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Carrera, E.

Publications and source records attributed to Carrera, E..

9 recordsLinked to original sources

The segregase CDC48 integrates blue light and hormonal cues to regulate photomorphogenesis in Arabidopsis

Photomorphogenesis allows plants to adjust growth to ambient light conditions and relies on protein quality control to ensure the timely turnover of signaling components. The conserved AAA+ ATPase CDC48, along with its cofactors NPL4 and UFD1, is a crucial regulator of proteasomal degradation. While well characterized in other organisms, its role in plant development remains largely unexplored. Here, we show that CDC48 is required for blue light-mediated photomorphogenesis in Arabidopsis. Under blue light, CDC48A accumulates at the plasma membrane and in the nucleus, and cdc48a mutants fail to repress hypocotyl elongation properly. Similar phenotypes are observed upon inhibition of CDC48 or in npl4 and ufd1 mutants. Genetic and biochemical analyses further reveal that CDC48A negatively regulates gibberellin (GA) signaling. Consistently, UFD1 directly interacts with the GA receptor GID1 to promote its degradation. Together, these findings demonstrate that CDC48A integrates light and hormonal cues through protein homeostasis to regulate photomorphogenic development.

plant biology↗

Attentional focus and emotion modulate voice recognition deficits in cerebellar stroke patients

The cerebellum, long regarded as a motor structure, is increasingly recognized for its role in higher-order cognitive and socio-emotional functions. Its contribution to vocal emotion decoding, however, remains insufficiently understood. While prior work has linked the cerebellum to attentional control and predictive coding, direct evidence for its role in modulating prosody recognition under explicit versus implicit attentional demands is lacking. This study investigated how cerebellar stroke--controlled for time since stroke in months, and with an equal number of left- and right-lateralized lesions--alters vocal emotion processing depending on attentional focus. We aimed to disentangle sensory encoding and integration from decisional contributions of the cerebellum by combining behavioral analyses, drift diffusion modeling (DDM), and functional MRI in cerebellar stroke. Fifteen patients with chronic, isolated cerebellar stroke and fifteen matched controls performed two tasks on vocal stimuli expressing anger, happiness, or neutrality. In the explicit task, participants categorized the expressed emotion; in the implicit task, they categorized speaker gender while ignoring emotional tone. Behavioral performance was analyzed using mixed-effects logistic regression and DDM (angle model). Functional MRI analyses included conventional contrasts as well as model-based regressors derived from behavioral and computational parameters. Patients showed lower accuracy than controls, with deficits particularly pronounced in the explicit task. Performance also varied by emotion: gender recognition for angry voices (implicit processing) was relatively preserved, whereas happy and neutral voices were more vulnerable. Contrary to predictions, DDM parameters did not differ between groups. Instead, task effects dominated: implicit processing yielded higher drift rates, larger boundary separation, faster non-decision times, and stronger attentional focus compared to explicit recognition, suggesting that explicit evaluation imposes additional cognitive costs. At the neural level, patients recruited extended networks during explicit processing, including orbitofrontal cortex, amygdala, anterior insula, and cerebellar lobule IX, alongside cerebello-cortical tracts. Implicit processing was associated with more restricted activations, particularly in frontal opercular and cerebellar regions (lobule IX). Model-based analyses further revealed that successful categorization in patients relied on the left inferior frontal gyrus, inferior parietal lobule, and pre-supplementary motor area, although these effects were not significant when controlling for time since stroke. Our findings demonstrate that the cerebellum does not primarily shape decision dynamics but optimizes sensory representations of prosodic cues for downstream evaluation. When predictive tuning is compromised, patients maintain intact decision processes yet rely on compensatory cortical recruitment, particularly during explicit tasks. This pattern supports predictive coding accounts of cerebellar function in socio-emotional communication and highlights the need to consider subtle socio-affective deficits in cerebellar patients.

neuroscience↗

Pioneer bark beetle attacks induce multifaceted localized defense responses in Norway spruce

Conifer forests worldwide are increasingly threatened by environmental stressors, especially bark beetle infestations. In a novel experimental field setup with controlled attacks on clonal trees, we investigated the molecular defense responses of 35-year-old Norway spruce trees to colonization attempts by the spruce bark beetle, Ips typographus. A multi-omics approach was used to study tree responses to bark beetle pioneers under natural conditions. At the site of the attacks, increased levels in jasmonic acid, together with changes in other phytohormones, induced differential gene expression of up to 1,900 genes from multiple defense-related pathways. These transcriptomic alternations were corroborated by proteomic and metabolomic shifts, which ultimately showed increased levels of compounds involved in deterring bark beetle attacks, such as phenolic aglycones, diterpene resin acids, mono- and sesquiterpenes, and lignin. Our study highlights the intricate yet rapid and effective local defense response of Norway spruce against pioneer bark beetle attacks and lays a foundation for in-depth studies of this and other conifers resistance to phloem-feeding insects.

plant biology↗

Morphological and functional alteration of light perception circuits in AD patients

Disruption of sleep and circadian rhythms is one of the earliest symptoms of Alzheimers disease (AD). Circadian entrainment and modulation of alertness are non-visual responses to light driven by intrinsically photosensitive retinal ganglion cells (ipRGCs). To explore structural and functional changes of ipRGCs and ipRGC circuits in AD, we analyzed the retinas and brains of 13 elderly patients ranging from normal cognition to AD and performed ex vivo extracellular electrophysiological recordings on freshly harvested retinas. While rods and cones were moderately impaired, there was a severe loss of ipRGCs in AD donors. Importantly, the remaining ipRGCs exhibited morphological alterations, hyperexcitability, and were not able to sustain high levels of activation. These changes may be ipRGC subtype-specific and correlated with disease progression. Altered ipRGC circuits and function could contribute to the disruption of sleep and circadian rhythms reported in AD patients. Measuring ipRGC-dependent responses to light could be a promising way to predict or monitor pathological changes in the brain.

neuroscience↗

Machine Learning identifies conserved traits that influence lifespan and healthspan responses to dietary restriction

Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. Employing two computational methods across species--random forest modeling within the DGRP and Mendelian randomization in the UK Biobank--we pinpointed key traits with cross-species relevance that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and counteracted DR effects in flies, while threonine extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.

systems biology↗

Transcriptomic and DNA methylation modifications during fruit ripening and in response to ABA treatment in sweet cherry

Abscisic acid (ABA) plays a key role in the ripening process of non-climacteric fruits, triggering pigment production, fruit softening, and sugar accumulation. Transcriptomic studies show that ABA modifies the expression of several ripening-related genes, but to date, the epigenetic approach has not been utilized to characterize the role of ABA during this process. Therefore, this work aimed to perform transcriptomic and DNA methylation analyses of fruit samples treated with ABA during the fruit ripening process in the non-climacteric sweet cherry model. RNA-seq analyses revealed an overrepresentation of transcripts annotated in functional categories related to ABA response, secondary metabolism, and sugar synthesis. In contrast, Whole Genome Bisulfite Sequencing (WGBS) revealed DNA hypomethylation in the 5UTR region of genes related to carotene catabolism. Genes encoding xyloglucan enzymes were regulated transcriptionally and epigenetically during ripening. ABA treatment enhanced color development and ripening. GO analysis of DEGs in the RNA-seq of the ABA treatment revealed expression variations in genes encoding members of the Aux/IAA and ARF families. In the WGBS, genes encoding enzymes of the cytokinin biosynthesis had differential DNA methylation after the ABA treatment. Our work shows the genetic factors modulated by ABA at the genetic and epigenetic levels during non-climacteric ripening.

plant biology↗

Preparing for a second attack: a lesion simulation study on network resilience after stroke

Background and PurposeDoes the brain become more resilient after a first stroke to reduce the consequences of a new lesion? Although recurrent strokes are a major clinical issue, whether and how the brain prepares for a second attack is unknown. This is due to the difficulties to obtain an appropriate dataset of stroke patients with comparable lesions, imaged at the same interval after onset. Furthermore, timing of the recurrent event remains unpredictable. MethodsHere we used a novel clinical lesion simulation approach to test the hypothesis that resilience in brain networks increases during stroke recovery. 16 patients with a lesion restricted to the primary motor cortex were recruited. At 3 time points of the index event (10 days, 3 weeks, 3 months), we mimicked recurrent infarcts by deletion of nodes in brain networks (resting-state fMRI). Graph measures were applied to determine resilience (global efficiency) and wiring cost (mean degree) of the network. ResultsAt 10 days and 3 weeks after stroke, resilience was similar in patients and controls. However, at 3 months, while motor function had fully recovered, resilience to clinically representative simulated lesions was higher compared to controls (cortical lesion p=0.012; subcortical: p=0.009; cortico-subcortical: p=0.009). Similar results were found after random (p=0.012) and targeted (p=0.015) attacks. ConclusionOur results suggest that, after a lesion, brain networks reconfigure to increase resilience to future insults. Lesion simulation is an innovative approach, which may have major implications for stroke therapy. Individualized neuromodulation strategies could be developed to foster resilient network reconfigurations after a first stroke to limit the consequences of future attacks.

neuroscience↗

A point mutation in the kinase domain of CRK10 leads to xylem vessel collapse and activates defence responses

Cysteine-rich receptor-like kinases (CRKs) are a large family of plasma membrane-bound receptors ubiquitous in higher plants. They are transcriptionally regulated by a wide variety of environmental cues and stresses, however their precise biological roles remain largely unknown. Here we report a novel mutant isolated for the CYSTEINE-RICH RECEPTOR-LIKE KINASE 10 (CRK10) of Arabidopsis thaliana which harbours the substitution of alanine 397 by a threonine in the C-helix of its kinase domain and which we registered as crk10-A397T in the community database. In situ phosphorylation assays with the His-tagged wild type (WT) and crk10-A397T versions of the CRK10 kinase domain revealed that both alleles are active kinases capable of auto-phosphorylation with the newly introduced threonine acting as an additional phosphorylation site in crk10-A397T. Phenotypically the mutant is a dwarf and the analysis of thin cross sections with light and transmission electron microscopy revealed that collapsed xylem vessels in roots and hypocotyls are very likely the cause for this reduction in stature. Transcriptomic analysis of WT and mutant hypocotyls revealed that predominantly biotic and abiotic stress-responsive genes are constitutively up-regulated in the mutant. Root-infection assays with the vascular pathogen Fusarium oxysporum demonstrated that the crk10-A397T mutant has enhanced resistance to this pathogen compared to WT plants. Taken together our results suggest that crk10-A397T is a gain-of-function allele of CRK10 and open up new avenues for the investigation of this elusive receptor-like kinase family.

plant biology↗

Nitrate-regulated growth processes involve activation of gibberellin pathway

Nitrate, one of the main nitrogen (N) sources for crops, acts as a nutrient and key signaling molecule coordinating gene expression, metabolism and various growth processes throughout the plant life cycle. It is widely accepted that nitrate-triggered developmental programs cooperate with hormone synthesis and transport, to finely adapt plant architecture to N availability. Here, we report that nitrate, acting through its signaling pathway, promotes growth in Arabidopsis and wheat, in part by modulating the accumulation of gibberellin (GA)-regulated DELLA growth repressors. We show that nitrate reduces the abundance of DELLAs by increasing GA contents through activation of GA metabolism gene expression. Consistently, the growth restraint conferred by nitrate deficiency is partially rescued in global-DELLA mutant that lacks all DELLAs. At the cellular level, we show that nitrate enhances both cell proliferation and elongation in a DELLA-dependent and -independent manner, respectively. Our findings establish a connection between nitrate and GA signaling pathways that allow plants to adapt their growth to nitrate availability.

plant biology↗