Biology subjects

Tomas, R.

Publications and source records attributed to Tomas, R..

3 recordsLinked to original sources

bioRxiv2025

Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons

Huntingtons Disease (HD) is caused by a CAG repeat expansion in the gene encoding Huntingtin (HTT). While normal HTT function appears impacted by the mutation, the specific pathways unique to CAG repeat expansion versus loss of normal function are unclear. To understand the impact of the CAG repeat expansion, we evaluated biological signatures of HTT knockout (HTT KO) versus those that occur from the CAG repeat expansion by applying multi-omics, live cell imaging, survival analysis and a novel feature-based pipeline to study cortical neurons (eCNs) derived from an isogenic human embryonic stem cell series (RUES2). HTT KO and the CAG repeat expansion influence developmental trajectories of eCNs, with opposing effects on the growth. Network analyses of differentially expressed genes and proteins associated with enriched epigenetic motifs identified subnetworks common to CAG repeat expansion and HTT KO that include neuronal differentiation, cell cycle regulation, and mechanisms related to transcriptional repression and may represent gain-of-function mechanisms that cannot be explained by HTT loss of function alone. A combination of dominant and loss-of-function mechanisms are likely involved in the aberrant neurodevelopmental and neurodegenerative features of HD that can help inform therapeutic strategies.

cell biology↗

bioRxiv2021

Structural and functional organization of visual responses in the inferior olive of larval zebrafish

The olivo-cerebellar system plays an important role in vertebrate sensorimotor control. According to a classical theory of cerebellar cortex, the inferior olive (IO) provides Purkinje cells with error information which drives motor learning in the cerebellum. Here we investigate the sensory representations in the IO of larval zebrafish and their spatial organization. Using single-cell labeling of genetically identified IO neurons we find that they can be divided into at least two distinct groups based on their spatial location, dendritic morphology, and axonal projection patterns. In the same genetically targeted population, we recorded calcium activity in response to a set of visual stimuli using 2-photon imaging. We found that most IO neurons showed direction selective and binocular responses to visual stimuli and that functional properties were spatially organized within the IO. Light-sheet functional imaging that allowed for simultaneous activity recordings at the soma and axonal level revealed tight coupling between soma location, axonal projections and functional properties of IO neurons. Taken together, our results suggest that anatomically-defined classes of inferior olive neurons correspond to distinct functional types, and that topographic connections between IO and cerebellum contribute to organization of the cerebellum into distinct functional zones.

neuroscience↗

bioRxiv2019

Agricultural impacts on streams near Nitrate Vulnerable Zones: a case study in the Ebro basin, northern Spain

Agricultural intensification during the last century has produced river degradation across Europe. From the wide range of pressures derived from agricultural activities that impact rivers, diffuse agricultural pollution has received most of the attention from managers and scientists. The aim of this study was to determine the main pressures exerted by intensive agriculture around Nitrate Vulnerable Zones (NVZs), which are areas of land that drain into waters polluted by nitrates according to the European Nitrate Directive (91/676/EEC). The study area was located in the NW of La Rioja (Northern Spain), which has the highest levels of nitrate concentrations within the Ebro basin. The relationships between forty environmental variables and the taxonomic and functional characteristics of macroinvertebrate assemblages (which are good indicators of water quality) were analyzed in 11 stream reaches differentially affected by upstream agricultural activity. The streams affected by a high percentage of agricultural area had significantly greater nitrate concentrations and distinct macroinvertebrate assemblages dominated by pollution tolerant taxa. Hydromorphological alteration (i.e. channel simplification, riparian forest degradation and sediment inputs), which is closely linked to agricultural practices, was the main factor affecting macroinvertebrate assemblages. Good agricultural practices should be implemented in streams affected by NVZs to reverse stream degradation, in consonance with the European Water Framework Directive (WFD). Management actions in these areas should not focus exclusively on nitrate reduction, but also on restoring riparian and aquatic habitats.

ecology↗