Biology subjects

Sala, R.

Publications and source records attributed to Sala, R..

8 recordsLinked to original sources

bioRxiv2025

Structural bases for Nuclear Factor 1-X activation and DNA recognition. Prototypic insight into the NFI transcription factor family

Nuclear Factor I (NFI) proteins were first identified in adenovirus DNA replication and later as regulators of gene transcription, stem cell proliferation, and differentiation. They play key roles in development, cancer and congenital disorders. Within the NFI family, NFI-X is critical for neural stem cell biology, hematopoiesis, muscle development, muscular dystrophies and oncogenesis. Here, we present the first structural characterization of the NFI transcription factor, NFI-X, both alone and bound to its consensus palindromic DNA site. Our analyses reveal a novel, MH1-like fold within NFI-X DNA-binding domain (DBD) and identify crucial structural determinants for activity, such as a Zn{superscript 2} binding site, dimeric assembly, activation mechanism and DNA-binding specificity. Given the >95% sequence identity within the NFI DBDs, our structural data are prototypic for the entire family; a NFI Rosetta Stone that allows decoding a wealth of biochemical and functional data and provides a precise target for drug design in a wider disease context.

biochemistry↗

bioRxiv2024

Benchmarking for the automated detection and classification of southern yellow-cheeked crested gibbon calls from passive acoustic monitoring data

Recent advances in deep and transfer learning have revolutionized our ability for the automated detection and classification of acoustic signals from long-term recordings. Here, we provide a benchmark for the automated detection of southern yellow-cheeked crested gibbon (Nomascus gabriellae) calls collected using autonomous recording units (ARUs) in Andoung Kraleung Village, Cambodia. We compared the performance of support vector machines (SVMs), a quasi-DenseNet architecture (Koogu), transfer learning with pretrained convolutional neural network (ResNet50) models trained on the ImageNet dataset, and transfer learning with embeddings from a global birdsong model (BirdNET) based on an EfficientNet architecture. We also investigated the impact of varying the number of training samples on the performance of these models. We found that BirdNET had superior performance with a smaller number of training samples, whereas Koogu and ResNet50 models only had acceptable performance with a larger number of training samples (>200 gibbon samples). Effective automated detection approaches are critical for monitoring endangered species, like gibbons. It is unclear how generalizable these results are for other signals, and future work on other vocal species will be informative. Code and data are publicly available for future benchmarking.

ecology↗

bioRxiv2024

Cardiovascular responses to natural and auditory evoked slow waves predict post-sleep cardiac function

The interplay between slow-wave sleep and cardiovascular health is increasingly recognized. Our prior research showed that auditory-enhanced slow waves can boost cardiac function, yet the mechanisms behind this remain unclear. Advancing these findings, our current analysis dissected the effects of two slow wave types on cardiovascular function, using data from 18 middle-aged men across three nights. We found that the strength of heart rate and blood pressure responses concurrent with slow waves predicts cardiac function post-sleep. Notably, we identified that highly synchronized type I slow waves, as opposed to lower-amplitude type II slow waves, primarily co-occur with these cardiovascular pulsations. While auditory stimulation enhances both types of slow waves, they exhibit distinct temporal dynamics, pointing to different underlying biological mechanisms. This study crucially addresses how distinct slow wave types can affect cardiovascular function, implying that targeted slow wave stimulation could be a strategic approach to improve heart health.

neuroscience↗

bioRxiv2022

Characterization of BoHV-4 ORF45

Bovine herpesvirus 4 (BoHV-4) is a Gammaherpesvirus of the genus Rhadinovirus, his natural host is the bovine whereas the African Buffalo the natural reservoir. Anyhow, BoHV-4 infection is not associated to a specific disease. Genome structure and genes are well conserved in Gammaherpesvirus, and orf45 gene and its product, ORF45, is one of those. BoHV-4 ORF45 has been suggested to be a tegument protein, however, BoHV-4 ORF45 structure and function have not yet been experimentally characterized. In the present study, it is shown that BoHV-4 ORF45, despite its poor homology with other characterized Rhadinovirus ORF45s, is structurally related to Kaposis sarcoma-associated herpesvirus (KSHV), is a phosphoprotein and localizes in the host cell nuclei. Through the generation of an ORF45-null mutant BoHV-4 and its pararevertant, it was possible to demonstrate that ORF45 is essential for BoHV-4 lytic replication and is associated to the viral particles, as for the other characterized Rhadinovirus ORF45s. Finally, the impact of BoHV-4 ORF45 on cellular transcriptome was investigated, an aspect poorly explored or not at all for other Gammaherpesvirus. Many cellular transcriptional pathways were found to be alterate, mainly those involving p90 ribosomal S6 kinase (RSK) and signal-regulated kinase (ERK) complex (RSK/ERK), thus highlighting the authentic character of BoHV-4 ORF45 and paving the way to further investigations.

microbiology↗

bioRxiv2022

Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics

Sleep modulation techniques to elucidate the functional role of sleep brain oscillations in brain and body functions have gained large interest. Slow waves, the hallmark feature of deep non-rapid eye movement sleep, do potentially drive restorative effects on brain and cardiovascular functions. Auditory stimulation to modulate slow waves is a promising tool, however, directly comparing different auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included stimulation nights. We found a large and global increase in slow wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA and thus, our findings provide mechanistic insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow wave enhancements translates into a more rested cardiovascular system on the subsequent day.

neuroscience↗

bioRxiv2021

Activity-dependent modulation of NMDA receptors by endogenous zinc shapes dendritic function in cortical neurons.

Activation of NMDA receptors (NMDARs) has been proposed to be a key component of single neuron computations in vivo. However is unknown if specific mechanisms control the function of such receptors and modulate input-output transformations performed by cortical neurons under in vivo-like conditions. Here we found that in layer 2/3 pyramidal neurons (L2/3 PNs), repeated synaptic stimulation results in an activity-dependent decrease in NMDARs activity by vesicular zinc. Such a mechanism shifted the threshold for dendritic non-linearities and strongly reduced LTP induction. Modulation of NMDARs was cell- and pathway-specific, being present selectively in L2/3-L2/3 connections but absent in ascending bottom-up inputs originating from L4 neurons. Numerical simulations highlighted that activity-dependent modulation of NMDARs has an important influence in dendritic computations endowing L2/3 PN dendrites with the ability to sustain dendritic non-linear integrations constant across different regimes of synaptic activity like those found in vivo. The present results therefore provide a new perspective on the action of vesicular zinc in cortical circuits by highlighting the role of this endogenous ion in normalizing dendritic integration of PNs during a constantly changing synaptic input pattern.

neuroscience↗

bioRxiv2020

Dual contributions of cerebellar-thalamic networks to learning and offline consolidation of a complex motor task.

The contribution of cerebellum to motor learning is often considered to be limited to adaptation, a short-timescale tuning of reflexes and previous learned skills. Yet, the cerebellum is reciprocally connected to two main players of motor learning, the motor cortex and the basal ganglia, via the ventral and midline thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. In the cerebellar nuclei, we found task-specific neuronal activities during the task, and lasting changes after the task suggesting an offline processing of task-related information. Using pathway-specific inhibition, we found that dentate neurons projecting to the midline thalamus contribute to learning and retrieval, while interposed neurons projecting to the ventral thalamus contribute to the offline consolidation of savings. Our results thus show that two parallel cerebello-thalamic pathways perform distinct computations operating on distinct timescales in motor learning.

neuroscience↗

bioRxiv2020

Functional abnormalities in the cerebello-thalamic pathways in an animal model of dystonia

Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia, mice carrying a heterozygous invalidation of Gnal gene which notably disrupts striatal function, exhibiting dystonic movements and postures following systemic or striatal administration of oxotremorine. Theta-burst optogenetic stimulations of the cerebellar nuclei evoked a potentiation of the responses to cerebellar stimulations in the thalamus and motor cortex in WT mice, without evident motor function disruption. In contrast, theta burst stimulations evoked a depression of these responses only in dystonia-manifesting Gnal+/- mice after oxotremorine administration, decreased the disabling dystonia attacks, and increased normal active wake behaviour in Gnal+/- mice. The cerebellum could thus offer a gateway for a corrective treatment of motor impairments in dystonia including striatal dysfunction. One sentence summaryA mouse model of DYT25 dystonia, carrying a Gnal mutation disrupting striatal neurotransmission, exhibits anomalous cerebello-thalamic plasticity in the non-manifesting state, but theta-burst cerebellar stimulations during cholinergic-induced dystonia depress the cerebello-thalamic transmission and reduce the severity of the motor symptoms.

neuroscience↗