Biology subjects

Zhou, X.

Publications and source records attributed to Zhou, X..

At least 235 records · Page 13Linked to original sources

bioRxiv2024

ELLA: Modeling Subcellular Spatial Variation of Gene Expression within Cells in High-Resolution Spatial Transcriptomics.

Spatial transcriptomic technologies are becoming increasingly high-resolution, enabling precise measurement of gene expression at the subcellular level. Here, we introduce a computational method called subcellular expression localization analysis (ELLA), for modeling the subcellular localization of mRNAs and detecting genes that display spatial variation within cells in high-resolution spatial transcriptomics. ELLA creates a unified cellular coordinate system to anchor diverse cell shapes and morphologies, utilizes a nonhomogeneous Poisson process to model spatial count data, leverages an expression gradient function to characterize subcellular expression patterns, and produces effective control of type I error and high statistical power. We illustrate the benefits of ELLA through comprehensive simulations and applications to four spatial transcriptomics datasets from distinct technologies, where ELLA not only identifies genes with distinct subcellular localization patterns but also associates these patterns with unique mRNA characteristics. Specifically, ELLA shows that genes enriched in the nucleus exhibit an abundance of long noncoding RNAs or protein-coding mRNAs, often characterized by longer gene lengths. Conversely, genes containing signal recognition peptides, encoding ribosomal proteins, or involved in membrane related activities tend to enrich in the cytoplasm or near the cellular membrane. Furthermore, ELLA reveals dynamic subcellular localization patterns during the cell cycle, with certain genes showing decreased nuclear enrichment in the G1 phase while others maintain their enrichment patterns throughout the cell cycle. Overall, ELLA represents a calibrated, powerful, robust, scalable, and versatile tool for modeling subcellular spatial expression variation across diverse high-resolution spatial transcriptomic platforms.

genomics↗

bioRxiv2024

High-Dimensional Mediation Analysis with Network Mediators: Applications to Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with survivors frequently experiencing long-term neurocognitive morbidities. Here, we utilize the TOTXVI clinical trial data to elucidate the mechanisms underlying treatment-related neurocognitive side effects in pediatric ALL patients by incorporating brain connectivity network data. To enable such analysis, we propose a high-dimensional mediation analysis method with a novel network mediation structural shrinkage (NMSS) prior, which is particularly suited for analyzing high-dimensional brain structural connectivity network data that serve as mediators. Our method is capable of addressing the structural dependencies of brain connectivity networks including sparsity, effective degrees of nodes, and modularity, yielding accurate estimates of the high-dimensional coefficients and mediation effects. We demonstrate the effectiveness and superiority of the proposed NMSS method through simulation studies and apply it to the TOTXVI data, revealing significant mediation effects of brain connectivity on visual processing speed directed by IT intensity. The findings shed light on the potential of targeted interventions to mitigate neurocognitive deficits in pediatric ALL survivors.

cancer biology↗

bioRxiv2024

Microbial Degradation of Contaminants of Emerging Concern by Pseudomonas putida in Wastewater Treatment Plants

Contaminants of Emerging Concern (CECs) are a class of contaminants that are commonly found in urban wastewater treatment plants (WWTP) at low concentrations. These compounds include antibiotic drugs, personal care products, and industrial chemicals, which are widely used in modern society. Although they provide undeniable benefits in our daily lives, their accumulation in the environment poses a significant risk to human health and the ecosystem. Due to the incomplete removal of these compounds by traditional WWTPs, there is a need to understand the interactions between microbes and CECs to develop effective solutions to this environmental challenge. Pseudomonas putida is a bacterium commonly found in water-related habitats, including freshwater streams, forests, and WWTPs. It is known for its ability to degrade various organic compounds, making it a suitable model for understanding the linkages between bacterial enzymes and CECs found in WWTPs. In this study, isolated Pseudomonas putida strain KT2440 was cultured in lab-scale reactors to mimic the WWTP environment. The degradation of this isolated strain towards different groups of CECs were studied over a 24-hour period using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Mass spectrometry-based quantitative proteomics was also performed at different sampling points to establish a linkage between the enzyme expression profile of this strain and its degradation of CECs via bioinformatics analysis. The results of this study demonstrated that Pseudomonas putida KT2440 is capable of degrading atrazine, acetamiprid, carbendazim, diclofenac acid, erythromycin, and sulfamethazine at lab scale. At the 20-hour time point, the enzyme expression profile indicated a high protein abundance of various oxidoreductases that could explain the observed CEC degradation.The studys findings provide important insights into the potential of Pseudomonas putida as a bioremediation agent for CECs in WWTPs. The degradation of CECs by Pseudomonas putida KT2440 is a significant contribution to the bioremediation process, and its enzyme expression profile can serve as a case study for more complex interactions of microbes and CECs in real WWTPs. Furthermore, this study supports the potential of Pseudomonas putida as a promising strain for various bioremediation applications. Finally, this studys results can help develop more efficient and effective methods for removing CECs from wastewater, which can contribute to the protection of public health and the environment.

microbiology↗

bioRxiv2024

Intermittent Perturbation with High-Frequency Aerobic-Anoxic Cycling Enhances N2O Reductase Activity during Wastewater Treatment

Nitrous oxide (N2O) emissions from wastewater treatment plants, with a warming potential 298 times that of CO2, pose a significant challenge to lowering their carbon footprint. Current mitigation strategies focus on limiting N2O formation during nitrification and denitrification but overlook microbial reduction mechanisms. This study examines the potential for enhancing nitrous oxide reductase (NosZ) activity to reduce N2O to N2. We hypothesize that strategic oxygen manipulation can enhance N2O destruction by continuous NosZ expression and enable NosZ activation in microorganisms with superior NosZ capabilities. We assess microbial community function and metabolic regulation using metagenomics and metaproteomics to clarify the effect of intermittent aeration regimes on N2O emission. Intermittent aeration with periodic anoxic exposure significantly reduced N2O emissions with 71% nitrogen removal by enhancing the metabolic activity of Hyphomicrobium. NosZ activity increased by 4- to 6.5-fold after system adaptation to oxygen modulations, compared to continuous oxic-anoxic cycling without the anoxic phase. The latter resulted in increased N2O emissions due to suppressed NosZ activity and higher N2O production from Methylobacillus, which uses nitric oxide as an alternative electron acceptor. Our finding that strategic oxygen manipulation can energize N2O destruction lays the foundation for developing next-generation wastewater treatment technologies for mitigating N2O emissions.

microbiology↗

bioRxiv2024

Investigating Potential Microbial Contributors to Enhanced Metabolite Production under Oxygen Perturbations: An Integrated Metagenomic and Metabolomic Approach

The specific impacts of oxygen perturbation on microbial communities and their synthesis of metabolites remain unclear. We systematically explored how oxygen perturbations alter microbial growth, subsequently affecting the abundance of functional genes and promoting the synthesis of metabolites such as amino acids. Analysis of microbial community structure indicates dynamic stability under oxygen perturbations, with only a fraction of the microbial abundance being altered. By comparing the abundance of functional genes with metabolic features, we revealed how changes in the microbial community impact the overall system performance. Amino acid biosynthesis has an enhanced potential under conditions of oxygen perturbation. Through biological and statistical correlation analyses, we identified microbial species significantly correlated with the efficiency of target metabolic reactions under oxygen perturbations. Mycolicibacterium madagascariense, Mycolicibacterium fortuitum, and Burkholderia pseudomallei displayed strong associations with proline and tryptophan synthesis reactions. Moreover, the abundance of microbial genera including Labrys, Actinomyces, and Nitrosopumilus exhibited a highlysignificant positive correlation with metabolite abundance in enriched metabolic pathways under oxygen perturbations. These results suggest that microbial systems might achieve dynamic stability in community structure under oxygen perturbations, while exhibiting slightly differential metabolic potentials. Notably, enhanced efficiency in amino acid biosynthesis could help to assimilate more carbon and nitrogen resources in activated sludge during wastewater treatment. SYNOPSISWe provide an in-depth investigation into the impact of oxygen perturbations on microbial growth in activated sludge systems and the subsequent variations in the abundance of metabolic genes. Our research highlights the potential for subtle changes in amino acid biosynthesis and identifies key microbial species associated with synthesis efficiency. These insights into the dynamic stability and differentiated metabolic potentials of microbial communities during oxygen perturbations can inform the development of more effective resource recovery strategies.

microbiology↗

bioRxiv2024

Assessing Oxygen Perturbation and Over-Aeration Impacts on Soluble Microbial Products (SMP) Production and Release in Activated Sludge Systems

Understanding the interplay between oxygen conditions and microbial activities in an activated sludge system is crucial for the optimization of wastewater treatment processes. This study explores the influence of various aeration patterns and dissolved oxygen (DO) levels on the microbial metabolic activities, with a particular focus on the synthesis and release of soluble microbial products (SMP), and the regulation of key metabolic genes and enzymes. The activated sludge system underwent different aeration patterns, including constant aeration, continuous perturbation, and intermittent perturbation under two distinct DO levels of 2mg/L and 8mg/L. We employed a combination of multi-omics techniques (metagenomics, metaproteomics, and metabolomics) along with chemical analytical methods for comprehensive sample analysis. Our results reveal an increased intracellular accumulation of amino acids and enhanced release of protein under the conditions of oxygen perturbation. Furthermore, elevated DO levels fostered the accumulation of poly-3-hydroxybutyrate intracellularly and the release of protein and fatty acids as SMP. This outcome is associated with the abundance of key metabolic genes and enzymes, thereby highlighting the metabolic flexibility of microbes under different oxygen conditions. These findings offer valuable insights into microbial metabolic dynamics under varying oxygen conditions, thereby providing guidance for more efficient and sustainable strategies in wastewater treatment and resource recovery. SYNOPSISThis study explores the complex interplay between varying oxygen conditions and microbial activity in activated sludge systems, focusing on the impact on the synthesis and release of soluble microbial products (SMP). Findings highlight the significant influence of oxygen perturbation and dissolved oxygen levels on protein synthesis and fatty acid metabolic processes.

microbiology↗

bioRxiv2024

Resource Recovery from Wastewater By Directing Microbial Metabolism Toward Production of Value-added Biochemicals

Transitioning wastewater treatment from mere pollutant removal to resource recovery necessitates exploiting the metabolic capabilities of microbial communities. Studies suggest that under low-oxygen conditions, microbes activate oxygen-responsive regulons that suppress the tricarboxylic acid (TCA) cycle, diverting carbon flux towards biosynthetic pathways and accumulating valuable organic metabolites. We hypothesized that dynamically altering dissolved oxygen levels in activated sludge would disrupt aerobic metabolic equilibrium, enhancing the production of valuable biochemicals like amino acids and fatty acids. To test this, batch experiments were conducted with activated sludge under constant aeration and rapid cycling between oxygen-rich and oxygen-poor states. Fluctuating oxygen concentrations between 0 and 2 mg/L significantly increased valuable biochemical production compared to constant aeration (P<0.05). Continuous oxygen perturbations increased free amino acids by 35.7{+/-}7.6% and free fatty acids by 76.4{+/-}13.0%, while intermittent perturbations with anoxic periods enhanced free amino acids by 42.4{+/-}8.1% and free fatty acids by 39.3{+/-}7.7%. Notably, 14 standard amino acids showed significant increases, and most fatty acids had carbon chain lengths between C12-C22. Mechanistically, compared to stable oxygen, oxygen perturbations activated the FNR and ArcA regulons, resulting in lower relative abundances of TCA cycle enzymes such as malate dehydrogenase, isocitrate dehydrogenase, and 2-oxoglutarate dehydrogenase, while higher relative abundances of amino acid (ilv cluster) and fatty acid (acc cluster) biosynthetic enzymes. Our findings demonstrate that introducing controlled oxygen fluctuations in wastewater treatment can enhance the biochemical value of activated sludge with minimal process modifications, facilitating resource recovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/614227v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@181590corg.highwire.dtl.DTLVardef@fd51c3org.highwire.dtl.DTLVardef@102ddd1org.highwire.dtl.DTLVardef@130dc73_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Integrated Transcriptome and Metabolome Analyses Reveal the Mechanism Regulating Bulbil Initiation and Development in Cystopteris chinensis

Cystopteris chinensis is an endangered fern endemic to China, which only has a small wild population due to its poor reproductive ability. However, we recently found that it can produce bulbils on its pinnule to generate new plants but the molecular mechanism underlying this unique phenomenon remained unknown. In this study, we have identified four distinct stages in the initiation and development of bulbils based on morphological and anatomical observation. We performed transcriptome and metabolome analyses on the collected samples at each stage. Through KEGG enrichment analysis, it was found that the phytohormone signal transduction, starch and sucrose metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis pathways play a significant role in regulating bulbil initiation and development. Specifically, the involvement of three phytohormones and sugar substances was identified in the process of bulbil initiation. Our study provides the first detailed observation of the bulbils in C. chinensis and explains their initiation and development at the molecular level. However, more in-depth studies are needed to discover the functions of key genes controlling the formation of bulbils to conserve the endangered C. chinensis population.

plant biology↗

bioRxiv2024

Feasibility of laminar functional quantitative susceptibility mapping

Layer fMRI is an increasingly utilized technique that provides insights into the laminar organization of brain activity. However, both blood-oxygen-level-dependent (BOLD) fMRI and vascular space occupancy data (VASO) have certain limitations, such as bias towards larger cortical veins in BOLD fMRI and high specific absorption rate in VASO. This study aims to explore the feasibility of whole-brain laminar functional quantitative susceptibility mapping (fQSM) compared to laminar BOLD fMRI and VASO at ultra-high field. Data were acquired using 3D EPI techniques. Complex data were denoised with NORDIC and susceptibility maps were computed using 3D path-based unwrapping, the variable-kernel sophisticated harmonic artifact reduction as well as the streaking artifact reduction for QSM algorithms. To assess layer-specific activation, twenty layers were segmented in the somatosensory and motor cortices, obtained from a finger tapping paradigm, and further averaged into six anatomical cortical layers. The magnitude of signal change and z-scores were compared across layers for each technique. fQSM showed the largest activation-dependent mean susceptibility decrease in Layers II/III in M1 and Layers I/ II in S1 with up to -1.3 ppb while BOLD fMRI showed the strongest mean signal increase in Layer I. Our data suggest that fQSM demonstrates less bias towards activation in superficial layers compared to BOLD fMRI. Moreover, activation-based susceptibility change was comparable to VASO data. Studying whole-brain, layer-dependent activation with submillimeter fQSM is feasible, and reduces bias towards venous drainage effects on the cortical surface compared to BOLD fMRI, thereby enabling better localization of laminar activation.

neuroscience↗

bioRxiv2024

Pervasive findings of directional selection realize the promise of ancient DNA to elucidate human adaptation

We present a method for detecting evidence of natural selection in ancient DNA time-series data that leverages an opportunity not utilized in previous scans: testing for a consistent trend in allele frequency change over time. By applying this to 8433 West Eurasians who lived over the past 14000 years and 6510 contemporary people, we find an order of magnitude more genome-wide significant signals than previous studies: 347 independent loci with >99% probability of selection. Previous work showed that classic hard sweeps driving advantageous mutations to fixation have been rare over the broad span of human evolution, but in the last ten millennia, many hundreds of alleles have been affected by strong directional selection. Discoveries include an increase from [~]0% to [~]20% in 4000 years for the major risk factor for celiac disease at HLA-DQB1; a rise from [~]0% to [~]8% in 6000 years of blood type B; and fluctuating selection at the TYK2 tuberculosis risk allele rising from [~]2% to [~]9% from [~]5500 to [~]3000 years ago before dropping to [~]3%. We identify instances of coordinated selection on alleles affecting the same trait, with the polygenic score today predictive of body fat percentage decreasing by around a standard deviation over ten millennia, consistent with the "Thrifty Gene" hypothesis that a genetic predisposition to store energy during food scarcity became disadvantageous after farming. We also identify selection for combinations of alleles that are today associated with lighter skin color, lower risk for schizophrenia and bipolar disease, slower health decline, and increased measures related to cognitive performance (scores on intelligence tests, household income, and years of schooling). These traits are measured in modern industrialized societies, so what phenotypes were adaptive in the past is unclear. We estimate selection coefficients at 9.9 million variants, enabling study of how Darwinian forces couple to allelic effects and shape the genetic architecture of complex traits.

evolutionary biology↗

bioRxiv2024

Haplotype-resolved assemblies provide insights into genomic makeup of the oldest grapevine cultivar (Munage) in Xingjiang

AbstractsMunage, an ancient grape variety that has been cultivated for thousands of years in Xinjiang, China, is recognized for its exceptional fruit traits. There are two main types of Munage: white fruit (WM) and red fruit (RM). However, the lack of a high-quality genomic resources has impeded effective breeding and restricted the potential for expanding these varieties to other growing regions. In this study, we assembled haplotype-resolved genome assemblies for WM and RM, alongside integrated whole genome resequencing (WGS) data and transcriptome data to illuminate specific mutations and associated genes in Munake and the genes associated with fruit color traits. Selective analysis between Munage clones and Eurasian grapes suggested that adaptive selection exists in Munage grapes, with genes enriched in processes including cell maturation, plant epidermal cell differentiation, and root epidermal cell differentiation. The study examined the mutations within Munage grapes and found that the genes PMAT2 on chromosome 12 and MYB123 on chromosome 13 are likely responsible for color variation in RM. These findings provide crucial genetic resources for investigating the genetics of the ancient Chinese grape variety, Munage, and will facilitate the genetic improvement in grapevine.

genomics↗

bioRxiv2024

HHIP's Dynamic Role in Epithelial Wound Healing Reveals a Potential Mechanism of COPD Susceptibility

A genetic variant near HHIP has been consistently identified as associated with increased risk for Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide. However HHIPs role in COPD pathogenesis remains elusive. Canonically, HHIP is a negative regulator of the hedgehog pathway and downstream GLI1 and GLI2 activation. The hedgehog pathway plays an important role in wound healing, specifically in activating transcription factors that drive the epithelial mesenchymal transition (EMT), which in its intermediate state (partial EMT) is necessary for the collective movement of cells closing the wound. Herein, we propose a mechanism to explain HHIPs role in faulty epithelial wound healing, which could contribute to the development of emphysema, a key feature of COPD. Using two different Boolean models compiled from the literature, we show dysfunctional HHIP results in a lack of negative feedback on GLI, triggering a full EMT, where cells become mesenchymal and do not properly close the wound. We validate these Boolean models with experimental evidence gathered from published scientific literature. We also experimentally test if low HHIP expression is associated with EMT at the edge of wounds by using a scratch assay in a human lung epithelial cell line. Finally, we show evidence supporting our hypothesis in bulk and single cell RNA-Seq data from different COPD cohorts. Overall, our analyses suggest that aberrant wound healing due to dysfunctional HHIP, combined with chronic epithelial damage through cigarette smoke exposure, may be a primary cause of COPD-associated emphysema. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/611545v2_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1396884org.highwire.dtl.DTLVardef@1fcb9eborg.highwire.dtl.DTLVardef@111f451org.highwire.dtl.DTLVardef@1bf2ee9_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2024

Targeting Specific Kinase Substrates Rescues Increased Colitis Severity Induced by the Crohn's Disease-Linked LRRK2-N2081D Variant

LRRK2 contains a kinase domain where both the N2081D Crohns disease (CD) risk and the G2019S Parkinsons disease (PD)-pathogenic variants are located. The mechanisms by which the N2081D variant increase CD risk, and how these adjacent mutations result in distinct diseases, remain unclear. To investigate the pathophysiology of the CD-linked LRRK2 N2081D variant, we generated a knock-in (KI) mouse model and compared its effects to those of the LRRK2-G2019S mutation. We find that Lrrk2N2081D KI mice demonstrate heightened sensitivity to induced colitis, resulting in more severe inflammation and intestinal damage than Lrrk2G2019SKI and wild-type mice. Analysis of Colon tissue revealed distinct mutation-dependent LRRK2 RAB substrate phosphorylation, with significantly elevated phosphorylated RAB10 levels in Lrrk2N2081D mice. In cells, we demonstrate that the N2081D mutation activates LRRK2 through a mechanism distinct from that of LRRK2-G2019S. We further find that proinflammatory stimulation enhances LRRK2 kinase activity, leading to mutation-dependent differences in RAB phosphorylation and inflammatory responses in dendritic cells. Finally, we show that genetic knockout of Rab12, but not pharmacological LRRK2 kinase inhibition, significantly reduced colitis severity in Lrrk2N2081D mice. Our study characterizes the pathogenic mechanisms of LRRK2-linked CD, highlights important structural and functional differences between disease-associated LRRK2 variants, and suggests RAB proteins as promising therapeutic targets for modulating LRRK2 activity in CD treatment.

molecular biology↗

bioRxiv2024

Microbial Metabolic Enzymes, Pathways and Microbial Hosts for Co-Metabolic Degradation of Organic Micropollutants in Wastewater

Organic micropollutants (OMPs) in wastewater present significant environmental challenges, but effective removal strategies are hindered by our limited understanding of their co-metabolic biodegradation. We aim to elucidate the microbial enzymes, metabolic pathways, and community members involved in OMP co-metabolic degradation, thereby paving the way for more effective wastewater treatment strategies. We integrated multi-omics (metagenomics, metaproteomics, and metabolomics) and functional group analysis to investigate 24 OMPs under three aeration conditions. Our findings reveal that oxidoreductases, particularly cytochrome P450s and peroxidases, are crucial for recalcitrant OMPs containing halogen groups (-Cl, -F) like fluoxetine and diuron. Hydrolases, including amidases, are instrumental in targeting amide-containing (-CONH2) OMPs such as bezafibrate and carbamazepine. Regarding microbial metabolism involved in OMP co-metabolic degradation, we found that amino acid metabolism is crucial for degrading amine-containing (-NH2) OMPs like metoprolol and citalopram. Lipid metabolism, particularly for fatty acids, contributes to the degradation of carboxylic acid (-COOH) containing OMPs such as bezafibrate and naproxen. Finally, with Actinobacteria, Bacteroidetes, and Proteobacteria emerging as primary contributors to these functionalities, we established connections between OMP functional groups, degradation enzymes, metabolic pathways, and microbial phyla. Our findings provide generalized insights into structure-function relationships in OMP co-metabolic degradation, offering the potential for improved wastewater treatment strategies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/611302v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1785fd8org.highwire.dtl.DTLVardef@1dc732dorg.highwire.dtl.DTLVardef@d9eaborg.highwire.dtl.DTLVardef@2c2813_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Long read sequencing and assembly of wild diploid relatives and cultivars in support of banana breeding programs

Banana is an important fruit and staple crop, which is vital for food and income security in developing countries. A genomics initiative was undertaken as part of the Global Alliance against TR4 (Tropical Race 4 of Fusarium Wilt of Banana) Alliance, with Bayer Crop Science, International Institute of Tropical Agriculture, and University of Queensland to collectively accelerate the breeding efforts in Eastern Africa. The goal of this project is to develop genomics resources to improve banana breeding, productivity, and quality traits amid a changing climate and shifting disease pressures for breeding. Here, we present the PacBio HiFi sequencing, assembly, and comparative analysis of seven genomes of wild and edible diploid banana accessions belonging to subspecies considered important progenitors to cultivated banana varieties and part of breeding programs. This banana genome resource will help power genome editing, a pangenome effort, and conventional breeding programs for germplasm improvement.

genomics↗

bioRxiv2024

Histone serves as an eat-me signal to induce RAGE-mediated phagocytosis

The receptor for advanced glycation end products (RAGE) is a multiligand receptor that can induce phagocytosis in both professional and nonprofessional phagocytes. We found that histones are another ligand for RAGE. Binding between histones and RAGE is increased when DNA is attached to histones. While histones are chromosomal proteins in healthy cells, they are exposed to the cell surface as a complex with DNA when cells undergo apoptosis. The phagocytosis of apoptotic cells by either professional or nonprofessional phagocytes is enhanced when histones are present on the surface of apoptotic cells. Thus, histones serve as eat-me signals. In RAGE knockout cells, the phagocytosis of apoptotic cells was not influenced by the removal of histones, indicating that RAGE is required for the removal of histones from histone-presenting cells. In RAGE knockout mice, wound healing and removal of apoptotic cells from wound sites are delayed, suggesting that RAGE-mediated phagocytosis functions under physiological conditions.

cell biology↗

bioRxiv2024

A Comparison of Skeletal Muscle Diffusion Tensor Imaging Tractography Seeding Methods

The internal arrangement of a muscles fibers with respect to its mechanical line of action (muscle architecture) is a major determinant of muscle function. Muscle architecture can be quantified using diffusion tensor magnetic resonance imaging-based tractography, which propagates streamlines from a set of seed points by integrating vectors that represent the direction of greatest water diffusion (and by inference, the local fiber orientation). Previous work has demonstrated that tractography outcomes are sensitive to the method for defining seed points, but this sensitivity has not been fully examined. To do so, we developed a realistic simulated muscle architecture and implemented four novel methods for tract seeding: seeding along the muscle-aponeurosis boundary with an updated procedure for rounding seed points prior to lookup in the muscle boundary mask and diffusion tensor matrix (APO-3); voxel-based seeding throughout the muscle volume at a user-specified spatial frequency (VXL-1); voxel-based seeding throughout the muscle volume at a variable spatial frequency (VXL-2), and seeding near external and internal muscle boundaries (VXL-3). We then implemented these methods in an example human dataset. The updated aponeurosis seeding procedures allow more accurate and robust tract propagation from seed points. The voxel-based seeding methods had quantification outcomes that closely matched the updated aponeurosis seeding method. Further, the voxel-based methods can accelerate the overall workflow and may be beneficial in high throughput analysis of multi-muscle datasets. Continued evaluation of these methods in a wider range of muscle architectures is warranted.

bioengineering↗

bioRxiv2024

Investigating the role of axonal localization of sex peptide receptor in post-mating responses of female Drosophila melanogaster

This study elucidates the molecular mechanisms underlying the axonal localization of the sex peptide receptor, a pivotal G-protein coupled receptor in the Drosophila melanogaster post-mating response cascade. Utilizing transgenic expression, neuronal labeling, and bioinformatics analyses, we demonstrate that the N-terminal domain of SPR is indispensable for its axonal targeting in both Drosophila larval ventral nerve cord neurons and mouse hippocampal neurons. Deletion of the N-terminal domain abolished axonal localization, highlighting its critical role in this process. Intriguingly, the C-terminal domain of SPR appears to play a subordinate role in axonal targeting. Bioinformatical analysis revealed a striking homology between the N-terminus of SPR and the Broad-complex, Tramtrack, and Bric-a-brac/poxvirus and zinc finger family of proteins. The BTB domain, a conserved protein-protein interaction domain within this family, is implicated in diverse cellular processes and axonal targeting. Further investigation into the role of the BTB domain-like region in SPR could provide valuable insights into the molecular underpinnings of axonal targeting and post-mating responses in Drosophila. This research contributes to our understanding of the intricate mechanisms governing GPCR localization and function in the context of reproductive biology and neuronal signaling.

neuroscience↗