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We integrate a spatial light modulator-based dispersion controller into a cascaded four-wave mixing (CFWM) system. By tuning the group delay dispersion (GDD) and fourth-order dispersion (FOD) terms, we control the CFWM phase matching and demonstrate an output bandwidth tuning of over 3.3×. At the maximum bandwidth, our system covers the telecommunications S-, C-, and L-bands (1466-1641 nm) with an average output power of 300 mW, which is contained in 52 individual lines spaced 374 GHz apart. This method represents a reconfigurable alternative to photonic crystal fibers for dispersion engineering and allows for the use of step-index fiber and customizable power spectral density (PSD) profiles.
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To begin to optimize the immunization routes for our reported PLGA-rMOMP nanovaccine [PLGA-encapsulated Chlamydia muridarum (Cm) recombinant major outer membrane protein (rMOMP)], we compared two prime-boost immunization strategies [subcutaneous (SC) and intramuscular (IM-p) prime routes followed by two SC-boosts)] to evaluate the nanovaccine-induced protective efficacy and immunogenicity in female BALB/c mice. Our results showed that mice immunized via the SC and IM-p routes were protected against a Cm genital challenge by a reduction in bacterial burden and with fewer bacteria in the SC mice. Protection of mice correlated with rMOMP-specific Th1 (IL-2 and IFN-γ) and not Th2 (IL-4, IL-9, and IL-13) cytokines, and CD4+ memory (CD44highCD62Lhigh) T-cells, especially in the SC mice. We also observed higher levels of IL-1α, IL-6, IL-17, CCL-2, and G-CSF in SC-immunized mice. Notably, an increase of cytokines/chemokines was seen after the challenge in the SC, IM-p, and control mice (rMOMP and PBS), suggesting a Cm stimulation. In parallel, rMOMP-specific Th1 (IgG2a and IgG2b) and Th2 (IgG1) serum, mucosal, serum avidity, and neutralizing antibodies were more elevated in SC than in IM-p mice. Overall, the homologous SC prime-boost immunization of mice induced enhanced cellular and antibody responses with better protection against a genital challenge compared to the heterologous IM-p.
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Anticuerpos Antibacterianos , Vacunas Bacterianas , Infecciones por Chlamydia , Chlamydia muridarum , Citocinas , Ratones Endogámicos BALB C , Animales , Femenino , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Chlamydia muridarum/inmunología , Citocinas/metabolismo , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/inmunología , Ratones , Anticuerpos Antibacterianos/sangre , Inyecciones Intramusculares , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Inmunización Secundaria , Modelos Animales de Enfermedad , Inmunogenicidad Vacunal , Inyecciones Subcutáneas , Nanopartículas/administración & dosificación , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/administración & dosificación , Eficacia de las Vacunas , Células TH1/inmunología , NanovacunasRESUMEN
Malate dehydrogenase (MDH) is a key enzyme in mammalian metabolic pathways in cytosolic and mitochondrial compartments. Regulation of MDH through phosphorylation remains an underexplored area. In this review we consolidate evidence supporting the potential role of phosphorylation in modulating the function of mammalian MDH. Parallels are drawn with the phosphorylation of lactate dehydrogenase, a homologous enzyme, to reveal its regulatory significance and to suggest a similar regulatory strategy for MDH. Comprehensive mining of phosphorylation databases, provides substantial experimental (primarily mass spectrometry) evidence of MDH phosphorylation in mammalian cells. Experimentally identified phosphorylation sites are overlaid with MDH's functional domains, offering perspective on how these modifications could influence enzyme activity. Preliminary results are presented from phosphomimetic mutations (serine/threonine residues changed to aspartate) generated in recombinant MDH proteins serving as a proof of concept for the regulatory impact of phosphorylation. We also examine and highlight several approaches to probe the structural and cellular impact of phosphorylation. This review highlights the need to explore the dynamic nature of MDH phosphorylation and calls for identifying the responsible kinases and the physiological conditions underpinning this modification. The synthesis of current evidence and experimental data aims to provide insights for future research on understanding MDH regulation, offering new avenues for therapeutic interventions in metabolic disorders and cancer.
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Introduction: Interleukin-10 (IL-10) is a key anti-inflammatory mediator in protecting host from over-exuberant responses to pathogens and play important roles in wound healing, autoimmunity, cancer, and homeostasis. However, its application as a therapeutic agent for biomedical applications has been limited due to its short biological half-life. Therefore, it is important to prolong the half-life of IL-10 to replace the current therapeutic application, which relies on administering large and repeated dosages. Therefore, not a cost-effective approach. Thus, studies that aim to address this type of challenges are always in need. Methods: Recombinant IL-10 was encapsulated in biodegradable nanoparticles (Poly-(Lactic-co-Glycolic Acid) and Chitosan)) by the double emulsion method and then characterized for size, surface charge, thermal stability, cytotoxicity, in vitro release, UV-visible spectroscopy, and Fourier Transform-Infrared Spectroscopy as well as evaluated for its anti-inflammatory effects. Bioactivity of encapsulated IL-10 was evaluated in vitro using J774A.1 macrophage cell-line and in vivo using BALB/c mice. Inflammatory cytokines (IL-6 and TNF-α) were quantified from culture supernatants using specific enzyme-linked immunosorbent assay (ELISA), and significance was analyzed using ANOVA. Results: We obtained a high 96% encapsulation efficiency with smooth encapsulated IL-10 nanoparticles of ~100-150 nm size and release from nanoparticles as measurable to 22 days. Our result demonstrated that encapsulated IL-10 was biocompatible and functional by reducing the inflammatory responses induced by LPS in macrophages. Of significance, we also proved the functionality of encapsulated IL-10 by its capacity to reduce inflammation in BALB/c mice as provoked by Chlamydia trachomatis, an inflammatory sexually transmitted infectious bacterium. Discussion: Collectively, our results show the successful IL-10 encapsulation, slow release to prolong its biological half-life and reduce inflammatory cytokines IL-6 and TNF production in vitro and in mice. Our results serve as proof of concept to further explore the therapeutic prospective of encapsulated IL-10 for biomedical applications, including inflammatory diseases.
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Quitosano , Nanopartículas , Ratones , Animales , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Interleucina-10 , Ácido Láctico/química , Quitosano/química , Ácido Poliglicólico/química , Interleucina-6 , Citocinas , Nanopartículas/química , Inflamación/tratamiento farmacológico , Chlamydia trachomatis , Antiinflamatorios/farmacologíaRESUMEN
Livestock contributes approximately one-third of global anthropogenic methane (CH4 ) emissions. Quantifying the spatial and temporal variations of these emissions is crucial for climate change mitigation. Although country-level information is reported regularly through national inventories and global databases, spatially explicit quantification of century-long dynamics of CH4 emissions from livestock has been poorly investigated. Using the Tier 2 method adopted from the 2019 Refinement to 2006 IPCC guidelines, we estimated CH4 emissions from global livestock at a spatial resolution of 0.083° (~9 km at the equator) during the period 1890-2019. We find that global CH4 emissions from livestock increased from 31.8 [26.5-37.1] (mean [minimum-maximum of 95% confidence interval) Tg CH4 yr-1 in 1890 to 131.7 [109.6-153.7] Tg CH4 yr-1 in 2019, a fourfold increase in the past 130 years. The growth in global CH4 emissions mostly occurred after 1950 and was mainly attributed to the cattle sector. Our estimate shows faster growth in livestock CH4 emissions as compared to the previous Tier 1 estimates and is ~20% higher than the estimate from FAOSTAT for the year 2019. Regionally, South Asia, Brazil, North Africa, China, the United States, Western Europe, and Equatorial Africa shared the majority of the global emissions in the 2010s. South Asia, tropical Africa, and Brazil have dominated the growth in global CH4 emissions from livestock in the recent three decades. Changes in livestock CH4 emissions were primarily associated with changes in population and national income and were also affected by the policy, diet shifts, livestock productivity improvement, and international trade. The new geospatial information on the magnitude and trends of livestock CH4 emissions identifies emission hotspots and spatial-temporal patterns, which will help to guide meaningful CH4 mitigation practices in the livestock sector at both local and global scales.
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Ganado , Metano , Animales , Bovinos , Cambio Climático , Comercio , InternacionalidadRESUMEN
Recently we reported the immune-potentiating capacity of a Chlamydia nanovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against a Chlamydia muridarum genital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge with C. muridarum on day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4+ proliferating T-cells and memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralized C. muridarum infectivity of McCoy fibroblasts in-vitro that correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genital C. muridarum. We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genital Chlamydia and advances the potential towards acquiring a nano-based Chlamydia vaccine.
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Péptidos Catiónicos Antimicrobianos/metabolismo , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Infecciones por Chlamydia/prevención & control , Chlamydia muridarum/efectos de los fármacos , Preparaciones de Acción Retardada/administración & dosificación , Genitales/efectos de los fármacos , Nanopartículas/química , Adyuvantes Inmunológicos , Animales , Anticuerpos Antibacterianos/sangre , Péptidos Catiónicos Antimicrobianos/administración & dosificación , Péptidos Catiónicos Antimicrobianos/química , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/genética , Vacunas Bacterianas/administración & dosificación , Citocinas/inmunología , Femenino , Genitales/microbiología , Ratones , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , VacunaciónRESUMEN
Capsules are one of the major solid dosage forms available in a variety of compositions and shapes. Developments in this dosage form are not new, but the production of non-gelatin capsules is a recent trend. In pharmaceutical as well as other biomedical research, alginate has great versatility. On the other hand, the use of inorganic material to enhance material strength is a common research topic in tissue engineering. The research presented here is a combination of qualities of alginate and montmorillonite (MMT). These two materials were used in this research to produce a soft non-gelatin modified-release capsule. Moreover, the research describes a facile benchtop production of these capsules. The produced capsules were critically analyzed for their appearance confirming resemblance with marketed capsules, functionality in terms of drug encapsulation, as well as release and durability.
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The association of amyotrophic lateral sclerosis and pancreatic cancer is rare. Amyotrophic lateral sclerosis is a neurodegenerative disease characterised by pure motor symptoms in the form of progressive muscle weakness and wasting, and can involve the bulbar and respiratory muscles, leading to significant morbidity. Successful surgery for patients with amyotrophic lateral sclerosis for pancreatic cancer has rarely been reported. Surgery in such patients is a dual-edged sword and is decided based on risk-benefit ratio. Patients are at high risk for general anaesthesia because of muscular weakness, increased sensitivity to muscle relaxants and certain anaesthetic drugs. There is a high chance of prolonged postoperative ventilatory support, aspiration pneumonia and pulmonary complications. We report a patient with cancer of the head of the pancreas who underwent successful elective pancreaticoduodenectomy.
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Esclerosis Amiotrófica Lateral/complicaciones , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/rehabilitación , Atención Perioperativa/métodos , Complicaciones Posoperatorias/prevención & control , Toma de Decisiones Clínicas , Ambulación Precoz , Humanos , Masculino , Persona de Mediana Edad , Páncreas/diagnóstico por imagen , Páncreas/patología , Páncreas/cirugía , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico , Pancreaticoduodenectomía/efectos adversos , Modalidades de Fisioterapia , Complicaciones Posoperatorias/etiología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias PancreáticasRESUMEN
Recent developments in diffuse reflectance soil spectroscopy have increasingly focused on building and using large soil spectral libraries with the purpose of supporting many activities relevant to monitoring, mapping and managing soil resources. A potential limitation of using a mid-infrared (MIR) spectral library developed by another laboratory is the need to account for inherent differences in the signal strength at each wavelength associated with different instrumental and environmental conditions. Here we apply predictive models built using the USDA National Soil Survey Center-Kellogg Soil Survey Laboratory (NSSC-KSSL) MIR spectral library (n = 56,155) to samples sets of European and US origin scanned on a secondary spectrometer to assess the need for calibration transfer using a piecewise direct standardization (PDS) approach in transforming spectra before predicting carbon cycle relevant soil properties (bulk density, CaCO3, organic carbon, clay and pH). The European soil samples were from the land use/cover area frame statistical survey (LUCAS) database available through the European Soil Data Center (ESDAC), while the US soil samples were from the National Ecological Observatory Network (NEON). Additionally, the performance of the predictive models on PDS transfer spectra was tested against the direct calibration models built using samples scanned on the secondary spectrometer. On independent test sets of European and US origin, PDS improved predictions for most but not all soil properties with memory based learning (MBL) models generally outperforming partial least squares regression and Cubist models. Our study suggests that while good-to-excellent results can be obtained without calibration transfer, for most of the cases presented in this study, PDS was necessary for unbiased predictions. The MBL models also outperformed the direct calibration models for most of the soil properties. For laboratories building new spectroscopy capacity utilizing existing spectral libraries, it appears necessary to develop calibration transfer using PDS or other calibration transfer techniques to obtain the least biased and most precise predictions of different soil properties.
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Nitrous oxide (N2O), like carbon dioxide, is a long-lived greenhouse gas that accumulates in the atmosphere. Over the past 150 years, increasing atmospheric N2O concentrations have contributed to stratospheric ozone depletion1 and climate change2, with the current rate of increase estimated at 2 per cent per decade. Existing national inventories do not provide a full picture of N2O emissions, owing to their omission of natural sources and limitations in methodology for attributing anthropogenic sources. Here we present a global N2O inventory that incorporates both natural and anthropogenic sources and accounts for the interaction between nitrogen additions and the biochemical processes that control N2O emissions. We use bottom-up (inventory, statistical extrapolation of flux measurements, process-based land and ocean modelling) and top-down (atmospheric inversion) approaches to provide a comprehensive quantification of global N2O sources and sinks resulting from 21 natural and human sectors between 1980 and 2016. Global N2O emissions were 17.0 (minimum-maximum estimates: 12.2-23.5) teragrams of nitrogen per year (bottom-up) and 16.9 (15.9-17.7) teragrams of nitrogen per year (top-down) between 2007 and 2016. Global human-induced emissions, which are dominated by nitrogen additions to croplands, increased by 30% over the past four decades to 7.3 (4.2-11.4) teragrams of nitrogen per year. This increase was mainly responsible for the growth in the atmospheric burden. Our findings point to growing N2O emissions in emerging economies-particularly Brazil, China and India. Analysis of process-based model estimates reveals an emerging N2O-climate feedback resulting from interactions between nitrogen additions and climate change. The recent growth in N2O emissions exceeds some of the highest projected emission scenarios3,4, underscoring the urgency to mitigate N2O emissions.
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Óxido Nitroso/análisis , Óxido Nitroso/metabolismo , Agricultura , Atmósfera/química , Productos Agrícolas/metabolismo , Actividades Humanas , Internacionalidad , Nitrógeno/análisis , Nitrógeno/metabolismoRESUMEN
Here, we report that a cationic bimetallic site consisting of one Pd and three Zn atoms (Pd1Zn3) supported on ZnO (Pd1Zn3/ZnO) exhibits an extraordinarily high catalytic activity for the generation of H2 through methanol partial oxidation (MPO) that is 2-3 orders of magnitude higher than that of a metallic Pd-Zn site on Pd-Zn nanoalloy (Pd-Zn/ZnO). Computational studies uncovered that the positively charged Pd atom of the subnanometer Pd1Zn3 bimetallic site largely decreases the activation barrier for dehydrogenation of methanol as compared to a metallic Pd atom of Pd-Zn alloy, thus switching the rate-determining step of MPO from methanol dehydrogenation over a Pd-Zn alloy with high barrier to the O2 dissociation step on a cationic Pd1Zn3 site with a low barrier, which is supported by our kinetics studies. The significantly higher catalytic activity and selectivity for H2 production over a cationic bimetallic site suggest a new approach to design bimetallic catalysts.
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Vaccine developmental strategies are utilizing antigens encapsulated in biodegradable polymeric nanoparticles. Here, we developed a Chlamydia nanovaccine (PLGA-rMOMP) by encapsulating its recombinant major outer membrane protein (rMOMP) in the extended-releasing and self-adjuvanting PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. PLGA-rMOMP was small (nanometer size), round and smooth, thermally stable, and exhibited a sustained release of rMOMP. Stimulation of mouse primary dendritic cells (DCs) with PLGA-rMOMP augmented endosome processing, induced Th1 cytokines (IL-6 and IL-12p40), and expression of MHC-II and co-stimulatory (CD40, CD80, and CD86) molecules. BALB/c mice immunized with PLGA-rMOMP produced enhanced CD4+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) phenotypes and functional antigen-specific serum IgG antibodies. In vivo biodistribution of PLGA-rMOMP revealed its localization within lymph nodes, suggesting migration from the injection site via DCs. Our data provide evidence that the PLGA (85:15) nanovaccine activates DCs and augments Chlamydia-specific rMOMP adaptive immune responses that are worthy of efficacy testing.
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Inmunidad Adaptativa/genética , Proteínas de la Membrana Bacteriana Externa/genética , Nanopartículas/química , Vacunas/inmunología , Inmunidad Adaptativa/inmunología , Animales , Proteínas de la Membrana Bacteriana Externa/inmunología , Antígenos CD4/química , Antígenos CD4/inmunología , Chlamydia/genética , Chlamydia/inmunología , Chlamydia/patogenicidad , Células Dendríticas/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Receptores de Hialuranos/química , Receptores de Hialuranos/inmunología , Subunidad p40 de la Interleucina-12/genética , Subunidad p40 de la Interleucina-12/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Selectina L/química , Selectina L/inmunología , Ratones , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/inmunología , Linfocitos T/inmunología , Vacunas/genéticaRESUMEN
The immunopathology of chlamydial diseases is exacerbated by a broad-spectrum of inflammatory mediators, which we reported are inhibited by IL-10 in macrophages. However, the chlamydial protein moiety that induces the inflammatory mediators and the mechanisms by which IL-10 inhibits them are unknown. We hypothesized that Chlamydia major outer membrane protein (MOMP) mediates its disease pathogenesis, and the suppressor of cytokine signaling (SOCS)1 and SOCS3 proteins are mediators of the IL-10 inhibitory actions. Our hypothesis was tested by exposing mouse J774 macrophages to chlamydial stimulants (live Chlamydia muridarum and MOMP) with and without IL-10. MOMP significantly induced several inflammatory mediators (IL-6, IL-12p40, CCL5, CXCL10), which were dose-dependently inhibited by IL-10. Chlamydial stimulants induced the mRNA gene transcripts and protein expression of SOCS1 and SOCS3, with more SOCS3 expression. Notably, IL-10 reciprocally regulated their expression by reducing SOCS1 and increasing SOCS3. Specific inhibitions of MAPK pathways revealed that p38, JNK, and MEK1/2 are required for inducing inflammatory mediators as well as SOCS1 and SOCS3. Chlamydial stimulants triggered an M1 pro-inflammatory phenotype evidently by an enhanced nos2 (M1 marker) expression, which was skewed by IL-10 towards a more M2 anti-inflammatory phenotype by the increased expression of mrc1 and arg1 (M2 markers) and the reduced SOCS1/SOCS3 ratios. Neutralization of endogenously produced IL-10 augmented the secretion of inflammatory mediators, reduced SOCS3 expression, and skewed the chlamydial M1 to an M2 phenotype. Inhibition of proteasome degradation increased TNF but decreased IL-10, CCL5, and CXCL10 secretion by suppressing SOCS1 and SOCS3 expressions and dysregulating their STAT1 and STAT3 transcription factors. Our data show that SOCS1 and SOCS3 are regulators of IL-10 inhibitory actions, and underscore SOCS proteins as therapeutic targets for IL-10 control of inflammation for Chlamydia and other bacterial inflammatory diseases.
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Proteínas de la Membrana Bacteriana Externa/toxicidad , Chlamydia muridarum/patogenicidad , Inflamación/metabolismo , Interleucina-10/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Animales , Línea Celular , Citometría de Flujo , Ratones , Microscopía Fluorescente , Proteína 1 Supresora de la Señalización de Citocinas/genética , Proteína 3 Supresora de la Señalización de Citocinas/genéticaRESUMEN
Fusarium crown rot (FCR) is one of the most important diseases of wheat (Triticum aestivum L.). FCR is mainly caused by the fungal pathogens Fusarium culmorum and F. pseudograminearum. In order to identify new sources of resistance to FCR and to dissect the complexity of FCR resistance, a panel of 161 wheat accessions was phenotyped under growth room (GR) and greenhouse conditions (GH). Analysis of variance showed significant differences in crown rot development among wheat accessions and high heritability of genotype-environment interactions for GR (0.96) and GH (0.91). Mixed linear model analysis revealed seven novel quantitative trait loci (QTLs) linked to F. culmorum on chromosomes 2AL, 3AS, 4BS, 5BS, 5DS, 5DL and 6DS for GR and eight QTLs on chromosomes on 3AS, 3BS, 3DL, 4BS (2), 5BS, 6BS and 6BL for GH. Total phenotypic variances (R²) explained by the QTLs linked to GR and GH were 48% and 59%, respectively. In addition, five favorable epistasis interactions among the QTLs were detected for both GR and GH with and without main effects. Epistatic interaction contributed additional variation up to 21% under GR and 7% under GH indicating strong effects of environment on the expression of QTLs. Our results revealed FCR resistance responses in wheat to be complex and controlled by multiple QTLs.
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Resistencia a la Enfermedad/genética , Fusarium/patogenicidad , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Triticum/genética , Triticum/microbiología , Mapeo Cromosómico , Cromosomas de las Plantas , Simulación por Computador , Epistasis Genética , Interacción Gen-Ambiente , Estudios de Asociación Genética , Genoma de Planta , Genotipo , Modelos Lineales , Desequilibrio de Ligamiento , Fenotipo , Polimorfismo de Nucleótido Simple , Análisis de Componente Principal , Sitios de Carácter CuantitativoRESUMEN
Plant extracts and their different growth phases have been manipulated for the fabrication of nanomaterials, which can be an eco-friendly alternative to the chemical methods that produce hazardous by-products. However, practical difficulties in isolation of the nanoparticles obtained through biological methods and the scanty control that these methods allow over their shapes and sizes impose limitations in their utility. For the first time, we report here a versatile system using cell suspension culture of Medicago sativa, which ensures control over the reaction to regulate size of the particles as well as their easier recovery afterwards. Isolated nanoparticles were characterized for their shape, size and functions. The particles varied in shapes from isodiametric spheres to exotic tetrahedrons, pentagons and pentagonal prisms. They clearly demonstrated catalytic activity in the reduction reaction of methylene blue by stannous chloride. Interestingly, the cell culture-derived particles were found less cytotoxic to healthy human cell line HEp-2 while more cytotoxic to the cancer cell line 4T-1 in comparison to those synthesized through citrate method. However, when administered in mice, these nanoparticles elicited similar inflammatory responses as those produced by chemically synthesized counterparts. These results envisage the utility of these particles for various biological applications.
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Oro , Nanopartículas del Metal , Células Vegetales , Catálisis , Técnicas de Cultivo de Célula , Células Cultivadas , Oro/efectos adversos , Oro/química , Tecnología Química Verde , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Metales Pesados/efectos adversos , Metales Pesados/química , Extractos VegetalesRESUMEN
Treatment drugs, besides their specific activity, often have multiple effects on the body. The undesired effect of the drug may be repurposed as therapeutics, saving significant investigative time and effort. Minocycline has anti-cancer, anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Presently, minocycline is also known to show anti-viral activity against Influenza virus, Japanese encephalitis virus, Simian immunodeficiency virus, Human immunodeficiency virus and West Nile virus. Here, we investigate the effect of minocycline on Respiratory syncytial virus (RSV), a common respiratory virus that causes severe mortality and morbidity in infants, children, and older adult populations. Currently, there is no effective vaccine or treatment for RSV infection; hence, there is a critical need for alternative and effective drug choices. Our study shows that minocycline reduces the RSV-mediated cytopathic effect and prevents RSV infection. This is the first study demonstrating the anti-viral activity of minocycline against RSV.
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Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Minociclina/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Antibacterianos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Humanos , Minociclina/farmacología , Infecciones por Virus Sincitial Respiratorio/virologíaRESUMEN
Introduction: Human respiratory syncytial virus (RSV) is a common respiratory virus that causes severe lower respiratory tract infection in infants, children and aged adults. Currently, there is no active prophylaxis present in the market for RSV infection; however, there are over a dozen compounds being tested in the laboratory as well as clinical trials. To increase the efficiency and safety of these therapeutics, there is a need for delivery vehicles. Areas covered: Liposomes can be used for delivering anti-RSV agents with the advantage of modulating and eliciting the desired adjuvant effect by the different combination of lipids. This review discusses the promising application of liposome for anti-RSV therapeutics. Expert opinion: Liposomes are attracting attention for delivery of pulmonary therapeutics, since they offer compatibility for delivering drugs, vaccines and other therapeutic molecules. Variation in liposome size and composition gives flexibility for the amount and number of deliverables, whilst targeted delivery with the capability for immunomodulation makes liposomes a promising candidate for RSV therapeutic applications.
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Antivirales/administración & dosificación , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Animales , Humanos , LiposomasRESUMEN
Accurate knowledge of 13C isotopic signature (δ13C) of methane from each source is crucial for separating biogenic, fossil fuel and pyrogenic emissions in bottom-up and top-down methane budget. Livestock production is the largest anthropogenic source in the global methane budget, mostly from enteric fermentation of domestic ruminants. However, the global average, geographical distribution and temporal variations of the δ13C of enteric emissions are not well understood yet. Here, we provide a new estimation of C3-C4 diet composition of domestic ruminants (cattle, buffaloes, goats and sheep), a revised estimation of yearly enteric CH4 emissions, and a new estimation for the evolution of its δ13C during the period 1961-2012. Compared to previous estimates, our results suggest a larger contribution of ruminants' enteric emissions to the increasing trend in global methane emissions between 2000 and 2012, and also a larger contribution to the observed decrease in the δ13C of atmospheric methane.
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Inflammation, as induced by the presence of cytokines and chemokines, is an integral part of chlamydial infections. The anti-inflammatory cytokine, interleukin (IL)-10, has been reported to efficiently suppress the secretion of inflammatory cytokines triggered by Chlamydia in mouse macrophages. Though IL-10 is employed in clinical applications, its therapeutic usage is limited due to its short half-life. Here, we document the successful encapsulation of IL-10 within the biodegradable polymeric nanoparticles of PLA-PEG (Poly (lactic acid)-Poly (ethylene glycol), to prolong its half-life. Our results show the encapsulated-IL-10 size (~238 nm), zeta potential (-14.2 mV), polydispersity index (0.256), encapsulation efficiency (~77%), and a prolonged slow release pattern up to 60 days. Temperature stability of encapsulated-IL-10 was favorable, demonstrating a heat capacity of up to 89 °C as shown by differential scanning calorimetry analysis. Encapsulated-IL-10 modulated the release of IL-6 and IL-12p40 in stimulated macrophages in a time- and concentration-dependent fashion, and differentially induced SOCS1 and SOCS3 as induced by chlamydial stimulants in macrophages. Our finding offers the tremendous potential for encapsulated-IL-10 not only for chlamydial inflammatory diseases but also biomedical therapeutic applications.