The impact of wildfires on the diet of <i>Podarcis lusitanicus</i> revealed by DNA metabarcoding

by Catarina Simões, Diana S. Vasconcelos, Raquel Xavier, Xavier Santos, Catarina Rato, D. James Harris

Fire has long been recognized as an important ecological and evolutionary force in plant communities, but its influence on vertebrate community ecology, particularly regarding predator-prey interactions, remains understudied. This study reveals the impact of wildfires on the diet of Podarcis lusitanicus, a lizard species inhabiting a fire-prone region in the Iberian Peninsula. In order to explore diet variability associated with different local burn histories, we evaluated P. lusitanicus diet across three types of sites in Northern Portugal: those had not burned since 2016, those burned in 2016, and those more recently burned in 2022. Podarcis lusitanicus is a generalist arthropod predator with dietary flexibility. Given the turnover of arthropod species after fire, it is expected to find variations in diet caused by different fire histories, especially between unburned and recently burned sites. From DNA metabarcoding of faecal samples, our study revealed that while prey richness remained unaffected by wildfire regime, significant shifts occurred in diet composition between more recently burned and unburned areas. Specifically, we found that differences in diet composition between these two fire regimes were due to the presence of Tapinoma ants and jumping spiders (Salticus scenicus). These prey were present in the diets of lizards occupying unburned areas, while these were absent in areas burned in 2022. Interestingly, diets in unburned areas and areas burned in 2016 showed no significant differences, highlighting the lizards’ ecological flexibility and the habitat’s resilience over time. The ant species T. topitotum was found in dominance in both burned areas, suggesting that this species may be fire tolerant. In addition, families such as Cicadellidae and Noctuidae were found to be more associated with more recently burned areas. The use of DNA metabarcoding in this study was essential to provide a more detailed and accurate view of predator-prey interactions in ecosystems susceptible to fire, and therefore a better understanding of changes in prey consumption in this fire-adapted ecosystem.

Mis-splicing drives loss of function of p53^E224D point mutation

by Ian C. Lock, Nathan H. Leisenring, Warren Floyd, Eric S. Xu, Lixia Luo, Yan Ma, Erin C. Mansell, Diana M. Cardona, Chang-Lung Lee, David G. Kirsch

Background

The tumor suppressor p53 (Trp53), also known as p53, is the most commonly mutated gene in cancer. Canonical p53 DNA damage response pathways are well characterized and classically thought to underlie the tumor suppressive effect of p53. Challenging this dogma, mouse models have revealed that p53-driven apoptosis and cell cycle arrest are dispensable for tumor suppression. Here, we investigated the inverse context of a p53 mutation predicted to drive the expression of canonical targets but is detected in human cancer.

Methods

We established a novel mouse model with a single base pair mutation (GAG>GAT, p53^E221D) in the DNA-Binding domain that has wild-type function in screening assays, but is paradoxically found in human cancer in Li-Fraumeni syndrome. Using mouse p53^E221D and the analogous human p53^E224D mutants, we evaluated expression, transcriptional activation, and tumor suppression in vitro and in vivo.

Results

Expression of human p53^E224D from cDNA translated to a fully functional p53 protein. However, p53^E221D/E221D RNA transcribed from the endogenous locus is mis-spliced resulting in nonsense-mediated decay. Moreover, fibroblasts derived from p53^E221D/E221D mice do not express a detectable protein product. Mice homozygous for p53^E221D exhibited increased tumor penetrance and decreased life expectancy compared to p53^WT/WT animals.

Conclusions

Mouse p53^E221D and human p53^E224D mutations lead to splice variation and a biologically relevant p53 loss of function in vitro and in vivo.

The choice of treatment and the motivations behind it impact clinical outcomes among patients with adequate control of their rheumatic disease: A real-life study

by Irazú Contreras-Yáñez, Guillermo A. Guaracha-Basáñez, Diana Padilla-Ortiz, Laura L. Franco-Mejía, Laura V. Vargas-Sánchez, Julia G. Jiménez-Decle, Virginia Pascual-Ramos

Introduction

Many factors influence how doctors make treatment decisions. The study compares the outcomes of patients with rheumatic diseases and adequate control (AC) whose treating rheumatologists prescribed their first choice of treatment (FCHO) versus the second choice (SCHO) and the motivations behind them. It also investigates the motivations associated with FCHO.

Patients and methods

The study was conducted at an outpatient clinic from February 2023 to February 2024. Patients with an RMD diagnosis were identified using systematic sampling (P-1). After their consultation, their rheumatologists detailed their treatment choice (FCHO vs. SCHO), the motivations behind it, and the outcomes. In a subsample of patients from P-1 and AC (SubP-1), treating rheumatologists repeated the assessment of outcomes at the next scheduled consultation. Descriptive statistics and multivariate regression analysis were used.

Results

There were 703 patients enrolled (P-1), 543 (77.2%) had AC, and 292 (Subp-1) underwent a follow-up evaluation. In P-1 and subP-1, FCHO was prescribed to 644 (91.5%) and 269 (92.1%) patients.Motivations related to evidence-based medicine and personal experience were more frequently referred to in FCHO. Concerns related to current or future drug shortages and a history of adverse events/intolerance were more frequent in SCHO.In SubP-1, a higher proportion of patients remained in AC and experienced remission/ improved disease activity with FCHO. Patients who received FCHO experienced a greater risk for favorable outcomes.The following motivations were associated with FCHO: “It aligns with guidelines”; “solid scientific evidence supporting the treatment effectiveness”; “I am concerned that the shortage of the drug may hinder the continuation of the treatment” and “history of adverse events or intolerance”.

Conclusions

Patients with AC of their underlying RMD, whose rheumatologists prescribed their FCHO, had better outcomes than those who were prescribed SCHO. Evidence-based motivations, rheumatologists´ concern of medication shortage, and patient-related motivations were associated with FCHO.