Biology subjects

Soler, M.

Publications and source records attributed to Soler, M..

6 recordsLinked to original sources

bioRxiv2026

Dual Role of Cx43 in Enhancing CDK4/6 Inhibitor Response and Promoting the Elimination of Therapy-Induced Senescent Tumor Cells

Breast cancer has become the most prevalent malignancy worldwide. A key clinical advance has been the introduction of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), that in combination with endocrine therapy has been a major advance for the treatment of luminal (ER/HER2-) breast cancer. CDK4/6i induce cell cycle arrest in G1 and cellular senescence improving clinical outputs. However, limited efficacy and therapeutic resistance remain major challenges due to incomplete effects or the failure to eliminate the accumulated tumor senescent cells. Here, we identify connexin 43 (Cx43), a membrane channel protein involved in cell-to-cell communication, identified as a novel target in luminal breast cancer that potentiates the effects of CDK4/6 inhibitors. We found that Cx43 not only reduces tumor cell proliferation by enhancing senescence but also reshapes the Senescence-Associated Secretory Phenotype (SASP) profile. We also demonstrate that, in combination with CDK4/6i, Cx43 reinforces G1 arrest via transcriptional downregulation of E2F targets including CDK4 and CDK6, and through interaction with p21/p27, deepens the senescent state. Importantly, the Cx43-associated senescent phenotype sensitizes tumor cells accumulated under CDK4/6i treatment to the senolytic agent Navitoclax. Our results demonstrate that upregulation of Cx43 in breast cancer reduces proliferation and enhances the clearance of therapy-induced senescent cells. The triple-drug strategy comprising CDK4/6i, Cx43 delivery, and a senolytic drug such as Navitoclax holds great promise for overcoming CDK4/6i resistance and improving clinical outcomes in ER/HER2- breast cancer and may also be applicable to other cancer types that respond to CDK4/6i or other pro-senescence antitumoral drugs.

cancer biology↗

bioRxiv2026

First outbreak of Lumpy Skin disease in Catalonia, Spain, 2025-2026

Lumpy skin disease (LSD) is an emerging cattle disease caused by lumpy skin disease virus (LSDV), with major impacts on the industry, being classified as a Category A disease. Although it was historically confined to Africa, LSD has expanded into the Middle East, Asia and Europe. Here, we report two LSDV genomes from the first outbreak detected in Catalonia, Spain, in October 2025. The genomes were assembled from high-throughput sequencing data generated from two homogenized skin nodules. Comparative phylogenetic analyses were performed using all available complete LSDV genomes and rpo30 gene sequences. These analyses placed the LSDV isolates detected in Catalonia within clade 1.2, closely related to the isolates recently reported in Sardinia, Italy. Our findings also support a connection between recent south-western Europe and central African strains, possibly through northern Africa, and highlight the need for more complete genomes to clarify the origin and connections among recent LSDV outbreaks.

genomics↗

bioRxiv2023

Rhytidome- and cork-type barks of holm oak, cork oak and their hybrids highlight processes leading to cork formation

The periderm is basic for land plants due to its protective role during radial growth, which is achieved by the polymers deposited in the cell walls. In most trees, like holm oak, the periderm is frequently replaced by subsequent internal periderms yielding a heterogeneous outer bark made of a mixture of periderms and phloem tissues, known as rhytidome. Exceptionally, cork oak forms a persistent or long-lived periderm which results in a homogeneous outer bark of thick phellem cell layers known as cork. Here we use the outer bark of cork oak, holm oak, and their natural hybrids to analyse the chemical composition, the anatomy and the transcriptome, and further understand the mechanisms underlying periderm development. The inclusion of hybrid samples showing rhytidome-type and cork-type barks is valuable to approach to cork and rhytidome development, allowing an accurate identification of candidate genes and processes. The present study underscores that biotic stress and cell death signalling are enhanced in rhytidome-type barks whereas lipid metabolism and cell cycle are enriched in cork-type barks. Development-related DEGs, showing the highest expression, highlight cell division, cell expansion, and cell differentiation as key processes leading to cork or rhytidome-type barks.

cell biology↗

bioRxiv2022

Physiological stress responses to non-mimetic model brood parasite eggs: leukocyte profiles and heat-shock protein Hsp70 levels

Obligate avian brood parasites lay their eggs in the nest of other bird species (hosts). Brood parasitism often imposes severe fitness costs on hosts, which selects for the evolution of effective anti-parasitic defences, such as recognition and rejection of brood parasite eggs. Glucocorticoids have been recently found to mediate host physiological and behavioural adjustments in response to brood parasite eggs; however, it remains unclear whether brood parasitism triggers a general response involving multiple physiological elements. In this study, we experimentally investigated whether a salient brood parasitic stimulus (the presence of a non-mimetic model egg in the nest) causes physiological adjustments in adult Eurasian blackbirds (Turdus merula) at immune (leukocyte profiles) and cellular (heat-shock protein Hsp70 synthesis) level. Also, we explored whether these physiological changes are mediated by variations in corticosterone levels. We found that experimental brood parasitism caused an increase in heterophils and a decrease in lymphocytes, leading to higher H/L ratios in parasitized birds. Nevertheless, we did not find trade-offs between immune function and corticosterone levels. Hsp70 synthesis was not affected by our experimental manipulation. Our findings provide evidence that brood parasite eggs trigger a general stress response in egg-rejecter hosts, including changes in cellular immune profiles.

animal behavior and cognition↗

bioRxiv2020

Parental feeding preferences rather than sibling competition determine the death of smaller nestlings in asynchronous broods

Hatching asynchrony is a reproductive tactic that, through the creation of competitive hierarchies among offspring, allows parents for a quick adjustment of brood size via the death of smaller nestlings. This strategy is considered to be adaptive in case of unpredictable and/or poor environments in which it would guarantee that at least larger nestlings will fledge. Brood reduction is the usual outcome in asynchronously hatched broods since first-hatched nestlings are larger and get a disproportionately larger share of the food delivered by parents, often leading the youngest nestling to starve to death soon after hatching. However, we still do not know the proximate mechanisms of such brood reduction. One possibility is that the smallest nestling is not fed because larger nestlings outcompete it, which implies that nestlings control resource allocation. Alternatively, parents might actively ignore the persistent begging from their smallest nestling, which would involve that parents control food allocation. To determine whether parents or nestlings ultimately induce brood reduction in this situation, we experimentally created asynchronous broods of Eurasian blackbird (Turdus merula) nestlings and quantified food allocation by parents in two different situations: when sibling competition was allowed and, alternatively, when competition was prevented by physically separating nestlings within the nests by using wooden barriers. Our results showed that experimentally introduced smaller nestlings received less food than their larger nestmates both when competition among nestlings was allowed and when it was prevented. When adult males and females are considered separately, males fed the smallest nestling less often regardless of whether sibling competition was allowed or not, but adult females showed no differences. We can conclude that the smallest nestling starves mainly because parents actively ignore its begging. The higher competitive ability of the larger nestlings seem to have little effect given that although the smallest nestling is fed at a higher rate when physical interactions are prevented by the wooden barrier than when not, this difference is not significant. These findings suggest that parents rather than nestlings have the main control over food allocation.

animal behavior and cognition↗

bioRxiv2020

Prolactin mediates behavioural rejection responses to avian brood parasitism

Even though adaptations resulting from co-evolutionary interactions between avian brood parasites and their hosts have been well studied, the hormonal mechanisms underlying behavioural host defences remain largely unexplored. Prolactin, the main hormone mediating avian parental behaviour, has been hypothesized to play a key role in the orchestration of host responses to brood parasitic eggs. Based on the positive association between plasma prolactin and parental attachment to eggs, decreasing levels of this hormone are expected to facilitate egg-rejection decisions in parasitized clutches. We tested this prediction by implanting Eurasian blackbirds (Turdus merula) females with an inhibitor of prolactin secretion, bromocriptine mesylate, to experimentally low their prolactin levels. We found that bromocriptine-treated females rejected mimetic model eggs at higher rates than placebo-treated individuals. To our knowledge, this is the first experimental evidence that host responses to brood parasitism are mediated by the primary endocrine pathway that orchestrates the expression of avian parental care.

animal behavior and cognition↗