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Biology subjects

Duan, Q.

Publications and source records attributed to Duan, Q..

At least 19 recordsLinked to original sources

Interactions between human milk components and infant polygenic risk predict childhood atopy

BackgroundAlthough human milk (HM) confers important health benefits, how bioactive milk components (e.g., microbiota, oligosaccharides, and fatty acids) interact with infant genetics to influence childhood atopy remains poorly understood. ObjectiveWe investigated interactions between infant genomic susceptibility and exposure to maternal human milk components (HMCs) and assessed whether integrating these genetic and milk features improves prediction of childhood atopy. MethodsLeveraging infant genomic and maternal HMC data from the CHILD Cohort Study, we conducted gene-milk interaction analysis using linear regression models that integrated polygenic risk scores (PRS) of nursing infants with multiple HMC types. Gradient-boosting machines (GBMs) were used to evaluate predictive performance of HMCs and infant PRS for childhood atopy. ResultsChildhood atopy was associated with interactions between infant genomics (e.g., PRS associated with atopy) and exposure to specific human milk microbes (e.g., Abiotrophia, PBonf=0.005, {beta}=0.29), as well as networks of co-occurring HMCs (e.g., a module containing Bifidobacterium longum, 2-fucosyllactose, and eicosapentaenoic acid, P=0.009, {beta}=-12.3). A GBM integrating HMCs and infant PRS achieved the highest predictive performance for childhood atopy with an area under the curve (AUC) of 0.78, outperforming models based on individual HMC types or PRS alone (AUC range: 0.54-0.63). ConclusionIntegration of maternal HMC exposures with infant genomics reveals interaction effects that contribute to prediction of childhood atopy. Understanding how early-life exposures such as HMCs impact the health of children differently depending on their genomic profiles may facilitate the development of personalized intervention strategies to reduce the burden of these health outcomes during childhood. Key messagesO_LIInteractions between infant polygenic risk and exposure to human milk components are associated with childhood atopy. C_LIO_LINetworks of co-occurring human milk microbiota, oligosaccharides, and fatty acids may influence childhood atopy, with effects varying by infant genomic susceptibility. C_LIO_LIIntegration of human milk components with infant genomics improves prediction of childhood atopy compared with individual milk components or genomics alone. C_LI Capsule SummaryThis study demonstrates that interactions between infant polygenic risk and maternal milk components improve prediction of childhood atopy, highlighting opportunities for personalized early-life prevention strategies.

genomics↗

Sulfidogenic Bacteria and the Risk of Colorectal Cancer

BackgroundSulfur-rich dietary patterns have been associated with colorectal cancer risk. Certain gut bacteria metabolize dietary sulfur compounds into hydrogen sulfide, which can damage the intestinal epithelium and promote carcinogenesis. We evaluated whether sulfur-metabolizing enzymes are enriched in colorectal cancer and whether associations differ by age. ResultsAcross eleven metagenomic cohorts, several sulfur-metabolizing enzymes were more prevalent in individuals with colorectal cancer than in healthy controls. Enzymes involved in sulfur reduction and detoxification, including sulfolactaldehyde reductase, peptide-methionine sulfoxide reductase, dimethylsulfoxide reductase, glutathione transferase, hydroxyacylglutathione hydrolase, and arylsulfatase, were consistently enriched in colorectal cancer. In contrast, enzymes involved in cysteine and methionine synthesis were more common in healthy controls. Age-stratified analyses showed minimal effect modification. Fusobacterium nucleatum, Intestinimonas butyriciproducens, and Bilophila wadsworthia carried more sulfur-metabolizing genes in colorectal cancer samples. Early-onset colorectal cancer samples were enriched for these genes in Citrobacter, Klebsiella, and Raoultella, whereas healthy controls showed greater representation of detoxification-associated genes in Bifidobacterium species. ConclusionsIndividuals with colorectal cancer harbor a greater abundance of sulfur-metabolizing enzymes, supporting a potential role for microbial conversion of dietary sulfur into hydrogen sulfide in colorectal carcinogenesis. Because these genes are distributed across many taxa, microbial function may better explain disease risk than individual species. Associations were consistent across age groups, suggesting that prolonged sulfur-rich dietary exposure may foster a microbial environment capable of generating carcinogenic metabolites. Microbial sulfur metabolism may therefore represent a modifiable pathway for prevention and further mechanistic study.

microbiology↗

Reachability-Preserving Minimum Edge Cut Problem and Applications in Biology

Biological pathway analysis often requires identifying interventions that block reachability to an undesirable state, such as a disease-associated module, toxic byproduct, or adverse phenotype, while preserving reachability among essential biological functions. Motivated by this setting, we study the Reachability Preserving Minimum Edge Cut (RPMEC) problem: given protected terminals s1 and s2 and a target terminal t, the goal is to remove a minimum-cost set of edges that separates s1 and s2 from t while keeping s1 and s2 connected. This formulation naturally models pathway-level intervention design, where one seeks to disrupt harmful signaling, metabolic, or interaction routes without breaking required functional connectivity. We revisit the three-terminal undirected edge-cut case and analyze a Dijkstra-style dynamic programming algorithm that is exact on planar graphs but fails on general graphs. We characterize the structural condition required for exactness, namely frontier-realizability of optimal source-side regions, and identify biological graph representations where this condition is likely to hold after appropriate preprocessing, including curated planar pathway maps, Reactome-style hierarchy trees, SCC-contracted feedback modules, metabolic building-block DAGs with dominator structure, and functional-module quotients of protein interaction networks. We further discuss directed variants, approximation strategies, and exact alternatives based on ASP, MILP, bounded-treewidth dynamic programming, and important separators. The results provide a graph-theoretic foundation for deciding when fast greedy computation is reliable for biological pathway intervention problems and when more expressive exact optimization methods are needed. Author SummaryMany real-world networks require interventions that separate harmful or undesirable states while preserving essential connectivity. This situation appears in biological pathway analysis, where one may want to block reachability to a disease-related module, toxic byproduct, or adverse phenotype without disrupting communication among essential genes, proteins, reactions, or metabolites. We study this problem through the Reachability Preserving Minimum Edge Cut formulation. Unlike ordinary minimum cut, the solution must satisfy both a separation requirement and a preservation requirement. We show why a natural Dijkstra-style algorithm works only under specific structural conditions, such as planar, laminar, or module-like pathway graphs, and why it may fail on general graphs. The results help identify when fast graph algorithms are reliable for biological intervention problems and when exact optimization tools such as Answer Set Programming or integer programming are more appropriate.

bioinformatics↗

Magnetically guided macrophage immunobots coordinate iron-metabolic cascades and immunogenic ferroptosis for tumor immunotherapy

Adoptive cell therapy (ACT) remains challenging in solid tumors, where poor tumor infiltration, metabolic heterogeneity, and an immunosuppressive tumor microenvironment (TME) constrain therapeutic efficacy. Here, we developed a magnetically actuated macrophage-based immune microrobot (immunobot) for active solid tumor immunotherapy. Immunobots were constructed by loading bone marrow-derived macrophages (BMDMs) with lipopolysaccharide-modified Janus L1-FePt magnetic microrollers (LMRs), enabling hard-magnetic actuation. Optimized LMR loading supported robust propulsion, retention under flow, and enhanced barrier penetration. LMRs further promoted M1-like polarization through LPS-driven inflammatory activation and FePt-derived labile iron-amplified oxidative stress, with altered iron homeostasis, increased reactive oxygen species (ROS), and enhanced NF-{kappa}B signaling. Immunobots also induced ferroptosis-associated immunogenic cell death in tumor cells. In vivo, magnetically guided immunobots suppressed tumor growth, reprogrammed tumor-associated macrophages (TAMs), promoted dendritic cell maturation, and enhanced CD8 T cell activation. This work establishes a microrobotic immunotherapy platform for active magnetic transport, iron-metabolic regulation, and immune remodeling in solid tumors.

bioengineering↗

Human milk components interact with infant genomics to modulate gut microbiota, childhood asthma and atopy

The benefits of breastfeeding are well established; however, the mechanisms by which human milk components (HMCs) impact childrens long-term health remain poorly understood. We leveraged datasets from the CHILD Cohort Study to explore how exposure to variable HMCs-- including oligosaccharides (HMOs), fatty acids (HMFAs), and microbiota (HMM)--may influence infants gut microbiota and risk of childhood asthma and atopy. We identified HMCs (e.g., HMO lacto-N-fucopentaose III and HMFA linoleic acid) associated with gut microbes and microbial networks implicated in atopic diseases. Additionally, we determined that HMCs (e.g., HMM Pseudomonas oryzihabitans) interact with infants polygenic risk scores (PRSs) to influence these gut microbial features. Integration of HMCs, gut microbiota, and disease-associated PRSs into an unsupervised machine-learning model that clustered two groups of infants with differing disease prevalence. Our findings suggest that HMCs influence childhood asthma and atopy through modifications to the gut microbiota and modulated by interactions with infant genomics.

genomics↗

Identifying intervention strategies from machine learning models with COALA: a counterfactual optimization framework

MotivationMachine learning (ML) models have become increasingly complex, often functioning as black boxes that limit our understanding of the features contributing to ML predictions. Common explainable AI (XAI) methods such as SHapley Additive exPlanations (SHAP) focus on feature importance but fall short in identifying interactions among features and informing targeted, personalized interventions. Counterfactuals are hypothetical events where specific variables are altered to cause a change in outcome. These causal statements can be applied to AI models to identify actionable interventions for different subjects in a population. ResultsWe propose the framework Counterfactual Optimization for Actionable interpretabiLity in AI (COALA). COALA interprets models by identifying optimal counterfactuals for each subject, which are defined as actionable changes that lead to the most positive change in predicted outcome. When applied to a gradient boosted tree model trained on the National Health and Nutrition Examination Survey (NHANES) dataset, COALA identifies different profiles of optimal counterfactuals across subjects. Features that remain constrained were able to predict the optimal counterfactual changes for a subject at 85.4%, revealing specific features that drive what a subjects optimal counterfactual is. Availability and ImplementationCode for COALA implementation, synthetic data, models trained on synthetic data, and code to replicate results and figures are available at https://github.com/brt-solo/COALA. The NHANES 2017-2018 dataset is publicly available from the National Center for Health Statistics (NCHS). The Framingham Heart Study dataset used in this study is a publicly available, Framingham-derived dataset distributed through the Massachusetts Institute of Technology OpenCourseWare (MIT OCW) repository.

bioinformatics↗

Deciphering the combinatorial expression pattern and genetic regulatory mechanisms of Beats and Sides in the olfactory circuits of Drosophila

Over the past decades, many critical molecular players have been uncovered to control distinct steps in olfactory circuit assembly in Drosophila. Among these, multi-member gene families of cell surface proteins are of interest because they can act as neuron-specific identification/recognition tags in combinations and contribute to circuit assembly in complex brains through their heterophilic or homophilic interactions. Recently, a multi-protein interactome has been described between the Beat and Side families of IgSF proteins. Here, we use the publicly available single-cell RNA-seq datasets and newly generated gene trap transgenic driver lines to probe the in vivo spatial expression pattern of the beat/side gene families in odorant receptor neurons (ORNs) and their synaptic target projection neurons (PNs). Our results revealed that each ORN and its synaptic target PN class expresses a class-specific combination of beat/side genes, hierarchically regulated by lineage-specific genetic programs. Though ORNs or PNs from closer lineages tend to possess more similar beat/side profiles, we also found many examples of divergence from this pattern among closely related ORNs and closely related PNs. To explore whether the class-specific combination of beats/sides defines ORN-PN matching specificity, we perturbed presynaptic beat-IIa and postsynaptic side-IV in two ORN-PN partners. However, disruption of Beat-IIa-Side-IV interaction did not produce any significant mistargeting in these two examined glomeruli. Though without affecting general glomerular targeting, knockdown of side in ORNs leads to the reduction of synaptic development. Interestingly, we found conserved expression patterns of beat/side orthologs across ORNs in ants and mosquitoes, indicating the shared regulatory strategies specifying the expression of these duplicated paralogs in insect evolution. Overall, this comprehensive analysis of expression patterns lays a foundation for in-depth functional investigations into how Beat/Side combinatorial expression contributes to the olfactory circuit assembly.

neuroscience↗

A General Framework for Predicting the Temperature-Dependence of Microbial Interactions

Despite its global importance, our ability to predict the impacts of temperature change on the community dynamics of heterotrophic microbes remains limited. Here, we develop a metabolic trait-based mathematical framework to predict the temperature dependence of pairwise interactions among heterotrophic microbial consumers, accounting for their resource environment and community composition. Applying this framework leads to two general predictions. First, microbial species interactions are typically more thermally sensitive than the underlying metabolic traits. Second, temperature systematically reshapes intra- and interspecific interactions: their variance peaks at intermediate temperatures, while mean interaction strengths increase with warming more rapidly than interspecific interaction strengths. We show that these features of temperature-dependent interactions have far-reaching implications for the temperature responses of community coexistence, diversity, and stability. Our framework provides a mechanistic foundation for predicting how temperature affects the dynamics of heterotrophic microbial communities across diverse biological and environmental contexts. SignificanceCommunities of heterotrophic microbes, including bacteria, archaea, protists, and fungi, play a fundamental role in human health, bioprocessing, and global biogeochemical cycles. Predicting their responses to environmental change is a major challenge, with a key missing link being the effects of temperature on species interactions that ultimately shape community dynamics. By integrating metabolic constraints into consumer-resource theory, we derive general predictions about how interactions among heterotrophic microbial species respond to temperature changes. We show that interactions are more sensitive to warming than individual metabolic traits and undergo systematic temperature-dependent changes that alter community-level coexistence, diversity, and stability. These results hold across diverse environmental contexts and heterotrophic systems, providing a foundation for predicting how microbial community dynamics respond to environmental temperature, from biotechnological applications to natural ecosystems.

ecology↗

Nociceptor clock genes control excitability and pain perception in a sex- and time-dependent manner

Nociception is critical for pain perception and survival and begins with the activation of nociceptors, specialized sensory neurons located in the dorsal root ganglia (DRGs). Both sex and circadian rhythms, governed by clock genes, seem to play a significant role in modulating pain perception. However, the potential interaction between circadian rhythms and sex differences in nociception at the peripheral level has been largely overlooked. Here, we first report that DRGs from mice express clock genes in a time- and sex-dependent manner. Using whole-cell recordings in whole-mounted DRGs and optogenetic stimulation of Nav1.8-expressing neurons, we demonstrate that male nociceptors exhibit reduced excitability during the night, while female nociceptor excitability remains stable across time points. Disruption of the core clock gene Bmal1 in Nav1.8-expressing neurons not only diminished nociceptor activity but also abolished the nighttime reduction in heat sensitivity, highlighting a pivotal role for the molecular clock in regulating nociception. Transcriptomic analyses, voltage-clamp recordings, and pharmacological experiments identified the voltage-gated chloride channel ClC-2, controlled by Bmal1, as a key mediator for the observed fluctuations in male nociceptor excitability. This work opens new avenues for chronobiology-inspired strategies in pain management tailored to sex-specific mechanisms.

neuroscience↗

Accuracy of the Lotka-Volterra Model fails in strongly coupled microbial consumer-resource systems

The generalized Lotka-Volterra (GLV) model is a cornerstone in theoretical ecology for modeling the dynamics emerging from pairwise species interactions within complex ecological communities. The GLV is also increasingly being used to infer species interactions and predict dynamics from empirical data on microbial communities in particular. However, despite its widespread use, the accuracy of the GLVs pairwise interaction structure in capturing the unseen dynamics of microbial consumer-resource interactions--arising from resource competition and metabolite exchanges--remains unclear. Here, we rigorously quantify how well the GLV can represent the dynamics of a general mathematical model that encapsulates key consumer-resource processes in microbial communities. We find that the GLV significantly misrepresents the feasibility, stability, and reactivity of microbial communities above a threshold, biologically feasible level of consumer-resource coupling because it omits higher-order nonlinear interactions. We show that the probability of the GLV making inaccurate predictions can be quantified by a simple, empirically accessible measure of timescale separation between consumers and resources. These insights advance understanding of the temporal dynamics in resource-mediated microbial interactions and provide a method to gauge the GLVs reliability under various empirical and theoretical scenarios.

ecology↗

Chronobiological rhythms control of site- and cell-specific miRNA and mRNA genes and networks across the central nervous system

Biological rhythms control gene expression, but effects on central nervous system (CNS) cells and structures remain undefined. While circadian (24-hour) rhythms are most studied, many genes have periods of greater and less than 24-hours; these fluctuations can be both site- and cell-specific. Identifying patterns of gene rhythmicity across the CNS is necessary for both the study of chronobiology and to make sense of data obtained in the laboratory. We now identify cycling mRNAs, miRNAs, gene networks and novel mRNA-miRNA co-expression pairs in the cortex, hypothalamus, and corpus striatum using high-dimensional datasets. A searchable catalogue (https://www.ghasemloulab.ca/chronoCNS) was created to help refine the analysis of cellular/molecular rhythmicity across the CNS. Immunofluorescence was also used to confirm the rhythmicity of key targets across cells in these structures, with strong cycling signatures in resting oligodendrocytes. Our study sheds light on the contribution of circadian, ultradian, and infradian rhythms and mRNA-miRNA interactions to CNS function.

neuroscience↗

The Role of Metabolic Strategies in Determining Microbial Community Diversity along Temperature Gradients

By conservative estimates, microbes make up about 17% of the worlds biomass and are essential for most ecosystem functions. However, the mechanisms driving the variation in microbial species diversity in response to both natural and anthropogenic temperature gradients remain unclear. In this study, we integrate ecological metabolic theory with a community assembly model to predict that microbial community diversity generally follows a unimodal pattern with temperature. The position and magnitude of peak diversity are determined by interaction-driven species sorting acting on variations in the temperature dependence of carbon use efficiency (CUE) and generalist-specialist tradeoff. Specifically, trait sorting across temperatures favours communities with high mean and low variance in species-level CUEs. We provide empirical evidence supporting our qualitative predictions of the unimodal temperature-diversity pattern along the global geological temperature gradient, which peaks at about 10-15 {degrees}C. Our findings indicate that the response of diversity as well as CUE to temperature of microbial communities can be predicted from relatively feasible life-history trait measurements, paving the way for interlinking microbial community diversity and carbon cycling along spatial and temporal thermal gradients.

ecology↗

Conserved atypical cadherin, Fat2, regulates axon terminal organization in the developing Drosophila olfactory sensory neurons

A unique and defining characteristic of the olfactory sensory circuit is its functionally organized topographic map, which requires widely dispersed olfactory sensory neurons with the same identity to converge their axons into one neuropil, a class-specific glomerulus. Understanding the process of how neuronal identity confers circuit organization is a major endeavor in the field of neurobiology due to its intricate connection to neurodegeneration and neuronal dysfunction. In the olfactory system, many aspects of circuit organization, from axon guidance to synaptic matching, are regulated by a variety of cell surface proteins (for example Robo/Slit and Toll receptors). In this paper, weve identified a novel atypical cadherin protein, Fat2 (also known as Kugelei), as a regulator of class-specific axon organization. Fat2 is expressed in olfactory receptor neurons (ORNs) and local interneurons (LNs) within the olfactory circuits, but little to no expression is found in projection neurons (PNs). Fat2 expression levels vary in a neuronal class-specific manner and peak during pupal development. In fat2 null mutants, ORN axon terminals belonging to different ORN classes present with varying phenotypic severity with the highest fat2 expressing classes being most severely affected. In the most extreme cases, fat2 mutations lead to ORN degeneration. We then show evidence that suggests Fat2 intracellular domain is necessary for Fat2 function in ORN axon organization. Within the developmental context, Fat2 is required starting at early stages of olfactory circuit development specifically for precise axon retraction to further condense class-specific glomeruli. Weve also shown that PNs and LNs expression of Fat2 likely does not contribute to ORN organization 1. Lastly, we narrow down potential Fat2 intracellular domain interactors, APC family proteins (Adenomatous polyposis coli) and dop (Drop out), that likely orchestrate the cytoskeletal remodeling required for axon retraction during protoglomerular development. Altogether, we provide a foundational understanding of how Fat2 functions in olfactory circuit organization and implicate the critical role of axon retraction during glomerular maturation.

developmental biology↗

Mechanism of ozone alleviation of malignant ascites in hepatocellular carcinoma through inhibition of NETs

Malignant ascites in hepatocellular carcinoma is usually a sign of advanced disease and poor prognosis and is also thought to be associated with chronic inflammation mediated by neutrophil extracellular trap networks (NETs). Whereas ozone, a strong oxidant, has significant antibacterial and anti-inflammatory effects, its effectiveness in treating malignant liver ascites is unclear.cOzone showed significant anti-peritoneal fluid production properties in H22 tumor-bearing mice, and ozone reduced peritoneal fluid production by activating AMPK and up-regulating SR-A phagocytosis damage-associated molecular patterns (DAMPs) to reduce the production of NETs. This suggests that ozone could be used as a new drug for the treatment of malignant ascites in hepatocellular carcinoma.

cancer biology↗

Persistent DNA methylation changes associated with prenatal NO2 exposure in a Canadian prospective birth study

BackgroundAccumulating evidence suggests prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. However, it remains unclear whether prenatal DNAm alterations persist through early life. Identifying DNAm changes that persist from birth into childhood would provide greater insight into the molecular mechanisms that most likely contribute to the association of prenatal air pollution exposure with health outcomes such as atopic disease. ObjectivesThis study investigated the persistence of DNAm changes associated with prenatal NO2 exposure (a surrogate measure of traffic-related air pollution) at age one to begin characterizing which DNAm changes most likely to contribute to atopic disease. MethodsWe used an atopy-enriched subset of CHILD study participants (N=145) to identify individual and regional cord blood DNAm differences associated with prenatal NO2, followed by an investigation of persistence in age one peripheral blood. As we had repeated DNAm measures, we also isolated postnatal-specific DNAm changes and examined their association with NO2 exposure in the first year of life. MANOVA tests were used to examine the association between DNAm changes associated with NO2 and child wheeze and atopy. ResultsWe identified 24 regions of altered cord blood DNAm, with several annotated to HOX genes. Two regions annotated to MPDU1 and C5orf63 were significantly associated with age one wheeze. Further, we found the effect of prenatal NO2 exposure across CpGs within all altered regions remained similar at age one. A single region of postnatal-specific DNAm annotated to HOXB6 was associated with year one NO2 and age one atopy. DiscussionRegional cord blood DNAm changes associated with prenatal NO2 exposure persist through at least the first year of life, and some of these changes are associated with age one wheeze. The early-postnatal period remains a sensitive window to DNAm perturbations that may also influence child health.

genetics↗

Stat3 has a different role in axon growth during development than it does in axon regeneration after injury

Signal transducer and activator of transcription 3 (STAT3) is essential for neural development and regeneration as a key transcription factor and mitochondrial activator. In this study, using zebrafish posterior lateral line (PLL) axons, we demonstrate that Stat3 plays distinct roles in PLL axon embryonic growth and regeneration. In zebrafish stat3 mutants the PLL axons were truncated during embryonic growth. Expressing stat3 in neurons of the PLL ganglion rescued their axon growth suggesting stat3 promoted PLL axon growth in a cell-autonomous manner. Using Jak/Stat signaling inhibitors or modified Stat3, we found Jak/Stat signaling was dispensable for PLL axon growth. We showed that Stat3 was co-localized with mitochondria in PLL axon and lower ATPase activity in stat3 mutant embryos than wild-type embryos. The PLL axon growth was affected by mitochondrial modulators indicating that Stat3 regulated PLL axon growth through mitochondrial Stat3 function. Mutation of stat3 or treating with Jak/Stat signaling inhibitors retarded PLL axon regeneration and Schwann cell migration. Taken together, Stat3 is required for embryonic PLL axon growth by regulating the ATP synthesis efficiency of mitochondria, whereas Stat3 stimulates PLL axon regeneration through regulating Schwann cell migration via Jak/Stat signaling. Our findings show a new mechanism of Stat3 in axon growth and regeneration. Author SummaryNeurons are one of the most specialized cell type in our body. A slender axon used for transmitting information between neuron and target cell extends from the cell body. Axon extension during both development and regeneration is regulated by intrinsic and extrinsic factors. In this study, we used the zebrafish posterior lateral line (PLL) axons which extends a long distance to study the regulation of axon extension. Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor in Jak/Stat signaling and an activator for mitochondria functions. Our results demonstrate that Stat3 plays distinct roles in PLL axons development and regeneration. During embryonic development, Jak/Stat signaling is dispensable for PLL axons extension, whereas the mitochondrial Stat3 is required for embryonic axon growth through promoting ATP synthesis. During PLL axons regeneration, Jak/Stat is essential for Schwann cells migration which mediates axon regeneration.

developmental biology↗

Drosophila attP40 background alters glomerular organization of the olfactory receptor neuron terminals

Bacteriophage integrase-directed insertion of transgenic constructs into specific genomic loci has been widely used by Drosophila community. The attP40 landing site located on the second chromosome gained popularity because of its high inducible transgene expression levels. Here, unexpectedly, we found that homozygous attP40 chromosome disrupts normal glomerular organization of Or47b olfactory receptor neuron (ORN) class in Drosophila. This effect is not likely to be caused by the loss of function of Msp300, where the attP40 docking site is inserted. Moreover, the attP40 background seems to genetically interact with the second chromosome Or47b-GAL4 driver, which results in a similar glomerular defect. Whether the ORN phenotype is caused by the neighboring genes around Msp300 locus in the presence of attP40-based insertions or a second unknown mutation in the attP40 background remains elusive. Our findings tell a cautionary tale about using this popular transgenic landing site, highlighting the importance of rigorous controls to rule out the attP40 landing site-associated background effects.

genetics↗

Transcriptome analysis of SARS-CoV-2 naive and recovered individuals vaccinated with inactivated vaccine

The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naive individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produces a strong immune response to a single dose of inactivated vaccine. These results help us understand the reaction mechanism of the hosts molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.

microbiology↗