Biology subjects

Rodrigues, L. C.

Publications and source records attributed to Rodrigues, L. C..

7 recordsLinked to original sources

bioRxiv2024

Impact of Run-of-River Damming on Increasing Phytoplankton Biomass and Species Shift in a Large Amazonian River: Ecological Implications and Recommendations

Run-of-river (ROR) dams, often perceived as having minimal environmental impact, can induce significant hydrodynamic changes that alter aquatic ecosystems. We investigated the impacts of an ROR dam on the Madeira River, the largest Amazon tributary, focusing on phytoplankton communities, their ecological implications, and related environmental factors. Our study examined changes in biomass and environmental factors (using General Linear Mixed Models - GLMM), species composition (using PERMANOVA) before and after damming, in both the main channel and tributaries (N=549 samples). We also identified indicator species associated with different damming phases and regions through an indicator value analysis. The results showed that, following dam construction, the phytoplankton community changed in both the main channel and tributaries, with a shift from lotic diatoms to lentic phytoflagellates. This transition was likely facilitated by altered hydrodynamics and possibly influenced by the decomposition of flooded vegetation in the dams influence zone. The decomposition of this vegetation could explain both the observed increase in oxygen consumption and the subsequent rise in phytoflagellate biomass after damming. However, despite the overall increase in phytoplankton biomass, the values remained within oligotrophic to mesotrophic conditions, consistent with the low nutrient concentrations recorded. However, we caution that the dam-created hydrodynamic conditions are optimal for phytoplankton growth, potentially exacerbating nutrient-related issues in the future. We recommend proactive management strategies to prevent nutrient enrichment from activities such as agriculture and livestock in isolated Amazon areas affected by dams, thereby mitigating potential water quality degradation linked to increased phytoplankton biomass.

ecology↗

bioRxiv2022

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

BackgroundCanine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells associated with short survival times. Understanding the genomic landscape of HSA is critical to developing more effective therapeutic strategies. ObjectivesTo determine the relationships between genomic and clinical features including treatment and outcome in canine splenic HSA. Animals109 dogs with primary splenic HSA treated by splenectomy that had tumor sequencing via the FidoCure(R) Precision Medicine Platform targeted sequencing panel. MethodsPatient signalment, weight, metastasis at diagnosis, treatment, and survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables and outcome were assessed. ResultsSomatic mutations in TP53 (n = 45), NRAS (n = 20), and PIK3CA (n = 19) were most common. Survival was associated with metastases at diagnosis, germline variants in SETD2 and NOTCH1, and nominally with breed. Age at diagnosis was associated with NRAS mutations and breed. TP53 and PIK3CA mutations were found in larger dogs, germline SETD2 variants in smaller dogs. Doxorubicin (DOX) treatment did not significantly improve survival time, while targeted therapies had a significant early survival benefit. Conclusions and clinical importanceDOX treatment may provide limited clinical benefit for dogs with splenic HSA, while targeted therapy may provide early survival benefit. Genetic signatures associated with splenic HSA may be useful in guiding targeted therapy to improve outcomes. Germline variants, age, size, and breed may be useful prognostic factors and provide insight into the genomic landscape of the tumor.

genomics↗

bioRxiv2021

Shared hotspot mutations in spontaneously arising cancers position dog as an unparalleled comparative model for precision therapeutics

Naturally occurring canine cancers have remarkable similarities to their human counterparts. In order to determine whether these similarities occur at the molecular level, we investigated hotspot mutations in a variety of spontaneously arising canine cancers and found high concordance in oncogenic drivers between cancers in both species. These findings suggest that canines may present a powerful and complementary model for preclinical investigations for targeted cancer therapeutics. Through analysis of 708 client-owned dogs from 96 breeds (plus mixed breeds) with 23 common tumor types, we discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. TP53 is the most commonly mutated gene, detected in 30.81% of canine tumors overall and >40% in hemangiosarcoma and osteosarcoma. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant (P<0.0001) association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E in urothelial carcinoma. This work positions canines as excellent spontaneous models of human cancers that can help to investigate a wide spectrum of targeted therapies.

cancer biology↗

bioRxiv2020

Endogenous Galectin-3 is Required for Skeletal Muscle Repair

Skeletal muscle has the intrinsic ability to self-repair through a multifactorial process, but many aspects of its cellular and molecular mechanisms are not fully understood. There is increasing evidence that some members of the mammalian {beta}-galactoside-binding protein family (galectins) are involved in the muscular repair process (MRP), including galectin-3 (Gal-3). However, there are many questions about the role of this protein on muscle self-repair. Here, we demonstrate that endogenous Gal-3 is required for: i) muscle repair in vivo using a chloride-barium myolesion mouse model, and ii) mouse primary myoblasts myogenic programming. Injured muscle from Gal-3 knockout mice (GAL3KO) showed persistent inflammation associated with compromised muscle repair and the formation of fibrotic tissue on the lesion site. In GAL3KO mice, osteopontin expression remained high even after 7 and 14 days of the myolesion, while MyoD and myogenin had decreased their expression. In GAL3KO mouse primary myoblast cell culture, Pax7 detection seems to sustain even when cells are stimulated to differentiation and MyoD expression is drastically reduced. These findings suggest that the detection and temporal expression levels of these transcriptional factors appear to be altered in Gal-3-deficient myoblast cell culture compared to Wild Type (WT) cells. We observed Gal-3 expression in WT states, both in vivo and in vitro, in sarcoplasm/cytoplasm and myonuclei; as differentiation proceeds, Gal-3 expression is drastically reduced, and its location is confined to the sarcolemma/plasma cell membrane. We also observed a change in the temporal-spatial profile of Gal-3 expression and muscle transcription factors levels during the myolesion. Overall, these results demonstrate that endogenous Gal-3 is required for the skeletal muscle repair process.

cell biology↗

bioRxiv2018

Abundance drives generalisation in hummingbird-plant pollination networks

Abundant pollinators are often more generalised than rare pollinators. This could be because abundance drives generalisation: neutral effects suggest that more abundant species will be more generalised simply because they have more chance encounters with potential interaction partners. On the other hand, generalisation could drive abundance, as generalised species could have a competitive advantage over specialists, being able to exploit a wider range of resources and gain a more balanced nutrient intake. Determining the direction of the abundance-generalisation relationship is therefore a chicken-and-egg dilemma. Here we determine the direction of the relationship between abundance and generalisation in plant-hummingbird pollination networks sampled from a variety of locations across the Americas. For the first time we resolve the direction of the abundance-generalisation relationship using independent data on animal abundance. We find evidence that hummingbird pollinators are generalised because they are abundant, and little evidence that hummingbirds are abundant because they are generalised. Additionally, a null model analysis suggests this pattern is due to neutral processes: most patterns of species-level abundance and generalisation were well explained by a null model that assumed interaction neutrality. These results suggest that neutral processes play a key role in driving broad patterns of generalisation in animal pollinators across large spatial scales.\n\nDeclarationsFunding - BIS is supported by the Natural Environment Research Council as part of the Cambridge Earth System Science NERC DTP [NE/L002507/1]. JVB was funded by CERL - Engineer Research and Development Center. PKM was funded by the Sao Paulo Research Foundation (FAPESP grant #2015/21457-4). PAC was funded by the David Lack studentship from the British Ornithologists Union and Wolfson College, University of Oxford. CL was funded by the ESDEPED-UAT grant. MAM acknowledges the Consejo Nacional para Investigaciones Cientificas y Tecnologicas (Costa Rica), German Academic Exchange Service and the research funding program LOEWE-Landes-Offensive zur Entwicklung Wissenschaftlicho konomischer Exzellenz of Hesses Ministry of Higher Education, Research, and the Arts (Germany). ROP was funded by CONACyT (project 258364). MAR was supported by the State of Sao Paulo Research Foundation (FAPESP) within the BIOTA/FAPESP, The Biodiversity Institute Program (www.biota.org.br) and the Parcelas Permanentes project, as well as by Coordenacao de Pessoal de Nivel Superior (CAPES), Fundo de Apoio ao Ensino e a Pesquisa (FAEP)/Funcamp/Unicamp and The Nature Conservancy (TNC) of Brazil. LCR was supported by CNPq and Capes. MS was funded by CNPq (grant #302781/2016-1). AMMG is supported through a Marie Skodowska-Curie Individual Fellowship (H2020-MSCA-IF-2016-704409). LVD was supported by the Natural Environment Research Council (grants NE/K015419/1 and NE/N014472/1). AMMG, JS, CR and BD thank the Danish National Research Foundation for its support of the Center for Macroecology, Evolution and Climate (grant no. DNRF96). WJS is funded by Arcadia.

ecology↗

bioRxiv2018

The impact of a governmental cash transfer programme on tuberculosis cure rate in Brazil: A quasi-experimental approach

BackgroundSocial vulnerability is strongly associated with tuberculosis (TB) indicators like cure rate. By addressing key social determinants, social protection policies such as Brazils Bolsa Familia Programme (BFP), a governmental conditional cash transfer, may play a role in TB control. Evidence is consolidating around a positive effect of social protection on TB outcomes, however methodological limitations prevent strong conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB cure rate.\n\nMethods & FindingsThe data source was Brazils TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll. Propensity scores (PSs) were estimated from a complete-case logistic regression using covariates from this linked dataset, informed by a directed acyclic graph. Control patients were matched to exposed patients on the PS and the average effect of treatment on the treated (ATT) was estimated as the difference in TB cure rate between matched groups (n = 2167). The ATT was estimated as 10{middle dot}58 (95% CIs: 4{middle dot}39, 16{middle dot}77). This suggests that 10{middle dot}58% of the TB patients receiving BFP who were cured would not have been cured had they not received BFP. The direction of this effect was robust to sensitivity analyses performed and the PS matching broadly improved balance, although missing data limited the sample size.\n\nConclusionsThis work is the first quasi-experimental evaluation of social protection in wide-scale practice on TB outcomes. It demonstrates a positive effect of conditional cash transfers on TB cure rate consistent with existing work, suggesting changes to policy and future research on increasing access to social protection for TB patients who remain uncovered by the programme.

epidemiology↗

bioRxiv2017

RSV Downregulates IL-21/IL-21R On TFH Cells Via PD-L1 Induction In APCs Impairing Protective Humoral Responses

Respiratory syncytial virus (RSV) is the major cause of hospitalization for children under two years of age. RSV vaccines are currently unavailable, and children suffering from multiple reinfections by the same viral strain, fail to develop protective memory responses. Follicular helper T (TFH) cells specialize in providing B cell help to antibody production and affinity maturation, mainly via IL-21 secretion. Although RSV-specific antibodies can be detected upon infection, how they are generated and their relevance against disease protection has not been fully examined. Here, we observed that RSV expands a functionally impaired murine TFH cell population in vitro and vivo, with downregulated IL-21R expression and IL-21 production. IL-21 treatment of RSV-infected mice, however, increased TFH cells frequency, enhanced the germinal center reaction and improved protective humoral immune responses by increasing viral protein F specific antibody avidity and neutralization capacity. In vivo, it protected from RSV infection, decreasing lung inflammation. Passive immunization with purified IgG from IL-21 treated RSV-infected mice protected against RSV infection. Both viable and UV-inactivated RSV induced PD-L1 expression on B cells and DCs, however, only in DCs a direct effect of RSV was detected. Blocking PD-L1 during infection recovered IL-21R expression in TFH and B cells and increased secretion of IL-21 by TFH cells in a DC-dependent manner. Our results unveil a novel pathway by which RSV affects TFH cells activity, reducing levels of IL-21 and its receptor, by increasing PD-L1 expression on APCs. These results highlight the PD-L1/IL-21 axis importance for the generation of protective responses to RSV infection.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC=\"FIGDIR/small/203133_figGA1.gif\" ALT=\"Figure 1\">\nView larger version (36K):\norg.highwire.dtl.DTLVardef@172470eorg.highwire.dtl.DTLVardef@197017eorg.highwire.dtl.DTLVardef@e31ae3org.highwire.dtl.DTLVardef@1fa4c4f_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACTRSV infection impairing IL-21 secretion by TFH cells via PD-L1induction in dendritic cells and B cells. Low levels of IL-21 lead to poor RSV-specific humoral immune responses, low antibody titer, avidity and neutralization capacity. PD-L1 blockade can upregulate IL-21 secretion, and IL-21 treatment restores the entire immune humoral responses, resulting in protection against RSV infection.\n\nC_FIG

immunology↗