Biology subjects

Sole, M.

Publications and source records attributed to Sole, M..

6 recordsLinked to original sources

bioRxiv2026

Combinatorial MAPK states drive opposing gene programmes: a reanalysis of MAP3K-driven transcriptional responses in MCF10A cells

BackgroundThe MAPK signalling network coordinates opposing cell fates -- proliferation versus apoptosis -- by combining the activities of ERK, JNK, and p38 kinases in patterns that depend on upstream MAP3K identity. Using multiplexed kinase translocation reporter (KTR) biosensors and functional assays in MCF10A mammary epithelial cells, Peterson et al. (Cell Systems, 2023) demonstrated that MAP3Ks co-activating ERK and JNK drive approximately tenfold more cell cycle entry than MAP3Ks activating ERK alone, and that both kinase activities are independently required for this proliferative response. The transcriptional mechanism underlying this quantitative difference was not identified in the original study. ResultsWe performed a systematic computational re-analysis of the RNA-seq data deposited by Peterson et al. (GEO: GSE213882), encompassing thirteen MAP3K perturbations in doxycycline-induced MCF10A mammary epithelial cells. Based on signalling responses reported by Peterson et al., MAP3Ks were grouped into ERK-only (RAF1, COT) or ERK+JNK co-activating kinases (MLK1, MLK3, ZAK, TAK1, MEKK2, MEKK3). This stratification identified JNK co-activation as the feature most strongly associated with E2F/MYC transcriptional polarity. ERK-only MAP3Ks showed negative enrichment of E2F TARGETS, G2M CHECKPOINT, and MYC TARGETS Hallmark gene sets, whereas ERK+JNK MAP3Ks showed positive enrichment (each MAP3K individually FDR < 0.05 by GSEA). Consistently, inferred activities of E2F1, E2F2, E2F4, and MYC shifted from negative mean ULM t-scores in the ERK group to strongly positive values in the ERK+JNK group (FDR < 0.05 using the CollecTRI regulon). The observed E2F/MYC polarity was robust to alternative transcription factor inference strategies, being reproduced using the DoRothEA A+B regulon and the multivariate model (MLM) framework (Pearson r = 0.77). The signal remained stable under leave-one-out sensitivity analysis and was independently reproduced in MAP3K overexpression signatures from the LINCS L1000 atlas (GEO: GSE92742). ConclusionsERK activation alone was associated with repression of E2F/MYC transcriptional programmes, whereas JNK co-activation was associated with their activation. These opposing transcriptional states provide a potential explanation for the [~]10-fold differences in cell cycle entry reported by Peterson et al. and supports a model in which pRb/E2F regulation integrates combinatorial MAPK co-activation states beyond the canonical ERK-cyclin D-CDK4/6 axis.

genomics↗

bioRxiv2025

Beyond Pollination: Computer Vision Reveals how Flower Visitors, Climate and Agroforestry Management Drive Cocoa Yields in China and Brazil

Cocoa (Theobroma cacao L.) is a multi-billion-dollar crop that is strongly affected by climate change. As a pollination-limited crop, improving little-understood pollination services in agroforestry systems may offer a scalable solution to increase yield sustainably in a changing climate. Here, we use embedded computer vision devices and structural equation models to quantify the interactions of flower visitors and temperature across shade tree-diversity and canopy cover gradients in cocoa systems on fruit set, as a yield precursor. In China and Brazil we show that flower visits are done by nectar and pollen foragers (23.1%), herbivores (6.1%), predators (2.3%), and visitors combining the three functions (63%). Forager visits were driven by increased shade-tree diversity and canopy cover management, with stronger effects in China than in Brazil. Foraging midges in China and multifunctional ants in Brazil enhanced fruit set, showing that diverse pollinators across continents affect cocoa yields. In China, higher canopy cover reduced aphids foraging and feeding on flower tissue, while in Brazil temperature increase reduced flowering. Overall, new technologies can guide implementation of agroforestry management strategies to enhance pollination while reducing pest pressures to ensure sustainable cocoa production under climate change.

ecology↗

bioRxiv2025

The proteostatic landscape of healthy human oocytes

Oocytes are among the longest-lived cells in the body. Recent studies on mouse oocytes highlight unique adaptations in protein homeostasis (proteostasis) within these cells. However, the mechanisms of proteostasis in human oocytes remain virtually unstudied. We present the first large-scale study of proteostatic activity in human oocytes using over 100 freshly-donated oocytes from 21 healthy women aged 19-34. We analyzed the activity and distribution of lysosomes, proteasomes, and mitochondria in both immature and mature oocytes. In contrast to mice, where degradative activity increases during oocyte maturation, human oocytes exhibit nearly 2-fold lower degradative activity than surrounding somatic cells, which decreases further as oocytes mature. Oocyte maturation is also coupled with a decrease in mitochondrial membrane potential. We propose that reduced organelle activity preserves cellular components during the prolonged maturation in human oocytes. Our findings highlight the need to directly investigate human oocyte biology to address challenges in female fertility.

cell biology↗

bioRxiv2024

Transcriptomic and Biochemical analysis of Procambarus clarkii upon exposure to Pesticides: Population-Specific responses as a sign of pollutant resistance?

The effects that anthropogenic stressors may have on modulating species plasticity has been relatively unexplored; however, it represents a scientific frontier that may offer insights into their ability to colonize new habitats. To explore the advantage that inhabiting polluted environments may offer to invasive species, we selected the crayfish Procambarus clarkii, a species that can colonize and thrive in a wide range of aquatic environments, including heavily polluted ones. Here, we studied the molecular and physiological responses of crayfish when experimentally exposed to a pesticide mix of azoxystrobin and oxadiazon at sublethal concentrations. We compared these responses in three isolated crayfish populations in Southern France that are established in areas with different pollution levels: a) Camargue, seasonally affected by pesticide pollution; b) Bages-Sigean, impacted all year-round by domestic effluents and; c) Salagou, a more pristine site. Gene expression analyses revealed that the response to the pesticide mix was the strongest in the Camargue crayfish. In this population, a total of 88 differentially expressed genes (DEGs) were identified in hepatopancreas and 78 in gills between exposed and control laboratory groups. Among genes that were differentially expressed and successfully annotated, those involved in stress, DNA repair, immune response, and translation and transcription processes stand out. Interestingly, the hepatopancreas responded mainly with upregulation, but with downregulation in the gills. This suggests that compared to naive individuals, when exposed to these biocides in their natural habitat crayfish respond with different mechanistic strategies that may confer them adaptability at the population level. Responses in terms of antioxidant and detoxification enzymes also corroborate differences to biocide inputs according to the origin of the crayfish.

molecular biology↗

bioRxiv2024

Efficacy of a new multivalent vaccine for the control of bovine respiratory disease (BRD) in commercial fattening units

Bovine respiratory disease (BRD) is the most common cause of morbidity and mortality in cattle. The effects of BRD are most marked during the first weeks after arrival in calf-rearing units. Vaccination is a tool that can help to control the disease by reducing both the incidence itself and the massive use of antibiotics. Recently, a new multivalent vaccine (DIVENCE(R)), containing live gE/tk double-gene deleted BoHV-1, live-attenuated BRSV, inactivated PI3, BVDV-1 recombinant protein and BVDV-2 recombinant protein, has been designed to protect cattle against the main viral pathogens associated with BRD. The aim of this study was to demonstrate the efficacy of DIVENCE(R) against BRD in field conditions. A total of 360 animals from three different batches were included in the study: one batch of 108 Holstein-Friesian males (Farm 1), another batch of 99 Holstein-Friesian males (Farm 2), and 153 Belgian-Blue cross males and females (Farm 3). On each feedlot, a single batch of animals was included in the study, with a mean age of approx. ten weeks (73.4{+/-}0.6 days). On the vaccination day (Day 0 of the study; D0), calves from the same batch were randomly distributed between the two study groups. The vaccinated group (n=183) received the DIVENCE(R) vaccine and the control group (n=177) received a placebo injection of phosphate-buffered saline (PBS) solution. Both groups were given two intramuscular doses (2 mL/dose) of the corresponding product three weeks apart. All animals were monitored during the entire fattening period (approx. 9 months) after vaccination to assess the incidence, severity, and morbidity of BRD as well as administered treatments and feed performance. Overall, vaccinated animals had significantly (p<0.004) lower morbidity than controls, with only 49 out of the 183 vaccinated calves (26.78%) presenting at least one episode of respiratory disease (RD), versus 73 out of the 177 control calves (41.24%). Thus, a reduction of 35.1% in morbidity was observed in the vaccinated animals. In terms of RD cases, vaccinated animals had a significantly (p<0.001) lower number of cases than control animals, with only 66 cases reported in the 183 vaccinated calves (0.36 cases/calf) versus 110 cases in the 177 control calves (0.62 cases/calf). A reduction of 42% in cases was observed in the vaccinated animals. During the study follow-up, a BRSV outbreak was reported in one of the farms (Farm 1) on Day 23, just two days after the second dose. The vaccinated group had significantly (p<0.02) lower morbidity (11 animals out of 54; 20.4%) and severity (score of 1.70) compared to the control group (29 animals out of 54; 53.70% and score of 2.11). Overall, vaccinated animals needed significantly (p=0.01) fewer antimicrobial treatments (at least one due to RD) than controls. Furthermore, vaccinated animals presented numerically higher average daily weight gain (p=0.07) and significantly higher carcass weight (p=0.01) than controls, at 35.78 g/day and 6.58 kg, respectively. Vaccination with DIVENCE(R) at the beginning of the fattening period decreased the incidence and morbidity of BRD following a BRSV outbreak only two days after the primary vaccination scheme. Additionally, the incidence and morbidity of BRD throughout the entire fattening period was reduced in the vaccinated animals. Thus, DIVENCE(R) can improve economic outcomes in fattening units by reducing antibiotic treatments and enhancing performance.

immunology↗

bioRxiv2023

Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials

In eutherian mammals, hundreds of programmed DNA double-strand breaks (DSBs) are generated at the onset of meiosis. The DNA damage response is then triggered. Although the dynamics of this response is well studied in eutherian mammals, recent findings have revealed different patterns of DNA damage signaling and repair in marsupial mammals. To better characterize these differences, here we analyzed synapsis and the chromosomal distribution of meiotic DSBs markers in three different marsupial species (Thylamys elegans, Dromiciops gliorides, and Macropus eugenii) that represent South American and Australian Orders. Our results revealed inter-specific differences in the chromosomal distribution of DNA damage and repair proteins, which were associated with differing synapsis patterns. In the American species T. elegans and D. gliroides, synapsis progressed exclusively from the chromosomal ends towards interstitial regions. This was accompanied by sparse H2AX phosphorylation, mainly accumulating at chromosomal ends, which appeared conspicuously polarized in a bouquet configuration at early stages of prophase I. Accordingly, RAD51 and RPA were mainly localized at chromosomal ends throughout prophaseI in both American marsupials, likely resulting in reduced recombination rates at interstitial positions. In sharp contrast, synapsis initiated at both interstitial and distal chromosomal regions in the Australian representative M. eugenii, {gamma}H2AX had a broad nuclear distribution, and RAD51 and RPA foci displayed an even chromosomal distribution. Given the basal evolutionary position of T. elegans, it is likely that the meiotic features reported in this species represent an ancestral pattern in marsupials and that a shift in the meiotic program occurred after the split of D. gliroides and the Australian marsupial clade. Our results open intriguing questions about the regulation and homeostasis of meiotic DSBs in marsupials. The low recombination rates observed at the interstitial chromosomal regions in American marsupials can result in the formation of large linkage groups, thus having an impact in the evolution of their genomes.

genetics↗