findings support allele specific LRP1 gene repression by the endothelial-to-mesenchymal transition regulator SNAIL. We propose decreased LRP1 expression in SMCs to remodel the ECM enhanced by TGF- {beta} as a potential mechanism of this pleiotropic locus for vascular diseases. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/539992v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@11926a8org.highwire.dtl.DTLVardef@390a37org.highwire.dtl.DTLVardef@cdad4dorg.highwire.dtl.DTLVardef@12cbf92_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2023

Theranostic gold in a gold cage nanoparticle for photothermal ablation and photoacoustic imaging of skin and oral infections

AbstractBiofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we describe a unique structure of dextran coated gold in a gold cage nanoparticle that enables photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser can selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observe a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections respectively. These effects were over 100 times greater than that seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We conclude that photothermal ablation using theranostic nanoparticles is a rapid, precise, and non-toxic method to detect and treat biofilm-associated infections.

bioengineering↗

bioRxiv2023

Sulfur oxidation and reduction are coupled to nitrogen fixation in the roots of a salt marsh foundation plant species

Symbiotic root microbiota are crucial for plant growth as they assist their hosts in nutrient acquisition. In the roots of coastal marine plants, heterotrophic activity in the rhizosphere by sulfate-reducing microorganisms has been linked to nitrogen fixation. In this study, we recovered 239 high-quality metagenome-assembled genomes (MAGs) from a salt marsh dominated by the foundation plant Spartina alterniflora, including diazotrophic sulfate-reducing and sulfur-oxidizing bacteria thriving in the root compartment. Here we show for the first time that highly-abundant sulfur-oxidizing bacteria in the roots of a coastal macrophyte encode and highly express genes for nitrogen fixation (nifHDK). Further, we leveraged a S. alterniflora biomass gradient to gain a mechanistic understanding on how root-microbe interactions respond to abiotic stress from anoxia and elevated sulfide concentration. We observed that the roots of the stressed S. alterniflora phenotype exhibited the highest rates of nitrogen fixation and expression levels of both the oxidative and reductive forms of the dissimilatory sulfite reductase gene (dsrAB). Approximately 25% and 15% of all sulfur-oxidizing dsrA and nitrogen-fixing nifK transcripts, respectively, were associated with novel MAGs of the Candidatus Thiodiazotropha genus in the roots of the stressed S. alterniflora phenotype. We conclude that the rapid cycling of sulfur in the dynamic S. alterniflora root zone is coupled to nitrogen fixation during both reductive and oxidative sulfur reactions, and that the S. alterniflora - Ca. Thiodiazotropha symbiosis is an adaptive response to anoxic and sulfidic sediment conditions, whereby the plants benefit from reduced sulfide toxicity and potential nitrogen acquisition.

microbiology↗

bioRxiv2023

Exploring the Role of Spatial Confinement in Immune Cell Recruitment and Regeneration of Skin Wounds

Microporous annealed particle (MAP) scaffolds are injectable granular materials comprised of micron sized hydrogel particles (microgels). The diameter of these microgels directly determines the size of the interconnected void space between particles where infiltrating or encapsulated cells reside. This tunable porosity allows us to use MAP scaffolds to study the impact of spatial confinement (SC) on both cellular behaviors and the host response to biomaterials. Despite previous studies showing that pore size and SC influence cellular phenotypes, including mitigating the macrophage inflammatory response, there is still a gap in knowledge regarding how SC within a biomaterial modulates immune cell recruitment in vivo in wounds and implants. Thus, we studied the immune cell profile within confined and unconfined biomaterials using small (40 m), medium (70 m), and large (130 m) diameter spherical microgels, respectively. We discovered that MAP scaffolds imparted regenerative wound healing with an IgG1-biased Th2 response. MAP scaffolds generated from 130 m diameter microgels have a median pore size that can accommodate [~]40 {micro}m diameter spheres induced a more balanced pro-regenerative macrophage response and better wound healing outcomes with more mature collagen regeneration and reduced levels of inflammation.

bioengineering↗