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The amount of carbon stored in deadwood is equivalent to about 8 per cent of the global forest carbon stocks1. The decomposition of deadwood is largely governed by climate2-5 with decomposer groups-such as microorganisms and insects-contributing to variations in the decomposition rates2,6,7. At the global scale, the contribution of insects to the decomposition of deadwood and carbon release remains poorly understood7. Here we present a field experiment of wood decomposition across 55 forest sites and 6 continents. We find that the deadwood decomposition rates increase with temperature, and the strongest temperature effect is found at high precipitation levels. Precipitation affects the decomposition rates negatively at low temperatures and positively at high temperatures. As a net effect-including the direct consumption by insects and indirect effects through interactions with microorganisms-insects accelerate the decomposition in tropical forests (3.9% median mass loss per year). In temperate and boreal forests, we find weak positive and negative effects with a median mass loss of 0.9 per cent and -0.1 per cent per year, respectively. Furthermore, we apply the experimentally derived decomposition function to a global map of deadwood carbon synthesized from empirical and remote-sensing data, obtaining an estimate of 10.9 ± 3.2 petagram of carbon per year released from deadwood globally, with 93 per cent originating from tropical forests. Globally, the net effect of insects may account for 29 per cent of the carbon flux from deadwood, which suggests a functional importance of insects in the decomposition of deadwood and the carbon cycle.
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Ciclo del Carbono , Bosques , Insectos/metabolismo , Árboles/metabolismo , Animales , Secuestro de Carbono , Clima , Ecosistema , Mapeo Geográfico , Cooperación InternacionalRESUMEN
Cancer is a multifaceted genetic disease characterized by the acquisition of several essential hallmarks. Notably, certain cancers exhibit horizontal transmissibility, observed across mammalian species and diverse bivalves, the latter referred to as hemic neoplasia. Within this complex landscape, epigenetic mechanisms such as histone modifications and cytosine methylation emerge as fundamental contributors to the pathogenesis of these transmissible cancers. Our study delves into the epigenetic landscape of Cerastoderma edule, focusing on whole-genome methylation and hydroxymethylation profiles in heathy specimens and transmissible neoplasias by means of Nanopore long-read sequencing. Our results unveiled a global hypomethylation in the neoplastic specimens compared to their healthy counterparts, emphasizing the role of DNA methylation in these tumorigenic processes. Furthermore, we verified that intragenic CpG methylation positively correlated with gene expression, emphasizing its role in modulating transcription in healthy and neoplastic cockles, as also highlighted by some up-methylated oncogenic genes. Hydroxymethylation levels were significantly more elevated in the neoplastic samples, particularly within satellites and complex repeats, likely related to structural functions. Additionally, our analysis also revealed distinct methylation and activity patterns in retrotransposons, providing additional insights into bivalve neoplastic processes. Altogether, these findings contribute to understanding the epigenetic dynamics of bivalve neoplasias and shed light on the roles of DNA methylation and hydroxymethylation in tumorigenesis. Understanding these epigenetic alterations holds promise for advancing our broader understanding of cancer epigenetics.
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Cardiidae , Metilación de ADN , Epigénesis Genética , Metilación de ADN/genética , Animales , Cardiidae/genética , Islas de CpG/genética , Genoma/genética , Neoplasias/genética , Neoplasias/patologíaRESUMEN
Bone tissue engineering is a promising alternative to repair wounds caused by cellular or physical accidents that humans face daily. In this sense, the search for new graphene oxide (GO) nanofillers related to their degree of oxidation is born as an alternative bioactive component in forming new scaffolds. In the present study, three different GOs were synthesized with varying degrees of oxidation and studied chemically and tissue-wise. The oxidation degree was determined through infrared (FTIR), X-ray diffraction (XRD), X-ray photoelectron (XPS), and Raman spectroscopy (RS). The morphology of the samples was analyzed using scanning electron microscopy (SEM). The oxygen content was deeply described using the deconvolution of RS and XPS techniques. The latter represents the oxidation degree for each of the samples and the formation of new bonds promoted by the graphitization of the material. In the RS, two characteristic bands were observed according to the degree of oxidation and the degree of graphitization of the material represented in bands D and G with different relative intensities, suggesting that the samples have different crystallite sizes. This size was described using the Tuinstra-Koenig model, ranging between 18.7 and 25.1 nm. Finally, the bone neoformation observed in the cranial defects of critical size indicates that the F1 and F2 samples, besides being compatible and resorbable, acted as a bridge for bone healing through regeneration. This promoted healing by restoring bone and tissue structure without triggering a strong immune response.
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Regeneración Ósea , Grafito , Ingeniería de Tejidos , Andamios del Tejido , Grafito/química , Regeneración Ósea/efectos de los fármacos , Ingeniería de Tejidos/métodos , Animales , Andamios del Tejido/química , Nanoestructuras/química , Huesos/efectos de los fármacos , Espectrometría Raman , Oxidación-Reducción , Difracción de Rayos X , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ratas , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Cancer stands as one of the deadliest diseases in human history, marked by an inferior prognosis. While traditional therapeutic methods like surgery, chemotherapy, and radiation have demonstrated success in inhibiting tumor cell growth, their side effects often limit overall benefits and patient acceptance. In this regard, three different graphene oxides (GO) with variations in their degrees of oxidation were studied chemically and tissue-wise. The accuracy of the synthesis of the different GO was verified by robust techniques using X-ray photoelectron spectroscopy (XPS), as well as conventional techniques such as infrared spectroscopy (FTIR), RAMAN spectroscopy, and X-ray diffraction (XRD). The presence of oxygenated groups was of great importance. It affected the physicochemical properties of each of the different graphene oxides demonstrated in the presence of new vibrational modes related to the formation of new bonds promoted by the graphitization of the materials. The toxicity analysis in the Hep-2 cell line of graphene oxide formulations at 250 µg/mL on the viability and proliferation of these tumor cells showed low activity. GO formulations did not show high antibacterial activity against Staphylococcus aureus and Escherichia coli strains. However, the different graphene oxides showed biocompatibility in the subdermal implantation model for 30, 60, and 90 days in the biomodels. This allowed healing by restoring hair and tissue architecture without triggering an aggressive immune response.
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Grafito , Neoplasias del Cuello Uterino , Humanos , Femenino , Grafito/farmacología , Antibacterianos/farmacología , Escherichia coli , Óxidos/farmacologíaRESUMEN
In recent years biomedical scientific community has been working towards the development of high-throughput devices that allow a reliable, rapid and parallel detection of several strains of virus or microparticles simultaneously. One of the complexities of this problem lies on the rapid prototyping of new devices and wireless rapid detection of small particles and virus alike. By reducing the complexity of microfluidics microfabrication and using economic materials along with makerspace tools (Kundu et al. 2018) it is possible to provide an affordable solution to both the problems of high-throughput devices and detection technologies. We present the development of a wireless, standalone device and disposable microfluidics chips that rapidly generate parallel readouts for selected, possible virus variants from a nasal or saliva sample, based on motorized and non-motorized microbeads detection, and imaging processing of the motion tracks of these beads in micrometers. Microbeads and SARS-CoV-2 COVID-19 Delta variant were tested as proof-of-concept for testing the microfluidic cartridges and wireless imaging module. The Microbead Assay (MA) system kit consists of a Wi-Fi readout module, a microfluidic chip, and a sample collection/processing sub-system. Here, we focus on the fabrication and characterization of the microfluidic chip to multiplex various micrometer-sized beads for economic, disposable, and simultaneous detection of up to six different viruses, microparticles or variants in a single test, and data collection using a commercially available, Wi-Fi-capable, and camera integrated device (Fig. 1).
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COVID-19 , Técnicas Analíticas Microfluídicas , Humanos , Microfluídica , Microesferas , Análisis Costo-Beneficio , SARS-CoV-2 , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/métodosRESUMEN
Prions are unconventional infectious agents composed exclusively of misfolded prion protein (PrP(Sc)), which transmits the disease by propagating its abnormal conformation to the cellular prion protein (PrP(C)). A key characteristic of prions is their species barrier, by which prions from one species can only infect a limited number of other species. Here, we report the generation of infectious prions by interspecies transmission of PrP(Sc) misfolding by in vitro PMCA amplification. Hamster PrP(C) misfolded by mixing with mouse PrP(Sc) generated unique prions that were infectious to wild-type hamsters, and similar results were obtained in the opposite direction. Successive rounds of PMCA amplification result in adaptation of the in vitro-produced prions, in a process reminiscent of strain stabilization observed upon serial passage in vivo. Our results indicate that PMCA is a valuable tool for the investigation of cross-species transmission and suggest that species barrier and strain generation are determined by the propagation of PrP misfolding.
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Proteínas PrPSc/metabolismo , Enfermedades por Prión/transmisión , Priones/metabolismo , Animales , Encéfalo/patología , Sistema Libre de Células , Cricetinae , Ratones , Enfermedades por Prión/patología , Pliegue de Proteína , Especificidad de la EspecieRESUMEN
This study aimed to investigate the recovery of neuromuscular performance using mechanical parameters collected during jump (vertical and horizontal) and strength-power exercises in youth soccer players after official soccer matches. Twenty-one outfield highly trained youth male soccer athletes (age: 18.23 ± 0.73 years; weight: 72.12 ± 6.99 kg; height: 1.78 ± 0.08 m) from two teams competing in the 1st division of U-19 Portuguese National Championship participated in this study. Players completed a battery of physical tests at -2h, +30 min, +24h, and +48h in relation to the match. Countermovement jump height, horizontal jump distance, and bar velocity during the half-squat, bench press, and hip-thrust exercises, at fixed loads, were recorded. Countermovement jump was impaired until 24h post-match (-1.7% from pre to 24h post, p=0.050; ES=-0.82). Half-squat bar velocity was reduced immediately following the match (-6.8 % from pre- p=0.004; ES=-0.64) but recovered at +24h (+2.9%, p=1.00; ES=0.02). Hip-thrust bar velocity was reduced for up to 48h post-match (-7.4% from pre to 48h post, p<0.001; ES=-0.80). No impairments were found in the horizontal jump and bench press at any moment. Our findings show prolonged decrements in strength of the posterior chain following a soccer match, measured in the hip-thrust exercise, while the other exercises displayed faster recovery dynamics.
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Biomaterials may enhance neural repair after spinal cord injury (SCI) and testing their functionality in large animals is essential to achieve successful clinical translation. This work developed a porcine contusion/compression SCI model to investigate the consequences of myelotomy and implantation of fibrin gel containing biofunctionalized carbon microfibers (MFs). Fourteen pigs were distributed in SCI, SCI/myelotomy, and SCI/myelotomy/implant groups. An automated device was used for SCI. A dorsal myelotomy was performed on the lesion site at 1 day post-injury for removing cloths and devitalized tissue. Bundles of MFs coated with a conducting polymer and cell adhesion molecules were embedded in fibrin gel and used to bridge the spinal cord cavity. Reproducible lesions of about 1 cm in length were obtained. Myelotomy and lesion debridement caused no further neural damage compared to SCI alone but had little positive effect on neural regrowth. The MFs/fibrin gel implant facilitated axonal sprouting, elongation, and alignment within the lesion. However, the implant also increased lesion volume and was ineffective in preventing fibrosis, thus precluding functional neural regeneration. Our results indicate that myelotomy and lesion debridement can be advantageously used for implanting MF-based scaffolds. However, the implants need refinement and pharmaceuticals will be necessary to limit scarring.
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Carbono , Traumatismos de la Médula Espinal , Animales , Porcinos , Fibrina , Traumatismos de la Médula Espinal/patología , Prótesis e Implantes , Materiales Biocompatibles , Médula Espinal/patologíaRESUMEN
Roughly 2 billion ha of land are degraded and in need of ecological restoration worldwide. Active restoration frequently involves revegetation, which leads to the dilemma of whether to conduct direct seeding or to plant nursery-grown seedlings. The choice of revegetation method can regulate plant survival and performance, with economic implications that ultimately feed back to our capacity to conduct restoration. We followed a peer-reviewed protocol to develop a systematic map that collates, describes and catalogues the available studies on how seeding compares to planting in achieving restoration targets. We compiled a database with the characteristics of all retrieved studies, which can be searched to identify studies of particular locations and habitats, objectives of restoration, plant material, technical aspects, and outcomes measured. The search was made in eight languages and retrieved 3355 publications, of which 178 were retained. The systematic map identifies research gaps, such as a lack of studies in the global South, in tropical rainforests, and covering a long time period, which represent opportunities to expand field-based research. Additionally, many studies overlooked reporting on important technical aspects such as seed provenance and nursery cultivation methods, and others such as watering or seedling protection were more frequently applied for planting than for seeding, which limits our capacity to learn from past research. Most studies measured outcomes related to the target plants but avoided measuring general restoration outcomes or economic aspects. This represents a relevant gap in research, as the choice of revegetation method is greatly based on economic aspects and the achievement of restoration goals goes beyond the establishment of plants. Finally, we identified a substantial volume of studies conducted in temperate regions and over short periods (0-5 y). This research cluster calls for a future in-depth synthesis, potentially through meta-analysis, to reveal the overall balance between seeding and planting and assess whether the response to this question is mediated by species traits, environmental characteristics, or technical aspects. Besides identifying research clusters and gaps, the systematic map database allows managers to find the most relevant scientific literature on the appropriateness of seeding vs. planting for particular conditions, such as certain species or habitats.
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Ecosistema , Plantas , Plantones , SemillasRESUMEN
Premature Ventricular Complexes (PVCs) refer to electrical activity arising from ventricles resulting in ventricular contraction independent of the native rhythm. PVCs by themselves are common in the general population but based on the origin of the PVCs, either related to anatomical or electrical substrate, the disease process has a widely varied presentation and prognosis. The clinical presentation of symptoms may vary from being extremely benign, or very severe (malignant). Benign PVCs include those that are asymptomatic or induce very mild symptoms including palpitations, lightheadedness, chest discomfort, or the sensation of skipped beats. The middle range of PVCs present as heart failure or heart failure complicated by PVCs. The malignant variety may present as syncope, or sudden cardiac death. In this review we describe the multiple facets of PVC presentation and strategies of clinical management.
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There are sex differences in microglia, which can maintain sex-related gene expression and functional differences in the absence of circulating sex steroids. The angiotensin type 2 (AT2) receptors mediate anti-inflammatory actions in different tissues, including brain. In mice, we performed RT-PCR analysis of microglia isolated from adult brains and RNA scope in situ hybridization from males, females, ovariectomized females, orchiectomized males and brain masculinized females. We also compared wild type and AT2 knockout mice. The expression of AT2 receptors in microglial cells showed sex differences with much higher AT2 mRNA expression in females than in males, and this was not dependent on circulating gonadal hormones, as observed using ovariectomized females, brain masculinized females and orchiectomized males. These results suggest genomic reasons, possibly related to sex chromosome complement, for sex differences in AT2 expression in microglia, as the AT2 receptor gene is located in the X chromosome. Furthermore, sex differences in expression of AT2 receptors were associated to sex differences in microglial expression of key anti-inflammatory cytokines such as interleukin-10 and pro-inflammatory cytokines such as interleukin-1ß and interleukin-6. In conclusion, sex differences in microglial AT2 receptor expression appear as a major factor contributing to sex differences in the neuroinflammatory responses beyond the effects of circulating steroids.
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Microglía , Receptor de Angiotensina Tipo 2 , Angiotensinas/metabolismo , Angiotensinas/farmacología , Animales , Antiinflamatorios/farmacología , Citocinas/metabolismo , Estrógenos/metabolismo , Estrógenos/farmacología , Femenino , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Microglía/metabolismo , ARN/metabolismo , ARN Mensajero/metabolismo , Receptor de Angiotensina Tipo 2/genética , Receptor de Angiotensina Tipo 2/metabolismoRESUMEN
Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest virus antigenic complex classified as belonging to the genus Alphavirus of the family Togaviridae. These viruses cause human disease, with sudden fever and joint inflammation that can persist for long periods. CHIKV is the causative agent of large outbreaks worldwide, and MAYV infection represents a growing public health concern in Latin America, causing sporadic cases and geographically limited outbreaks. Considering the relationship between CHIKV and MAYV, the present study aimed to evaluate if preexisting CHIKV immunity protects against MAYV infection. Immunocompetent C57BL/6 mice were intraperitoneally infected with CHIKV and, 4 weeks later, they were infected with MAYV in their hind paw. We observed that the preexistence of CHIKV immunity conferred partial cross-protection against secondary MAYV infection, reducing disease severity, tissue viral load, and histopathological scores. Interestingly, CHIKV antibodies from humans and mice showed low cross-neutralization to MAYV, but neutralizing activity significantly increased after secondary infection. Furthermore, depletion of adaptive immune cells (CD4+ T, CD8+ T, and CD19+ B cells) did not alter the cross-protection phenotype, suggesting that distinct cell subsets or a combination of adaptive immune cells stimulated by CHIKV are responsible for the partial cross-protection against MAYV. The reduction of proinflammatory cytokines, such as interferon gamma (IFN-γ), in animals secondarily infected by MAYV, suggests a role for innate immunity in cross-protection. Our findings shed light on how preexisting immunity to arthritogenic alphaviruses may affect secondary infection, which may further develop relevant influence in disease outcome and viral transmission. IMPORTANCE Mosquito-borne viruses have a worldwide impact, especially in tropical climates. Chikungunya virus has been present mostly in developing countries, causing millions of infections, while Mayaro virus, a close relative, has been limited to the Caribbean and tropical regions of Latin America. The potential emergence and spread of Mayaro virus to other high-risk areas have increased the scientific community's attention to an imminent worldwide epidemic. Here, we designed an experimental protocol of chikungunya and Mayaro virus mouse infection, which develops a measurable and quantifiable disease that allows us to make inferences about potential immunological effects during secondary virus infection. Our results demonstrate that previous chikungunya virus infection is able to reduce the severity of clinical outcomes during secondary Mayaro infection. We provide scientific understanding of immunological features during secondary infection with the closely related virus, thus assisting in better comprehending viral transmission and the pathological outcome of these diseases.
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Infecciones por Alphavirus/inmunología , Infecciones por Alphavirus/prevención & control , Virus Chikungunya/inmunología , Protección Cruzada/inmunología , Alphavirus/inmunología , Infecciones por Alphavirus/patología , Animales , Anticuerpos Antivirales/inmunología , Fiebre Chikungunya/virología , Modelos Animales de Enfermedad , Epidemias , Femenino , Inflamación , Ratones , Ratones Endogámicos C57BL , Carga ViralRESUMEN
Viral stability under stress conditions may directly affect viral dissemination, seasonality, and pathogenesis. We exposed airborne viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mumps virus, coxsackievirus B5, human rhinovirus A16, and respiratory syncytial virus, to different temperatures, UV light exposure time, pH values, and osmotic pressures and measured the remaining viral infectivity. Reduced thermal stability was observed for coxsackievirus B5 at 45 °C, while SARS-CoV-2 demonstrated residual infectivity at 55 °C. UV light exposure was an efficient means of viral inactivation but was less efficient for non-enveloped viruses. Rhinovirus A16 and respiratory syncytial virus demonstrated extreme sensitivity to acid conditions, while SARS-CoV-2, rhinovirus A16, and respiratory syncytial virus were unstable in an alkaline environment. The information obtained in this study will be useful for the development of viral inactivation methods and may be correlated with epidemiological and seasonal viral characteristics.
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COVID-19 , Virosis , Virus , Humanos , SARS-CoV-2 , Inactivación de VirusRESUMEN
The knowledge about amino acid metabolism in trypanosomatids is a valuable source of new therapeutic targets. l-arginine is an essential amino acid for Leishmania parasites, and it participates in the synthesis of polyamines, a group of essential nutrients used for nucleic acids, proteins biosynthesis, and redox modulation necessary for proliferation. In the present study, we evaluated the effect of changes in the availability of this amino acid on promastigotes and intracellular amastigotes on U937 macrophages and showed that the absence of l-arginine in culture medium negatively influences the growth and infectivity of Leishmania (Viannia) braziliensis, causing a decrease in the percentage of the infected cells and parasite load tested through light microscopy. In addition, the absence of l-arginine resulted in the parasite's inability to regulate its reactive oxygen species (ROS) production, which persisted for up to 24 h by flow cytometry following the probe H2DCF-DA dye. Moreover, the differentiation of promastigote to amastigote in axenic culture was more significant at low concentrations of l-arginine suggesting that this depletion induces a stress environment to increase this transformation under axenic conditions. No association was established between the availability of l-arginine and the effectiveness of antileishmanial drugs. All these results confirm the importance of l-arginine in L. braziliensis life cycle vital processes, such as its replication and infectivity, as documented in other Leishmania species. Based on these results, we proposed that the l-arginine uptake/metabolism route is possible in exploring new antileishmanial drugs.
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Leishmania braziliensis , Leishmania , Ácidos Nucleicos , Animales , Ratones , Especies Reactivas de Oxígeno/metabolismo , Arginina , Poliaminas/metabolismo , Poliaminas/farmacología , Ácidos Nucleicos/farmacología , Ratones Endogámicos BALB CRESUMEN
The indiscriminate use of plastic in food packaging contributes significantly to environmental pollution, promoting the search for more eco-friendly alternatives for the food industry. This work studied five formulations (T1-T5) of biodegradable cassava starch/gelatin films. The results showed the presence of the starch/gelatin functional groups by FT-IR spectroscopy. Differential scanning calorimetry (DSC) showed a thermal reinforcement after increasing the amount of gelatin in the formulations, which increased the crystallization temperature (Tc) from 190 °C for the starch-only film (T1) to 206 °C for the film with 50/50 starch/gelatin (T3). It also exhibited a homogeneous surface morphology, as evidenced by scanning electron microscopy (SEM). However, an excess of gelatin showed low compatibility with starch in the 25/75 starch/gelatin film (T4), evidenced by the low Tc definition and very rough and fractured surface morphology. Increasing gelatin ratio also significantly increased the strain (from 2.9 ± 0.5% for T1 to 285.1 ± 10.0% for T5) while decreasing the tensile strength (from 14.6 ± 0.5 MPa for T1 to 1.5 ± 0.3 MPa for T5). Water vapor permeability (WVP) increased, and water solubility (WS) also decreased with gelatin mass rising in the composites. On the other hand, opacity did not vary significantly due to the films' cassava starch and gelatin ratio. Finally, optimizing the mechanical and water barrier properties resulted in a mass ratio of 53/47 cassava starch/gelatin as the most appropriate for their application in food packaging, indicating their usefulness in the food-packaging industry.
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Embalaje de Alimentos , Almidón , Animales , Pollos , Gelatina/química , Permeabilidad , Espectroscopía Infrarroja por Transformada de Fourier , Almidón/química , Resistencia a la TracciónRESUMEN
Scaffolds based on biopolymers and nanomaterials with appropriate mechanical properties and high biocompatibility are desirable in tissue engineering. Therefore, polylactic acid (PLA) nanocomposites were prepared with ceramic nanobioglass (PLA/n-BGs) at 5 and 10 wt.%. Bioglass nanoparticles (n-BGs) were prepared using a sol-gel methodology with a size of ca. 24.87 ± 6.26 nm. In addition, they showed the ability to inhibit bacteria such as Escherichia coli (ATCC 11775), Vibrio parahaemolyticus (ATCC 17802), Staphylococcus aureus subsp. aureus (ATCC 55804), and Bacillus cereus (ATCC 13061) at concentrations of 20 w/v%. The analysis of the nanocomposite microstructures exhibited a heterogeneous sponge-like morphology. The mechanical properties showed that the addition of 5 wt.% n-BG increased the elastic modulus of PLA by ca. 91.3% (from 1.49 ± 0.44 to 2.85 ± 0.99 MPa) and influenced the resorption capacity, as shown by histological analyses in biomodels. The incorporation of n-BGs decreased the PLA crystallinity (from 7.1% to 4.98%) and increased the glass transition temperature (Tg) from 53 °C to 63 °C. In addition, the n-BGs increased the thermal stability due to the nanoparticle's intercalation between the polymeric chains and the reduction in their movement. The histological implantation of the nanocomposites and the cell viability with HeLa cells higher than 80% demonstrated their biocompatibility character with a greater resorption capacity than PLA. These results show the potential of PLA/n-BGs nanocomposites for biomedical applications, especially for long healing processes such as bone tissue repair and avoiding microbial contamination.
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Nanocompuestos , Poliésteres , Escherichia coli , Células HeLa , Humanos , Nanocompuestos/química , Poliésteres/química , Poliésteres/farmacología , Ingeniería de TejidosRESUMEN
Mayaro virus (MAYV) is an arbovirus that circulates in Latin America and is emerging as a potential threat to public health. Infected individuals develop Mayaro fever, a severe inflammatory disease characterized by high fever, rash, arthralgia, myalgia and headache. The disease is often associated with a prolonged arthralgia mediated by a chronic inflammation that can last months. Although the immune response against other arboviruses, such as chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV), has been extensively studied, little is known about the pathogenesis of MAYV infection. In this study, we established models of MAYV infection in macrophages and in mice and found that MAYV can replicate in bone marrow-derived macrophages and robustly induce expression of inflammasome proteins, such as NLRP3, ASC, AIM2, and Caspase-1 (CASP1). Infection performed in macrophages derived from Nlrp3-/-, Aim2-/-, Asc-/-and Casp1/11-/-mice indicate that the NLRP3, but not AIM2 inflammasome is essential for production of inflammatory cytokines, such as IL-1ß. We also determined that MAYV triggers NLRP3 inflammasome activation by inducing reactive oxygen species (ROS) and potassium efflux. In vivo infections performed in inflammasome-deficient mice indicate that NLRP3 is involved with footpad swelling, inflammation and pain, establishing a role of the NLRP3 inflammasome in the MAYV pathogenesis. Accordingly, we detected higher levels of caspase1-p20, IL-1ß and IL-18 in the serum of MAYV-infected patients as compared to healthy individuals, supporting the participation of the NLRP3-inflammasome during MAYV infection in humans.
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Infecciones por Alphavirus/inmunología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Adulto , Anciano , Infecciones por Alphavirus/metabolismo , Animales , Proteínas Portadoras/metabolismo , Caspasa 1/metabolismo , Virus Chikungunya/metabolismo , Virus del Dengue/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Inflamasomas/inmunología , Inflamación/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Especies Reactivas de Oxígeno/metabolismo , Togaviridae/patogenicidad , Virus Zika/metabolismoRESUMEN
The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.
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Artritis/inmunología , Fiebre Chikungunya/inmunología , Virus Chikungunya/fisiología , Citidina Desaminasa/inmunología , Proteínas/inmunología , Replicación Viral/inmunología , Adulto , Animales , Artritis/patología , Artritis/virología , Fiebre Chikungunya/patología , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Femenino , Fiebre/inmunología , Fiebre/patología , Fiebre/virología , Estudios de Seguimiento , Humanos , Interleucina-1beta/inmunología , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/inmunologíaRESUMEN
Recently, the interest in donkey milk has increased considerably because it proved high nutritive and functional values of their ingredients. Its chemical composition is widely studied, but its microbiota, especially lactic acid bacteria, remains less studied. This study focuses on analyzing, isolating, and identifying lactic acid bacteria and evaluating their capacity to produce biomolecules with antibacterial activity. Among 44 strains identified, 43 are Gram-positive, and most are catalase-negative and cocci-shaped. Five strains were selected to evaluate their antibacterial activity against Listeria monocytogenes, Staphylococcus aureus, and Escherichia coli. Different induction methods allowed to amplify the antibacterial effects against these pathogenic strains.
Asunto(s)
Aerococcus/aislamiento & purificación , Antibacterianos/farmacología , Medios de Cultivo Condicionados/farmacología , Enterococcus faecalis/aislamiento & purificación , Enterococcus/aislamiento & purificación , Leuconostoc mesenteroides/aislamiento & purificación , Aerococcus/química , Aerococcus/metabolismo , Animales , Industria Lechera/métodos , Enterococcus/química , Enterococcus/metabolismo , Enterococcus faecalis/química , Enterococcus faecalis/metabolismo , Equidae , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/patogenicidad , Femenino , Microbiología de Alimentos , Lactancia/fisiología , Leuconostoc mesenteroides/química , Leuconostoc mesenteroides/metabolismo , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Listeria monocytogenes/patogenicidad , Pruebas de Sensibilidad Microbiana , Leche/microbiología , Marruecos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/patogenicidadRESUMEN
Forage dry matter is the main source of nutrients in the diet of ruminant animals. Thus, this trait is evaluated in most forage breeding programs with the objective of increasing the yield. Novel solutions combining unmanned aerial vehicles (UAVs) and computer vision are crucial to increase the efficiency of forage breeding programs, to support high-throughput phenotyping (HTP), aiming to estimate parameters correlated to important traits. The main goal of this study was to propose a convolutional neural network (CNN) approach using UAV-RGB imagery to estimate dry matter yield traits in a guineagrass breeding program. For this, an experiment composed of 330 plots of full-sib families and checks conducted at Embrapa Beef Cattle, Brazil, was used. The image dataset was composed of images obtained with an RGB sensor embedded in a Phantom 4 PRO. The traits leaf dry matter yield (LDMY) and total dry matter yield (TDMY) were obtained by conventional agronomic methodology and considered as the ground-truth data. Different CNN architectures were analyzed, such as AlexNet, ResNeXt50, DarkNet53, and two networks proposed recently for related tasks named MaCNN and LF-CNN. Pretrained AlexNet and ResNeXt50 architectures were also studied. Ten-fold cross-validation was used for training and testing the model. Estimates of DMY traits by each CNN architecture were considered as new HTP traits to compare with real traits. Pearson correlation coefficient r between real and HTP traits ranged from 0.62 to 0.79 for LDMY and from 0.60 to 0.76 for TDMY; root square mean error (RSME) ranged from 286.24 to 366.93 kg·ha-1 for LDMY and from 413.07 to 506.56 kg·ha-1 for TDMY. All the CNNs generated heritable HTP traits, except LF-CNN for LDMY and AlexNet for TDMY. Genetic correlations between real and HTP traits were high but varied according to the CNN architecture. HTP trait from ResNeXt50 pretrained achieved the best results for indirect selection regardless of the dry matter trait. This demonstrates that CNNs with remote sensing data are highly promising for HTP for dry matter yield traits in forage breeding programs.