•The mRNA expression of the bitter taste receptor T2R38 is differentially regulated by SNPs.•Genotype- and bacteria-specific reduction of antimicrobial peptide hBD-2 secretion is observed in the ...absence of T2R38.•IL-1a and IL-8 secretion is also genotype-specific for T2R38.•T2R38 modulates innate oral immunity in a genotype-specific manner.•Modulation of hBD-2 secretion via T2R38 may be the mechanism by which the PAV haplotype confers caries protection.
The bitter taste receptor T2R38 has been shown to regulate mucosal innate immune responses in the upper airway epithelium. Furthermore, SNPs in T2R38 influence the sensitivity to 6-n-propylthiouracil (PROP) and are associated with caries risk/protection. However, no study has been reported on the role of T2R38 in the innate immune responses to oral bacteria. We hypothesize that T2R38 regulates oral innate immunity and that this regulation is genotype-specific. Primary gingival epithelial cells carrying three common genotypes, PAV/PAV (PROP super-taster), AVI/PAV (intermediate) and AVI/AVI (non-taster) were stimulated with cariogenic bacteria Streptococcus mutans, periodontal pathogen Porphyromonas gingivalis or non-pathogen Fusobacterium nucleatum. QRT-PCR analyzed T2R38 mRNA, and T2R38-specific siRNA and ELISA were utilized to evaluate induction of hBD-2 (antimicrobial peptide), IL-1α and IL-8 in various donor-lines. Experiments were set up in duplicate and repeated three times. T2R38 mRNA induction in response to S. mutans was highest in PAV/PAV (4.3-fold above the unstimulated controls; p<0.05), while lowest in AVI/AVI (1.2-fold). In PAV/PAV, hBD-2 secretion in response to S. mutans was decreased by 77% when T2R38 was silenced. IL-1α secretion was higher in PAV/PAV compared to AVI/PAV or AVI/AVI with S. mutans stimulation, but it was reduced by half when T2R38 was silenced (p<0.05). In response to P. gingivalis, AVI/AVI showed 4.4-fold increase (p<0.05) in T2R38 expression, whereas the levels in PAV/PAV and AVI/PAV remained close to that of the controls. Secretion levels of IL-1α and IL-8 decreased in AVI/AVI in response to P. gingivalis when T2R38 was silenced (p<0.05), while the changes were not significant in PAV/PAV. Our data suggest that the regulation of gingival innate immunity by T2R38 is genotype-dependent and that the ability to induce a high level of hBD-2 by PAV/PAV carriers may be a reason for protection against caries in this group.
In this work we synthesized mesoporous bioactive glass nanospheres (nMBG) with the aim to utilize them as substrates for loading one of the most potent amino-bisphosphonates, alendronate (AL). The ...results of the chemical and structural characterization show that the nMBG display a relatively high surface area (528 m²/g) and a mean pore volume of 0.63 cm³/g, both of which decrease on increasing alendronate content. It is possible to modulate the amount of AL loaded into the nanospheres up to a maximum value of about 17 wt %.
tests were performed using a human osteosarcoma cell line (MG63) and a murine monocyte/macrophage cell line as osteoclast model (RAW 264.7). The results indicate that even the lower concentration of alendronate provokes decreased tumor cell viability, and that osteoclast activity exhibits an alendronate dose-dependent inhibition. The data suggest that nMBG can act as a suitable support for the local delivery of alendronate, and that the antiresorptive and antitumor properties of the functionalized mesoporous nanospheres can be modulated by varying the amount of alendronate loading.
The effect of the nanoscale structure of bioceramics on their in vitro bioactivity and capacity to osteogenically differentiate stem cell is studied. Nanoparticles of hydroxyapatite (nHA), bioactive ...glass (nBG), nanoporous bioactive glass (MBG), and nanoporous bioactive glass nanospheres (nMBG) are investigated. The nanometric particle size of bioceramics seems to be more determining in controlling the ability to induce bone-like apatite as compared to the nanoporous structure. At short incubation time, nBG also produces a bioactive extracellular medium capable of upregulating key osteogenic markers involved in the development of a mineralizing phenotype in DPSCs. The bioactive properties of nBG are promissory for accelerating the bone regeneration process in tissue engineering applications.
La citometría de flujo es un método analítico que permite la medición rápida de ciertas características físicas y químicas de células o partículas suspendidas en líquido que producen una señal de ...forma individual al interferir con una fuente de luz. Una de las características analíticas más importantes de los citómetros de flujo es su capacidad de medir múltiples parámetros celulares, como el tamaño, forma y complejidad y, por supuesto, cualquier componente celular o función que pueda ser marcada con un fluorocromo. Las aplicaciones más relevantes de la citometría de flujo en la práctica médica se relacionan con la hematología e inmunología clínicas, midiendo parámetros como número y clasificación de células sanguíneas. Esta técnica es empleada también en el conteo de subpoblaciones de linfocitos en pacientes con el virus de la inmunodeficiencia humana, así como la caracterización de leucemias agudas y síndromes linfoproliferativos crónicos, entre otros padecimientos. En los últimos 20 años, el análisis de enfermedades pulmonares de origen inmunológico por citometría de flujo ha jugado un papel importante en el entendimiento y diagnóstico de enfermedades como sarcoidosis, neumonía eosinofílica o neumonitis por hipersensibilidad. Las aplicaciones de la citometría de flujo son numerosas, lo cual ha permitido el empleo de estos instrumentos de manera amplia en los campos, tanto de la investigación biológica como médica. Esta revisión brinda un panorama general de los principios básicos de la citometría de flujo y la muestra como una herramienta reproducible y aplicable a una gran variedad de campos médicos, así como su empleo en el campo de las enfermedades pulmonares.
Trabajo de Investigacion Requisito para optar al grado de Cirujano Dentista
Introducción: La reconstrucción de defectos del complejo;
craneomaxilofacial es un actual desafío clínico en odontología. ...Actualmente se;
requieren sistemas y terapias clínicas más eficientes para lograr la;
regeneración de tejido óseo; especialmente en aplicaciones de cirugía;
maxilofacial, implantología y periodoncia. El desarrollo de la nanotecnología en;
conjunto con la ingeniería de tejidos ofrece innovadoras soluciones, mediante;
el estudio, diseño y uso de nanopartículas cerámicas bioactivas. Sin embargo,;
actualmente se requiere conocer de qué forma las diferentes características;
estructurales a nano escala de estos biomateriales afectan sus propiedades;
bioactivas. En este trabajo se sintetizan nanobiomateriales cerámicos con;
propiedades potenciales para regeneración ósea, nanopartículas de;
hidroxiapatita (n-HA), nanopartículas de vidrio bioactivo (n-BG) y vidrio;
bioactivo mesoporoso (MBG) y se estudia el efecto de su características;
estructurales sobre sus propiedades de bioactividad in vitro.;
Objetivos: Sintetizar materiales cerámicos bioactivos (n-HA, n-BG y;
MBG) con diferente nanoestructura (tamaño de partícula y nanoporosidad) y;
naturaleza química y evaluar sus propiedades osteogénicas in vitro.;
Metodología: Se sintetizaron partículas de n-HA, n-BG y MBG utilizando;
la técnica de síntesis sol-gel. Estos materiales fueron caracterizados por medio;
de difracción de rayos-X (DRX), microscopía electrónica de transmisión (TEM),;
espectroscopía de infrarrojo (FTIR-ATR), y mediciones de área superficial y;
tamaño de nanoporos por sortometría de N2.;
La bioactividad in vitro se evaluó mediante la capacidad para inducir la;
formación de apatita tipo ósea en fluido fisiológico simulado (SBF) a 36.5°C;;
analizado mediante microscopía electrónica de barrido (SEM-EDX) y DRX. Se;
evaluó preliminarmente la capacidad de adsorción de proteínas, de;
citocompatibilidad y diferenciación osteogénica de células madres dentales.;
Resultados y discusión: Las partículas n-HA y n-BG presentaron;
tamaño nanométrico (40 nm, 70 nm), con áreas superficiales entre 66 y 76;
m2/g, mientras que MBG un tamaño micrométrico (2 μm) pero con una;
nanoestructura interna altamente ordenada, compuesta de poros de 4 nm y un;
área superficial de 480 m2/g.;
Todas las partículas presentaron capacidad para inducir formación de;
apatita en SBF, para adsorber proteínas extracelulares, así como de;
diferenciación celular osteogénica, siendo estas propiedades mayores para;
la partícula de n-BG. Estos resultados se explican, debido a que el tamaño de;
partícula parece ser la propiedad más determinante en el comportamiento;
bioactivo (n-BG), en comparación con la nanoestructura porosa interna (MBG).;
La formación de apatita parece estar determinada por la superficie externa más;
que por la superficie interna que produce la nanoporosidad. Por otra parte, los;
biomateriales de vidrio bioactivo (n-BG y MBG) resultan más bioactivos que la;
hidroxiapatita (n-HA), como consecuencia de su estructura amorfa, mayor;
producción de productos de iónicos de disolución, y por lo tanto reactividad en;
condiciones fisiológicas.;
Conclusión: El tipo de nanoestructura afecta las propiedades de;
bioactividad osteogénica de los biomateriales cerámicos. Un tamaño;
nanométrico de partícula (n-BG) parece ser más favorable que una;
nanoestructura porosa interna (MBG) para acelerar la formación de apatita tipo;
ósea y estimular la diferenciación osteogénica de células madres in vitro. Las;
propiedades demostradas en estas bionanocerámicas parecen ser promisorias;
en el campo de regeneración ósea.
Advanced hybrid closed-loop (AHCL) systems represent the next step of automation intended to maximize normoglycemia in people with type 1 diabetes (T1D). In the AHCL MiniMed 780G system, different ...algorithm glucose targets for insulin infusion are available and autocorrection boluses are delivered. The aim was to prospectively evaluate the impact of the implementation of this AHCL system in a clinical setting.
T1D subjects using a sensor-augmented pump with predictive low-glucose suspend (SAP-PLGS) were upgraded to AHCL. Baseline, every 3 days, 2-week and 1-month sensor and pump data were downloaded. Glucose target was set to 100 mg/dL and active insulin time to 2 h for all the subjects. Time in different glucose ranges was compared.
Fifty-two T1D subjects were included (age: 43 ± 12 years, 73% females, diabetes duration: 27 ± 11 years, HbA1c: 7.2% ± 0.9%, time in SAP-PLGS: 5 ± 2 years). Time in range (TIR) 70-180 mg/dL increased from 67.3% ± 13.6% at baseline to 79.6% ± 7.9% at 1 month (
= 0.001). Time in hyperglycemia >180 and >250 mg/dL decreased from 29.4% ± 15.1% to 17.3% ± 8.6% and from 6.9% ± 7.8% to 2.5% ± 2.4%, respectively (
= 0.001). No differences in time in hypoglycemia <70 or <54 mg/dL were found. Time in Auto Mode was 97% ± 4%, and autocorrection insulin was 31% ± 14% of bolus insulin. Four hours postprandial glucose was improved from 162 ± 26 mg/dL at baseline to 142 ± 16 mg/dL at 1 month (
= 0.001). No severe hypoglycemia or diabetic ketoacidosis episodes occurred.
AHCL systems allow well-controlled T1D patients to rapidly increase their TIR. The most aggressive settings allow optimal outcomes in TIR, without increasing hypoglycemia frequency.
Elucidating molecular links between cell‐fate regulatory networks and dynamic patterning modules is a key for understanding development. Auxin is important for plant patterning, particularly in ...roots, where it establishes positional information for cell‐fate decisions. PIN genes encode plasma membrane proteins that serve as auxin efflux transporters; mutations in members of this gene family exhibit smaller roots with altered root meristems and stem‐cell patterning. Direct regulators of PIN transcription have remained elusive. Here, we establish that a MADS‐box gene (XAANTAL2, XAL2/AGL14) controls auxin transport via PIN transcriptional regulation during Arabidopsis root development; mutations in this gene exhibit altered stem‐cell patterning, root meristem size, and root growth. XAL2 is necessary for normal shootward and rootward auxin transport, as well as for maintaining normal auxin distribution within the root. Furthermore, this MADS‐domain transcription factor upregulates PIN1 and PIN4 by direct binding to regulatory regions and it is required for PIN4‐dependent auxin response. In turn, XAL2 expression is regulated by auxin levels thus establishing a positive feedback loop between auxin levels and PIN regulation that is likely to be important for robust root patterning.
The XAL2/AGL14 transcription factor regulates the expression of several members of the auxin efflux family to control auxin gradients and root development in Arabidopsis.
Fructose in sweetened beverages (SB) increases the risk for metabolic and cardiorenal disorders, and these effects are in part mediated by a secondary increment in uric acid (UA). Rodents have an ...active uricase, thus requiring large doses of fructose to increase plasma UA and to induce metabolic syndrome and renal hemodynamic changes. We therefore hypothesized that the effects of fructose in rats might be enhanced in the setting of uricase inhibition. Four groups of male Sprague-Dawley rats (n = 7/group) were studied during 8 wk: water + vehicle (V), water + oxonic acid (OA; 750 mg/k BW), sweetened beverage (SB; 11% fructose-glucose combination) + V, and SB + OA. Systemic blood pressure, plasma UA, triglycerides (TG), glucose and insulin, glomerular hemodynamics, renal structural damage, renal cortex and liver UA, TG, markers of oxidative stress, mitDNA, fructokinase, and fatty liver synthase protein expressions were evaluated at the end of the experiment. Chronic hyperuricemia and SB induced features of the metabolic syndrome, including hypertension, hyperuricemia, hyperglycemia, and systemic and hepatic TG accumulation. OA alone also induced glomerular hypertension, and SB alone induced insulin resistance. SB + OA induced a combined phenotype including metabolic and renal alterations induced by SB or OA alone and in addition also acted synergistically on systemic and glomerular pressure, plasma glucose, hepatic TG, and oxidative stress. These findings explain why high concentrations of fructose are required to induce greater metabolic changes and renal disease in rats whereas humans, who lack uricase, appear to be much more sensitive to the effects of fructose.
A Greenhouse Gas Budget for Mexico During 2000–2019 Murray‐Tortarolo, Guillermo; Perea, Kevin; Mendoza‐Ponce, Alma ...
Journal of geophysical research. Biogeosciences,
January 2024, 2024-01-00, 20240101, Letnik:
129, Številka:
1
Journal Article
Recenzirano
Application of the best available science to improve quantification of greenhouse gas (GHG) emissions at regional and national scales is key to climate action. Here, we present a two‐decade ...(2000–2019) GHG (CO2, CH4, and N2O) budget for Mexico derived from multiple products. Data from the National GHG Inventory, global observations, and the scientific literature were compared to identify knowledge gaps on GHG flux dynamics and discrepancies among estimates. Total mean annual GHG emissions were estimated at 695–910 TgCO2‐eq year−1 over these two decades, with 70% of the emissions attributable to CO2, 23% to CH4, and 5% to N2O (2% to other gases). When divided by sectors, we found agreement across emission estimates from various sources for fossil fuels, cattle, agriculture, and waste for all GHGs. However, considerable discrepancies were identified in the fluxes from terrestrial ecosystems. The disagreement was particularly large for the land CO2 sink, where net biome production estimations from the national inventory were double those from any other observational product. Extensive knowledge gaps exist, mainly related to aquatic systems (e.g., outgassing in rivers) and the lateral fluxes (e.g., wood trade). In addition, limited information is available on CH4 emissions from wetlands and soil CH4 consumption. We expect these results to guide future research to reduce estimation uncertainties and fill the information gaps across Mexico.
Plain Language Summary
Mexico represents the 13th global emitter of greenhouse gases (GHGs) and the second among Latin American countries, releasing roughly 485 million tons of CO2, six million tons of CH4 (equivalent to 160 million tons of CO2), and 0.1 million tons of N2O (equivalent to 35 million tons of CO2). However, large uncertainties prevail in the estimation of several components of each flux; thus, the application of the best available science to account for and improve these estimations is essential for sound mitigation policies. Here, we used multiple available products (national inventories, satellites, flux towers, dynamic global vegetation models, inversion models, and other data sources) to advance our understanding of the GHG budget of Mexico over the last 20 years. We found that fluxes from fossil fuel combustion (including energy production, transportation, industry, etc.), agriculture, livestock, and waste management agree remarkably well across products. In contrast, we documented large differences among products for land‐based fluxes (e.g., CO2 capture) and scant available information on aquatic ecosystems (e.g., CH4 emission from wetlands) and on lateral fluxes (e.g., emissions from trade). We expect these results to help in guiding future measuring efforts and policies to mitigate GHG emissions from Mexico.
Key Points
A greenhouse gas (GHG) budget for Mexico was calculated based on multiple products. We estimated fluxes for CO2, CH4, and N2O over the 2000–2019 period
Total GHG emissions were 695 TgCO2‐eq year−1 in the national inventory and as much as a mean 910 TgCO2‐eq year−1 across products
GHG fluxes agreed well across products for emissions, but large discrepancies exist for the land CO2 and CH4 sinks
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