Epidemiological and molecular analysis of circulating fowl adenoviruses and emerging of serotypes 1, 3, and 8b in Egypt

Fowl adenoviruses (FAdVs) are a large group of viruses of different serotypes. They are responsible for inclusion body hepatitis, adenoviral gizzard erosion, and hepatitis hydropericardium syndrome. The present study presents a comprehensive overview of FAdVs in Egypt, with a focus on the epidemiological features of virus serotypes across the country. We conducted molecular investigation of multiple FAdV species based on the genetic signature of hypervariable regions 1-4 in the loop1 (L1) region of the hexon gene. Epidemiologically, the Nile Delta governorates showed high positivity of FAdVs, which were more commonly found in broilers than in layers. Genetically, species D and serotype 8a/E dominated, and the findings also revealed the emergence of new FAdV serotypes 1, 3, and 8b. The comparative analysis of hypervariable regions in the L1 region of the hexon gene revealed variables specific to each virus serotype. In silico predictions of L1 region revealed variations in the molecular structure and predicted the antigenic epitopes which may affect the cross-antigenicity between the different FAdV species and serotypes

Exploring the influence of indololactone structure on selectivity for binding to the C1 domains of PKCα, PKCε, and RasGRP

C1 domain-containing proteins, such as protein kinase C (PKC), have a central role in cellular signal transduction. Their involvement in many diseases, including cancer, cardiovascular disease, and immunological and neurological disorders has been extensively demonstrated and has prompted a search for small molecules to modulate their activity. By employing a diacylglycerol (DAG)-lactone template, we have been able to develop ultra potent analogs of diacylglycerol with nanomolar binding affinities approaching those of complex natural products such as phorbol esters and bryostatins. One current challenge is the development of selective ligands capable of discriminating between different protein family members. Recently, structure-activity relationship studies have shown that the introduction of an indole ring as a DAG-lactone substituent yielded selective Ras guanine nucleotide-releasing protein (RasGRP1) activators when compared to PKCα and PKCε. In the present work, we examine the effects of ligand selectivity relative to the orientation of the indole ring and the nature of the DAG-lactone template itself. Our results show that the indole ring must be attached to the lactone moiety through the sn-2 position in order to achieve RasGRP1 selectivity.Fil: Elhalem, Eleonora. Instituto Nacional de Tecnología Industrial; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gandolfi Donadío, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Industrial; ArgentinaFil: Zhou, Xiaoling. National Cancer Institute; Estados UnidosFil: Lewin, Nancy E.. National Cancer Institute; Estados UnidosFil: Garcia, Lia Cynthia. Instituto Nacional de Tecnología Industrial; ArgentinaFil: Lai, Christopher C.. National Institutes of Health; Estados UnidosFil: Kelley, James A.. National Institutes of Health; Estados UnidosFil: Peach, Megan L.. National Institutes of Health; Estados UnidosFil: Blumberg, Peter M.. National Cancer Institute; Estados UnidosFil: Comin, Maria Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Industrial; Argentin