Search bioRxiv⌕ Search

Biology subjects

Amat, I.

Publications and source records attributed to Amat, I..

4 recordsLinked to original sources

Protein arginine-methyltransferase 1 (PRMT1): a new pharmacological target in cholangiocarcinoma

Cholangiocarcinoma (CCA) is a highly aggressive malignancy characterized by poor prognosis, limited therapeutic options, and a predominantly immunosuppressive tumor microenvironment. Protein arginine methyltransferase 1 (PRMT1), the major mediator of asymmetric arginine dimethylation, has been implicated in multiple oncogenic processes, although its role in CCA remains unknown. Here, we demonstrate that PRMT1 is frequently overexpressed in human CCA and is associated with aggressive molecular subtypes and immune-desert tumors. Genetic dependency analyses and pharmacological inhibition using type I PRMT inhibitors markedly impaired CCA cell proliferation, clonogenicity, and tumoroid growth. Transcriptomic profiling revealed that PRMT1 inhibition induces broad alterations in gene expression and alternative splicing, affecting pathways involved in proliferation, apoptosis, DNA damage response, metabolism, and immune signaling. Mechanistically, PRMT1 targeting promoted genomic stress, accumulation of cytosolic double-stranded DNA, and activation of the cGAS-STING-TBK1-IRF3 signaling axis, resulting in enhanced interferon signaling and increased expression of T cell-recruiting chemokines, including CXCL9 and CXCL10. PRMT1 inhibition also synergized with cisplatin, poly-ADP-ribose polymerase (PARP) inhibition, and PRMT5 blockade in vitro and in patient-derived tumoroids. Importantly, in an aggressive orthotopic murine model of intrahepatic CCA, combined treatment with the PRMT1 inhibitor GSK3368715 and anti-PD-1 antibodies significantly reduced tumor burden and increased CD4+ and CD8+ T-cell infiltration compared with monotherapies. Collectively, these findings identify PRMT1 as a critical regulator of CCA growth and immune evasion and support the therapeutic potential of PRMT1 inhibition, particularly in combination with immunotherapy.

cancer biology↗

Same-sex sexual behaviours in a wasp despite sex recognition cues: the broad mating filter hypothesis

Same-sex sexual behaviour (SSB) in animals, once considered an evolutionary dead end, is surprisingly widespread, particularly among male insects. These behaviours may arise from either adaptive or non-adaptive processes. Over shorter timescales, SSB can occur when courtship costs are low or when missing a mating opportunity is costly, leading to a reduced behavioural threshold for courtship--a "broad mating filter," as predicted by threshold acceptance theory. We investigated SSB in males of the parasitoid wasp Venturia canescens (Hymenoptera: Ichneumonidae), a species where encounters are infrequent and male courtship is energetically not costly. We hypothesised that males exhibit a broad mating filter, accepting conspecifics for courtship regardless of sex. First, behavioural assays assessed whether SSB correlated with higher reproductive success. Second, we compared cuticular hydrocarbon (CHC) profiles between sexes, as these compounds may serve as cues for sex recognition. Our chemical analyses revealed clear quantitative CHC differences between males and females, indicating potential for sex recognition. Nonetheless, 18% of males displayed SSB, and these behaviours had no detectable effect on either courting or mating success. Moreover, males receiving SSB did not experience any reproductive advantage. Our findings support the hypothesis of a broad mating filter in V. canescens males. In this species, where conspecific encounters are rare, SSB appears to arise from reduced discrimination rather than adaptive benefits, consistent with a low-cost courtship strategy and high opportunity costs of missed mating events.

animal behavior and cognition↗

Foraging at night under artificial light: consequences on reproductive senescence and lifetime reproductive success for a diurnal insect

O_LIThe increasing use of artificial light at night (ALAN) is currently a major anthropogenic disturbance, with largely unappreciated eco-evolutionary consequences for nocturnal but also diurnal organisms. It has been hypothesized that light pollution could create new opportunities for the latter to forage and reproduce at night, which is called the night-light niche, with fitness consequences still scarcely explored. C_LIO_LIWe exposed diurnal parasitoid wasps (Venturia canescens) to one of three light-at-night conditions: control (0 lux), low intensity (0.7 lux) or high intensity (20 lux) throughout their lives. We then monitored changes in both behavioural and life-history traits, namely daytime and nighttime feeding and egg-laying activity, reproductive senescence, lifespan and lifetime reproductive success. C_LIO_LILight pollution influenced the nighttime activity of wasps. The proportion of wasps feeding and laying eggs at night increased, and we also detected a tendency for a higher nighttime reproductive success under a high intensity of light pollution. Surprisingly, high intensity of light pollution also increased the wasps lifespan. Such changes did not affect the lifetime reproductive success of the wasps, but influenced the distribution of ovipositions between day and night. C_LIO_LIReproductive senescence occurs in V. canescens, evidenced by the linear decline in daily reproductive success with age regardless of the light condition. ALAN conditions, in interaction with mother age, affected developmental time in offspring, highlighting an effect on reproductive senescence. C_LIO_LIWe demonstrated that light pollution induced the use of the night-light niche in a diurnal insect, with a shift in the distribution of egg-laying events between day and night. While we did not observe strong consequences on individual fitness, such changes in the dynamics of parasitism behaviour may nevertheless have major consequences for population dynamics, especially in natural conditions. C_LI

animal behavior and cognition↗

Insects and incest: field evidence for dangerous liaisons in a parasitoid wasp

O_LISib mating avoidance is a pervasive behaviour, which likely evolves in species that sare subject to inbreeding depression. Laboratory studies have provided elegant demonstrations, but small-scale bioassays often minimize the costs associated with mate finding and mate-choice and may for this reason produce spurious findings.\nC_LIO_LIWe inferred the mating behaviour of the parasitoid wasp Venturia canescens from the genetic analyses of natural populations. We used V. canescens as a model organism because in this species, laboratory experiments have shown that sib mating yields a 25% decrease in fertile offspring, and congruently, sib mating is partially avoided.\nC_LIO_LIOur study consisted in genotyping 86 wild-caught males, 155 wild-caught-females and their 226 daughters at eighteen microsatellite loci. With these data, we were able to reconstruct the genotype of females mate and estimate the relatedness of each mating pairs.\nC_LIO_LIWe found that the effective rate of sib mating does not differ from the probability that sibs encounter one another at random, which suggest a sib mating tolerance in this species. However, complementary lab experiments confirmed that kin discrimination exist in this species, with related pairs having a lower mating latency.\nC_LIO_LIThese results suggest that V. canescens tolerate sib mating in the field despite kin discrimination, and therefore call into question the common beliefs on inbreeding depression in species with single-locus complementary sex determination. This inbreeding tolerance also opens up the question of the maintenance of the kin discrimination in this species.\nC_LI

animal behavior and cognition↗