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KRAS is one of the most commonly mutated proteins in cancer, and efforts to directly inhibit its function have been continuing for decades. The most successful of these has been the development of covalent allele-specific inhibitors that trap KRAS G12C in its inactive conformation and suppress tumour growth in patients1-7. Whether inactive-state selective inhibition can be used to therapeutically target non-G12C KRAS mutants remains under investigation. Here we report the discovery and characterization of a non-covalent inhibitor that binds preferentially and with high affinity to the inactive state of KRAS while sparing NRAS and HRAS. Although limited to only a few amino acids, the evolutionary divergence in the GTPase domain of RAS isoforms was sufficient to impart orthosteric and allosteric constraints for KRAS selectivity. The inhibitor blocked nucleotide exchange to prevent the activation of wild-type KRAS and a broad range of KRAS mutants, including G12A/C/D/F/V/S, G13C/D, V14I, L19F, Q22K, D33E, Q61H, K117N and A146V/T. Inhibition of downstream signalling and proliferation was restricted to cancer cells harbouring mutant KRAS, and drug treatment suppressed KRAS mutant tumour growth in mice, without having a detrimental effect on animal weight. Our study suggests that most KRAS oncoproteins cycle between an active state and an inactive state in cancer cells and are dependent on nucleotide exchange for activation. Pan-KRAS inhibitors, such as the one described here, have broad therapeutic implications and merit clinical investigation in patients with KRAS-driven cancers.
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Neoplasias , Proteínas Proto-Oncogénicas p21(ras) , Transducción de Señal , Animales , Ratones , Peso Corporal , Activación Enzimática , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Nucleótidos/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Transducción de Señal/efectos de los fármacos , División Celular/efectos de los fármacos , Especificidad por SustratoRESUMEN
BACKGROUND: Primary Health Care (PHC) is essential for effective, efficient, and more equitable health systems for all people, including those living with HIV/AIDS. This study evaluated the impact of the exposure to one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality. METHODS AND FINDINGS: A retrospective cohort study carried out in Brazil from January 1, 2007 to December 31, 2015. We conducted an impact evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the impact of FHS on AIDS incidence and mortality and compared outcomes between residents of municipalities with low or no FHS coverage (unexposed) with those in municipalities with 100% FHS coverage (exposed). We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated the FHS impact by sex and age and performed a wide range of sensitivity and triangulation analyses; 100% FHS coverage was associated with lower AIDS incidence (rate ratio [RR]: 0.76, 95% CI: 0.68 to 0.84) and mortality (RR: 0.68, 95%CI: 0.56 to 0.82). FHS impact was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR: 0.62, 95% CI: 0.53 to 0.72) and mortality (RR: 0.56, 95% CI: 0.43 to 0.72). The absence of important confounding variables (e.g., sexual behavior) is a key limitation of this study. CONCLUSIONS: AIDS should be an avoidable outcome for most people living with HIV today and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.
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Síndrome de Inmunodeficiencia Adquirida , Atención Primaria de Salud , Humanos , Brasil/epidemiología , Masculino , Femenino , Incidencia , Adulto , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Adulto Joven , Adolescente , Estudios de Cohortes , Pueblos SudamericanosRESUMEN
Challenges imposed by geographical barriers during migration are selective agents for animals. Juvenile soaring landbirds often cross large water bodies along their migratory path, where they lack updraft support and are vulnerable to harsh weather. However, the consequences of inexperience in accomplishing these water crossings remain largely unquantified. To address this knowledge gap, we tracked the movements of juvenile and adult black kites Milvus migrans over the Strait of Gibraltar using high-frequency tracking devices in variable crosswind conditions. We found that juveniles crossed under higher crosswind speeds and at wider sections of the strait compared with adults during easterly winds, which represent a high risk owing to their high speed and steady direction towards the Atlantic Ocean. Juveniles also drifted extensively with easterly winds, contrasting with adults who strongly compensated for lateral displacement through flapping. Age differences were inconspicuous during winds with a west crosswind speed component, as well as for airspeed modulation in all wind conditions. We suggest that the suboptimal sea-crossing behaviour of juvenile black kites may impact their survival rates, either by increasing chances of drowning owing to exhaustion or by depleting critical energy reserves needed to accomplish their first migration.
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Migración Animal , Viento , Animales , Factores de Edad , Falconiformes/fisiología , Vuelo Animal , Océano AtlánticoRESUMEN
[This corrects the article DOI: 10.3389/ti.2022.10528.][This corrects the article DOI: 10.3389/ti.2023.12367.].
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AIM: To assess the effectiveness of Bacillus subtilis strain LN8B as a biocollector for recovering pyrite (Py) and chalcopyrite (CPy) in both seawater (Sw) and deionized water (Dw), and to explore the underlying adhesion mechanism in these bioflotation experiments. MATERIALS AND METHODS: The bioflotation test utilized B. subtilis strain LN8B as the biocollector through microflotation experiments. Additionally, frother methyl isobutyl carbinol (MIBC) and conventional collector potassium amyl xanthate (PAX) were introduced in some experiments. The zeta potential (ZP) and Fourier-transform infrared spectroscopy (FTIR) was employed to explore the adhesion mechanism of Py and CPy interacting with the biocollector in Sw and Dw. The adaptability of the B. subtilis strain to different water types and salinities was assessed through growth curves measuring optical density. Finally, antibiotic susceptibility tests were conducted to evaluate potential risks of the biocollector. RESULTS: Superior outcomes were observed in Sw where Py and CPy recovery was â¼39.3% ± 7.7% and 41.1% ± 5.8%, respectively, without microorganisms' presence. However, B. subtilis LN8B potentiate Py and CPy recovery, reaching 72.8% ± 4.9% and 84.6% ± 1.5%, respectively. When MIBC was added, only the Py recovery was improved (89.4% ± 3.6%), depicting an adverse effect for CPy (81.8% ± 1.1%). ZP measurements indicated increased mineral surface hydrophobicity when Py and CPy interacted with the biocollector in both Sw and Dw. FTIR revealed the presence of protein-related amide peaks, highlighting the hydrophobic nature of the bacterium. The adaptability of this strain to diverse water types and salinities was assessed, demonstrating remarkable growth versatility. Antibiotic susceptibility tests indicated that B. subtilis LN8B was susceptible to 23 of the 25 antibiotics examined, suggesting it poses minimal environmental risks. CONCLUSIONS: The study substantiates the biotechnological promise of B. subtilis strain LN8B as an efficient sulfide collector for promoting cleaner mineral production. This effectiveness is attributed to its ability to induce mineral surface hydrophobicity, a result of the distinct characteristics of proteins within its cell wall.
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Bacillus subtilis , Cobre , Hierro , Minerales , Bacillus subtilis/metabolismo , Agua de Mar , Sulfuros/farmacología , Sulfuros/metabolismo , Agua/metabolismo , Antibacterianos/farmacología , Antibacterianos/metabolismoRESUMEN
The phytochemical investigation of the leaves and trunk bark of a specimen of Ocotea aciphylla collected in the southern portion of the Amazon forest led to the isolation of an oxabicyclo[3.2.2]nonane-type neolignan and 15 bicyclo[3.2.1]octanoid neolignans, 14 of which are unreported compounds (2-15), including one with an unusual oxidation pattern of the side chain at C-1' and two rare 7.1',8.3'-connected bicyclo[3.2.1]octanoid derivatives. Their structures and relative configurations were determined by extensive spectrometric analysis based on 1D- and 2D-NMR spectroscopy and HRESIMS data, while their absolute configurations were unambiguously assigned using electronic and vibrational circular dichroism data assisted by density functional theory calculations. Additionally, known sesquiterpenes, phenylpropanoids, and phytosterols were also isolated.
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Lignanos , Ocotea , Lignanos/química , Ocotea/química , Alcanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Dicroismo CircularRESUMEN
Two components of gender identity are gender similarity, how one's self-concept relates to the major gender collectives (i.e., female, male), and felt pressure to conform to gender norms. The development of these components across ages and contexts has been understudied. The focus of this study was to examine variations in gender similarity and felt pressure across multiple intersecting contexts: developmental stage, gender, and ethnic-racial group. Six data sets were harmonized and means were compared across 2628 participants (51% girls, 49% boys) from four different developmental cohorts (childhood n = 678, early adolescence n = 1322, adolescence n = 415, and young adulthood n = 213) from diverse ethnic-racial backgrounds (45% White, 23% Latinx/Hispanic, 11% Black/African-American, 7% Asian-American, 5% American Indian, and 5% Multiracial). Results revealed nuanced patterns: Gender intensification was supported in early adolescence, primarily for boys. Young adult men reported lower levels of pressure and gender typicality than younger boys, but young adult women's levels were generally not different than younger girls. Surprisingly, young adult women's levels of own-gender similarity and pressure from parents were higher than adolescent girls. Expectations of gender differences in gender typicality and felt pressure were supported for all ages except young adults, with higher levels for boys. Finally, there were more similarities than differences across ethnic-racial groups, though when there were differences, minoritized participants reported heightened gender typicality and pressure (largely accounted for by higher scores for Black and Latinx participants and lower scores for White and Multiracial participants). These results add to what is understood about contextually dependent gender development.
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Identidad de Género , Humanos , Masculino , Femenino , Adolescente , Niño , Adulto Joven , Etnicidad/estadística & datos numéricos , Etnicidad/psicología , Adulto , Autoimagen , Factores de EdadRESUMEN
One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.
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Trastornos del Movimiento , Rotenona , Animales , Drosophila melanogaster , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Antioxidantes/farmacología , Óxido Nítrico/metabolismoRESUMEN
Amoebiasis is a disease caused by Entamoeba histolytica, affecting the large intestine of humans and occasionally leading to extra-intestinal lesions. Entamoeba dispar is another amoeba species considered commensal, although it has been identified in patients presenting with dysenteric and nondysenteric colitis, as well as amoebic liver abscess. Amoebic virulence factors are essential for the invasion and development of lesions. There is evidence showing that the association of enterobacteria with trophozoites contributes to increased gene expression of amoebic virulence factors. Enteropathogenic Escherichia coli is an important bacterium causing diarrhea, with high incidence rates in the world population, allowing it to interact with Entamoeba sp. in the same host. In this context, this study aims to evaluate the influence of enteropathogenic Escherichia coli on ACFN and ADO Entamoeba dispar strains by quantifying the gene expression of virulence factors, including galactose/N-acetyl-D-galactosamine-binding lectin, cysteine proteinase 2, and amoebapores A and C. Additionally, the study assesses the progression and morphological aspect of amoebic liver abscess and the profile of inflammatory cells. Our results demonstrated that the interaction between EPEC and ACFN Entamoeba dispar strains was able to increase the gene expression of virulence factors, as well as the lesion area and the activity of the inflammatory infiltrate. However, the association with the ADO strain did not influence the gene expression of virulence factors. Together, our findings indicate that the interaction between EPEC, ACFN, and ADO Entamoeba dispar strains resulted in differences in vitro and in vivo gene expression of Gal/GalNAc-binding lectin and CP2, in enzymatic activities of MPO, NAG, and EPO, and consequently, in the ability to cause lesions.
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Entamoeba , Escherichia coli Enteropatógena , Factores de Virulencia , Escherichia coli Enteropatógena/patogenicidad , Escherichia coli Enteropatógena/genética , Entamoeba/patogenicidad , Entamoeba/genética , Entamoeba/fisiología , Factores de Virulencia/genética , Virulencia , Animales , Ratones , Absceso Hepático Amebiano/parasitología , Entamebiasis/parasitología , Humanos , Expresión GénicaRESUMEN
PURPOSE: The use of tracheoesophageal prostheses has become the gold standard in vocal rehabilitation of patients undergoing total laryngectomy. However, this method also has limitations, such as the need for frequent replacement of prostheses due to leakage or other complications. We have designed a study to access the clinical profile of patients using tracheoesophageal prostheses as vocal rehabilitation after total laryngectomy and to determine the average rate of changes, as well as the main causes of prostheses replacement. METHODS: A retrospective cohort study was performed based on patients who underwent rehabilitation with voice prostheses after total laryngectomy between 2008 and 2017. RESULTS: The sample consisted of 93 patients and 432 vocal prostheses replacement events. The median change of prostheses per patient was 210.25 days, (range 57.33 to 651.50). The most frequent cause of prostheses replacement was leakage through the prostheses, 218 (50.46%). Lower level of education was associated to higher prostheses replacement rate. CONCLUSION: The results of this study show that the median of prostheses durability is higher than that presented in the literature, the main cause of replacement was protheses leakage and that low educational level is associated to higher replacement rate.
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Neoplasias Laríngeas , Laringe Artificial , Humanos , Laringectomía/rehabilitación , Estudios Retrospectivos , Falla de Prótesis , Neoplasias Laríngeas/cirugíaRESUMEN
The rupture of the Fundão dam (Brazil) spread tailings contaminated with sodium and ether-amine into the Doce River Basin. Aiming at rehabilitating a contaminated riparian site, phytoremediation with native species of the Atlantic Forest was performed under four treatments: ES-1: physical remediation (sediment scraping) + chemical remediation (organic matter) + bioremediation (double inoculation with the arbuscular mycorrhizal fungus (AMF) Rhizophagus irregularis and the plant growth-promoting bacteria Bacillus subtilis); ES-2: chemical remediation + bioremediation; ES-3: physical remediation + chemical remediation; ES-4: chemical remediation. Ether-amine and sodium contents, plant growth and, soil quality parameters were compared among treatments and relative to preserved and degraded sites. Two years after planting, the outstanding plant growth was attributed to the phytoremediation of ether-amine and ammonium, followed by a significant increase in soil microbial biomass (Phospholipid fatty acids-PLFAs), particularly the Gram+ bacteria and total fungi but not AMF, whose response was independent of the inoculation. While sodium and ether-amine declined, soil K, P, NO3- contents, dehydrogenase and acid phosphatase activities, cation exchange capacity (CEC) and soil aggregation increased, especially in ES-1. Thus, such remediation procedures are recommended for the restoration of riparian areas affected by the Fundão tailings, ultimately improving sediment fertility, aggregation and stabilization.
To the best of our knowledge, this is the only successful example of fragment of riparian Atlantic Forest successfully rehabilitated using native trees from the Atlantic Forest in the riparian zone affected by the contaminated Fundão dam tailings. For that, phytoremediation and bioremediation procedures were adopted to alleviate etheramine and sodium toxicity, resulting in the amelioration of soil fertility and particularly the stabilization of such highly disaggregated sediments, ultimately protecting the Doce river basin against these contaminants.
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Biodegradación Ambiental , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Brasil , Micorrizas/fisiología , Microbiología del SueloRESUMEN
The present study proposes a fiducial marker for location systems that uses computer vision. The marker employs a set of tape-shaped markers that facilitate their positioning in the environment, allowing continuous reading to cover the entire perimeter of the environment and making it possible to minimize interruptions in the location service. Because the marker is present throughout the perimeter of the environment, it presents hierarchical coding patterns that allow it to be robust against multiple detection scales. We implemented an application to help the user generate the markers with a floor plan image. We conducted two types of tests, one in a 3D simulation environment and one in a real-life environment with a smartphone. The tests made it possible to measure the performance of the tape-shaped marker with readings at multiple distances compared to ArUco, QRCode, and STag with detections at distances of 10 to 0.5 m. The localization tests in the 3D environment analyzed the time of marker detection during the journey from one room to another in positioning conditions (A) with the markers positioned at the baseboard of the wall, (B) with the markers positioned at camera height, and (C) with the marker positioned on the floor. The localization tests in real conditions allowed us to measure the time of detections in favorable conditions of detections, demonstrating that the tape-shaped-marker-detection algorithm is not yet robust against blurring but is robust against lighting variations, difficult angle displays, and partial occlusions. In both test environments, the marker allowed for detection at multiple scales, confirming its functionality.
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Efficient and reliable data routing is critical in Advanced Metering Infrastructure (AMI) within Smart Grids, dictating the overall network performance and resilience. This paper introduces Q-RPL, a novel Q-learning-based Routing Protocol designed to enhance routing decisions in AMI deployments based on wireless mesh technologies. Q-RPL leverages the principles of Reinforcement Learning (RL) to dynamically select optimal next-hop forwarding candidates, adapting to changing network conditions. The protocol operates on top of the standard IPv6 Routing Protocol for Low-Power and Lossy Networks (RPL), integrating it with intelligent decision-making capabilities. Through extensive simulations carried out in real map scenarios, Q-RPL demonstrates a significant improvement in key performance metrics such as packet delivery ratio, end-to-end delay, and compliant factor compared to the standard RPL implementation and other benchmark algorithms found in the literature. The adaptability and robustness of Q-RPL mark a significant advancement in the evolution of routing protocols for Smart Grid AMI, promising enhanced efficiency and reliability for future intelligent energy systems. The findings of this study also underscore the potential of Reinforcement Learning to improve networking protocols.
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This work proposes an implementation of the SHA-256, the most common blockchain hash algorithm, on a field-programmable gate array (FPGA) to improve processing capacity and power saving in Internet of Things (IoT) devices to solve security and privacy issues. This implementation presents a different approach than other papers in the literature, using clustered cores executing the SHA-256 algorithm in parallel. Details about the proposed architecture and an analysis of the resources used by the FPGA are presented. The implementation achieved a throughput of approximately 1.4 Gbps for 16 cores on a single FPGA. Furthermore, it saved dynamic power, using almost 1000 times less compared to previous works in the literature, making this proposal suitable for practical problems for IoT devices in blockchain environments. The target FPGA used was the Xilinx Virtex 6 xc6vlx240t-1ff1156.
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In sugarcane, sequences related to the genus Sphingomonas have been widely detected by microbiome studies. In this work, the presence of bacteria of this genus was confirmed using culture-dependent and independent techniques. A collection of thirty isolates was obtained using semispecific cultivation conditions, and a specific PCR assay was applied to help confirm the isolates as belonging to the genus. A series of laboratory evaluations were carried out to identify potential properties among the isolates in the collection, which consequently allowed the identification of some most promising isolates for the development of new agricultural bioinputs. In a separate analysis, the culture-independent fluorescence in situ hybridization (FISH) methodology was applied to demonstrate the natural occurrence of Sphingomonas in different organs and tissues of sugarcane. The results showed the presence of bacteria of the genus in the spaces between cells (apoplast) of the culm parenchyma, in vessels in the region of the leaf vein, on the adaxial surface of the leaf blade, and on the root surface, sometimes close to the base of root hairs, which suggests extensive colonization on the host plant. In summary, the present study corroborates previous metagenomic amplicon sequencing results that indicated a high occurrence of Sphingomonas associated with sugarcane. This is the first study that uses approaches other than amplicon sequencing to confirm the occurrence of the genus in sugarcane and, at the same time, demonstrates potentially beneficial activities to be explored by sugarcane cultivation.
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Hibridación Fluorescente in Situ , Filogenia , ARN Ribosómico 16S , Saccharum , Sphingomonas , Saccharum/microbiología , Sphingomonas/aislamiento & purificación , Sphingomonas/clasificación , Sphingomonas/genética , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Raíces de Plantas/microbiología , Hojas de la Planta/microbiología , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.
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COVID-19 , Humanos , Anciano , COVID-19/prevención & control , Vacuna BCG , SARS-CoV-2 , Vacunas contra la COVID-19 , Estudios de Casos y Controles , Vacunación , Progresión de la EnfermedadRESUMEN
Pompe disease is an inherited metabolic myopathy caused by deficiency of acid alpha-glucosidase (GAA), resulting in lysosomal glycogen accumulation. Residual GAA enzyme activity affects disease onset and severity, although other factors, including dysregulation of cytoplasmic glycogen metabolism, are suspected to modulate the disease course. In this study, performed in mice and patient biopsies, we found elevated protein levels of enzymes involved in glucose uptake and cytoplasmic glycogen synthesis in skeletal muscle from mice with Pompe disease, including glycogenin (GYG1), glycogen synthase (GYS1), glucose transporter 4 (GLUT4), glycogen branching enzyme 1 (GBE1), and UDP-glucose pyrophosphorylase (UGP2). Expression levels were elevated before the loss of muscle mass and function. For first time, quantitative mass spectrometry in skeletal muscle biopsies from five adult patients with Pompe disease showed increased expression of GBE1 protein relative to healthy controls at the group level. Paired analysis of individual patients who responded well to treatment with enzyme replacement therapy (ERT) showed reduction of GYS1, GYG1, and GBE1 in all patients after start of ERT compared to baseline. These results indicate that metabolic changes precede muscle wasting in Pompe disease, and imply a positive feedforward loop in Pompe disease, in which lysosomal glycogen accumulation promotes cytoplasmic glycogen synthesis and glucose uptake, resulting in aggravation of the disease phenotype.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Ratones , Animales , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Glucógeno/metabolismo , alfa-Glucosidasas/genética , Músculo Esquelético/patología , Lisosomas/metabolismo , Glucosa/metabolismoRESUMEN
BACKGROUND: Genetic variability is the most important parameter in plant breeding based on selection. There is a need for morpho-agronomic and molecular characterization of Passiflora species, to exploit their genetic resources more efficiently. No study has yet been carried out to compare half-sib and full-sib families in relation to the magnitude of the genetic variability obtained in them, and then to elucidate the advantages or disadvantages of each one. METHODS AND RESULTS: In the present study, SSR markers were used to evaluate the genetic structure and diversity of half-sib and full-sib progenies of sour passion fruit. Two full-sib progenies (PSA and PSB), and a half-sib progeny (PHS), together with their parents, were genotyped with a set of eight pairs of SSR markers. Discriminant Analysis of Principal Components (DAPC) and Structure software were used to study the genetic structure of the progenies. The results indicate that the half-sib progeny has lower genetic variability, although it has higher allele richness. By the AMOVA most of the genetic variability was found within the progenies. Three groups were clearly observed in the DAPC analysis, while two hypothetical groups (k = 2) were observed in the Bayesian approach. The PSB progeny showed a high genetic mixture between the PSA and PHS progenies. CONCLUSION: Lower genetic variability is found in half-sib progenies. The results obtained here allow us to suppose that the selection within full-sib progenies will possibly provide better estimates of genetic variance in sour passion fruit breeding programs, since they provide greater genetic diversity.
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Passiflora , Humanos , Masculino , Passiflora/genética , Frutas/genética , Teorema de Bayes , Antígeno Prostático Específico , Fitomejoramiento , Variación GenéticaRESUMEN
The pyrolysis process consists of the thermal decomposition of biomass in an inert atmosphere, which produces a liquid (bio-oil) composed of a complex mixture of organic compounds, including an oil and water phase. The aqueous fraction can reach up to 45% w/w, and understanding its composition is of utmost importance in determining its intended destination, whether for the reuse of compounds in industrial applications or for treating the effluent for disposal. In this study, a fast, direct, and efficient method using ultra-high-performance supercritical fluid chromatography (UHPSFC) was developed and optimized for monitoring phenols in aqueous samples obtained from the pyrolysis processing of six different biomass sources. The following parameters were evaluated for method optimization: stationary phase type, mobile phase flow, organic modifier, sample diluent, temperature, pressure, and modifier gradient time. With a total analysis time of 26 min, out of the fourteen (14) investigated phenolic compounds, eleven (11) were successfully separated after method optimization, and among them, five (5) were quantified in all six aqueous fractions. The aqueous fractions of residue from cowpea pod (1.89 mg.mL-1), sugar apple (3.09 mg.mL-1), and acerola (4.79 mg.mL-1) presented lower concentrations compared to grape (8.16 mg.mL-1), pine nuts (6.68 mg.mL-1), and guava (6.05 mg.mL-1) fractions. However, even at lower concentrations, all biomasses showed promising results regarding the phenolic compound content, analytes that have high added value for the chemical industry.
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INTRODUCTION: Artificial intelligence models and networks can learn and process dense information in a short time, leading to an efficient, objective, and accurate clinical and histopathological analysis, which can be useful to improve treatment modalities and prognostic outcomes. This paper targets oral pathologists, oral medicinists, and head and neck surgeons to provide them with a theoretical and conceptual foundation of artificial intelligence-based diagnostic approaches, with a special focus on convolutional neural networks, the state-of-the-art in artificial intelligence and deep learning. METHODS: The authors conducted a literature review, and the convolutional neural network's conceptual foundations and functionality were illustrated based on a unique interdisciplinary point of view. CONCLUSION: The development of artificial intelligence-based models and computer vision methods for pattern recognition in clinical and histopathological image analysis of head and neck cancer has the potential to aid diagnosis and prognostic prediction.