Biology subjects

Cruz, V.

Publications and source records attributed to Cruz, V..

5 recordsLinked to original sources

bioRxiv2025

Radiation damage to a three-dimensional hydrogel model of the brain perivascular niche

Glioblastoma (GBM) is a highly aggressive and recurrent brain cancer characterized by diffuse metastasis at the tumor margins. Radiation therapy is a standard component of current treatment and offers potential for improved patient outcomes. While radiation therapy targets GBM cells in the tumor margins, it may also significantly damage adjacent non-cancerous tissues, leading to reduced quality of life and potentially creating a tumor-supportive microenvironment. The perivascular niche (PVN) in the tumor margins is believed to play a significant role in regulating the glioblastoma stem cell subpopulation as well as serving as a site for cancer recurrence and migration. Understanding the impact of radiation on the PVN can better inform radiation schemes and improve our understanding of GBM recurrence, but is difficult in vivo. Here we adapt a previously developed three-dimensional hydrogel model of the brain perivascular niche to investigate the impact of radiation dosage and delivery rate on perivascular niche properties in vitro. Effects of radiation on vessel architecture can be measured in this hydrogel-based model, suggesting an approach that can provide insight into the effects of radiation on a shorter time scale relative to in vivo experiments. IMPACT STATEMENTGlioblastoma (GBM) is a highly aggressive and recurrent brain cancer characterized by diffuse metastasis at the tumor margins. The perivascular niche (PVN) in the tumor margins plays a significant role in GBM progression and is a target for radiation therapy. We report a method to use three-dimensional hydrogel models of the brain perivascular niche to benchmark the impact of radiation dosage and delivery rate on perivascular niche properties in vitro. This approach provides new insight into the effects of radiation on a shorter time scale relative to in vivo experiments.

bioengineering↗

bioRxiv2022

Chimeric mRNA based COVID-19 vaccine elicits potent neutralizing antibodies and protection against Omicron and Delta

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines. Here, we explored various strategies to develop novel mRNAs vaccines to achieve safer and wider coverage of VOCs. Firstly, we constructed a cohort of mRNAs that feature a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Not present in the mRNA vaccines currently in use, the mutation abolished the cleavage between the S1 and S2 subunits, potentially enhancing the safety profile of the immunogen. Secondly, we systematically evaluated the induction of neutralizing antibodies (nAb) in vaccinated mice, and discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. Thirdly, the IgG produced in mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs, which was further corroborated by challenging vaccinated mice with the live virus of VOCs. However, neither WA-Furin nor Beta-Furin mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original and the sublineages of Omicron variant. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we tested the concept of bivalent immunogen. Instead of just fusing two RBDs head-to-tail, we for the first time constructed an mRNA-based chimeric immunogen by introducing the RBD of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA was capable of inducing potent and broadly acting nAb against Omicron (both BA.1 and BA.2) and Delta, which paves the way to develop new vaccine candidate to target emerging variants in the future.

immunology↗

bioRxiv2018

Hydrodynamic and electrophoretic properties of Trastuzumab/HER2 complexes. Experiments and modeling.

The combination of hydrodynamic and electrophoretic experiments and computer simulations is indeed a powerful approach to study the interaction between proteins. In this work, we present hydrodynamic and electrophoretic experiments in aqueous solution along with molecular dynamics and hydrodynamic modeling to monitor and compute biophysical properties of the interactions between the extracellular domain of the HER2 protein (eHER2) and the monoclonal antibody trastuzumab (TZM). The importance of this system relies on the fact that the overexpression of HER2 protein is related with the poor prognosis breast cancers (HER2++ positives) being the TZM a monoclonal antibody for the treatment of this cancer. We have found and characterize two different complexes between the TZM and eHER2 proteins (1:1 and 1:2 TZM:eHER2 complexes). The conformational features of these complexes regulate their hydrodynamic and electrostatic properties. Thus, the results indicate a high degree of molecular flexibility in the systems, that ultimately leads to higher values of the intrinsic viscosity and as well as lower values of diffusion coefficient than those expected for simple globular proteins. A highly asymmetric charge distribution is detected for the monovalent complex (1:1 complex), which has strong implications in correlations between the experimental electrophoretic mobility and the modeled net charge. In order to understand the dynamics of these systems and the role of the specific domains involved, it is essential to find biophysical correlations between dynamics, macroscopic transport and electrostatic properties. The results should be of general interest for researchers working in this area.

biophysics↗

bioRxiv2018

When an insecticide affects the adaptive value of Intraguild predation by an invader

Biological invasions can generate major ecological disturbances, such as changes in species diversity and structure of communities. It is believed that the multicolored Asian ladybeetle, Harmonia axyridis Pallas (Col, Coccinellidae), recognized as one of the most invasive insects in the world, has reduced native coccinellids populations in several areas and is considered as a threat for biodiversity at large. A significant trait, favoring its invasiveness and its dominance over indigenous ladybeetles, is intraguild predation (IGP). IGP has advantageous adaptive value for individuals, removing competitors, potential predators and providing an alternative nutritive resource, when main resources are scarce. Previous research demonstrated that this invasive ladybeetle is highly susceptible to the reduced-risk insecticide novaluron, a chitin synthesis inhibitor, whereas the North American indigenous competitor, Coleomegilla maculata DeGeer (Col, Coccinellidae), is not. Our study explores the adaptive value of IGP for each of the two coccinellids after preying on each others larvae, previously treated with insecticide. Our first hypothesis is that the invasive ladybeetle, susceptible to the insecticide, should lose the adaptive value of IGP, while the native predator not. Our second hypothesis is that the adaptive value of IGP for the invasive predator will be recovered over time, as a result of neutralisation of the insecticide by the intraguild prey (native species). The results support both hypotheses, and show that an insecticide can completely remove the adaptive value of IGP for the invader, while it does not change for the indigenous ladybeetle. Moreover, the study demonstrates that if the intraguild prey (non-susceptible to the insecticide) undergoes molt after being exposed to the insecticide, the adaptive value for the intraguild predator is restored.

ecology↗

bioRxiv2017

The drivers and consequences of unstable Plasmodium dynamics: A 26-year study of three malaria parasite species infecting a tropical lizard

O_LIThe dynamics of vector-borne parasites are driven by interactions between factors intrinsic to the parasite, its host, as well as environmental fluctuations. Understanding these interactions requires a long-term view, especially to predict the consequences of climate change on parasite dynamics.\nC_LIO_LIThe goal of this study is to evaluate temporal fluctuations in individual probability of infection, its environmental drivers and consequences for host body condition, of three malaria parasites (Plasmodium azurophilum, P. leucocytica, and P. floridense) infecting the lizard, Anolis gundlachi, in the rainforest of Puerto Rico.\nC_LIO_LIWe conducted 13 surveys totaling N > 8000 lizards over 26 years. During the early years of the study, the lizards probability of infection by all three Plasmodium species appeared stable despite disturbances from short droughts and small to moderate hurricanes.\nC_LIO_LIOver a longer timescale, we found that the individual lizard probability of infection and overall prevalence varied significantly over the years, and this fluctuation was driven in non-linear ways by variations in temperature and rainfall. The probability of infection was maximized at intermediate levels of temperature and precipitation. This temporal variability in Plasmodium prevalence driven by environmental factors had two important consequences. First, temperature-mediated a decrease in body condition in infected female lizards relative to non-infected ones. Second, Plasmodium parasite species composition varied through time.\nC_LIO_LIOverall, the results show how environmental conditions, such a severe drought, can drive disease dynamics outside of their apparent stable equilibrium and mediate the potential negative effects of parasite infection on the host. Our results also emphasize the need for long-term studies to reveal host-parasite dynamics, their drivers and consequences.\nC_LI

ecology↗