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BACKGROUND: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS: We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS: This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.
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COVID-19 , MicroARNs , Humanos , COVID-19/genética , SARS-CoV-2/genética , Genómica , MicroARNs/genética , ARN MensajeroRESUMEN
Dengue virus (DENV) is a highly perilous virus that is transmitted to humans through mosquito bites and causes dengue fever. Consequently, extensive efforts are being made to develop effective treatments and vaccines. Mathematical modeling plays a significant role in comprehending the dynamics of DENV within a host in the presence of cytotoxic T lymphocytes (CTL) immune response. This study examines two models for secondary DENV infections that elucidate the dynamics of DENV under the influence of two types of CTL responses, namely non-specific and strain-specific responses. The first model encompasses five compartments, which consist of uninfected monocytes, infected monocytes, free DENV particles, non-specific CTLs, and strain-specific CTLs. In the second model, latently infected cells are introduced into the model. We posit that the CTL responsiveness is determined by a combination of self-regulating CTL response and a predator-prey-like CTL response. The model's solutions are verified to be nonnegativity and bounded and the model possesses two equilibrium states: the uninfected equilibrium EQ0 and the infected equilibrium EQâ. Furthermore, we calculate the basic reproduction number R0, which determines the existence and stability of the model's equilibria. We examine the global stability by constructing suitable Lyapunov functions. Our analysis reveals that if R0≤1, then EQ0 is globally asymptotically stable (G.A.S), and if R0>1, then EQ0 is unstable while EQâ is G.A.S. To illustrate our findings analytically, we conduct numerical simulations for each model. Additionally, we perform sensitivity analysis to demonstrate how the parameter values of the proposed model impact R0 given a set of data. Finally, we discuss the implications of including the CTL immune response and latently infected cells in the secondary DENV infection model. Our study demonstrates that incorporating the CTL immune response and latently infected cells diminishes R0 and enhances the system's stability around EQ0.
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This paper studies the global stability of discrete-time viral infection models with humoural immunity. We consider both latently and actively infected cells. We study also a model with general production and clearance rates of all compartments as well as general incidence rate of infection. We use nonstandard finite difference method to discretize the continuous-time models. The positivity and boundedness of solutions of the discrete models are established. We establish by using Lyapunov method, the global stability of equilibria in terms of the basic reproduction number [Formula: see text] and the humoural immune response activation number [Formula: see text]. The results signify that the infection dies out if [Formula: see text]. Moreover, the infection persists with inactive immune response if [Formula: see text] and with active immune response if [Formula: see text]. We illustrate our theoretical results by using numerical simulations.
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Inmunidad Humoral , Modelos Biológicos , Virosis/epidemiología , Virosis/inmunología , Latencia del Virus/fisiología , Número Básico de Reproducción , Simulación por Computador , Humanos , Análisis Numérico Asistido por Computador , Factores de TiempoRESUMEN
The camel industry uses traditional (i.e., iron brands and ear tags) and modern (i.e., microchips) identification (ID) systems without having performance results of reference. Previously iron-branded ( = 45; 1 yr) and microchipped ( = 59; 7 yr) camels showed problems of healing (8.6% of brands) and reading (only 42.9% of brands and 69.5% of microchips were readable), which made their use inadvisable. With the aim of proposing suitable ID systems for different farming conditions, an on-field study was performed using a total of 528 dromedaries at 4 different locations (Egypt, = 83; Spain, = 304; Saudi Arabia, = 90; and Tunisia, = 51). The ID devices tested were visual (button ear tags, 28.5 mm diameter, = 178; double flag ear tags, 50 by 15 mm, = 83; both made of polyurethane) and electronic (ear tags, = 90, and rumen boluses, = 555). Electronic ear tags were polyurethane-loop type (75 by 9 mm) with a container in which a 22-mm transponder of full-duplex technology was lodged. Electronic boluses of 7 types, varying in dimensions (50 to 76 mm length, 11 to 21 mm width, and 12.7 to 82.1 g weight) and specific gravity (SG; 1.49 to 3.86) and each of them containing a 31-mm transponder of half-duplex technology, were all administered to the dromedaries at the beginning of the study. When a low-SG bolus was lost, a high-SG bolus was readministered. Readability rates of each ID system were evaluated during 1 to 3 yr, according to device and location, and yearly values were estimated for comparison. On a yearly basis, visual ear tag readability was not fully satisfactory; it was lower for rectangular ear tags (66.3%) than for button ear tags (80.9%). Yearly readability of electronic ear tags was 93.7%. Bolus readability dramatically varied according to their SG; the SG < 2.0 boluses were fully lost after 8 mo. In contrast, the SG > 3.0 boluses were efficiently retained (99.6 to 100%) at all locations. In conclusion, according to the expected long lifespan of camels, low ID performances were observed for iron brands, injectable microchips, and ear tags (visual and electronic), making their use inadvisable as unique ID systems in camels. The high readability of dense electronic boluses recommended their use as a permanent ID device of reference in camels.
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Crianza de Animales Domésticos/instrumentación , Sistemas de Identificación Animal/veterinaria , Camelus , Crianza de Animales Domésticos/métodos , Sistemas de Identificación Animal/instrumentación , Sistemas de Identificación Animal/métodos , Animales , Peso Corporal , Electrónica/instrumentación , Granjas , Femenino , MasculinoRESUMEN
10-(Hetero/arylthio)acetyl-2-chlorophenothiazines II have been synthesized via interaction of 10-chloroacetyl-2-chlorophenothiazine I with heterocyclic and/or aromatic potassium mercaptide in ethanol. Oxidation of II using H2O2/CH3COOH mixture was studied. Structures of the products were verified by elemental and spectral analyses. Some compounds were screened in vitro for their antibacterial activities.
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Fenotiazinas/síntesis química , Antibacterianos/síntesis química , Bacterias/efectos de los fármacos , Biotecnología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fenotiazinas/farmacologíaRESUMEN
Sixty growing Najedi ram lambs (23.5 kg BW: 3 months old) were divided randomly to 6 equal groups. Each group was fed on different (isonitrogenous) diet, being either high energy (2.79 Mcal ME/kg DM) or low energy (2.15 Mcal Me/kg DM), supplemented with either 0.5 or 10% poultry offal meal (POM) in replacement of an equal amount of soybean meal (SBM). Feeding was ad libitum for 15 weeks experimental period. Thyroid hormones levels in plasma were determined during the last 7 weeks of the experiment and were related to feed intake and body weight during the same period. Lambs fed high-energy diets showed higher (P < 0.01) levels of both thyroxine (T4) and triiodothyronine (T3) compared to those fed low-energy diets leading to lower T4 to T3 ratios. There was more conversion of T4 to T3 for more utilization of food by the lambs fed the 10% POM diet of the high-energy content.
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Alimentación Animal , Aves de Corral , Ovinos/sangre , Tiroxina/sangre , Triyodotironina/sangre , Residuos , Animales , Proteínas Sanguíneas/análisis , Masculino , Glycine max , VíscerasRESUMEN
During March 2009, we evaluated the hemostatic profile and platelet indices of 18 Arabian sand gazelles (Gazella subgutturosa marica) and compared the results with those from humans and camels (Camelus dromedarius). Gazelles and camels had shorter activated partial thromboplastin times, lower proconvertin and higher antihemophilic factor coagulation activity, and plasma fibrinogen levels than humans. Prothrombin time was longer in sand gazelles and shorter in camels than it was in humans. Plasma thromboplastin component, Stuart factor, and plasma thromboplastin antecedent were similar in gazelles, humans, and camels, whereas the platelet count of the sand gazelle was significantly higher than it was for camels and humans.
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Antílopes/sangre , Coagulación Sanguínea/fisiología , Plaquetas/fisiología , Camelus/sangre , Animales , Pruebas de Coagulación Sanguínea/veterinaria , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Tiempo de Tromboplastina Parcial/veterinaria , Recuento de Plaquetas/veterinaria , Arabia SauditaRESUMEN
The effect of milking interval on secretion rates of milk and milk constituents was studied in four milking camels during late lactation. An interval of 4 h produced the highest milk secretion rate compared with 8, 12 and 16 h intervals, and rates tended to decline with increasing milking intervals. Secretion rates of organic (lactose, SNF, fat and protein) and inorganic milk constituents (sodium, potassium, calcium and magnesium) generally followed similar patterns of decreasing secretion with increasing milking intervals. Many of the values for different intervals were significantly different.