Departament de Medicina i Ciències de la Vida

Documents de recerca, en accés obert, com ara articles de revista, llibres, comunicacions, ponències o posters a jornades i congressos, etc., del Departament de Ciències Experimentals i de la Salut de la UPF.

URI permanent per a aquesta comunitat http://hdl.handle.net/10230/6237

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  • Open AccessItem type: Ítem ,
    Thermal evolution of gene expression profiles in Drosophila subobscura
    (BioMed Central, 2007) Laayouni, Hafid, 1968-; García-Franco, Francisco; Chávez-Sandoval, Blanca E.; Trotta, Vincenzo; Beltran, Sergi; Corominas Guiu, Montserrat; Santos, Mauro
    Background: Despite its pervasiveness, the genetic basis of adaptation resulting in variation directly or indirectly related to temperature (climatic) gradients is poorly understood. By using 3-fold replicated laboratory thermal stocks covering much of the physiologically tolerable temperature range for the temperate (i.e., cold tolerant) species Drosophila subobscura we have assessed whole-genome transcriptional responses after three years of thermal adaptation, when the populations had already diverged for inversion frequencies, pre-adult life history components, and morphological traits. Total mRNA from each population was compared to a reference pool mRNA in a standard, highly replicated two-colour competitive hybridization experiment using cDNA microarrays. Results: A total of 306 (6.6%) cDNA clones were identified as 'differentially expressed' (following a false discovery rate correction) after contrasting the two furthest apart thermal selection regimes (i.e., 13°C vs. 22°C), also including four previously reported candidate genes for thermotolerance in Drosophila (Hsp26, Hsp68, Fst, and Treh). On the other hand, correlated patterns of gene expression were similar in cold- and warm-adapted populations. Analysis of functional categories defined by the Gene Ontology project point to an overrepresentation of genes involved in carbohydrate metabolism, nucleic acids metabolism and regulation of transcription among other categories. Although the location of differently expressed genes was approximately at random with respect to chromosomes, a physical mapping of 88 probes to the polytene chromosomes of D. subobscura has shown that a larger than expected number mapped inside inverted chromosomal segments. Conclusion: Our data suggest that a sizeable number of genes appear to be involved in thermal adaptation in Drosophila, with a substantial fraction implicated in metabolism. This apparently illustrates the formidable challenge to understanding the adaptive evolution of complex trait variation. Furthermore, some clustering of genes within inverted chromosomal sections was detected. Disentangling the effects of inversions will be obviously required in any future approach if we want to identify the relevant candidate genes.
  • Open AccessItem type: Ítem ,
    Implementation of community screening strategies for depression
    (Nature Research, 2024) Arias de la Torre, Jorge; Ronaldson, Amy; Vilagut Saiz, Gemma, 1975-; Martinez-Alés, Gonzalo; Dregan, Alex; Bakolis, Ioannis; Valderas Martínez, José María; Molina, Antonio J.; Martín, Vicente; Bellón, Juan Ángel; Alonso Caballero, Jordi
  • Open AccessItem type: Ítem ,
    Astroglial reactivity is a key modulator of Alzheimer's disease pathological progression
    (Oxford University Press, 2024) Pelkmans, Wiesje; Gispert López, Juan Domingo
    This scientific commentary refers to 'Association of glial fibrillary acid protein, Alzheimer's disease pathology and cognitive decline' by Peretti et al. (https://doi.org/10.1093/brain/awae211).
  • Embargoed AccessItem type: Ítem ,
    Prognostic value of PARP1 and PARP2 copy number alterations in prostate cancer
    (Elsevier, 2025) Segalés Tañà, Laura, 1994-; Bellmunt Molins, Joaquim, 1959-; Perera Bel, Júlia; Vargas-Parra, Gardenia; Juanpere, Nuria; Lopez-Segura, David; Rodriguez-Vida, Alejo; Colomo Saperas, Luis Alberto; Cecchini Rosell, Lluís; Lloreta, Josep, 1958-; Yélamos López, José; Fumadó Ciutat, Lluis; Hernández Llodrà, Silvia
    PARP1/2 have overlapping yet nonredundant biological functions in DNA repair and androgen receptor-transcriptional regulation. Studies on PARP alterations in human tumors have yielded conflicting results. In prostate cancer (PCa), PARP1/2 protein overexpression has been related to androgen deprivation therapy resistance, biochemical recurrence, and progression to metastases. PARP inhibitors have been approved for treating metastatic castration-resistant PCa with homologous recombination repair gene mutations. However, the significance of PARP1/2 genomic alterations is not fully studied. We aimed to analyze PARP1/2 alterations in PCa, assess their value as prognostic markers, and explore their relevance for potential therapeutic stratification. PARP1/2 copy number status was evaluated in 121 PCa primary tumors using real-time PCR. In 29 of them, a regional pelvic lymph node involvement was also analyzed. BRCA1/2 somatic mutations were analyzed in 24 PCa cases. Relationship with clinicopathological features, progression to metastases, and prostate-specific antigen recurrence was assessed. PARP1 loss and PARP2 gain were detected in 34.7% and 32.2% of primary tumors, respectively, with a high frequency of co-occurrence (P < .001). Both alterations were statistically associated with locally advanced disease at the time of diagnosis (P = .036; P = .006), metastatic dissemination (P = .014; P = .003), and other aggressive clinicopathological characteristics (such as the presence of Gleason pattern 5, high-grade, and high-stage). Cases with exclusive PARP2 gain had the shortest time to prostate-specific antigen recurrence, whereas double wt patients displayed the best outcome (P = .007). In 29 paired primary tumors and regional pelvic lymph node involvement, PARP1 loss showed strong concordance (P = .001), whereas PARP2 gain did not (P = .411). In conclusion, loss of PARP1 and gain of PARP2 show strong co-occurrence and are associated with clinicopathological characteristics of aggressiveness. PARP2 alterations appear to have a particularly significant impact on disease prognosis. Furthermore, these data suggest that the analysis of PARP1/2 copy number status could be useful in predicting PCa outcomes. Its role in therapy warrants further evaluation.
  • Open AccessItem type: Ítem ,
    Prenatal alcohol exposure dysregulates the expression of clock genes and alters rhythmic behaviour in mice
    (Royal Society, 2025) Reina-Campos, Maria; Gallego-Landin, Ines; Medrano, Mireia; García Baos, Alba; Valverde Granados, Olga
    Foetal alcohol spectrum disorders (FASDs) refer to a range of adverse physical, behavioural and cognitive effects caused by perinatal alcohol exposure. While cognitive impairments are well documented, FASD has also been associated with sleep disturbances and circadian rhythm disruptions. This study aimed to examine the effects of perinatal alcohol exposure on circadian rhythms at behavioural and gene expression levels across two developmental stages (adolescence and adulthood) in both male and female mice. Using a validated prenatal and lactation alcohol exposure (PLAE) protocol, we assessed circadian patterns of locomotor activity under free-running conditions and spatial memory performance during adolescence and adulthood. Additionally, we evaluated the impact of PLAE on circadian expression of clock and non-circadian genes involved in neurotransmission across key brain regions, including the medial prefrontal cortex and hippocampus. PLAE altered circadian rhythmicity and impaired spatial memory. Gene expression analyses revealed disrupted oscillatory patterns in clock genes and in genes related to plasticity and cognition, including those from the expanded endocannabinoid system (e.g. Cnr1, Dagla, Faah) and other neurotransmitter systems (e.g. Oprm1, Slc17a8, Drd1, Gabra1). These findings underscore the impact of early alcohol exposure on biological rhythms and neurobehavioural function, highlighting circadian dysregulation as a contributing factor to FASD.