Biology subjects

Gonzalez, P.

Publications and source records attributed to Gonzalez, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Cross-Tissue Concordance of Blood-Trained Protein EpiScores in Donor-Matched GTEx Tissues

Background: Protein EpiScores are DNA methylation (DNAm)-derived predictors of circulating protein levels that may provide accessible biomarkers of disease-related molecular variation. However, because these models were developed in blood, it remains unclear whether they preserve interindividual variation when applied to other tissues. We evaluated the cross-tissue concordance of blood-trained protein EpiScores in matched donors from the Genotype-Tissue Expression (GTEx) project. Methods: We applied 109 published protein EpiScores to DNAm data from whole blood and six matched non-blood tissues using MethylDetectR. The analysis included 54 unique donors contributing 158 blood-tissue pairs: transverse colon (n=45), lung (n=37), prostate (n=33), kidney cortex (n=24), breast mammary tissue (n=10), and ovary (n=9). Fifteen EpiScores had unusable variation, leaving 94 estimable scores per tissue and 564 protein-tissue comparisons. Positive concordance required Pearson and Spearman correlation coefficients to each be at least 0.50; strong concordance required both to be at least 0.70. Benjamini-Hochberg false-discovery-rate (FDR) correction was applied separately across all comparisons for each method. Leave-one-out analyses assessed sensitivity to individual donors, and partial Pearson correlations evaluated sensitivity to available covariates. Protein secretion categories, functional groups, and exploratory demographic and donor-cohort strata were also examined. Results: Ninety-seven of 564 comparisons (17.2%) met the positive-concordance criterion, and 73 of these (75.3%) met the leave-one-out stability criteria. Lung showed the broadest correspondence, with median absolute Pearson and Spearman correlations of 0.594 and 0.555, respectively; 56 of 94 lung EpiScores (59.6%) were concordant, 26 were strongly concordant, and 49 were stable. Other tissues showed more selective concordance, including 10 scores in transverse colon, three in prostate, two in kidney cortex, 15 in breast, and 11 in ovary. After covariate adjustment, median absolute partial r in lung was 0.522, and 68/94 scores had global q-values below 0.05. Among initially concordant pairs, 48/56 in lung retained positive partial r of at least 0.50 and q-values below 0.05, compared with 3/10 in colon, 1/2 in kidney cortex, and 0/3 in prostate. Breast and ovary were too small for adjusted analyses. Lung concordance extended across multiple target-protein secretion categories and functional groups. Exploratory donor-cohort differences did not survive FDR correction. Conclusions: Blood-trained protein EpiScores showed broad correspondence in lung that persisted after adjustment for available covariates. Initially concordant findings in the other tissues eligible for adjustment were mostly covariate-sensitive. These findings identify score-tissue combinations for independent replication and molecular validation and support evaluating cross-tissue correspondence separately for each score and tissue. Concordance between methylation-derived scores does not establish that blood EpiScores measure local tissue protein abundance.

genomics↗

bioRxiv2025

A chromosome-level assembly and functional genomic resources for the model annelid Capitella teleta

BackgroundThe polychaete Capitella teleta is a commonly used annelid for studies in evolutionary developmental biology, comparative genomics, conservation, and ecotoxicology. Over a decade ago, it was the first polychaete to have its genome sequenced and assembled, contributing to pioneering studies that transformed our understanding of animal genomes and their evolution. However, this early resource is now outdated compared to current genome sequencing standards, limiting the use of modern functional genomic tools that could further our understanding of numerous biological processes. ResultsWe combine long-read and short-read sequencing with Hi-C chromatin conformation capture data to assemble the chromosome-level nuclear and mitochondrial genomes of the laboratory strain of C. teleta. This reference assembly more accurately reflects the expected genome size for this polychaete ([~]243.6 Mb) and contains a highly complete, evolutionarily conserved gene repertoire. Notably, the nuclear and mitochondrial genomes are heavily rearranged, indicating a decoupling between gene family repertoire and chromosomal evolution. The analyses of multi-omic datasets available for C. teleta, including developmental time courses of bulk and single-cell RNA-seq, ATAC-seq, and EM-seq, using the new reference assembly, resulted in a significant quality improvement, allowing us to identify new cell-type-specific gene markers and gain additional insights of biological relevance. Finally, we generated a publicly available genome browser that ensures all these resources are easily findable, accessible, interoperable, and reusable. ConclusionsOur study provides state-of-the-art genomic resources for the polychaete model C. teleta, addressing a pressing community need that will open new research opportunities in animal and genome evolution.

genomics↗

bioRxiv2025

Long Non-Coding RNAs in Response to Ebola Virus Vaccine-Induced Immunity

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their role in shaping human responses to vaccination remains largely uncharacterized. Here, we analyzed RNA-sequencing data from three independent human cohorts vaccinated with the rVSV{Delta}G-ZEBOV-GP Ebola vaccine to profile lncRNA expression dynamics. Using differential expression analysis and correlation meta-analysis across cohorts, we identified an expression signature with several lncRNAs, including LEF1-AS1 and DOCK8-AS1, that exhibit conserved transcriptional activation following vaccination. Correlation of lncRNA expression with gene targets and IgG titers revealed putative roles for lncRNAs in regulating and/or participate in both innate immune responses and adaptive antibody production. Functional enrichment of lncRNA co-expressed protein-coding genes highlighted involvement in T-cell differentiation, interferon signaling, and leukocyte activation. Integrating global run-on sequencing data and comparative transcriptomic analysis across other vaccine studies suggests that LEF1-AS1 modulation is distinctively associated with Ebola vaccination. Our findings demonstrate that lncRNAs are potential integral components of the human vaccine response and provide a foundation for future mechanistic studies targeting noncoding RNA regulation of immunity SignificanceEbola virus remains a significant global health threat due to its high mortality rate and potential for widespread outbreaks, underscoring the urgent need for effective and durable vaccines to control future epidemics. Understanding the transcriptional mechanisms underlying immune responses to vaccination is important to improving vaccine design and efficacy. While protein-coding genes have been extensively studied, the role of long noncoding RNAs (lncRNAs) in vaccine-induced immunity remains poorly understood. Here, we characterize the dynamics of lncRNA expression following administration of the rVSV{Delta}G-ZEBOV-GP Ebola vaccine across multiple human cohorts and identify conserved lncRNA signatures associated with both innate and adaptive immunity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/671152v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@25581aorg.highwire.dtl.DTLVardef@1bb31cforg.highwire.dtl.DTLVardef@c3299eorg.highwire.dtl.DTLVardef@e176b9_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

Bioelectric and Epigenetic Landscapes in Lateralized Breast Tumors Reveal Distinct Tumor Microenvironment Signatures.

Breast cancer heterogeneity is shaped not only by intrinsic tumor properties but by the surrounding microenvironment (TME). Here we report a left-right (L-R) asymmetry in the breast TME associated to tumor features. Bioinformatic analysis of TCGA RNA-seq and histological data revealed that R-sided tumors display higher stromal scores and are cancer-associated fibroblasts (CAFs) signatures. This difference was validated in paired L-R PDX and xenograft models, in which R-sided tumors showed increased -SMA expression. The asymmetry extended to tumor bioelectricity: across PDX and xenograft models, and in cells cultured with L- or R-conditioned media, L-sided tumors consistently displayed a more depolarized membrane potential than their R counterparts. In vitro, this bioelectric difference was methylation-dependent - abolished by the DNA methyltransferase inhibitor decitabine -and reversible when the laterality of the conditioned media was inverted. Methylome analysis of animal models identified the gap--unction gene GJA1 as significantly hypermethylated in L-sided tumors, accompanied by reduced expression of connexin genes. A computational model showed that membrane potential and methylation form two stable states, depending on gap-junction coupling strength. Together, these findings identify L-R asymmetry as an overlooked layer of breast tumor heterogeneity that integrates stromal, bioelectric, and epigenetic features. This framework may extend to other paired organs and suggests that tumor laterality could have biological and therapeutic relevance.

cancer biology↗

bioRxiv2025

Environmental dependence of colony morphologies in Labyrinthula species

Labyrinthula species are protist organisms found across a variety of marine environments whose defining characteristic is the secretion of an extracellular ectoplasmic net. Under certain conditions, colonies form a spatial network of tracks through which cells move bidirectionally. We show that this network morphology depends on the presence of a liquid overlay, with air exposed colonies exhibiting instead a dense, aggregated morphology. We demonstrate dynamic restructuring between these two morphologies upon addition or removal of the liquid overlay, and investigate growth behaviour under varying nutrient conditions. Given the inter-tidal environment of certain seagrass species colonised by Labyrinthula, our results may shed light on the relationship between this organism and its seagrass host, for which it is an opportunistic pathogen associated with seagrass wasting disease.

biophysics↗

bioRxiv2025

Cellular characterization of the peritumoral brain zone of glioblastomas: heterogenous nature and clinical relevance.

BackgroundGlioblastoma (GBM) is a highly aggressive cancer with near-universal recurrence, often due to residual tumor cells that persist after aggressive standard of care treatment. This study aimed to characterize tumor infiltration and microenvironment in the GBM periphery. MethodsWe prospectively collected 161 radiologically guided biopsies from 45 GBM patients and conducted an immunohistochemical analysis. We also integrated single-cell RNA sequencing data to select specific markers for immune, glial, and vascular cells. We measured the expression of these genes in samples from contrast-enhancing (CE) and non-enhancing (nCE) tumor areas, vasogenic edema, and radiologically normal tissue. Correlations with resection extent and clinical outcomes were evaluated. ResultsnCE biopsies exhibited neoplastic features similar to those of the tumor core. However, tumor infiltration was also found in regions classified radiologically as edema, particularly in elderly patients. We found important differences in the composition of the peripheral microenvironment between male and female GBM patients. Prognostic associations with specific cell types, such as myeloid cells, showed intertumor heterogeneity, with variations depending on patient sex, age and extent of resection. Furthermore, in our cohort, minimal residual CE tumor following surgery was associated with significantly poorer patient survival. ConclusionsThe GBM periphery includes regions of active tumor growth that are visible on MRI, as well as infiltrated areas that resemble edema radiologically. Tumor infiltration and microenvironmental features are influenced by patient sex and age, which has major implications for recurrence rates, highlighting the need to tailor surgical and therapeutic strategies based on tumor biology and patient subgroup. Key pointsnCE areas show similar neoplastic traits to the CE tumor. GBM infiltrates edema tissue, predominantly in older adult patients. Prognostic value of the peritumoral phenotype depends on resection extent and patient age/sex. Importance of the studyThis study shows that the impact of peripheral and core cellular features on prognosis differs between patients who undergo complete versus incomplete CE tumor resection. Our results suggest a paradigm shift in the classification and management of these patients, encouraging the inclusion of detailed post-surgical MRI analyses to guide the design of future clinical trials according to the nature and extent of the residual disease. Furthermore, our data confirm the presence of tumorigenic features in non-enhancing areas, supporting the benefits of supratotal resections according to the new RANO classification. Our findings also underscore the need to refine surgical and therapeutic strategies based on a more detailed understanding of the tumor microenvironment beyond the GBM core. This understanding may help identify novel targets for more effective and personalized GBM therapies.

cancer biology↗

bioRxiv2024

Selecting sites for strategic surveillance of zoonotic pathogens: a case study in Panama

Surveillance and monitoring of zoonotic pathogens is key to identifying and mitigating emerging public health threats. Surveillance is often designed to be taxonomically targeted or systematically dispersed across geography, however, those approaches may not represent the breadth of environments inhabited by a host, vector, or pathogen, leaving significant gaps in our understanding of pathogen dynamics in their natural reservoirs and environments. As a case study on the design of pathogen surveillance programs, we assess how well 20 years of small mammal surveys in Panama have sampled available environments and propose a multistep approach to selecting survey localities in the future. We use >8,000 georeferenced mammal specimen records, collected as part of a long-term hantavirus surveillance program, to test the completeness of country-wide environmental sampling. Despite 20 years of surveillance, our analyses identified a few key environmental sampling gaps. To refine surveillance strategies, we selected a series of core historically sampled localities, supplemented with additional environmentally distinct sites to more completely represent Panamas environments. Based on lessons learned through decades of surveillance, we propose a series of recommendations to improve strategic sampling for zoonotic pathogen surveillance.

ecology↗

bioRxiv2023

Single cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.

Normal hematopoiesis requires constant prolific production of different blood cell lineages by multipotent hematopoietic stem cells (HSC). Stem- and progenitor- cells need to balance dormancy with proliferation. How genetic alterations impact frequency, lineage potential, and metabolism of HSC is largely unknown. Here, we compared induced expression of KRASG12D or RasGRP1 to normal hematopoiesis. At low-resolution, both Ras pathway lesions result in skewing towards myeloid lineages. Single-cell resolution CyTOF proteomics unmasked an expansion of HSC- and progenitor- compartments for RasGRP1, contrasted by a depletion for KRASG12D. SCENITH quantitates protein synthesis with single-cell precision and corroborated that immature cells display low metabolic SCENITH rates. Both RasGRP1 and KRASG12D elevated mean SCENITH signals in immature cells. However, RasGRP1-overexpressing stem cells retain a metabolically quiescent cell-fraction, whereas this fraction diminishes for KRASG12D. Our temporal single cell proteomics and metabolomics datasets provide a resource of mechanistic insights into altered hematopoiesis at single cell resolution.

developmental biology↗

bioRxiv2023

Failed reprogramming of transformed cells due to induction of apoptosis and senescence impairs tumor progression in lung cancer

Cell reprogramming to pluripotency applied to the study of cancer has identified transformation and pluripotency as two independent and incompatible cell fates. A detailed knowledge of the relationship between transformation and reprogramming could lead to the identification of new vulnerabilities and therapeutic targets in cancer. Here, we explore this interplay and find that OSKM expression limits tumor cell growth by inducing apoptosis and senescence. We identify Oct4 and Klf4 as the main individual reprogramming factors responsible for this effect. Mechanistically, the induction of cell cycle inhibitor p21 downstream of the reprogramming factors acts as mediator of cell death and senescence. Using a variety of in vivo systems, including allografts, orthotopic transplantation and KRAS-driven lung cancer mouse models, we demonstrate that OSKM expression impairs tumor growth and reduces tumor burden.

cell biology↗

bioRxiv2023

Choclo virus (CHOV) recovered from deep metatranscriptomics of archived museum tissues

BackgroundHantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans. MethodsWe extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from the heart and kidney tissue of a two decade old sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected in Panama. Reads mapped to the CHOV reference were assembled and then validated by visualization of the mapped reads against the assembly. ResultsWe recovered a 91% complete consensus sequence from a reference-guided assembly to CHOV with an average of 16X coverage. The S and M segments used in our phylogenetic analyses were nearly complete (98% and 99%, respectively). There were 1,199 ambiguous base calls of which 93% were present in the L segment. Our assembled genome varied 1.3% from the CHOV reference sequence resulting in 11 nonsynonymous mutations. Further analysis of all publicly available partial S segment sequences support a clear relationship between CHOV clinical cases and O. costaricensis acquired strains. ConclusionsViruses occurring at extremely low abundances can be recovered from deep metatranscriptomics of archival tissues housed in museums or biorepositories. Our efforts resulted in the second CHOV genome publicly available. This genomic data is important for future surveillance and diagnostic tools as well as understanding the evolution and pathogenicity of CHOV. Author SummaryHantavirus cardiopulmonary syndrome (HCPS) in Panama, caused by Choclo virus (CHOV, Orthohantavirus chocloense), is intimately linked to the primary mammalian reservoir host, the Costa Rican pygmy rice rat (Oligoryzomys costaricensis). Although the prevalence of hantavirus disease is relatively low in Panama, over a quarter of the country has the agroecological conditions that favor this rodent. In addition, serologic evidence suggests infections are under-reported. Sequence data of the pathogen and host collected across temporal and spatial scales is necessary for diagnostics, surveillance, and forecasting; however, only one complete genome is available in NCBI GenBank. By leveraging deep metatranscriptomics of archived frozen mammal tissues, we generated a low-coverage genome using a reference-guided assembly approach. Sequence data can be used to develop pan-hantavirus diagnostic tools to facilitate acquisition of more detailed genetic data from archival samples to increase our understanding of the evolutionary and population dynamics of rare and neglected hantaviruses. Generating additional genomic sequence data will also be essential for developing a rigorous taxonomic framework to improve the understanding of hantavirus diversity and distribution.

genomics↗

bioRxiv2023

The genome of the colonial hydroid Hydractinia reveals their stem cells use a toolkit of genes shared with all animals

Hydractinia is a colonial marine hydroid that exhibits remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, H. symbiolongicarpus and H. echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult male H. symbiolongicarpus and identified cell type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed that Hydractinias i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given that Hydractinia has a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate that Hydractinias stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources for Hydractinia presented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from non-self.

genomics↗

bioRxiv2023

HNF4a regulates acyl chain remodeling and ether lipid accumulation in hepatic steatosis

Hepatocyte nuclear factor 4 (HNF4) is an established transcriptional master regulator of differentiation, maintenance, and metabolism. Polymorphisms in HNF4 are linked to several diseases in humans including diabetes and nonalcoholic fatty liver disease (NAFLD). Identifying novel regulation of lipid metabolism by HNF4 would inform on NAFLD development and progression. We directly assessed HNF4 activity through chromatin immunoprecipitation (ChIP)-sequencing and integration of untargeted lipidomics. Direct regulation by HNF4 can be difficult to assess due to the role of HNF4 in liver homeostasis; to rapidly disrupt activity, mice were exposed to cold stress which induces hepatic steatosis in several hours. Cold exposure shifted HNF4 activity with differential genome occupancy of more than 50% of HNF4 binding sites. Focusing on HNF4 binding to promoter with active transcription determined that HNF4 directly regulates fatty acid desaturation, ether lipid synthesis, and peroxisomal biogenesis in response to cold exposure. Integration of lipidomics found that cold exposure increases the very long chain polyunsaturated fatty acid composition of the hepatic lipid pool, including ether lipids, in an HNF4 dependent manner. Because portions of ether lipid synthesis are in the peroxisome and peroxisomal biogenesis is directly HNF4 regulated, we analyzed peroxisomal abundance and found increases with cold exposure that are ablated with loss of HNF4. This peroxisomal regulation was independent of PPAR-- a known regulator of peroxisomes and lipid metabolism--since loss of HNF4 was not rescued by PPAR overexpression. These data determined that regulation of hepatic steatosis by HNF4 is more complex than triglyceride accumulation and includes acyl chain modifications, ether lipid synthesis, and peroxisomal oxidation.

molecular biology↗

bioRxiv2023

Characterization of the bioaccumulation and toxicity of copper pyrithione, an antifouling compound, on juveniles of rainbow trout

Since the global ban on tributyltin in antifouling paints in 2008 by the International Maritime Organization, new products have been developed and brought to the market. Among them, copper pyrithione (CuPT) is used, but its mechanisms of toxicity remain little known. This project aimed to identify and measure the impacts of aqueous exposure to CuPT, an organic compound, and compare it to ionic Cu2+ added in the form of its inorganic salt CuSO4, in equivalent Cu2+ molar concentrations, on rainbow trout (Oncorhynchus mykiss) juveniles under controlled laboratory conditions. A 24-hour acute exposure was performed with nominal concentrations of 50 and 100 {micro}g/L Cu from either CuSO4 or CuPT (labelled CuSO4_50, CuSO4_100, CuPT_50 and CuPT_100, respectively). The CuPT_100 condition induced 85 % mortality in 15 hours and the CuPT_50 condition induced 5 % mortality in the same period. A chronic exposure was then performed with nominal concentrations of 1 and 10 {micro}g/L Cu from CuPT and 10 {micro}g/L Cu2+ from CuSO4 (labelled CuSO4_1, CuSO4_10, CuPT_1 and CuPT_10, respectively). Measured aqueous concentrations of Cu2+ were slightly higher than nominal concentrations for the lower concentrations, but lower for the CuPT_10 condition. The 8- and 16-day toxicokinetics showed a greater accumulation of copper in the gills of fish exposed to CuPT compared to fish exposed to Cu2+ from CuSO4. The CuPT_10 condition induced 35 and 38 % mortality after 8 and 16 days of exposure, while no mortality was observed in the CuSO4_10 condition. The growth of juveniles was not impacted during the 16 days of exposure for any condition. The activity of antioxidant enzymes (CAT, SOD, GPx) did not respond to exposure to either contaminant. The expression of genes involved in the antioxidant response (sod1, sod2, gpx), detoxification (cyp1a, mt1x, mt2x), Cu transport (ctr1, ctr2, slc11a2), energy metabolism (AcoAc, cox, 12S) and cell cycle regulation (bax) strongly decreased at Day 8 in the gills and at Day 16 in the liver of CuPT-exposed fish in comparison to controls at the same time point. This study clearly showed that the toxicity of Cu in the form of CuPT was much higher than that of ionic Cu from CuSO4 and provides new information on the compound that will be useful to develop regulations concerning its use and release in the aquatic environment. Credit author statementCharlotte Bourdon: Methodology, Validation, Investigation, Writing - Original Draft. Jerome Cachot: Conceptualization, Methodology, Validation, Investigation, Writing - Original Draft, Supervision. Patrice Gonzalez: Validation, Investigation, Writing - Original Draft, Supervision, Funding acquisition. Patrice Couture: Conceptualization, Methodology, Validation, Investigation, Writing - Original Draft, Supervision, Project administration, Funding acquisition.

pharmacology and toxicology↗

bioRxiv2023

miR-203 drives breast cancer cell differentiation

A hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report here that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells, and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.

cancer biology↗

bioRxiv2022

Thermal phenotypic plasticity of pre- and post-copulatory male harm buffers sexual conflict in wild Drosophila melanogaster

Strong sexual selection frequently leads to sexual conflict and ensuing male harm, whereby males increase their reproductive success at the expense of harming females. Male harm is a widespread evolutionary phenomenon with a strong bearing on population viability. Thus, understanding how it unfolds in the wild is a current priority. Here, we sampled a wild Drosophila melanogaster population and studied male harm across the normal range of temperatures under which it reproduces optimally in nature by comparing female lifetime reproductive success and underlying male harm mechanisms under monogamy (i.e., low male competition/harm) vs. polyandry (i.e., high male competition/harm). While females had equal lifetime reproductive success across temperatures under monogamy, polyandry resulted in a maximum decrease of female fitness at 24{degrees}C (35%), reducing its impact at both 20{degrees}C (22%), and 28{degrees}C (10%). Furthermore, female fitness components and pre- (i.e., harassment) and post-copulatory (i.e., ejaculate toxicity) mechanisms of male harm were asymmetrically affected by temperature. At 20{degrees}C, male harassment of females was reduced, and polyandry accelerated female actuarial ageing. In contrast, the effect of mating on female receptivity (a component of ejaculate toxicity) was affected at 28{degrees}C, where the mating costs for females decreased and polyandry mostly resulted in accelerated reproductive ageing. We thus show that, across a natural thermal range, sexual conflict processes and their effects on female fitness components are plastic and complex. As a result, the net effect of male harm on overall population viability is likely to be lower than previously surmised. We discuss how such plasticity may affect selection, adaptation and, ultimately, evolutionary rescue under a warming climate.

evolutionary biology↗

bioRxiv2022

Influence of circular RNA topology on microRNA stability

A subset of circular RNAs (circRNAs) and linear RNAs have been proposed to "sponge" or block microRNA activity. Additionally, certain RNAs induce microRNA destruction through the process of Target RNA-Directed MicroRNA Degradation (TDMD), but whether both linear and circular transcripts are equivalent in driving TDMD is unknown. Here we study whether circular/linear topology of endogenous and artificial RNA targets affects TDMD. Consistent with previous knowledge that Cdr1as (ciRS-7) circular RNA protects miR-7 from Cyrano-mediated TDMD, we demonstrate that depletion of Cdr1as reduces miR-7 abundance. In contrast, overexpression of an artificial linear version of Cdr1as drives miR-7 degradation. Using plasmids that express a circRNA with minimal co-expressed cognate linear RNA, we show differential effects on TDMD that cannot be attributed to the nucleotide sequence, as the TDMD properties of a sequence often differ between its circular and linear forms. By analysing RNA sequencing data of a neuron differentiation system, we further detect potential effects of circRNAs on microRNA stability. Our results support the view that RNA circularity influences TDMD, either enhancing or inhibiting it on specific microRNAs.

molecular biology↗

bioRxiv2022

A cellular and molecular analysis of SoxB-driven neurogenesis in a cnidarian

Neurogenesis is the generation of neurons from stem cells, a process that is regulated by SoxB transcription factors (TFs) in many animals. Although the roles of these TFs are well understood in bilaterians, how their neural function evolved is unclear. Here, we use Hydractinia symbiolongicarpus, a member of the early-branching phylum Cnidaria, to provide insight into this question. Using a combination of mRNA in situ hybridization, transgenesis, gene knockdown, transcriptomics, and in-vivo imaging, we provide a comprehensive molecular and cellular analysis of neurogenesis during embryogenesis, homeostasis, and regeneration in this animal. We show that SoxB genes act sequentially. Stem cells expressing Piwi1 and Soxb1, which have a broad developmental potential, become neural progenitors that express Soxb2 before differentiating into mature neural cells. Knockdown of SoxB genes resulted in complex defects in embryonic neurogenesis. Hydractinia neural cells differentiate while migrating from the aboral to the oral end of the animal, but it is unclear whether migration per se or exposure to different microenvironments is the main driver of their fate determination. Our data constitute a rich resource for studies aiming at addressing this question, which is at the heart of understanding neurological disorders in all animals, including humans.

developmental biology↗

bioRxiv2022

Antifungal activity of Cinnamomum cassia and Origanum compactum essential oils against Aspergillus oryzae

Aspergillosis is a nosocomial disease that usually affects the respiratory system. While most patients develop mild symptoms, aspergillosis can become a serious health threat in immunocompromised populations and patients with pre-existing respiratory conditions. Aspergillosis is caused by fungi of the Aspergillus genus. Existing treatments include drugs such as amphotericin B, with strong side effects. Numerous studies have shown the antifungal properties of essential oils (EOs), which represent potential alternative treatments against fungal infections. Here, we screened the antifungal properties of five EOs against Aspergillus oryzae: Melaleuca alternifolia, Mentha x piperita, Thymus zygis, Origanum compactum, and Cinnamomum cassia. Of the five EOs, two demonstrated antifungal activity: Origanum compactum acted as a fungistatic, while Cinnamomum cassia showed both fungistatic and fungicidal effects against A. oryzae. Therefore, both EOs represent potential alternative treatments against Aspergillosis.

microbiology↗