In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ...ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellular translational apparatus. While transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cellular translational control pathways in enabling the latent-lytic switch have not been described. Using PEL-derived B-cells naturally infected with KSHV as a model, we define efficient reactivation conditions and demonstrate that reactivation substantially changes the protein synthesis profile. New polypeptide synthesis correlates with 4E-BP1 translational repressor inactivation, nuclear PABP accumulation, eIF4F assembly, and phosphorylation of the cap-binding protein eIF4E by Mnk1. Significantly, inhibiting Mnk1 reduces accumulation of the critical viral transactivator RTA through a post-transcriptional mechanism, limiting downstream lytic protein production, and impairs reactivation efficiency. Thus, herpesvirus reactivation from latency activates the host cap-dependent translation machinery, illustrating the importance of translational regulation in implementing new developmental instructions that drastically alter cell fate.
Drug delivery systems such as liposomes are widely used to stabilize and increase the plasma half-life of therapeutics. In this article, we have investigated two strategies to increase the half-life ...of deoxyribonuclease I, an FDA-approved enzyme used for the treatment of cystic fibrosis, and a potential candidate for the reduction of uncontrolled inflammation induced by neutrophil extracellular traps. We demonstrate that our optimized preparation procedure resulted in nanoparticles with improved plasma half-life and total exposure relative to native protein, while maintaining enzymatic activity.
The emergence of the SARS-CoV-2 Omicron variant in 2021 is associated with a global surge of cases in late 2021 and early 2022. Identifying the introduction of novel SARS-CoV-2 variants to a ...population is imperative to inform decisions by clinicians and public health officials. Here, we describe a quantitative reverse transcription PCR-based assay (RT-qPCR) targeting unique mutations in the Omicron BA.1/BA1.1 and BA.2 viral genomes. This assay accurately and precisely detect the presence of these Omicron variants in patient samples in less than four hours. Using this assay, we tested 270 clinical samples and detected the introduction of Omicron BA.1/BA1.1 and BA.2 in the Santa Barbara County (SBC) population in December 2021 and February 2022, respectively. Identifying Omicron variants using this RT-qPCR assay showed complete concordance with whole viral genome sequencing; both assays indicated that Omicron was the dominant variant in SB County. Our data substantiate that RT-qPCR-based virus detection assays offer a fast and inexpensive alternative to NGS for virus variant-specific detection approach, which allows streamlining the detection of Omicron variants in patient samples.
The impact of three air pollutants, carbon monoxide, nitrogen dioxide, and fine particulate matter (PM
) on the diversity and abundance of insect fauna associated with Chinese thuja, Platycladus ...orientalis, was evaluated for the first time in Iran. Sampling was performed in Lashkar, Sadaf, and Sajjad, three urban green spaces in Mashhad, a city located in Razavi Khorasan province. A total of 29 insect species including 16 natural enemies and 13 herbivores were identified. The results indicated that herbivore abundance was positively and significantly correlated with the level of carbon monoxide and nitrogen dioxide, but not with the level of fine particulate matter. In contrast, herbivore diversity was negatively and significantly correlated only with the level of carbon monoxide. As for natural enemies, abundance and diversity both were not significantly correlated with the levels of none of all three pollutants. The aphid, Cinara thujafilina Del Guercio was the most dominant herbivore species in all the sampling sites with a relative abundance of 86% at Lashkar, 93% at Sadaf, and 95% at Sajjad. Regarding natural enemies, the ladybird, Coccinella septempunctata was the most abundant species both at Lashkar (49%) and Sadaf (35%) while the ladybird, Oenopia conglubata was the most abundant at Sajjad (21%). The highest diversity of herbivores and natural enemies across the four seasons were at the Lashkar and Sadaf sites. The results highlight that of the three air pollutants, carbon monoxide is the one that affects both on abundance and diversity of herbivore guild associated with Platycladus orientalis in urban green spaces.
Este trabajo se concentra en las prácticas científicas vinculadas a la formación de colecciones, considerando su articulación con distintas prácticas comerciales, la recolección de los objetos en “el ...campo” y el papel de diferentes individuos que intervienen en la obtención y recopilación de los objetos. Para examinar estas cuestiones, se analizan las publicaciones y la documentación de la médica y exploradora austriaca Wanda Hanke. Sus actividades son comprendidas en un contexto de expansión de los museos en diferentes ciudades y provincias en las décadas de 1930 y 1940. El análisis permite comparar sus prácticas con las de aquellos personajes itinerantes que desde el siglo XIX recorrieron el continente sudamericano adoptando la identidad de explorador, pero también desarrollando prácticas ligadas a la medicina, el periodismo y el mercado del coleccionismo, articulando actividades científicas y mercantiles alrededor del conocimiento y de los objetos de pueblos indígenas.
Quantum Field Theory, as the keystone of particle physics, has offered great insights into deciphering the core of Nature. Despite its striking success, by adhering to local interactions, Quantum ...Field Theory suffers from the appearance of divergent quantities in intermediary steps of the calculation, which encompasses the need for some regularization/renormalization prescription. As an alternative to traditional methods, based on the analytic extension of space–time dimension, frameworks that stay in the physical dimension have emerged; Implicit Regularization is one among them. We briefly review the method, aiming to illustrate how Implicit Regularization complies with the BPHZ theorem, which implies that it respects unitarity and locality to arbitrary loop order. We also pedagogically discuss how the method complies with gauge symmetry using one- and two-loop examples in QED and QCD.
Treatment and follow-up in Hereditary Tyrosinemia type 1 (HT-1) patients require comprehensive clinical and dietary management, which involves drug therapy with NTBC and the laboratory monitoring of ...parameters, including NTBC levels, succinylacetone (SA), amino acids, and various biomarkers of liver and kidney function. Good adherence to treatment and optimal adjustment of the NTBC dose, according to clinical manifestations and laboratory parameters, can prevent severe liver complications such as hepatocarcinogenesis (HCC). We analyzed several laboratory parameters for 15 HT-1 patients over one year of follow-up in a cohort that included long-term NTBC-treated patients (more than 20 years), as well as short-term patients (one year). Based on this analysis, we described the overall adherence by our cohort of 70% adherence to drug and dietary treatment. A positive correlation was found between blood and plasma NTBC concentration with a conversion factor of 2.57. Nonetheless, there was no correlation of the NTBC level with SA levels, αFP, liver biomarkers, and amino acids in paired samples analysis. By separating according to the range of the NTBC concentration, we therefore determined the mean concentration of each biochemical marker, for NTBC ranges above 15-25 μmol/L. SA in urine and αFP showed mean levels within controlled parameters in our group of patients. Future studies analyzing a longer follow-up period, as well as SA determination in the blood, are encouraged to confirm the present findings.
Worldwide, iron deficiency anaemia (IDA) is one the most significant nutritional maladies, especially in low and middle-income countries. This is mainly due to the associated morbidity, economic ...implications on the health system and the welfare state. One of the most prevalent causes of IDA in children is insufficient food intake, which has an obvious connection with the social environment. The main strategy in the management of this condition is counteracting such deficiency through the improvement of nutrition and family upbringing. Aiming to explore affordable, novel and straightforward approaches to treat this nutritional condition, we developed a descriptive study associated with the incorporation of Moringa Oleifera in homemade fruit beverages delivered to 32 children from low-income families, in order to assess the evolution of IDA, evaluating specific clinical parameters such as red blood cells volume, as well as hemoglobin, ferritin and serum iron levels, within a two months lapse. At the end of this period, we observed a significant statistical rise in the levels of all the assessed parameters, finding about a 1.3-fold increase in hemoglobin and ferritin levels and in red blood cells volume; serum iron was 1.1 times higher. These findings are demonstrative of the wide spectrum of the medicinal features of Moringa and establish a promising and accessible strategy easy to incorporate into the diet of families of children suffering this pathology.
Background: This study aimed at determining the validity of the Pediatric Quality of Life Inventory 4.0 (PedsQL™ 4.0) for the measurement of health-related quality of life (HRQOL) in Colombian ...children. Methods: Validation study of measurement instruments. The PedsQL™ 4.0 was applied by convenience sampling to 375 pairs of children and adolescents between the ages of 5 and 17 and to their parents-caregivers, as well as to 125 parents-caregivers of children between the ages of 2 and 4 in five cities of Colombia (Bogota, Medellin, Cali, Barranquilla and Bucaramanga). Construct validity was assessed through the use of exploratory and confirmatory factor analysis, and criterion validity was assessed by correlations between the PedsQL™ 4.0 and the KIDSCREEN-27. Results: The instrument was applied to 375 children (ages 5-18) and 125 parents of children between the ages of 2 and 4. Factor analysis revealed four factors considered suitable for the sample in both the child and parent reports, whereas Bartlett's test of sphericity showed inter-correlation between variables. Scale and subscales showed proper indicators of internal consistency. It is recommended not to include or review some of the items in the Colombian version of the scale. Conclusions: The Spanish version for Colombia of the PedsQL™ 4.0 displays suitable indicators of criterion and construct validity, therefore becoming a valuable tool for measuring HRQOL in children in our country. Some modifications are recommended for the Colombian version of the scale.
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