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Tettamanti, M.

Publications and source records attributed to Tettamanti, M..

7 recordsLinked to original sources

Atonosomes, compartments involved in membrane tension decrease

To ensure survival, cells need to buffer the effects of environmental stress on their plasma membrane, yet the structural mechanisms by which this is acutely achieved remain largely unknown. Here, we propose atonosomes as a unifying identity for a class of previously observed but enigmatic, tension-responsive, plasma membrane-derived compartments that arise across contexts of acute and chronic membrane tension loss. Leveraging unprecedented high resolution cryo-FIB-ET imaging in yeast, we show that atonosomes are complex, organelle-containing structures bounded by membranes and cell wall material, spanning hundreds of nanometers, and displaying a remarkable morphological diversity. Atonosomes form within seconds in response to reduced plasma membrane tension, and their emergence appears to require no dedicated molecular machinery, arising instead as a direct consequence of membrane biophysics. Upon formation, they recruit key membrane-associated proteins, including TORC2, Slm1, and septins. Under conditions of chronic disruption of PM homeostasis, atonosomes become constitutively present. Their stability and reversibility are further modulated by the cell wall, whose polymerization state influences atonosome dynamics. Structural conservation in fungi and ichthyosporea, demonstrates that atonosomes are a conserved stress-triggered response of cell-wall enclosed organisms. Together, these findings establish atonosomes as a novel compartment that mediates cellular responses to plasma membrane tension variation, coupling membrane remodeling and lipid homeostasis to preserve cellular integrity under stress.

cell biology↗

Functional projection of cognitive functions through the human corpus callosum

Reconciling the anatomical observation that the human brain comprises two asymmetrical halves with the phenomenal unity of the mind is a puzzle that has challenged neuroscientists since the dawn of research in the field. White-matter commissural fibres of the corpus callosum constitute a critical anatomical substrate for the functional resolution of this anatomical duality. However, the extent of the functional involvement of the callosum in different domains of cognition represents, to this day, a mostly uncharted territory. Here we present a probabilistic characterization of callosal involvement in a set of cognitive functions. In particular, we estimated structural callosal connections by means of the Disconnectome approach applied to a reference sample of healthy participants while using the macro-anatomical cortical areas contained in the Harvard-Oxford template as seeds. By multiplying structural connectivity by the involvement of each cortical area in a set of cognitive functions (as derived from Neurosynth meta-analyses), we produced a voxel-wise characterization of the corpus callosum in different functional domains. We were able to highlight greater involvement of posterior callosal regions in vision and episodic memory, greater involvement of more anterior callosal regions in decision making and working memory, with somatosensory and motor functions more related to the central dorsal portion of the callosum.

neuroscience↗

Brain signatures of semantic activation for words that do not exist.

The experience of making sense of novel words is ubiquitous in human communication. Still, novel words have traditionally been considered as meaningless by cognitive research. Here we combined behavioral, univariate and multivariate fMRI techniques, and computational modelling to explore whether and how novel words activate the neurocognitive hallmarks of semantic processing triggered by existing words, and whether this process is influenced by the presence of familiar functional linguistic elements, i.e., morphemes. We observed that semantic activation for novel words is comparable to that of existing words, provided that novel words contain a concatenation of identifiable morphemes. In addition, representational similarity analysis highlighted that existing words and novel words containing morphemes (but not novel words not containing morphemes) can activate fine-grained semantic representations. These results suggest that the difference in the neurocognitive underpinnings of semantic processing for existing and novel words might be quantitative rather than qualitative and based on how reliably linguistic form points to meaning.

neuroscience↗

Multi-center Translational Trial of Remote Ischemic Conditioning in Acute Ischemic Stroke (TRICS BASIC)

BackgroundBasic science studies have reported remote ischemic conditioning (RIC) as neuroprotective in acute ischemic stroke, while clinical evidence remains conflicting. The TRICS BASIC study investigated the efficacy and safety of RIC in experimental ischemic stroke using a rigorous clinical trial methodology. MethodsMulti-center, multi-species, parallel group, randomized, controlled, preclinical trial of transient femoral artery clipping to induce RIC in female and male rats and mice subjected to transient endovascular occlusion of the middle cerebral artery. Animals were randomized to receive RIC, or sham surgery, after reperfusion. The primary endpoint was good functional outcome at 48 hours, assessed using a composite functional neuroscore. Secondary endpoints was infarct volume at 48 hours and safety, assessed using a standardized health report at 24 and 48 hours. Pre-enrollment harmonization, centralized monitoring, allocation concealment, blinded outcome assessment and intention-to-treat analysis were applied. ResultsThe trial enrolled 164 rodents (82 mice and 82 rats) of both sexes (53% females), across seven laboratories. A greater proportion of RIC-treated rodents achieved a favorable functional outcome compared to controls, at 48 hours post-ischemia (55% versus 36%; OR 2.2, 95% CI [1.23-4.4], p=0.009). RIC was associated with a small reduction in infarct volume (standardized mean difference -0.38, 95% CI [-0.70, -0.05], p=0.024). Health monitoring indicated no major safety concerns, and post-operative analgesia requirements were lower in RIC-treated mice. ConclusionsSurgically-induced RIC provided a modest but evident neuroprotective effect in experimental ischemic stroke, underscoring the potential of this strategy as an adjunctive treatment in stroke care. The findings of the TRICS BASIC study highlighted the importance of multicenter preclinical trials in addressing variability and enhancing translational validity. Registrationregistered at preclinicaltrials.eu, identifier PCTE0000177.

neuroscience↗

Multimodal investigation of the neurocognitive deficits underlying dyslexia in adulthood

Dyslexia is a neurobiological disorder characterised by reading difficulties, yet its underlying causes remain unclear. Neuroimaging and behavioural studies found anomalous responses in tasks requiring phonological processing, motion perception, and implicit learning, and showed gray and white matter abnormalities in several brain regions of dyslexics compared to controls, indicating that dyslexia is a heterogeneous condition and promoting a multifactorial approach. In order to evaluate whether the combination of behavioural and multimodal MRI can have greater sensitivity in identifying neurocognitive traits of dyslexia compared to monocomponential approaches, in 19 dyslexic and 19 control subjects we acquired behavioural cognitive assessments, multiple (phonological, visual motion, rhythmic) mismatch-response functional MRI tasks, structural diffusion-weighted and T1-weighted images. To examine between-group differences in the multimodal neurocognitive measures, we applied univariate and multivariate approaches. Results showed that dyslexics performed worse than controls in behavioural phonological tasks. Neuroimaging analyses revealed that individuals with dyslexia present reduced cerebellar responses to mismatching rhythmic stimuli, as well as structural disorganization in several white matter tracts and cortical regions previously implicated in dyslexia. Most importantly, in line with the view of dyslexia as a multifactorial phenomenon, a machine learning model trained with features from all three MRI modalities (functional, diffusion, and T1-weighted) discriminated between dyslexics and controls with greater accuracy than models including just one modality. The individual classification scores in the multimodal machine learning model correlated with behavioural reading accuracy. These results confirm that dyslexia should be approached as a composite condition characterised by multiple distinctive cognitive and brain features.

neuroscience↗

Unaware Processing of Words Activates Experience-Derived Information in Conceptual-Semantic Brain Networks

The recognition of manipulable objects results from the encoding of sensory input in combination with predictive decoding of experience-derived visuomotor information stored in conceptual-semantic representations. This grounded interpretive processing was previously found to subsist even under unaware perception of manipulable object pictures. In this fMRI study, we first aimed to extend this finding by testing whether experientially grounded visuomotor representations are unawarely recruited when manipulable objects are not visually depicted, but only referred to by words presented subliminally through continuous flash suppression. Second, we assessed the generalizability of decoding experience-derived conceptual information to other semantic categories, by extending our investigation to subliminally presented emotion words and testing for unaware recruitment of grounded emotion representations in the limbic system. Univariate analysis of data sampled from 21 human participants (14 females) showed that manipulable object words selectively activated a left-lateralized visuomotor network, both when words were presented below perceptual threshold and when participants subjectively reported lack of stimulus awareness. Emotion words selectively engaged the bilateral limbic network, although univariate analysis did not provide evidence for its recruitment under subliminal perceptual conditions. In turn, multivariate pattern analysis showed that neural codes associated with both manipulable object and emotion words could be decoded even in the absence of perceptual awareness. These findings suggest that the brain automatically engages in conceptual-semantic decoding of experience-derived information not only when circumstances require to interact with manipulable objects and emotions, but also when these referents are dislocated in time and space and only referred to by words.

neuroscience↗

Unaware processing of tools in the neural system for object-directed action representation

The hypothesis that the brain constitutively encodes observed manipulable objects for the actions they afford is still debated. Yet, crucial supporting evidence demonstrating that such visuo-motor embodiment occurs even without awareness has hitherto not been provided. In this fMRI study, we reliably instantiated unaware visual perception conditions by means of Continuous Flash Suppression, and found consistent activation in the target visuo-motor, action representation system, specifically for manipulable versus non-manipulable objects

neuroscience↗