Immunization of the neonate is a highly desirable goal for vaccine developers, since the neonate is profoundly susceptible to a number of viral and bacterial pathogens. The neonatal immune system tends to generate Th2 recall responses, known as neonatal tolerance, which may not protect against viral challenge later in life. In this study we demonstrate that a potent immune proinflammatory stimulator, heat-shock protein 70 (hsp70), can act as an effective and safe adjuvant in neonates. Priming of neonates with hsp70 coupled to a viral MHC Class I-restricted epitope (gB498-505) and injection with recombinant gB generated strong cytotoxic T lymphocyte (CTL) responses and a Th1 primary T helper cell response during the neonatal period. In addition, enhanced CTL and predominant Th1 recall responses to viral antigens were observed following secondary challenge as adults. These responses were sufficient to allow protection against a lethal challenge with Herpes Simplex Virus Type-1 (HSV-1). Therefore, hsp70 in conjunction with viral epitopes and recombinant viral protein can perhaps prime protective immune responses to herpes viruses early in life when infection, which can be life-threatening, and the establishment of latency frequently occur.
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http://dx.doi.org/10.1016/j.vaccine.2005.01.152 | DOI Listing |
J Vis Exp
January 2025
Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara; Neuroscience Research Institute, University of California, Santa Barbara.
The tardigrade Hypsibius exemplaris is an emerging model organism renowned for its ability to survive environmental extremes. To explore the molecular mechanisms and genetic basis of such extremotolerance, many studies rely on RNA-sequencing (RNA-seq), which can be performed on populations ranging from large cohorts to individual animals. Reverse transcription polymerase chain reaction (RT-PCR) and RNA interference (RNAi) are subsequently used to confirm RNA-seq findings and assess the genetic requirements for candidate genes, respectively.
View Article and Find Full Text PDFCureus
December 2024
Department of Biology, College of Education, Salahaddin University-Erbil, Erbil, IRQ.
Background: Synthesis of the original Schiff base CdCl (CHNO) compound (Schiff base complex) displays an extensive range of bioactivities and was predictably utilized to treat several syndromes.
Purpose: The goal of the existing experiment is to evaluate the gastroprotective effects of a novel Schiff base CdCl₂ (C14H21N3O2) compound in alcohol-induced gastric ulcers in rats by examining its antioxidant activity, anti-inflammatory effects, and modulation of key molecular markers, including heat shock protein-70 (HSP-70) and Bcl-2-associated X protein (Bax) proteins.
Methods: Five groups of rats were utilized in the current study.
Embryogenesis is remarkably robust to temperature variability, yet there is limited understanding of the homeostatic mechanisms that offset thermal effects during early development. Here, we measured the thermal acclimation response of upper thermal limits and profiled chromatin state and the transcriptome of embryos (Bownes Stage 11) using single-nuclei multiome ATAC and RNA sequencing. We report that thermal acclimation, while preserving a common set of primordial cell types, rapidly shifted the upper thermal limit.
View Article and Find Full Text PDFis an obligate human parasite of the phylum Apicomplexa and is the causative agent of the most lethal form of human malaria. Although N6-methyladenosine modification is thought to be one of the major post-transcriptional regulatory mechanisms for stage-specific gene expression in apicomplexan parasites, the precise base position of m6A in mRNAs or noncoding RNAs in these parasites remains unknown. Here, we report global nucleotide-resolution mapping of m6A residues in using DART-seq technology, which quantitatively displayed a stage-specific, dynamic distribution pattern with enrichment near mRNA 3' ends.
View Article and Find Full Text PDFACS Omega
January 2025
Department of Chemistry and Biochemistry, Warren Center for Drug Discovery, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, Indiana 46556, United States.
Selective inhibition of glucose regulated protein 94 (Grp94), the most structurally unique isoform of heat shock protein 90 (Hsp90), has been implicated in the treatment of various disease states, including primary open-angle glaucoma and metastatic cancer. In this study, nine analogues were designed and synthesized by conformationally restricting , a second generation Grp94-selective inhibitor. Conformational constraints were applied to restrict the rotatable bonds and to bias the benzyl moiety into the Grp94 site 1 pocket as well as to reduce the entropic penalty paid upon binding.
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