Biology subjects

Coelho, R.

Publications and source records attributed to Coelho, R..

7 recordsLinked to original sources

bioRxiv2026

Autonomous sampling and eDNA metabarcoding for offshore biodiversity monitoring: a pilot study around an FPSO in the Southwestern Atlantic

Characterizing biodiversity around offshore infrastructure is necessary to assess possible influences of industrial activities on marine communities and distinguish persistent ecological change from short-term variability. Combining environmental DNA (eDNA) metabarcoding with autonomous sampling offers a way to expand biological, spatial and temporal coverage while reducing dependence on crewed field operations. We evaluated this approach around a floating production, storage and offloading unit (FPSO) in the Santos Basin, Brazil, to establish an initial biodiversity reference and inform subsequent monitoring. A third-generation Environmental Sample Processor integrated into the W Tupan II uncrewed surface vessel enabled autonomous water sampling at coastal sites, transit locations and the FPSO area, yielding 64 biological samples. We used mitochondrial 12S and 16S metabarcoding to assess taxonomic diversity, sampling completeness and spatial and short-term temporal variation. Around the FPSO, 47 samples from 21 points detected 34 species with 12S and 28 with 16S, representing 74.3% and 65.4% of the respective estimated species richness. Local analyses showed weak radial differentiation across 300-1,500 m around the FPSO, with no near-far taxonomic indicators remaining significant after multiple-testing corrections. Samples collected at the same point approximately 1-2 h apart were almost as dissimilar as samples from different points, whereas technical replicates of post-extraction processing closely matched their source DNA profiles. Taxon turnover accounted for approximately 73% and 80% of temporal Jaccard dissimilarity for 12S and 16S, respectively. Regional analyses recovered a coastal-offshore compositional contrast, with geography and sampling date jointly represented. This pilot supports autonomous eDNA sampling as an operational approach to offshore biodiversity monitoring. The findings favour repeated sampling across campaigns to distinguish transient detections from recurrent patterns and persistent compositional changes.

molecular biology↗

bioRxiv2024

Enhancing lysosome function via mTOR/TFEB activation reduces lipofuscin-like granules in early Age-related Macular Degeneration

Age-related macular degeneration (AMD) is the most common blinding disease in the western world and is currently incurable. Although the exact causes of AMD are not clear, the primary origin of pathology appears to be in the retinal pigment epithelium (RPE). RPE is responsible for the daily digestion of photoreceptor outer segments (POS), which imposes a heavy continuous burden on the lysosomal network. POS feeding assay in vitro suggested that the accumulation of autofluorescence granules (AFG), similar to lipofuscin in vivo, derives from lysosomal dysfunction. Here we show that synchronous phagocytosis of POS leads to early transient mTOR activation followed by inhibition in late phagosome maturation. One of its substrates, the transcription factor EB (TFEB) increases during phagosome maturation albeit mostly in its inactive phosphorylated form. We questioned whether induction of the mTOR/TFEB axis could improve digestion of POS and hence reduce AFG load. Treatment of POS-fed cells with rapamycin, an mTORC1 inhibitor after the appearance of AFG results in 30% reduction of AFG load. This effect is dependent on active lysosomal enzymes and induction of active dephosphorylated TFEB with consequent activation of GADD34 and lysosomal biogenesis. As a proof of concept, we show that overexpressing a constitutively active form of unphosphorylated TFEB dramatically reduces POS-dependent AFG accumulation. Overall, this study suggests that viral or pharmacological approaches activating the mTOR/TFEB axis in the RPE could be beneficial as cell-protective treatment of early/intermediate cases of AMD, acting to delay progression of the disease.

molecular biology↗

bioRxiv2024

Orthohantavirus Diversity in Central-East Argentina: Insights from Complete Genomic Sequencing on Phylogenetics, Geographic patterns and Transmission scenarios.

Hantavirus Pulmonary Syndrome (HPS), characterized by its high fatality rate, poses a significant public health concern in the Americas. Phylogenetic relationships of orthohantaviruses in the country were inferred from partial genomic sequences. The objectives of this work were to report new complete viral genomes of the known viral variants associated with HPS cases in Central-East region of Argentina, to assess viral diversity, phylogenetic relationships, and to elucidate the geographic patterns of distribution of each variant. To accomplish this, a detailed analysis was conducted of the geographic distribution of reported cases within the most impacted province of the region. The phylogenetic analysis defined clearly separated clades in the country according to their geographic origin. Andes virus (ANDV) segregated from the rest of the sequences, and those representative from the Central East region, Buenos Aires (BAV) and Lechiguanas virus (LECV), were grouped in the same cluster but segregated in two different branches. ImportanceIn Argentina, most of the HPS cases were associated with ANDV and closely related viruses distributed in four endemic regions. This work focused on obtaining and studying the complete genome of the orthohantaviruses present in the Central East (CE) region (BAV and LECV). Both viruses were responsible for major and minor outbreaks of person- to-person transmission in the country, and the findings may pave the way to study the impact of genetic determinants of viral transmission and to consider the reclassification of the species Orthohantavirus andesense.

genomics↗

bioRxiv2024

SMAC mimetics overcome apoptotic resistance in ovarian cancer through MSLN-TNF alpha axis

Resistance to chemotherapy and PARPi inhibitors remains a critical challenge in the treatment of epithelial ovarian cancer, mainly due to disabled apoptotic responses in tumor cells. Given mesothelins pivotal role in ovarian cancer and its restricted expression in healthy tissues, we conducted a drug-screening discovery analysis across a range of genetically modified cancer cells to unveil mesothelins therapeutic impact. We observed enhanced cell death in cancer cells with low mesothelin expression when exposed to a second mitochondria-derived activator of caspases (SMAC) mimetics, and demonstrated a compelling synergy when combined with chemotherapy in ex vivo patient-derived cultures and zebrafish tumor xenografts. Mechanistically, the addition of the SMAC mimetics drug birinapant to either carboplatin or paclitaxel triggered the activation of the Caspase 8-dependent apoptotic program facilitated by TNFLJ signaling. Multimodal analysis of neoadjuvant-treated patient samples further revealed an association between tumor-associated macrophages and the activation of TNFLJ-related pathways. Our proposed bimodal treatment shows promise in enhancing the clinical management of patients by harnessing the potential of SMAC mimetics alongside conventional chemotherapy.

cancer biology↗

bioRxiv2023

Andes virus genome mutations that are likely associated with animal-model attenuation and human person-to-person transmission

STRUCTURED ABSTRACTO_ST_ABSAbstractC_ST_ABSWe performed whole-genome sequencing with bait-enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo; early, intermediate, and late cell-culture passages of an ANDV isolate from that animal; and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino-acid substitutions related to cell-culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Mutations in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased pathogenesis in the small animal model. Finally, we identified three amino-acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with person-to-person efficient transmission. Our results indicate that there are virulence-associated and transmission-associated single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. ImportanceSeveral orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public-health concern because it is associated with the highest case-fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.

microbiology↗

bioRxiv2021

Emerging Hantaviruses in Central Argentina: first case of Hantavirus Pulmonary Syndrome caused by Alto Paraguay Virus and a novel orthohantavirus in Scapteromys aquaticus rodent.

Orthohantaviruses are emerging rodent-borne pathogens that cause Hantavirus Pulmonary Syndrome in humans. They have a wide range of rodent reservoir hosts and are transmitted to humans through aerosolized viral particles generated by the excretions of infected individuals. Since the first description of HPS in Argentina, new hantaviruses have been reported throughout the country, most of which are pathogenic to humans. We present here the first HPS case infected with Alto Paraguay virus reported in Argentina. Until now, Alto Paraguay virus was considered a non-pathogenic orthohantavirus since it was identified in a rodent, Hollochilus chacarius. In addition to this, with the goal of identifying potential hantavirus host species in the province of Santa Fe, we finally describe a novel orthohantavirus found in the native rodent Scapteromys aquaticus, which differed from other hantaviruses described in the country so far. Our findings implicate an epidemiological warning regarding these new orthohantaviruses circulating in Central Argentina as well as new rodent species that must be considered as hosts from now on.

pathology↗

bioRxiv2020

A screening of the MMV Pathogen Box(R) reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box(R) compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1M was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 M. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxytrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25 - 2.5M) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10M). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.

microbiology↗