Biology subjects

Ortega, F.

Publications and source records attributed to Ortega, F..

7 recordsLinked to original sources

bioRxiv2025

Modeling the acutely injured brain environment in vitro.

A major challenge to study the regenerative potential of the injured brain is the limited access to this organ in vivo. To address this, we developed an innovative gliosis model that, although established in vitro, originates from a genuine injury in vivo. The model relies on reactive glia acquiring enhanced adhesion, facilitating their rapid adaptation to in vitro conditions, where it faithfully recapitulates key features of brain injury. These include a secretome associated with injury pathways, degenerative responses like neuronal death and neuroinflammation, and regenerative processes such as progenitor proliferation, recruitment and commitment to oligodendrocytes. Moreover, the exposure of adult glial cells to this culture medium recapitulates their acquisition of multipotency observed in both mouse and human injured brains. Finally, our approach allows studying glia-to-neuron reprogramming, a process challenging to tackle in vivo. Consequently, we present a novel tool for exploring stem cell dynamics and regenerative behaviors in CNS pathology.

neuroscience↗

bioRxiv2024

Purinergic Receptor P2Y13 Controls Activation and Mode of Division in Subependymal Adult Neural Stem Cells

The subependymal zone (SEZ) of the mammalian brain is the most active germinal area that continues to generate newborn neurons throughout life. This area harbors a population of neural stem cells (NSCs) that can be found in different states of activation, each differing in proliferative capacity and molecular signature: quiescent NSCs (qNSCs), primed NSCs (pNSCs), and activated NSCs (aNSCs). There is currently a void in terms of the specific markers available to effectively discern between these transient states. Likewise, the molecular signaling mechanisms controlling the transition from quiescence to activation remain largely unexplored, as do the factors influencing the decision between differentiation and self-renewal during NSC division. Here, we present evidence that the metabotropic P2Y13 purinergic receptor plays a critical role in regulating adult neurogenesis. We found that P2Y13 is specifically expressed in NSCs within the adult SEZ and that its levels can be used to distinguish qNSCs from aNSCs. Functionally, P2Y13 signaling promotes NSC activation, enhancing lineage progression, while dampening their self-renewal capacity. Conversely, pharmacological blockade or genetic silencing of the P2Y13 receptor favors NSC quiescence. Thus, we identified the metabotropic P2Y13 purinergic receptor as a pivotal modulator of NSC dynamics, influencing both the balance between NSC quiescence and activation and the mode of NSC division at the subependymal zone.

neuroscience↗

bioRxiv2023

Evolution of hind limb morphology of Titanosauriformes (Dinosauria, Sauropoda) via 3D Geometric Morphometrics reveals wide-gauge posture as an exaptation for gigantism

The sauropod hind limb was the main support that allowed their gigantic body masses and a wide range of dynamic stability adaptations. It was closely related to the position of the centre of masses of their multi-ton barrel-shaped bodies, and experienced one of the most noticeable posture changes during macronarian evolution. Deeply branched macronarians achieved increasingly arched hind limbs in what is known as wide-gauge posture. However, it is not clear if this evolutionary trend is related to the evolutionary cascade toward gigantism even though some titanosaurians were the largest terrestrial vertebrates that ever existed. We tested evolutionary changes in hind limb morphology in the Macronaria phylogenetic tree by 3D geometric morphometrics. The macronarian hind limb does become progressively more arched toward deeply-branched groups, specifically Saltasauridae. However, there is morphological convergence between different macronarian subclades. Wide-gauge posture does not correlate with changes in body size deeper in the macronarian evolutionary tree, and acted as an exaptation to gigantism. Despite some titanosaurian subclades becoming some of the largest vertebrates, there is not a statistically-significant trend toward a particular body size but we identify a phyletic body size decrease in Macronaria.

paleontology↗

bioRxiv2017

Rational cell culture optimization enhances experimental reproducibility in cancer cells.

Optimization of experimental conditions is critical in ensuring robust experimental reproducibility. Through detailed metabolomic analysis we found that cell culture conditions significantly impacted on glutaminase (GLS1) sensitivity resulting in variable sensitivity and irreproducibility in data.\n\nBaseline metabolite profiling highlighted that untreated cells underwent significant changes in metabolic status. Both the extracellular levels of glutamine and lactate and the intracellular levels of multiple metabolites changed drastically during the assay. We show that these changes compromise the robustness of the assay and make it difficult to reproduce.\n\nWe then devised metabolically rationalized standard assay conditions, in which glutaminase-1 inhibition reduced glutamine metabolism differently in both cell lines assayed, and decreased the proliferation of one of them. The adoption of optimized conditions such as the ones described here should lead to an improvement in reproducibility and help eliminate false negatives as well as false positives in these assays.

cell biology↗

bioRxiv2017

Programming of neural progenitors of the adult subependymal zone towards a glutamatergic identity by neurogenin2

While the adult subependymal zone (SEZ) harbors pools of distinct neural stem cells that generate different types of GABAergic interneurons, a small progenitor population in the dorsal SEZ expresses Neurog2 and gives rise to glutamatergic neurons. Here we investigated whether SEZ progenitors can be programmed towards glutamatergic neurogenesis through forced expression of Neurog2. Retrovirus-mediated expression of Neurog2 induced the glutamatergic neuron lineage markers Tbr2 and Tbr1 in cultured SEZ progenitors which subsequently differentiated into functional glutamatergic neurons. Likewise, retrovirus-mediated expression of Neurog2 in dividing SEZ progenitors within the adult SEZ induced Tbr2 and Tbr1 expression, hallmarking entry into the glutamatergic lineage also in vivo. Intriguingly, Neurog2-expressing progenitors failed to enter the rostral migratory stream (RMS) and instead differentiated directly within the SEZ or the adjacent striatum. In sharp contrast, lentivirus-mediated postmitotic expression of Neurog2 failed to reprogram early SEZ neurons, which instead maintained their GABAergic identity and migrated along the RMS towards the olfactory bulb. Thus, our data show that Neurog2 can program SEZ progenitors towards a glutamatergic identity, but fails to reprogram their postmitotic progeny.\n\nSummary statementOur study identifies a critical developmental time window during which progenitors of the adult subependymal zone, specified for generating GABAergic neurons, can be reprogrammed towards glutamatergic neurogenesis.

neuroscience↗

bioRxiv2017

Dengue fever and Aedes aegypti risk in the Galapagos Islands, Ecuador

IntroductionDengue fever is an emerging infectious disease in the Galapagos Islands of Ecuador, with the first cases reported in 2002 and periodic outbreaks since then. Here we report the results of a pilot study conducted in two cities in 2014: Puerto Ayora (PA) on Santa Cruz Island, and Puerto Baquerizo Moreno (PB) on Santa Cristobal Island. The aims of this study were to assess the social-ecological risk factors associated with dengue and mosquito presence at the household-level.\n\nMethodsIn 2014 we conducted 100 household surveys (50 on each island) in neighborhoods with prior reported dengue. Adult mosquitoes were collected inside and outside the home, larval indices were determined through container surveys, and heads of households were interviewed to determine demographics, prior dengue infections, housing conditions, and knowledge, attitudes and practices regarding dengue. Multimodel selection methods were used to derive best-fit generalized linear regression (GLM) models of prior dengue infection, and the presence of Ae. aegypti in the home.\n\nResultsWe found that 24% of PB and 14% of PA respondents self-reported a prior dengue infection, and more PB homes than PA homes had Ae. aegypti. The top-ranked model for prior dengue infection included human movement - travel between neighborhoods, between islands, and to the mainland; demographics including salary level and education of the head of household, and increase with more people per room in a house, house condition, access to water quality issues, and dengue awareness. The top-ranked model for the presence of Ae. aegypti included housing conditions, including the presence of window screens and air conditioners, mosquito control actions, and dengue risk perception.\n\nDiscussion/conclusionTo our knowledge, this is the first study of dengue risk and Aedes aegypti in the Galapagos Islands. The findings that human movement within and between islands, and to and from the mainland, were important to reported dengue cases confirms concerns of this route of introduction and repeated transmission.

epidemiology↗

bioRxiv2017

A cautionary tale on using tumour growth rate to predict survival

A recurrent question within oncology drug development is predicting phase III outcome for a new treatment using early clinical data. One approach to tackle this problem has been to derive metrics from mathematical models that describe tumour size dynamics termed re-growth rate and time to tumour re-growth. They have shown to be strong predictors of overall survival in numerous studies but there is debate about how these metrics are derived and if they are more predictive than empirical end-points. This work explores the issues raised in using model-derived metric as predictors for survival analyses. Re-growth rate and time to tumour re-growth were calculated for three large clinical studies by forward and reverse alignment. The latter involves re-aligning patients to their time of progression. Hence it accounts for the time taken to estimate re-growth rate and time to tumour re-growth but also assesses if these predictors correlate to survival from the time of progression. We found that neither re-growth rate nor time to tumour re-growth correlated to survival using reverse alignment. This suggests that the dynamics of tumours up until disease progression has no relationship to survival post progression. For prediction of a phase III trial we found the metrics performed no better than empirical end-points. These results highlight that care must be taken when relating dynamics of tumour imaging to survival and that bench-marking new approaches to existing ones is essential.

cancer biology↗