Vaccines for Respiratory Viruses-COVID and Beyond.

The COVID-19 (coronavirus disease 2019) pandemic had an extensive impact on global morbidity and mortality. Several other common respiratory viruses, such as the influenza virus and respiratory syncytial virus (RSV), are endemic or epidemic agents causing acute respiratory infections that are easily transmissible and pose a significant threat to communities due to efficient person-to-person transmission. These viruses can undergo antigenic variation through genetic mutations, resulting in the emergence of novel strains or variants, thereby diminishing the effectiveness of current vaccines, and necessitating ongoing monitoring and adjustment of vaccine antigens.

Epigenetic Switches in Retinal Homeostasis and Target for Drug Development.

Retinal homeostasis, a tightly regulated process maintaining the functional integrity of the retina, is vital for visual function. Emerging research has unveiled the critical role of epigenetic regulation in controlling gene expression patterns during retinal development, maintenance, and response to mutational loads and injuries. Epigenetic switches, including DNA methylation, histone modifications, and non-coding RNAs, play pivotal roles in orchestrating retinal gene expression and cellular responses through various intracellular, extracellular, and environmental modulators.

Gβγ signaling regulates microtubule-dependent control of Golgi integrity.

Gβγ subunits regulate several non-canonical functions at distinct intracellular organelles. Previous studies have shown that Gβγ signaling at the Golgi is necessary to mediate vesicular protein transport function and to regulate mitotic Golgi fragmentation. Disruption of Golgi structure also occurs in response to microtubule depolymerizing agents, such as nocodazole.

Gβγ regulates mitotic Golgi fragmentation and G2/M cell cycle progression.

Heterotrimeric G proteins (αβγ) function at the cytoplasmic surface of a cell's plasma membrane to transduce extracellular signals into cellular responses. However, numerous studies indicate that G proteins also play noncanonical roles at unique intracellular locations. Previous work has established that G protein βγ subunits (Gβγ) regulate a signaling pathway on the cytoplasmic surface of Golgi membranes that controls the exit of select protein cargo.

In Vitro Analysis of Hedgehog Acyltransferase and Porcupine Fatty Acyltransferase Activities.

Hedgehog and Wnt proteins are modified by covalent attachment of the fatty acids palmitate and palmitoleate, respectively. These lipid modifications are essential for Hedgehog and Wnt protein signaling activities and are catalyzed by related, but distinct fatty acyltransferases: Hedgehog acyltransferase (Hedgehog) and Porcupine (Wnt). In this chapter, we provide detailed methods to directly monitor Hedgehog and Wnt protein fatty acylation in vitro.

Emery-Dreifuss muscular dystrophy mutations impair TRC40-mediated targeting of emerin to the inner nuclear membrane.

Emerin is a tail-anchored protein that is found predominantly at the inner nuclear membrane (INM), where it associates with components of the nuclear lamina. Mutations in the emerin gene cause Emery-Dreifuss muscular dystrophy (EDMD), an X-linked recessive disease. Here, we report that the TRC40/GET pathway for post-translational insertion of tail-anchored proteins into membranes is involved in emerin-trafficking.

Phosphorylation of nucleoporin Tpr governs its differential localization and is required for its mitotic function.

A major constituent of the nuclear basket region of the nuclear pore complex (NPC), nucleoporin Tpr, plays roles in regulating multiple important processes. We have previously established that Tpr is phosphorylated in both a MAP-kinase-dependent and MAP-kinase-independent manner, and that Tpr acts as both a substrate and as a scaffold for ERK2 (also known as MAPK1). Here, we report the identification of S2059 and S2094 as the major novel ERK-independent phosphorylation sites and T1677, S2020, S2023 and S2034 as additional ERK-independent phosphorylation sites found in the Tpr protein in vivo.

Localization of nucleoporin Tpr to the nuclear pore complex is essential for Tpr mediated regulation of the export of unspliced RNA.

Nucleoporin Tpr is a component of the nuclear pore complex (NPC) that localizes exclusively to intranuclear filaments. Tpr functions as a scaffolding element in the nuclear phase of the NPC and plays a role in mitotic spindle checkpoint signalling. Export of intron-containing mRNA in Mason Pfizer Monkey Virus is regulated by direct interaction of cellular proteins with the cis-acting Constitutive Transport Element (CTE).

Histone H4 lysine 14 acetylation in Leishmania donovani is mediated by the MYST-family protein HAT4.

Post-translational modifications (PTMs) of histones regulate almost all facets of DNA metabolism in eukaryotes, such as replication, repair, transcription and chromatin condensation. While histone PTMs have been exhaustively examined in yeast and higher eukaryotes, less is known of their functional consequences in trypanosomatids. Trypanosome histones are highly divergent from those of other eukaryotes, and specific PTMs have been identified in histones of Trypanosoma species.

Characterization of Leishmania donovani MCM4: expression patterns and interaction with PCNA.

Events leading to origin firing and fork elongation in eukaryotes involve several proteins which are mostly conserved across the various eukaryotic species. Nuclear DNA replication in trypanosomatids has thus far remained a largely uninvestigated area. While several eukaryotic replication protein orthologs have been annotated, many are missing, suggesting that novel replication mechanisms may apply in this group of organisms.

Kinetoplast morphology and segregation pattern as a marker for cell cycle progression in Leishmania donovani.

Trypanosomatids are typified by uniquely configured mitochondrial DNA--the kinetoplast. The replication timing of kinetoplast DNA (kDNA) is closely linked to nuclear S phase, but nuclear and kinetoplast compartments display staggered timing of segregation, post-replication. Kinetoplast division is completed before nuclear division in Trypanosoma species while nuclear division is completed first in Crithidia species.

The distribution pattern of proliferating cell nuclear antigen in the nuclei of Leishmania donovani.

DNA replication in eukaryotes is a highly conserved process marked by the licensing of multiple origins, with pre-replication complex assembly in G1 phase, followed by the onset of replication at these origins in S phase. The two strands replicate by different mechanisms, and DNA synthesis is brought about by the activity of the replicative DNA polymerases Pol delta and Pol epsilon. Proliferating cell nuclear antigen (PCNA) augments the processivity of these polymerases by serving as a DNA sliding clamp protein.