Biology subjects

Galvan, S.

Publications and source records attributed to Galvan, S..

5 recordsLinked to original sources

bioRxiv2025

In vivo MRI measurement of microstructural constraints for direct delivery of therapeutics within the brain

Brain tissue microstructure influences the efficient delivery of therapeutics within the brain. Diffusion Tensor Imaging (DTI) enables the depiction of tissue properties in vivo, and thus is potentially relevant for planning convection-enhanced delivery (CED) within the brain. We report on the quantitative assessment of the distribution of a Gadolinium solution infused by CED within the brain of a live ovine model. Infusate distributions were measured at multiple timepoints and compared to microstructural properties as depicted by DTI, thus demonstrating the impact of tissue features and catheter positioning on drug distribution in vivo. This study contributed to the clinical translation of the CED for flow-based therapy to ultimately provide new therapeutic approaches for several brain diseases, by providing essential tools and results used to develop a better prediction model and a delivery platform to reach the therapeutic target more precisely and non-invasively.

neuroscience↗

bioRxiv2025

Decoding Brain Interstitial Transport In Vivo: A Fully Validated Bottom-Up Mechanistic Prediction Framework

The transport of fluids and substances within the brain parenchyma (i.e. interstitial transport) is fundamental to maintaining brain health and delivering treatments for neurological disorders. However, accurately predicting these transport processes has remained a formidable challenge due to the intricate and dynamic nature of the brains microenvironment. Here, we report a novel, fully validated bottom-up mechanistic framework that bridges advanced mathematical modelling, ultra-high-resolution imaging, and biomechanical testing to achieve precise, in vivo predictions of interstitial transport. Using this approach, we accurately modelled the transport of MRI tracers in living sheep brains, offering unprecedented insights into the interplay between fluid dynamics and tissue properties. This platform is a transformative step forward, with the potential to revolutionise drug delivery strategies not only in the brain but also in cancer therapy and other soft biological systems. By addressing limitations in modelling complex transport in soft tissue, our work establishes a significant tool with profound implications for biomedical engineering and translational medicine.

biophysics↗

bioRxiv2024

HEXIM1 homodimer binds two sites on 7SK RNA to release autoinhibition for P-TEFb inactivation

Hexim proteins are key RNA-dependent regulators of eukaryotic transcription through 7SK-dependent sequestration and inactivation of the kinase P-TEFb (Cdk9-CyclinT1/2) in the 7SK RNP. P-TEFb activity drives release of RNA polymerase II from promoter-proximal pausing for eukaryotic and HIV-1 transcription. The molecular mechanism by which 7SK binding overcomes an intrinsic Hexim autoinhibition for subsequent P-TEFb inactivation has remained unresolved. Here, using NMR and biophysical methods we demonstrate that Hexim1 homodimer engages two high-affinity sites on 7SK RNA. This dual-site binding triggers a conformational rearrangement in Hexim1s disordered central region that unmasks the Cdk9-binding site, which is otherwise sequestered within an intermonomer dimer interface. These findings reveal how Hexim autoinhibition dictates its specificity for 7SK RNA and prevents premature P-TEFb inhibition in the absence of 7SK, thereby providing a mechanistic understanding of Hexim/P-TEFb assembly into the 7SK RNP and further considerations for understanding Hexim-Tat competition during viral transcription.

biophysics↗

bioRxiv2023

Early Jurassic origin of avian endothermy and thermophysiological diversity in Dinosauria

A fundamental question in dinosaur evolution is how they adapted to substantial long-term shifts in Earth System during the Mesozoic and when they developed environmentally independent, avian-style acclimatization due to the evolution of an endothermic physiology. Combining fossil occurrences with macroevolutionary and paleoclimatic models, we unveil distinct evolutionary pathways in the main dinosaur lineages: ornithischians and theropods diversified across broader climatic landscapes, trending toward cooler niches. An Early Jurassic shift to colder climates in Theropoda suggests an early adoption of endothermic thermophysiology. Conversely, sauropodomorphs exhibited prolonged climatic conservatism associated with higher thermal conditions. Paleo-biome mapping emphasizes temperature, rather than plant productivity, as the primary driver of this pattern, suggesting poikilothermic physiology with a stronger dependence on higher temperatures in sauropods since the Early Jurassic. One-Sentence SummaryDinosaur climatic evolution reveals early endothermy emergence in theropods, ornithischians but heterotherm sauropodomorphs.

paleontology↗

bioRxiv2022

DISSECTING LIGHT SENSING AND METABOLIC PATHWAYS ON THE MILLIMETER SCALE IN HIGH-ALTITUDE MODERN STROMATOLITES

Modern non-lithifying stromatolites (STs) on the shore of the volcanic lake Socompa in the Puna are affected by several extreme conditions. Although STs were proposed as ecologic models for understanding stress response and resilience in microbial ecosystems constituting a window into the past, our knowledge of ST function is still nascent. The present study assesses for the first time light utilization and functional metabolic stratification of STs on a millimeter scale through shotgun metagenomics. In addition, a scanning-electron-microscopy approach was used to explore the community. Our results demonstrated that Bacteroidetes and Cyanobacteria play major roles as ST builders and primary producers to sustain a diverse community of heterotrophs. STs manifest a high occurrence of genes for the synthesis of UV-protecting pigments, the cryptochrome-photolyase family (CPF), and rhodopsins in the surface layers. Three different ecologic niches involving the use of light in energy production were defined. Calvin-Benson and Wood-Ljungdahl pathways were proposed as the main mechanisms for carbon fixation. Several genes account for the microelectrode chemical data and pigment measurements performed in previous publications. We also provide here an explanation for the vertical microbial mobility within the ST described previously. Finally, our study points to STs as ideal modern analogues of ancient STs.

ecology↗