Biology subjects

Cooper, C.

Publications and source records attributed to Cooper, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Sex-Dependent Microbiome-Metabolome Remodeling Associated with Bacteroides acidifaciens Modulation of Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a severe lung disorder influenced by the interplay between the intestinal microbiome, host metabolism, and immune function. We previously found that Bacteroides acidifaciens (BA) has opposing effects on staphylococcal enterotoxin B (SEB)-induced ARDS, worsening the condition in female mice while alleviating it in males. This study aimed to examine whether these outcomes are linked to sex-dependent changes in the intestinal microbiome and gut-lung metabolome. C3H/HeJ mice of both sexes were orally colonized with Bacteroides acidifaciens before SEB exposure. Stool and bronchoalveolar lavage fluid (BALF) were collected for analysis using 16S rRNA sequencing and untargeted liquid chromatography mass spectrometry metabolomics. Our findings revealed distinct sex-dependent metabolic and microbial responses. In females, disease exacerbation correlated with elevated lipid mediators (leukotriene B4, 13-oxoODE, and 13S-HODE) alongside shifts in bile acid and redox metabolism. The intestinal microbiome showed changes in Bacteroides, Akkermansia, and Lachnospiraceae. Conversely, males showed a protective phenotype characterized by increased butyrate and alterations in sphingolipid, amino acid, redox, and nucleotide pathways. Integrated analyses identified sex-associated microbial communities and metabolomic profiles, highlighting distinct patterns of lipid and redox associations in females versus sphingolipid and short-chain fatty acid patterns in males. These results suggest that host sex influences how a commensal bacterium affects inflammatory lung injury and point to pathways for future research.

microbiology↗

bioRxiv2026

Widespread coupling of promoters and terminators of transcription in bacteria

Transcription underpins the expression of genetic information and is viewed as a series of independent initiation and termination events. In bacteria, promoters and terminators of transcription are therefore considered distinct regulatory elements. Here, we challenge this view. Genome-scale analyses reveal that promoters and terminators are extensively coupled. Thus, initiation and termination sites, for adjacent transcription units, frequently overlap. This conserved organisation arises because the DNA sequences, which direct termination, also contribute to promoter function. This couples neighbouring transcription units and generates regulatory interference between RNA polymerases. These findings define a universal mechanism for coordinating transcription across bacterial genomes.

microbiology↗

bioRxiv2025

Agent SPI-WSI: In context learning for computationally spatial pathwayinferring on whole slide histopathology images conditioned on bulk RNAsequencing using pathologist in the loop.

Bulk RNA sequencing, while cost-effective compared to high-resolution spatial transcriptomics, averages gene expression across heterogeneous cell populations and thus lacks spatial context. To address this limitation, we introduce a structured, human-guided, multi-stage computational AI agent SPI-WSI, that iteratively generates, evaluates, and refines biologically informative natural-language prompts, thereby localizing bulk-derived pathway activity within histopathology slides. Our pipeline uses in-context prompting in large language models (LLMs) to adapt dynamically to the task of prompt generation. Candidate prompts are first produced by the LLM and then subjected to a secondary pathologist critiquing by the same LLM that cross-references PubMed to ensure both biological plausibility and specificity. Each approved prompt against their image tile is scored using the vision language foundation model (CONCH). We benchmarked different LLMs, Gemini 2.0, Gemini 2.5, Claude 3.7 and Claude 4.0, and found that Claude 4.0 achieves the highest cosine similarity (0.7) between image and prompt embeddings. Pathologist-driven scoring and manual segmentation confirm that our method accurately identifies clusters of spatial pathological morphologies. In addition, we have validated the method against ground-truth spatial transcriptomic spots using inhouse and public datasets. Overall, the trend emphasized by ground-truth spatial RNA sequencing prompts is closely aligned with those from bulk prompt. This pathologist-in-the-loop workflow enables large-scale, reproducible tissue profiling and grounds AI-driven spatial annotations.

bioinformatics↗

bioRxiv2025

Divergent Pathways of Surfactant Protein C Maturation for Disease-Associated Isoforms

Surfactant Protein C (SP-C), a hydrophobic protein exclusively synthesized and secreted by alveolar type II (AT2) cells, is important for reducing alveolar surface tension in the distal lung. Chronic interstitial pulmonary diseases have been associated with SFTPC mutations. However, a detailed understanding of SP-C maturation in the secretory pathway and disruptions caused by mutations has remained incomplete. The goal of this study was to comprehensively ascertain differences in trafficking and post-translational processing between wild-type and disease-associated SP-C mutants using doxycycline-inducible mouse lung epithelial (MLE-12) cell lines expressing either wildtype SP-C or the common clinical variant SP-CI73T, validated using primary AT2 cells isolated from a murine SP-CI73T pulmonary fibrosis model and induced pluripotent stem cell (iPSC)-derived human alveolar type 2 cells (iAT2s) expressing the same mutant. In all 3 models SP-CWT was highly concentrated in acidic LROs while SP-CI73T accumulated on the plasma membrane, which was corroborated by inhibition of clathrin-mediated endocytosis, surface biotinylation, immunogold EM, immunofluorescent staining in non-permeabilized cells, and proteinase K protection assays supporting divergence of SP-CI73T trafficking from SP-CWT. The exclusion of SP-CI73T from normal routing occurred early in the biosynthetic pathway as Brefeldin A blocked processing of both SP-C proproteins, while a 20{degrees}C temperature shift caused selective accumulation of a processed proSP-CWT intermediate, suggesting initial C-terminal cleavage of proSP-CWT occurs in late-Golgi/ trans-Golgi network (TGN). This cleavage event was sensitive to DC1, an inhibitor of furin-related subtilisin-like proprotein convertase (PPC) family members. Site-directed mutagenesis of canonical residues K160, R167 within a predicted PPC recognition site in the proSP-C BRICHOS domain blocked its processing. Expression constructs encoding inhibitory pre-proprotein (pp) peptide fragments of Furin and ppPC7 each inhibited cleavage of proSP-CWT by MLE-12 cells. Collectively, our data demonstrate that trafficking pathways for maturation of WT and mutant I73T SP-C diverge prior to the TGN where initial cleavage of the COOH-terminal SP-C propeptide occurs via a Furin-like proprotein convertase.

cell biology↗

bioRxiv2025

eDNA on the go: a direct comparison of fixed and vehicle mounted airborne eDNA sampling methods for terrestrial vertebrate species detection at large spatial scales

Air is receiving increasing recognition as a biologically rich source of taxonomically diverse environmental DNA (eDNA). Multiple proof-of-concept studies have explored air as a medium for the detection of single terrestrial species, and even entire terrestrial communities, including mammals, non-anemophilous plants and insects. Airborne eDNA has been sampled using various stationary devices but if we can access it using mobile collection methods, we can rapidly assess biodiversity at large spatial scales. We therefore compared passive eDNA filters deployed for short (30 mins) and long periods (24 hrs) with filters attached to cars that sampled transects through natural and human-modified environments. Our metabarcoding procedure detected 49 vertebrate taxa (33 birds, 15 mammals and 1 amphibian) from all three eDNA air sampling approaches combined, with 29 of these taxa detected in samples collected using the mobile method. The total number of taxa, or proportions of unique taxa detected, did not differ by sampling method, land use or day. Community composition was not significantly impacted by sampling method or sampling day but differed significantly between land uses. We propose that our car-mounted air eDNA sampler could be a game changer for large scale, rapid biomonitoring efforts.

ecology↗

bioRxiv2025

Efficient CRISPR-Cas9-mediated genome editing of the cane toad (Rhinella marina)

Invasive species inflict major ecological, economic, social, and cultural harm worldwide, highlighting the urgent need for innovative and effective control strategies. Genome editing offers exciting possibilities for creating highly targeted control methods for invasive species. Here, we demonstrate CRISPR-Cas9 genome editing in the cane toad (Rhinella marina), one of Australias most notorious invasive species, by targeting the tyrosinase gene to produce albino phenotypes that provide clear visual markers for assessing editing efficiency. Microinjection of Cas9 protein and guide RNAs into one-cell zygotes resulted in 87.6% of mosaic larvae displaying nearly complete albinism, with 2.3% exhibiting complete albinism. For completely albino individuals, genomic analysis confirmed predominantly frameshift mutations or large deletions at the target site, with no wild-type alleles detected. Germline transmission rates reflected the extent of albinism in the mosaic adult, where we achieved maternal germline transmission rates of almost 100%. This technology, representing the first application of CRISPR-Cas9 in the Bufonidae family, opens possibilities for exploring both basic research questions and strategies for population control.

synthetic biology↗

bioRxiv2025

Distinct druggable biological processes in early-onset prostate cancer

Despite advances in understanding and treating Prostate Cancer (PCa), there has been little effort to systematically map the biology distinguishing Early-(EOPCa) and Late-(LOPCa) onset PCa. Around 25% of EOPCa cases present with metastatic spread or aggressive disease with earlier metastatic development. Some available lines of therapy are extending treatment trajectories and prolonging lives. However, there remains a critical clinical need to identify new therapeutic targets for EOPCa where life expectancy necessitates safer, more targeted treatment options. To our knowledge, here we present the largest systematic analysis of molecular profiles in EOPCa versus LOPCa, employing machine-learning-enabled algorithms to identify distinguishing biology and druggable targets for each age group. Distinct stromal signatures are uncovered in EOPCa, which are used to propose therapeutic opportunities herein. Moreover, our analysis identifies 50 druggable targets, 11 of which we confirm in PCa cell line genetic/pharmacological perturbation data. These findings provide the first specific, testable hypotheses in EOPCa, offering avenues for experimental validation and potential therapeutic exploitation, and, more generally, shed light on the intricate and distinguished molecular profile of this aggressive, poorly understood disease. One Sentence SummaryMachine learning-enabled algorithms were utilized to identify distinguishing biology and associated druggable targets for early-onset prostate cancers.

cancer biology↗

bioRxiv2025

SM3DD with Segmented PCA: A Comprehensive Method for Interpreting 3D Spatial Transcriptomics

We developed Standardised Minimum 3D Distance (SM3DD), an entirely cell segmentation/annotation-free approach to the analysis of spatial RNA datasets, using it to compare lung tissue from 16 clinically normal individuals to those of 18 SARS-CoV-2 patients who died from acute respiratory distress syndrome. RNA spatial coordinates were determined using the CosMx Spatial Molecular Imager (Bruker Spatial Biology, US). For each individual transcript location, we calculated the three-dimensional distances to the nearest transcript of each transcript type, standardising the distances to each transcript type. Mean SM3DDs were compared between normal and SARS-CoV-2 patients. Notably, hierarchical clustering of the directional log10(P) values organized genes by functionality, making it easier to interpret biological contexts and for FKBP11, where a decrease in distance to MZT2A was the most significant difference, suggesting a role in interferon signaling. Using a segmented principal components analysis of the entire SM3DD dataset, we identified multiple pathways, including SARS-CoV-2 infection, even though the assay did not include any SARS-CoV-2 transcripts.

bioinformatics↗

bioRxiv2024

Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6R followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. A critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies are in clinical use that either target IL-6R or hIL-6 to inhibit signaling. Here, we perform high throughput structure-based computational screening using ensemble docking for small molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein. Prior knowledge of the contact sites from binary complex studies and experimental work was incorporated into the docking studies. The top 20 scored ligands from the in silico studies after post analysis were subjected to in vitro functional assays. Among these compounds, the ligand with second-highest calculated binding affinity showed experimentally [~]84% inhibitory effect on IL6-induced STAT3 reporter activity at 10-5 molar concentration. This finding may pave the way for designing small molecule inhibitors of hIL-6 of therapeutic significance.

bioinformatics↗

bioRxiv2024

Delivery of novel replicating vectors to Synechococcus sp. PCC 7002 via natural transformation of plasmid multimers

In most cyanobacteria, genetic engineering efforts currently rely upon chromosomal integration; a time-consuming process due to their polyploid nature. To enhance strain construction, here we develop and characterize two novel replicating plasmids for use in Synechococcus sp. PCC 7002. Following an initial screen of plasmids comprising seven different origins of replication, two were found capable of replication: one based on the WVO1 broad host range plasmid and the other a shuttle vector derived from pCB2.4 from Synechocystis sp. PCC 6803. These were then used to construct a set of new replicating plasmids, which were shown to be both co-transformable and stably maintained in PCC 7002 at copy numbers between 0.6-1.4 and 7-16, respectively. Lastly, we demonstrate the importance of using multimeric plasmids during natural transformation of PCC 7002, with higher order multimers providing a 30-fold increase in transformation efficiency relative to monomeric plasmids. Useful considerations and methods for enhancing multimer content in plasmid samples are also presented.

synthetic biology↗

bioRxiv2024

Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking

Beyond the vast array of functional roles attributed to serotonin (5-HT) in the brain, changes in 5-HT levels have been shown to accompany changes in behavioral states, including WAKE, NREM and REM sleep. Whether 5-HT dynamics at shorter time scales can be seen to delineate substates within these larger brain states remains an open question. Here, we performed simultaneous recordings of extracellular 5-HT using a recently-developed G Protein-Coupled Receptor-Activation-Based 5-HT sensor (GRAB5-HT3.0) and local field potential (LFP) in the hippocampal CA1, which revealed the presence of prominent ultraslow (<0.05 Hz.) 5-HT oscillations both during NREM and WAKE states. Interestingly, the phase of these ultraslow 5-HT oscillations was found to distinguish substates both within and across larger behavioral states. Hippocampal ripples occurred preferentially on the falling phase of ultraslow 5-HT oscillations during both NREM and WAKE, with higher power ripples concentrating near the peak specifically during NREM. By contrast, hippocampal-cortical coherence was strongest and microarousals and intracranial EMG peaks were most prevalent during the rising phase in both wake and NREM. Overall, ultraslow 5-HT oscillations delineate substates within the larger behavioral states of NREM and WAKE, thus potentially temporally segregating internal memory consolidation processes from arousal-related functions.

neuroscience↗

bioRxiv2024

Analyzing high-throughput assay data to advance the rapid screening of environmental chemicals for human reproductive toxicity

While high-throughput (HTP) assays have been proposed as platforms to rapidly assess reproductive toxicity, there is currently a lack of established assays that specifically address germline development/function and fertility. We assessed the applicability domains of yeast (S. cerevisiae) and nematode (C. elegans) HTP assays in toxicity screening of 124 environmental chemicals, determining their agreement in identifying toxicants and their concordance with reproductive toxicity in vivo. We integrated data generated in the two models and compared results using a streamlined, semi-automated benchmark dose (BMD) modeling approach. We then extracted and modeled relevant mammalian in vivo data available for the matching chemicals included in the Toxicological Reference Database (ToxRefDB). We ranked potencies of common compounds using the BMD and evaluated correlation between the datasets using Pearson and Spearman correlation coefficients. We found moderate to good correlation across the three data sets, with r = 0.48 (95% CI: 0.28-1.00, p<0.001) and rs = 0.40 (p=0.002) for the parametric and rank order correlations between the HTP BMDs; r = 0.95 (95% CI: 0.76-1.00, p=0.0005) and rs = 0.89 (p=0.006) between the yeast assay and ToxRefDB BMDs; and r = 0.81 (95% CI: 0.28-1.00, p=0.014) and rs = 0.75 (p=0.033) between the worm assay and ToxRefDB BMDs. Our findings underscore the potential of these HTP assays to identify environmental chemicals that exhibit reproductive toxicity. Integrating these HTP datasets into mammalian in vivo prediction models using machine learning methods could further enhance the predictive value of these assays in future rapid screening efforts.

developmental biology↗

bioRxiv2024

Screening and characterization of 133 physiologically-relevant environmental chemicals for reproductive toxicity

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals is remarkably painstaking in conventional toxicological animal models and does not scale up to the number of chemicals present in our environment and requiring testing. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

pharmacology and toxicology↗

bioRxiv2024

H-NS is a bacterial transposon capture protein

The histone-like nucleoid structuring (H-NS) protein is a DNA binding factor, found in {gamma}-proteobacteria, with functional equivalents in diverse microbes. Universally, such proteins are understood to silence transcription of horizontally acquired genes. Here, we identify transposon capture as a major overlooked function of H-NS. Using genome scale approaches, we show that H-NS bound chromosomal regions are transposition "hotspots". Since H-NS often interacts with pathogenicity islands, such targeting creates clinically relevant phenotypic diversity. For example, in Acinetobacter baumannii, we identify altered motility, biofilm formation, and interactions with the human immune system. Transposon capture is mediated by the DNA bridging activity of H-NS and, if absent, more ubiquitous transposition results. Consequently, transcribed and essential genes are disrupted. Hence, H-NS directs transposition to favour evolutionary outcomes useful for the host cell.

microbiology↗

bioRxiv2023

A Refined Phylochronology of the Second Plague Pandemic in Western Eurasia

Although dozens of ancient Yersinia pestis genomes and a vast corpus of documentary data are available, the origin and spread of consecutive outbreaks of the Second Plague Pandemic in Europe (14th-18th c.) are still poorly understood. For the majority of ancient genomes, only radiocarbon dates spanning several decades are available, hampering an association with historically recorded plague outbreaks. Here, we present new genomic evidence of the Second Pandemic from 11 sites in England, Estonia, the Netherlands, Russia, and Switzerland yielding 11 Y. pestis genomes with >4-fold mean coverage dating to between 1349 and 1710. In addition, we present a novel approach for integrating the chronological information retrieved from phylogenetic analysis with their respective radiocarbon dates, based on a novel methodology offering more precise dating intervals. Together with a fine-grained analysis of documentarily recorded plague outbreaks, this allows us to tentatively associate all available Y. pestis genomes of the Second Pandemic with historically documented plague outbreaks. Through these combined multidisciplinary analytical efforts, our newly sequenced genomes can be attributed to the Black Death in Cambridge (England), the pestis tertia or pestis quarta in the late 14th century (Estonia), previously unknown branches emerging in the 15th century (Estonia, the Netherlands and England), and a widespread pandemic in Eastern Europe around 1500 (western Russia), which all seem to have originated from one or multiple reservoirs located in Central Europe. While the latter continued to harbour a major Y. pestis lineage at least until the 1630s, represented by new genomes of the Thirty Years War plague (Switzerland), another lineage consecutively spread into Europe between the 17th and 18th century from the Ottoman Empire, as evidenced by a genome associated with the Great Northern War plague (Estonia). By combining phylogenetic analysis with a systematic historical reconstruction based on textual sources and an innovative phylogenetically informed radiocarbon modelling (PhIRM), we offer a new groundbreaking interdisciplinary approach that solves several fundamental methodological challenges associated with phylogenetic and spatio-temporal reconstruction of historical pandemics.

genomics↗

bioRxiv2023

Single-cell Spatial Metabolic and Immune Phenotyping of Head and Neck Cancer Tissues Identifies Tissue Signatures of Response and Resistance to Immunotherapy

Head and neck squamous cell carcinomas (HNSCC) are the seventh most common cancer and represent a global health burden. Immune checkpoint inhibitors (ICIs) have shown promise in treating recurrent/metastatic cases, with durable benefit in [~]30% of patients. Current biomarkers for head and neck tumors are limited in their dynamic ability to capture tumor microenvironment (TME) features, with an increasing need for deeper tissue characterization. Therefore, new biomarkers are needed to accurately stratify patients and predict responses to therapy. Here, we have optimized and applied an ultra-high plex, single-cell spatial protein analysis in HNSCC. Tissues were simultaneously analyzed with a panel of 101 antibodies that targeted biomarkers related to tumor immune, metabolic and stress microenvironments. Our data uncovered a high degree of intra-tumoral heterogeneity intrinsic to head and neck tumors and provided unique insights into the biology of the tumor. In particular, a cellular neighborhood analysis revealed the presence of 6 unique spatial tumor-immune neighborhoods enriched in functionally specialized immune cell subsets across the patient tissue. Additionally, functional phenotyping based on key metabolic and stress markers identified four distinct tumor regions with differential protein signatures. One tumor region was marked by infiltration of CD8+ cytotoxic T cells and overexpression of BAK, a proapoptotic regulator, suggesting strong immune activation and stress. Another adjacent region within the same tumor had high expression of G6PD and MMP9, known drivers of tumor resistance and invasion respectively. This dichotomy of immune activation-induced death and tumor progression in the same sample demonstrates the heterogenous niches and competing microenvironments that underpin clinical responses of therapeutic resistance. Our data integrate single-cell ultra-high plex spatial information with the functional state of the tumor microenvironment to provide insights into a partial response to immune checkpoint inhibitor therapy in HNSCC. We believe that the approach outlined in this study will pave the way towards a new understanding of TME features associated with response and sensitivity to ICI therapies.

cancer biology↗

bioRxiv2023

A robust Platform for Integrative Spatial Multi-omics Analysis to Map Immune Responses to SARS-CoV-2 infection in Lung Tissues

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid, and similar, but a robust platform for deep tissue characterisation of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterise and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.

bioinformatics↗

bioRxiv2021

Novel murine models of post-implantation and midgestional malaria-induced preterm birth

Despite major advances made in malaria treatment and control over recent decades, the development of new models for studying disease pathogenesis remains a vital part of malaria research efforts. The study of malaria infection during pregnancy is particularly reliant on mouse models, as a means of circumventing many challenges and costs associated with pregnancy studies in endemic human populations. Here, we introduce three novel murine models that will further our understanding of how post-implantation and midgestional malaria infection affects pregnancy outcomes. When C57BL/6J (B6) mice are infected with Plasmodium chabaudi chabaudi AS on either embryonic day (E) 6.5, 8.5, or 10.5, preterm birth occurs in all animals by E16.5, E17.5, or E18.5 respectively, with no evidence of intrauterine growth restriction. We found that the time to delivery, placental inflammatory and antioxidant transcript upregulation, and the relationships between parasitemia and transcript expression prior to preterm birth are different based on the embryonic day of infection. On the day before preterm delivery, E6.5 infected mice did not experience significant upregulation of the inflammatory or antioxidant gene transcripts examined; however, parasitemia correlated positively with Il1{beta}, Cox1, and Hmox1 placental transcript abundance. E8.5 infected mice had elevated transcripts for Ifn{gamma}, Tnf, Il10, Cox1, Cox2, Sod1, Sod2, Cat, and Nrf2, while Sod3 was the only transcript that correlated with parasitemia. Finally, E10.5 infected mice had elevated transcripts for Ifn{gamma} only, with a tendency for Tnf transcripts to correlate with parasitemia. Tumor necrosis factor deficient (TNF-/-) and TNF receptor 1 deficient (TNFR1-/-) mice infected on E8.5 experienced preterm birth at the same time as B6 controls. Further characterization of these models is necessary to discover new and/or existing mechanism(s) or trigger(s) responsible for malaria-driven preterm birth that is determined by gestational age upon maternal infection, parasite-host dynamics, or both.

physiology↗