Explore the vast range of titles available.

Preclinical mouse models that recapitulate some characteristics of coronavirus disease (COVID-19) will facilitate focused study of pathogenesis and virus–host responses. Human agniotensin-converting enzyme 2 (hACE2) serves as an entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to infect people via binding to envelope spike proteins. Herein we report development and characterization of a rapidly deployable COVID-19 mouse model. C57BL/6J (B6) mice expressing hACE2 in the lung were transduced by oropharyngeal delivery of the recombinant human adenovirus type 5 that expresses hACE2 (Ad5-hACE2). Mice were infected with SARS-CoV-2 at Day 4 after transduction and developed interstitial pneumonia associated with perivascular inflammation, accompanied by significantly higher viral load in lungs at Days 3, 6, and 12 after infection compared with Ad5-empty control group. SARS-CoV-2 was detected in pneumocytes in alveolar septa. Transcriptomic analysis of lungs demonstrated that the infected Ad5-hACE mice had a significant increase in IFN-dependent chemokines Cxcl9 and Cxcl10, and genes associated with effector T-cell populations including Cd3 g, Cd8a, and Gzmb. Pathway analysis showed that several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the data set, including cytokine–cytokine receptor interaction, the chemokine signaling pathway, the NOD-like receptor signaling pathway, the measles pathway, and the IL-17 signaling pathway. This response is correlative to clinical response in lungs of patients with COVID-19. These results demonstrate that expression of hACE2 via adenovirus delivery system sensitized the mouse to SARS-CoV-2 infection and resulted in the development of a mild COVID-19 phenotype, highlighting the immune and inflammatory host responses to SARS-CoV-2 infection. This rapidly deployable COVID-19 mouse model is useful for preclinical and pathogenesis studies of COVID-19.

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina ) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over four million people worldwide as of July 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics. Competing Interest Statement The authors have declared no competing interest.

Paramutation is an allele-dependent transfer of epigenetic information, which results in the heritable silencing of one allele by another. Paramutation at the b1 locus in maize is mediated by unique tandem repeats that communicate in trans to establish and maintain meiotically heritable transcriptional silencing. The mop1 (mediator of paramutation1) gene is required for paramutation, and mop1 mutations reactivate silenced Mutator elements. Plants carrying mutations in the mop1 gene also stochastically exhibit pleiotropic developmental phenotypes. Here we report the map-based cloning of mop1, an RNA-dependent RNA polymerase gene (RDRP), most similar to the RDRP in plants that is associated with the production of short interfering RNA (siRNA) targeting chromatin. Nuclear run-on assays reveal that the tandem repeats required for b1 paramutation are transcribed from both strands, but siRNAs were not detected. We propose that the mop1 RDRP is required to maintain a threshold level of repeat RNA, which functions in trans to establish and maintain the heritable chromatin states associated with paramutation.

Structural racism inflicts a disproportionate burden of stress and trauma within Black communities, resulting in physical and mental health inequities that impact Black youth. Yet few multilevel interventions exist to address these deeply rooted inequities from a preventive standpoint, and even fewer are informed by the participatory input of the impacted communities. To bridge these gaps, we developed a community-based prevention strategy that promotes agency and active resistance to structural racism, Youth Empowered Advocating for Health (YEAH), and implemented it across various settings. We outline the development, implementation, and expansion of YEAH as a tool for promoting optimal health among Black communities. Lastly, we discuss lessons learned and offer a framework outlining key principles for prevention scientists to partner with Black youth and engage them in translational science to address structural racism. This framework is aimed at driving policies, practices, and procedures that promote equitable and sustainable change for and with Black communities.

Increasing levels of provitamin A carotenoids in maize (Zea mays L.) grain through plant breeding has potential to help humans suffering from vitamin A deficiency. In parts of Africa where this deficiency is prevalent, there is a consumer preference for white maize grain and an avoidance of yellow maize grain. White grain has minimal levels of carotenoids whereas yellow grain can have appreciable levels of carotenoids. There is a new effort to introduce orange maize that contains high levels of provitamin A, which appears to be a more acceptable color than yellow to consumers in Africa. The implementation of this program requires backcross selection to convert African‐adapted germplasm with white grain to orange. We conducted a study to assess the heritability of visual scores for relative intensity of orange kernel color and identify genetic markers associated with orange color across and within 10 families of the maize nested association mapping population. We found visually scored kernel color to have a moderately high heritability and identified five common quantitative trait loci (QTL) and six rare QTL for intensity of orange color. Notably, half of them coincided with carotenoid biosynthetic genes. Our results indicate that breeders in Africa, Asia, and throughout the world would have flexibility to select for orange kernel color visually and/or with gene‐specific markers. Such selection can be combined with marker‐assisted selection efforts to increase provitamin A levels in maize grain.

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.