Desarrollo de nanocompositos de cápside viral P22 para la terapia con profármacos enzimáticos en cáncer de mama

Development of P22 viral capsid nanocomposites for enzymatic prodrug therapy in breast cancer

Astrid Rebeca Luna Rios (2024, [Tesis de maestría])

Las estrategias actuales contra el cáncer de mama presentan limitaciones debido a la falta de selectividad, disminuyendo su efectividad. La mayoría de los fármacos, como el tamoxifeno, requieren la activación metabólica por parte de las enzimas de la familia citocromo P450 (CYP) para ejercer mayores efectos anticancerígenos. Sin embargo, la concentración del CYP es variable y baja en las células tumorales, especialmente en el cáncer de mama, lo que provoca efectos secundarios. En la terapia de activación enzimática de profármacos (EPT), las enzimas se dirigen al tumor para transformar el profármaco, lo que normalmente implica la administración de la enzima seguida del profármaco. Sin embargo, las diferencias entre la farmacocinética y farmacodinamia son un obstáculo para mejorar el tratamiento. Por lo tanto, la administración conjunta de profármaco y enzima es esencial para garantizar su interacción favorable en el tumor. Este trabajo reporta una nueva clase de nanocompositos terapéuticos basados en partículas tipo virus P22 confinando CYP, funcionalizadas superficialmente con glucosa oxidasa (GOx) que transforma la glucosa en D-glucono-δ-lactona produciendo H2O2, el aceptor final de electrones en la transformación de tamoxifeno mediado por CYP, y conjugadas con un derivado de tamoxifeno como profármaco y ligando dirigido utilizando polietilenglicol como conector. En un microambiente tumoral rico en glucosa, estos nanocompuestos pueden producir fármaco activo in situ. Se caracterizaron las propiedades fisicoquímicas y la catálisis secuencial mediada por glucosa de los nanocompositos. Los estudios in vitro demostraron una disminución en la viabilidad celular en líneas celulares de cáncer de mama ER+ y ER-. Sin embargo, la internalización celular en ausencia de glucosa mostró ser preferencial con las VLPs dirigidas en ambas líneas celulares. La administración conjunta de enzimas y profármacos con una localización mejorada de las VLPs desarrolladas después de la funcionalización del tamoxifeno, lo que sugiere el potencial de los nanocompositos desarrollados para superar los desafíos existentes de la EPT y mejorar los resultados terapéuticos con efectos secundarios reducidos.

Current treatment strategies against breast cancer have limitations due to lack in selectivity. Most drugs, such as tamoxifen, require metabolic activation by cytochrome P450 (CYP) enzymes to perform greater anticancer effects. However, the concentration of CYP varies and is low in tumor cells, especially in breast cancer, resulting in side-effects. In enzyme prodrug therapy (EPT), enzymes are targeted to the tumor cells for prodrug transformation, typically involving the sequential delivery of the enzyme followed by the prodrug. However, differences in pharmacokinetics and pharmacodynamics are a major hindrance for improving treatment. Therefore, co-delivery of prodrug and enzyme is essential to ensure their favorable interaction in tumor. This work reports a new class of therapeutic nanocomposites based on P22 virus like particles (VLPs) confining the CYP activity, surface functionalized with glucose oxidase (GOx) that transforms glucose into D-glucono-δ-lactone producing hydrogen peroxide, the final electron acceptor in the CYP-mediated transformation of tamoxifen, and together conjugated with a tamoxifen derivative as prodrug and targeting ligand using polyethylene glycol as a linker. In glucose-rich tumor microenvironment, these nanocomposites can produce active drug in situ. The physicochemical properties and sequential glucose-mediated catalysis of the nanocomposites were characterized. In vitro studies demonstrated a decrease in cell viability in both ER+ and ER- breast cancer cell lines. However, cellular internalization in the absence of glucose showed improved uptake of targeted VLPs in both cell lines. The co-delivery of enzymes and prodrug with improved localization of developed VLPs after tamoxifen functionalization, suggests the potential of developed nanocomposites to overcome the existing challenges of EPT and improve the therapeutic outcomes with reduced side effects.

VLP-P22, Citocromo P45O, Glucosa oxidasa, Tamoxifeno, Terapia de activación enzimática de profármacos VLP-P22, Cytochrome P45O, Glucose oxidase, Tamoxifen, Enzyme prodrug therapy BIOLOGÍA Y QUÍMICA QUÍMICA QUÍMICA FARMACÉUTICA DISEÑO.SÍNTESIS Y ESTUDIO NUEVOS FÁRMACOS DISEÑO.SÍNTESIS Y ESTUDIO NUEVOS FÁRMACOS

Insights into the transboundary stock structure of white seabass, Atractoscion nobilis, along the coast of California and Baja California

Perspectivas sobre la estructura del stock transfronterizo de la corvina blanca, Atractoscion nobilis, a lo largo de la costa de California y de Baja California

ARTURO FAJARDO YAMAMOTO (2023, [Tesis de doctorado])

The white seabass (Atractoscion nobilis) is a transboundary fishery resource that ranges from California, U.S., to Baja California Sur, Mexico, and within the north of the Gulf of California. It has been proposed two stock structure hypotheses that exist across their range in the eastern Pacific. However, still there are important data gaps to fill to understand the stock structure of this species. The aim of this study was to develop more information to understand the Pacific stock structure of the white seabass by (1) enhancing the baseline (catch-effort) information for the Mexican WSB fishery, (2) estimating the size-at-maturity and (3) describe the horizontal movement patterns and habitat utilization of adult WSB. Results suggest that the landings of the Mexican white seabass fishery showed an overall increase over the past 70 years. Landing fluctuations were associated with shifts in contextual factors, such as market changes and geopolitical events. For the past 20 years, the majority of harvest has come from Baja California Sur, with landings concentrated primarily in the fishery offices of Ciudad Constitución, Punta Abreojos, and San Carlos. White seabass females from southern Baja California mature at a size of 72.7 cm, while the males mature at a size of 58 cm. Moreover, regional differences of maturity were estimated where WSB from California matures larger than those from southern Baja California. A connectivity degree of white seabass adult was estimated between the coast of California and the west coast of the Baja California Peninsula. Overall, areas around islands and coastal areas are high-use areas for adult WSB. The Channel Islands, the region off Coronado Islands-Ensenada, the San Quintin region, and the Vizcaino Bay region are essential areas for WSB since different WSB ontogenic stages have been recorded. The spawning (March-September) and none spawning (October-February) seasons for adult WSB have marked differences in habitat utilization. Two migration pathways were estimated: one, a dispersal movement where adult white seabass moved northward to an area around the Channel Islands in California and a southward movement along the coast of the west coast of the Baja California Peninsula where multiple high-use areas were occupied and, second a return movement from north and south areas to a constrained and restricted area off the coast of Tijuana and San Quintin. Considering the information generated in this thesis, we have ...

La corvina blanca (Atractoscion nobilis) es un recurso pesquero transfronterizo que se extiende desde California, EE. UU., hasta Baja California Sur, México, y dentro del norte del Golfo de California. Se han propuesto dos hipótesis que describen la estructura del stock de la corvina blanca a lo largo de su área de distribución en el Pacífico oriental. Sin embargo, aún quedan vacíos en la información biológica-pesquera que nos permita comprender de una manera más robusta la estructura del stock. El objetivo de este estudio fue el desarrollar más información que nos permita comprender la estructura del stock de la corvina blanca que habita el Pacífico mediante (1) la reconstrucción de los desembarques de la pesquería mexicana, (2) la estimación del tamaño de madurez y (3) la descripción de los patrones de movimiento horizontal y el uso de hábitat de la corvina blanca adulta. Los resultados sugieren que los desembarques de la pesquería mexicana de corvina blanca mostraron un aumento en los últimos 70 años. Durante los últimos 20 años, la mayor parte de la captura proviene de Baja California Sur, concentrándose los desembarques en las oficinas pesqueras de Ciudad Constitución, Punta Abreojos y San Carlos. Las hembras de corvina blanca del sur de la Península de Baja California Sur maduran a una talla de 72,7 cm, mientras que los machos lo hacen a una talla de 58 cm. Además, se estimaron diferencias regionales de madurez, siendo que las corvinas blancas de California maduran a una talla mayor que las del sur de la Península de Baja California. Se estimó un cierto grado de conectividad de la corvina blanca adulta entre la costa de California y la costa oeste de la península de Baja California. En general, las áreas alrededor de las islas y las zonas costeras son zonas de alto uso para la corvina blanca adulta. Las islas del Canal, la región frente a las islas Coronado-Ensenada, la región de San Quintín y la región de la bahía Vizcaíno son zonas esenciales para la corvina blanca, ya que se han registrado diferentes fases ontogénicas en dichas zonas. El uso del hábitat de las corvinas blancas adultas durante la temporada de desove (marzo-septiembre) y la no desove (octubre-febrero) fue diferente. Se estimaron dos rutas migratorias: una, con movimientos de dispersión donde la corvina blanca adulta se desplazó hacia el norte alcanzando el área alrededor de las Islas del Canal en California, y un movimiento hacia el sur, a lo largo de la costa del litoral oeste...

White seabass, stock structure, landings reconstruction, size-at-maturity, habitat utilization Corvina blanca, estructura del stock, reconstrucción de desembarques, talla de madurez sexual, uso de hábitat CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA CIENCIAS AGRARIAS PECES Y FAUNA SILVESTRE DINÁMICA DE LAS POBLACIONES DINÁMICA DE LAS POBLACIONES

Contrasting spatial patterns in active-fire and fire-suppressed mediterranean climate old-growth mixed conifer forests

Danny L. Fry  (2014, [Artículo])

In Mediterranean environments in western North America, historic fire regimes in frequent-fire conifer forests are highly variable both temporally and spatially. This complexity influenced forest structure and spatial patterns, but some of this diversity has been lost due to anthropogenic disruption of ecosystem processes, including fire. Information from reference forest sites can help management efforts to restore forests conditions that may be more resilient to future changes in disturbance regimes and climate. In this study, we characterize tree spatial patterns using four-ha stem maps from four old-growth, Jeffrey pine-mixed conifer forests, two with active-fire regimes in northwestern Mexico and two that experienced fire exclusion in the southern Sierra Nevada. Most of the trees were in patches, averaging six to 11 trees per patch at 0.007 to 0.014 ha-1, and occupied 27-46% of the study areas. Average canopy gap sizes (0.04 ha) covering 11-20% of the area were not significantly different among sites. The putative main effects of fire exclusion were higher densities of single trees in smaller size classes, larger proportion of trees (≥56%) in large patches (≥10 trees), and decreases in spatial complexity. While a homogenization of forest structure has been a typical result from fire exclusion, some similarities in patch, single tree, and gap attributes were maintained at these sites. These within-stand descriptions provide spatially relevant benchmarks from which to manage for structural heterogeneity in frequent-fire forest types.

article, climate, controlled study, ecosystem fire history, forest structure, geographic distribution, geographic mapping, land use, mathematical computing, mathematical model, Mexico, spatial analysis, taiga, United States, comparative study, conife CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA

Gamma-diversity partitioning of gobiid fishes (Teleostei: Gobiidae) ensemble along of Eastern Tropical Pacific: Biological inventory, latitudinal variation and species turnover

OMAR VALENCIA MENDEZ (2018, [Artículo])

Gobies are the most diverse marine fish family. Here, we analysed the gamma-diversity (γ-diversity) partitioning of gobiid fishes to evaluate the additive and multiplicative components of α and β-diversity, species replacement and species loss and gain, at four spatial scales: sample units, ecoregions, provinces and realms. The richness of gobies from the realm Eastern Tropical Pacific (ETP) is represented by 87 species. Along latitudinal and longitudinal gradients, we found that the γ-diversity is explained by the β-diversity at both spatial scales, ecoregions and provinces. At the ecoregion scale, species are diverse in the north (Cortezian ecoregion) and south (Panama Bight ecoregion) and between insular and coastal ecoregions. At the province scale, we found that the species turnover between the warm temperate Northeast Pacific (WTNP), Tropical East Pacific (TEaP) and the Galapagos Islands (Gala) was high, and the species nestedness was low. At the ecoregion scale, historical factors, and phylogenetic factors have influenced the hotspots of gobiid fish biodiversity, particularly in the Cortezian, Panama Bight and Cocos Island ecoregions, where species turnover is high across both latitudinal and longitudinal gradients. At the provincial level, we found that the contributions of the β-diversity from north to south, in the WTNP, TEaP and Gala were high, as result of the high number of unique species. Species turnover was also high at this scale, with a low contribution from species nestedness that was probably due to the low species/gene flow within the provinces. These results highlight the importance and successful inclusion of a cryptobenthic fish component in ecological and biogeographical studies. © 2018 Valencia-Méndez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Article, biodiversity, biogeographic region, biogeography, gene flow, goby fish, nonhuman, phylogeny, species distribution, species diversity, taxonomic identification, teleost, animal, animal dispersal, fish, Pacific Ocean, phylogeography, Animal Di CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA CIENCIAS AGRARIAS PECES Y FAUNA SILVESTRE PECES Y FAUNA SILVESTRE

Assessing the Response of Nematode Communities to Climate Change-Driven Warming: A Microcosm Experiment

RUTH GINGOLD WERMUTH (2013, [Artículo])

Biodiversity has diminished over the past decades with climate change being among the main responsible factors. One consequence of climate change is the increase in sea surface temperature, which, together with long exposure periods in intertidal areas, may exceed the tolerance level of benthic organisms. Benthic communities may suffer structural changes due to the loss of species or functional groups, putting ecological services at risk. In sandy beaches, free-living marine nematodes usually are the most abundant and diverse group of intertidal meiofauna, playing an important role in the benthic food web. While apparently many functionally similar nematode species co-exist temporally and spatially, experimental results on selected bacterivore species suggest no functional overlap, but rather an idiosyncratic contribution to ecosystem functioning. However, we hypothesize that functional redundancy is more likely to observe when taking into account the entire diversity of natural assemblages. We conducted a microcosm experiment with two natural communities to assess their stress response to elevated temperature. The two communities differed in diversity (high [HD] vs. low [LD]) and environmental origin (harsh vs. moderate conditions). We assessed their stress resistance to the experimental treatment in terms of species and diversity changes, and their function in terms of abundance, biomass, and trophic diversity. According to the Insurance Hypothesis, we hypothesized that the HD community would cope better with the stressful treatment due to species functional overlap, whereas the LD community functioning would benefit from species better adapted to harsh conditions. Our results indicate no evidence of functional redundancy in the studied nematofaunal communities. The species loss was more prominent and size specific in the HD; large predators and omnivores were lost, which may have important consequences for the benthic food web. Yet, we found evidence for alternative diversity-ecosystem functioning relationships, such as the Rivets and the Idiosyncrasy Model. © 2013 Gingold et al.

aquaculture, article, bacterivore, benthos, biodiversity, biomass, climate, community dynamics, controlled study, ecosystem, environmental temperature, microcosm, nematode, nonhuman, population abundance, species diversity, species richness, taxonomy CIENCIAS FÍSICO MATEMÁTICAS Y CIENCIAS DE LA TIERRA CIENCIAS DE LA TIERRA Y DEL ESPACIO OCEANOGRAFÍA OCEANOGRAFÍA