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Cuevas, P.

Publications and source records attributed to Cuevas, P..

2 recordsLinked to original sources

The processing of semantic complexity and co-speech gestures in schizophrenia: a naturalistic, multimodal fMRI study

Schizophrenia is marked by aberrant processing of complex speech and gesture, which may contribute functionally to its impaired social communication. To date, extant neuroscientific studies of schizophrenia have largely investigated dysfunctional speech and gesture in isolation, and no prior research has examined how the two communicative channels may interact in more natural contexts. Here, we tested if patients with schizophrenia show aberrant neural processing of semantically complex story segments, and if speech-associated gestures (co-speech gestures) might modulate this effect. In a functional MRI study, we presented to 34 participants (16 patients and 18 matched-controls) an ecologically-valid retelling of a continuous story, performed via speech and spontaneous gestures. We split the entire story into ten-word segments, and measured the semantic complexity for each segment with idea density, a linguistic measure that is commonly used clinically to evaluate aberrant language dysfunction at semantic level. Per segment, the presence of numbers of gestures varied (n = 0, 1, +2). Our results suggest that, in comparison to controls, patients showed reduced activation for more complex segments in the bilateral middle frontal and inferior parietal regions. Importantly, this neural aberrance was reduced in segments presented with gestures. Thus, for the first time with a naturalistic multimodal stimulation paradigm, we show that gestures reduced group differences when processing a natural story, probably by facilitating the processing of semantically complex segments of the story in schizophrenia.

neuroscience↗

Renal tubule Cpt1a overexpression mitigates kidney fibrosis by restoring mitochondrial homeostasis

Chronic kidney disease (CKD) remains a major epidemiological, clinical and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) suffer a persistent inflammatory and profibrotic response. Fatty acid oxidation (FAO), the main source of energy for TECs, is reduced in kidney fibrosis and contributes to its pathogenesis. To determine if FAO gain-of-function (FAO-GOF) could protect from fibrosis, we generated a conditional transgenic mouse model with overexpression of the fatty acid shuttling enzyme carnitine palmitoyl-transferase 1 A (CPT1A) in TECs. Cpt1a knock-in (CPT1A KI) mice subjected to three different models of renal fibrosis (unilateral ureteral obstruction, folic acid nephropathy-FAN and adenine induced nephrotoxicity) exhibited decreased expression of fibrotic markers, a blunted pro-inflammatory response and reduced epithelial cell damage and macrophage influx. Protection from fibrosis was also observed when Cpt1a overexpression was induced after FAN. FAO-GOF restituted oxidative metabolism and mitochondrial number and enhanced bioenergetics increasing palmitate oxidation and ATP levels, changes also recapitulated in TECs exposed to profibrotic stimuli. Studies in patients evidenced decreased CPT1 levels and increased accumulation of short and middle chain acyl-carnitines, reflecting impaired FAO in human CKD. We propose that strategies based on FAO-GOF may constitute powerful alternatives to combat fibrosis inherent to CKD. Graphical abstractOverexpression of CPT1A impedes tubular epithelial renal cell dedifferentiation and a pro-fibrotic phenotype by restoring mitochondrial metabolic bioenergetics. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

biochemistry↗