RESUMEN

Testudines possess a rigid shell that influences the mechanics of the respiratory system. We studied respiratory mechanics in the terrestrial red-footed tortoise Chelonoidis carbonarius (Cryptodira), comparing juvenile individuals with a less ossified and more flexible carapace to adults with a well-ossified rigid shell. Combined with these ontogenetic differences, we analyzed respiratory system mechanics with animals in a supine and a prone position, as well as in the isolated lungs, to evaluate the impact of the viscera onto breathing mechanics. To do so, we used established protocols to measure pulmonary volumes (i.e., resting, VLr; and maximum, VLm), static (Cstat) and dynamic (Cdyn) compliances, and the work of breathing (W). We observed that isolated lungs displayed increased VLr, VLm, Cstat,Cdyn and decreased W. Additionally, pulmonary volumes, compliances, and W were affected by evaluated positions, such as a smaller VLr in a supine position. Cdyn and W showed a volume dependency while frequency had less influence on these variables. At similar levels of ventilation, juveniles showed a lower W than adults when standardized by body mass, but similar W when standardized by VLr. Clear ontogenetic changes could be observed in breathing mechanics between juvenile and adult C. carbonarius. While these differences might largely be explained by variations in shell ossifications, other explanations such as differences in visceral proportions or developmental degree of the post-pulmonary septum should also be taken into account.

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The use of effect biomarkers has contributed to the understanding of the sublethal effects of contaminants on different organisms. However, the analysis of genotoxic markers as an indicator of organism and environmental health in sharks is underexplored. Thus, the present study investigated the relationship between the genomic damage frequency in erythrocytes and metal(loid) concentrations in whole blood of three shark species (Galeocerdo cuvier, Negaprion brevirostris and Ginglymostoma cirratum), taking into account climatic seasonality. The results showed that G. cuvier, an apex predator, presented the highest total erythrocyte genomic damage frequencies together with the highest mean whole blood concentrations of Al, Cd, Cr, Fe, Mn, Ni, Pb and Zn. The shark N. brevirostris also presented high levels of metal(loid), indicating a greater susceptibility to these contaminants in species that preferentially feed on fish. In contrast, G. cirratum, a mesopredator, presented the lowest erythrocyte damage frequencies and whole blood metal(loid) concentrations. The presence of micronuclei was the most responsive biomarker, and Al, As and Zn had an important effect on the genomic damage frequencies for all species evaluated. Zn concentration influenced the binucleated cells frequencies and Al concentration had an effect on the total damage and micronuclei frequencies in G. cuvier and N. brevirostris. Binucleated cells and blebbed nuclei frequencies were affected by As concentration, especially in G. cirratum, while showing a strong and positive correlation with most of the metals analyzed. Nonetheless, baseline levels of metal(loid) blood concentrations and erythrocyte genomic damage frequencies in sharks have not yet been established. Therefore, minimum risk levels of blood contaminants concentrations on the health of these animals have also not been determined. However, the high genomic instability observed in sharks is of concern considering the current health status of these animals, as well as the quality of the environment studied.

Asunto(s)

Daño del ADN , Eritrocitos , Metales , Tiburones , Contaminantes Químicos del Agua , Animales , Tiburones/genética , Tiburones/sangre , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/sangre , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Metales/sangre , Metales/toxicidad , Monitoreo del Ambiente/métodos , Pruebas de Micronúcleos , Biomarcadores/sangre , Metales Pesados/sangre , Metales Pesados/toxicidad

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This review aims to provide an overview of sustainable approaches that can be incorporated into well-known procedures for the development of materials, pre- and post-treatments, modifications, and applications of 3D-printed objects, especially for fused filament fabrication (FFF). Different examples of conductive and non-conductive bespoke filaments using renewable biopolymers, bioplasticizers, and recycled materials are presented and discussed. The main final characteristics of the polymeric materials achieved according to the feedstock, preparation, extrusion, and treatments are also covered. In addition to recycling and remanufacturing, this review also explores other alternative approaches that can be adopted to enhance the sustainability of methods, aiming to produce efficient and environmentally friendly 3D printed products. Adjusting printing parameters and miniaturizing systems are also highlighted in this regard. All these recommended strategies are employed to minimize environmental damage, while also enabling the production of high-quality, economical materials and 3D printed systems. These efforts align with the principles of Green Chemistry, Sustainable Development Goals (SDGs), 3Rs (Reduce, Reuse, Recycle), and Circular Economy concepts.

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Alcohol use disorder (AUD) remains a critical public health issue worldwide, characterized by high relapse rates often triggered by contextual cues. This research investigates the neural mechanisms behind context-induced reinstatement of alcohol-seeking behavior, focusing on the nucleus accumbens and its interactions with the prelimbic cortex, employing Male Long-Evans rats in an ABA renewal model. In our experimental setup, rats were trained to self-administer 10 % ethanol in Context A, followed by extinction of lever pressing in the presence of discrete cues in Context B. The context-induced reinstatement of ethanol-seeking was then assessed by re-exposing rats to Context A or B under extinction conditions, aiming to simulate the environmental cues' influence on relapse behaviors. Three experiments were conducted: Experiment 1 utilized Fos-immunohistochemistry to examine neuronal activation in the nucleus accumbens; Experiment 2 applied the baclofen + muscimol inactivation technique to probe the functional importance of the nucleus accumbens core; Experiment 3 used Fos-immunofluorescence along with Retrobeads injection to investigate activation of neurons projecting from the prelimbic cortex to the nucleus accumbens core. Our findings revealed significant increases in Fos-immunoreactive nuclei within the nucleus accumbens core and shell during the reinstatement phase in Context A, underscoring the environment's potent effect on ethanol-seeking behavior. Additionally, inactivation of the nucleus accumbens core markedly reduced reinstatement, and there was a notable activation of neurons from the prelimbic cortex to the nucleus accumbens core in the ethanol-associated context. These results highlight the critical role of the nucleus accumbens core and its corticostriatal projections in the neural circuitry underlying context-driven ethanol seeking.

Asunto(s)

Comportamiento de Búsqueda de Drogas , Etanol , Extinción Psicológica , Núcleo Accumbens , Ratas Long-Evans , Animales , Núcleo Accumbens/efectos de los fármacos , Masculino , Etanol/administración & dosificación , Etanol/farmacología , Comportamiento de Búsqueda de Drogas/fisiología , Ratas , Extinción Psicológica/fisiología , Extinción Psicológica/efectos de los fármacos , Autoadministración , Vías Nerviosas/fisiología , Alcoholismo , Señales (Psicología) , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de los fármacos , Baclofeno/farmacología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Muscimol/farmacología

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Obesity, a burgeoning global health crisis, has tripled in prevalence over the past 45 years, necessitating innovative research methodologies. Adipocytes, which are responsible for energy storage, play a central role in obesity. However, most studies in this field rely on animal models or adipocyte monolayer cell cultures, which are limited in their ability to fully mimic the complex physiology of a living organism, or pose challenges in terms of cost, time consumption, and ethical considerations. These limitations prompt a shift towards alternative methodologies. In response, here we show a 3D in vitro model utilizing the 3T3-L1 cell line, aimed at faithfully replicating the metabolic intricacies of adipocytes in vivo. Using a workable cell line (3T3-L1), we produced adipocyte spheroids and differentiated them in presence and absence of TNF-α. Through a meticulous proteomic analysis, we compared the molecular profile of our adipose spheroids with that of adipose tissue from lean and obese C57BL/6J mice. This comparison demonstrated the model's efficacy in studying metabolic conditions, with TNF-α treated spheroids displaying a notable resemblance to obese white adipose tissue. Our findings underscore the model's simplicity, reproducibility, and cost-effectiveness, positioning it as a robust tool for authentically mimicking in vitro metabolic features of real adipose tissue. Notably, our model encapsulates key aspects of obesity, including insulin resistance and an obesity profile. This innovative approach has the potential to significantly impact the discovery of novel therapeutic interventions for metabolic syndrome and obesity. By providing a nuanced understanding of metabolic conditions, our 3D model stands as a transformative contribution to in vitro research, offering a pathway for the development of small molecules and biologics targeting these pervasive health issues in humans.

Asunto(s)

Células 3T3-L1 , Adipocitos , Obesidad , Esferoides Celulares , Animales , Ratones , Obesidad/metabolismo , Adipocitos/metabolismo , Adipocitos/citología , Esferoides Celulares/metabolismo , Ratones Endogámicos C57BL , Redes y Vías Metabólicas , Diferenciación Celular , Factor de Necrosis Tumoral alfa/metabolismo , Proteómica/métodos

RESUMEN

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

Asunto(s)

Neoplasias de la Boca , Proteoma , Saliva , Humanos , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Neoplasias de la Boca/diagnóstico , Saliva/química , Saliva/metabolismo , Proteoma/análisis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , Femenino , Biomarcadores de Tumor/metabolismo , Masculino , Metástasis Linfática , Conformación Proteica , Persona de Mediana Edad , Pronóstico , Proteómica/métodos , Transcetolasa/metabolismo , Anciano , Espectrometría de Masas , Proteínas y Péptidos Salivales/metabolismo , Proteínas y Péptidos Salivales/análisis

RESUMEN

BACKGROUND: Distillery vinasse is one of the promising bio-fertilizers, as it contains significant amounts of essential chemical elements, allied with sorghum that is widely used in the diet of ruminant animals and has been considered as an alternative to the production of other cereals or forages. This study aimed to evaluate saccharin sorghum silage from fertilization with vinasse. METHODS: The research was conducted using the BRS-511, CR-1339, and CR-1342 geno-types. The silage was held for 170 days after sowing, with experimental design in blocks with triple factorial (genotypes x fertilization x inoculation) totaling 54 installments. At 95 days, the silos were opened for sample collection and analysis bromatological analysis. RESULTS: The results indicate the primary source of variation was genotype, characterizing them with different potentials in productivity and better results for BRS-511, CR-1339, and CR-1342. The bromatological results indicate good quality for CR-1339 and CR-1342 hybrids, however, better digestability for BRS-511. There was no observable difference between the factors of fertilization. The inoculation additive assists in the reduction of lignin appears to be high. PCA analysis showed differences between cultivars (BRS-511, CR-1339, and CR-1342) and fertili-zation. However, the PCAs showed the genotypes show similar results with conventional ferti-lization and sugarcane vinasse. CONCLUSION: The study reflected the possibility of producing sweet sorghum silage with soil sugarcane vinasse fertilization as fertilizer.

RESUMEN

Due to the anthropogenic pressures of expansion areas for livestock and agricultural production in the Brazilian Cerrado, it is of paramount importance to understand the dynamics of land use/land cover (LULC) changes in this region. Thus, we investigated LULC changes in two sub-basins of the Tocantins-Araguaia River basin from 1997 to 2015 and consequently projected future changes for the timespan between 2030 and 2050. The Formoso sub-basin experienced significant expansion of agricultural and pasture areas, whereas the Sono sub-basin limited farmland expansion (more stable native vegetation) due to substantial protected areas, trends that were also observed for future projections (2030 and 2050). Pastureland in the Formoso sub-basin increased by 5.8%, while the Sono sub-basin saw significant gains in cultivated land, according to change detection analyses during the 1997-2015 period. High stability probabilities of no change (> 70%) for grassland areas in the Sono River sub-basin and pasturelands in the Formoso River sub-basin were computed. The CA-Markov model demonstrated a high consistency level with actual LULC classes for both sub-basins, as indicated by an overall Kappa coefficient above 0.8. Future projections for 2030 and 2050 show a substantial expansion of agriculture and pasture in both sub-basins, driven by specific factors such as soil organic carbon stocks, distance from rural settlements, and proximity to rivers. Short- and mid-term simulations indicate substantial expansion of agriculture and pasture in both basins, with potential adverse impacts on water erosion. Consequently, developing policies for soil management and sustainable land use planning is essential for agroecosystem sustainability, promoting a balanced approach to economic development while addressing climate change and anthropogenic challenges.

Asunto(s)

Agricultura , Conservación de los Recursos Naturales , Monitoreo del Ambiente , Ríos , Ríos/química , Monitoreo del Ambiente/métodos , Brasil

RESUMEN

OBJECTIVES: Evaluate, in vitro, the effect of incorporating nano-sized sodium trimetaphosphate (TMPnano) and phosphorylated chitosan (Chi-Ph) into resin-modified glass ionomer cement (RMGIC) used for orthodontic bracket cementation, on mechanical, fluoride release, antimicrobial and cytotoxic properties. METHODS: RMGIC was combined with Chi-Ph (0.25%/0.5%) and/or TMPnano (14%). The diametral compressive/tensile strength (DCS/TS), surface hardness (SH) and degree of conversion (%DC) were determined. For fluoride (F) release, samples were immersed in des/remineralizing solutions. Antimicrobial/antibiofilm activity was evaluated by the agar diffusion test and biofilm metabolism (XTT). Cytotoxicity in fibroblasts was assessed with the resazurin method. RESULTS: After 24 h, the RMGIC-14%TMPnano group showed a lower TS value (p < 0.001); after 7 days the RMGIC-14%TMPnano-0.25%Chi-Ph group showed the highest value (p < 0.001). For DCS, the RMGIC group (24 h) showed the highest value (p < 0.001); after 7 days, the highest value was observed for the RMGIC-14%TMPnano-0.25%Chi-Ph (p < 0.001). RMGIC-14%TMPnano, RMGIC-14%TMPnano-0.25%Chi-Ph, RMGIC-14%TMPnano-0.5%Chi-Ph showed higher and similar release of F (p > 0.001). In the SH, the RMGIC-0.25%Chi-Ph; RMGIC-0.5%Chi-Ph; RMGIC-14%TMPnano-0.5%Chi-Ph groups showed similar results after 7 days (p > 0.001). The RMGIC-14%TMPnano-0.25%Chi-Ph group showed a better effect on microbial/antibiofilm growth, and the highest efficacy on cell viability (p < 0.001). After 72 h, only the RMGIC-14%TMPnano-0.25%Chi-Ph group showed cell viability (p < 0.001). CONCLUSION: The RMGIC-14%TMPnano-0.25%Chi-Ph did not alter the physical-mechanical properties, was not toxic to fibroblasts and reduced the viability and metabolism of S. mutans. CLINICAL RELEVANCE: The addition of phosphorylated chitosan and organic phosphate to RMGIC could provide an antibiofilm and remineralizing effect on the tooth enamel of orthodontic patients, who are prone to a high cariogenic challenge due to fluctuations in oral pH and progression of carious lesions.

Asunto(s)

Antibacterianos , Biopelículas , Quitosano , Fibroblastos , Fluoruros , Cementos de Ionómero Vítreo , Ensayo de Materiales , Quitosano/farmacología , Antibacterianos/farmacología , Cementos de Ionómero Vítreo/farmacología , Cementos de Ionómero Vítreo/química , Biopelículas/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fosforilación , Fluoruros/farmacología , Dureza , Resistencia a la Tracción , Propiedades de Superficie , Fuerza Compresiva , Nanopartículas , Cementos de Resina/química , Polifosfatos/farmacología , Cementos Dentales/farmacología , Cementos Dentales/química , Supervivencia Celular/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Animales , Fosfatos/farmacología , Humanos , Soportes Ortodóncicos

RESUMEN

Deep learning methods, trained on the increasing set of available protein 3D structures and sequences, have substantially impacted the protein modeling and design field. These advancements have facilitated the creation of novel proteins, or the optimization of existing ones designed for specific functions, such as binding a target protein. Despite the demonstrated potential of such approaches in designing general protein binders, their application in designing immunotherapeutics remains relatively unexplored. A relevant application is the design of T cell receptors (TCRs). Given the crucial role of T cells in mediating immune responses, redirecting these cells to tumor or infected target cells through the engineering of TCRs has shown promising results in treating diseases, especially cancer. However, the computational design of TCR interactions presents challenges for current physics-based methods, particularly due to the unique natural characteristics of these interfaces, such as low affinity and cross-reactivity. For this reason, in this study, we explored the potential of two structure-based deep learning protein design methods, ProteinMPNN and ESM-IF, in designing fixed-backbone TCRs for binding target antigenic peptides presented by the MHC through different design scenarios. To evaluate TCR designs, we employed a comprehensive set of sequence- and structure-based metrics, highlighting the benefits of these methods in comparison to classical physics-based design methods and identifying deficiencies for improvement.

RESUMEN

Bottom-up mechanochemical synthesis (BUMS) has been demonstrated to be an efficient approach for the preparation of metal nanoparticles (NPs), protected by surface agents or anchored on solid supports. However, there are limitations, such as precise size and morphological control, due to a lack of knowledge about the mechanically induced processes of NP formation under milling. In this article, we further investigate the BUMS of AuNPs. Using SiO2 as a solid support, we studied the effect of typical reducing agents, namely NaBH4, L-ascorbic acid, and hydroquinone (HQ), on the conversion of a AuIII source. XANES showed that HQ is the strongest reducing agent under our experimental conditions, leading to the quantitative conversion of gold salt in a few minutes. Interestingly, even when HQ was used in sub-stoichiometric amounts, AuIII could be reduced to ratios higher than 85% after two minutes of milling. Investigations into the byproducts by 1H NMR and GC-FID/MS enabled the identification HQ regeneration and the formation of its derivatives. We mainly focused on benzoquinone (BQ), which is the product of the oxidation of HQ as it reduces the gold salt. We could demonstrate that HQ is regenerated from BQ exclusively under milling and acidic conditions. The regenerated HQ and other HQ-chlorinated molecules could then reduce gold-oxidized species, leading to higher conversions and economy of reactants. Our study highlights the intriguing and complex mechanisms of mechanochemical systems, in addition to fostering the atom and energy economy side of mechanochemical means to produce metal nanoparticles.

RESUMEN

Cardiac function requires appropriate proteins in each chamber. Atria requires slow myosin to act as reservoirs, while ventricles demand fast myosin for swift pumping. Myosins are thus under chamber-biased cis-regulation, with myosin gene expression imbalances leading to congenital heart dysfunction. To identify regulatory inputs leading to cardiac chamber-biased expression, we computationally and molecularly dissected the quail Slow Myosin Heavy Chain III (SMyHC III) promoter that drives preferential expression to the atria. We show that SMyHC III gene states are orchestrated by a complex Nuclear Receptor Element (cNRE) of 32 base pairs. Using transgenesis in zebrafish and mice, we demonstrate that preferential atrial expression is achieved by a combinatorial regulatory input composed of atrial activation motifs and ventricular repression motifs. Using comparative genomics, we show that the cNRE might have emerged from an endogenous viral element through infection of an ancestral host germline, revealing an evolutionary pathway to cardiac chamber-specific expression.

Asunto(s)

Atrios Cardíacos , Pez Cebra , Ratones , Animales , Pez Cebra/genética , Atrios Cardíacos/metabolismo , Ventrículos Cardíacos , Miosinas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo

RESUMEN

This work emphasizes the utilization of biochar, a renewable material, as an interesting platform for anchoring redox mediators and bioreceptors in the development of economic, environmentally friendly biosensors. In this context, Fe(III) ions were preconcentrated on highly functionalized activated biochar, allowing the stable synthesis of Prussian blue nanostructures with an average size of 58.3 nm. The determination of glucose was carried out by indirectly monitoring the hydrogen peroxide generated through the enzymatic reaction, followed by its subsequent redox reaction with reduced Prussian blue (also known as Prussian white) in a typical electrochemical-chemical mechanism. The EDC/NHS (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-Hydroxysuccinimide) pair was employed for the stable covalent immobilization of the enzyme on biochar. The biosensor demonstrated good enzyme-substrate affinity, as evidenced by the Michaelis-Menten apparent kinetic constant (4.16 mmol L-1), and analytical performance with a wide linear dynamic response range (0.05-5.0 mmol L-1), low limits of detection (0.94 µmol L-1) and quantification (3.13 µmol L-1). Additionally, reliable repeatability, reproducibility, stability, and selectivity were obtained for the detection of glucose in both real and spiked human saliva and blood serum samples.

Asunto(s)

Técnicas Biosensibles , Carbón Orgánico , Ferrocianuros , Glucosa , Nanoestructuras , Ferrocianuros/química , Técnicas Biosensibles/métodos , Nanoestructuras/química , Carbón Orgánico/química , Glucosa/análisis , Glucosa/química , Humanos , Enzimas Inmovilizadas/química , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Glucemia/análisis , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Límite de Detección

RESUMEN

Polystyrene (PS) is one of the main synthetic polymers produced around the world, and it is present in the composition of a wide variety of single-use objects. When released into the environment, these materials are degraded by environmental factors, resulting in microplastics. We investigated the ability of Chironomus sancticaroli (Diptera, Chironomidae) to promote the fragmentation of PS microspheres (24.5 ± 2.9 µm) and the toxic effects associated with exposure to this polymer. C. sancticaroli larvae were exposed to 3 different concentrations of PS (67.5, 135, and 270 particles g-1 of dry sediment) for 144 h. Significant lethality was observed only at the highest concentration. A significant reduction in PS particle size as well as evidence of deterioration on the surface of the spheres, such as grooves and cracks, was observed. In addition, changes in oxidative stress biomarkers (SOD, CAT, MDA, and GST) were also observed. This is the first study to report the ability of Chironomus sp. to promote the biofragmentation of microplastics. The information obtained demonstrates that the macroinvertebrate community can play a key role in the degradation of plastic particles present in the sediment of freshwater environments and can also be threatened by such particle pollution.

Asunto(s)

Chironomidae , Contaminantes Químicos del Agua , Animales , Microplásticos/toxicidad , Larva , Poliestirenos/toxicidad , Chironomidae/metabolismo , Plásticos/toxicidad , Contaminantes Químicos del Agua/análisis

RESUMEN

Plasmonic photocatalysis has been limited by the high cost and scalability of plasmonic materials, such as Ag and Au. By focusing on earth-abundant photocatalyst/plasmonic materials (HxMoO3) and Pd as a catalyst, we addressed these challenges by developing a solventless mechanochemical synthesis of Pd/HxMoO3 and optimizing photocatalytic activities in the visible range. We investigated the effect of HxMoO3 band gap excitation (at 427 nm), Pd interband transitions (at 427 nm), and HxMoO3 localized surface plasmon resonance (LSPR) excitation (at 640 nm) over photocatalytic activities toward the hydrogen evolution and phenylacetylene hydrogenation as model reactions. Although both excitation wavelengths led to comparable photoenhancements, a 110% increase was achieved under dual excitation conditions (427 + 640 nm). This was assigned to a synergistic effect of optical excitations that optimized the generation of energetic electrons at the catalytic sites. These results are important for the development of visible-light photocatalysts based on earth-abundant components.

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0258679.].

RESUMEN

The presence of Andean plant genera in moist forests of the Brazilian Atlantic Coast has been historically hypothesized as the result of cross-continental migrations starting at the eastern Andean flanks. Here we test hypotheses of former connections between the Atlantic and Andean forests by examining distribution patterns of selected cool and moist-adapted plant arboreal taxa present in 54 South American pollen records of the Last Glacial Maximum (LGM), ca. 19-23 cal ka, known to occur in both plant domains. Pollen taxa studied include Araucaria, Drimys, Hedyosmum, Ilex, Myrsine, Podocarpus, Symplocos, Weinmannia, Myrtaceae, Ericaceae and Arecaceae. Past connectivity patterns between these two neotropical regions as well as individual ecological niches during the LGM were explored by cluster analysis of fossil assemblages and modern plant distributions. Additionally, we examined the ecological niche of 137 plant species with shared distributions between the Andes and coastal Brazil. Our results revealed five complex connectivity patterns for South American vegetation linking Andean, Amazonian and Atlantic Forests and one disjunction distribution in southern Chile. This study also provides a better understanding of vegetation cover on the large and shallow South American continental shelf that was exposed due to a global sea level drop.

Asunto(s)

Ecosistema , Bosques , Brasil , Chile , Árboles

RESUMEN

(R,S)-methadone ((R,S)-MTD) is a µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers. (S)-MTD is being developed as an antidepressant and is considered an N-methyl-D-aspartate receptor (NMDAR) antagonist. We compared the pharmacology of (R)-MTD and (S)-MTD and found they bind to MORs, but not NMDARs, and induce full analgesia. Unlike (R)-MTD, (S)-MTD was a weak reinforcer that failed to affect extracellular dopamine or induce locomotor stimulation. Furthermore, (S)-MTD antagonized motor and dopamine releasing effects of (R)-MTD. (S)-MTD acted as a partial agonist at MOR, with complete loss of efficacy at the MOR-galanin Gal1 receptor (Gal1R) heteromer, a key mediator of the dopaminergic effects of opioids. In sum, we report novel and unique pharmacodynamic properties of (S)-MTD that are relevant to its potential mechanism of action and therapeutic use. One-sentence summary: (S)-MTD, like (R)-MTD, binds to and activates MORs in vitro, but (S)-MTD antagonizes the MOR-Gal1R heteromer, decreasing its abuse liability.

Asunto(s)

Analgésicos Opioides , Metadona , Receptores Opioides mu , Receptores Opioides mu/metabolismo , Receptores Opioides mu/efectos de los fármacos , Animales , Metadona/farmacología , Masculino , Analgésicos Opioides/farmacología , Humanos , Ratones , Dopamina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Ligandos , Estereoisomerismo

RESUMEN

BACKGROUND: Scaffold (SCA) functionalization with aptamers (APT) provides adsorption of specific bioactive molecules on biomaterial surfaces. The aim of this study was to observe if SCA enriched with anti-fibronectin APT can favor coagulum (PhC) and osteoblasts (OSB) differentiation. METHODS: 20 µg of APT was functionalized on SCA by simple adsorption. For PhC formation, SCAs were inserted into rat calvaria defects for 17 h. Following proper transportation (buffer solution PB), OSBs (UMR-106 lineage) were seeded over PhC + SCAs with and without APT. Cells and PhC morphology, PhC cell population, protein labeling and gene expression were observed in different time points. RESULTS: The APT induced higher alkaline phosphatase and bone sialoprotein immunolabeling in OSB. Mesenchymal stem cells, leukocytes and lymphocytes cells were detected more in the APT group than when scaffolds were not functionalized. Additionally, an enriched and dense fibrin network and different cell types were observed, with more OSB and white blood cells in PhC formed on SCA with APT. The gene expression showed higher transforming growth factor beta 1 (TGF-b1) detection in SCA with APT. CONCLUSIONS: The SCA functionalization with fibronectin aptamers may alter key morphological and functional features of blood clot formation, and provides a selective expression of proteins related to osteo differentiation. Additionally, aptamers increase TGF-b1 gene expression, which is highly associated with improvements in regenerative therapies.