Background: The development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. Genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection.
Methodology/principal Findings: In this study, we measured early transcriptional responses in the peripheral blood of cynomolgus macaques following vaccination with a live, attenuated tetravalent dengue vaccine candidate, TDV, which is based on a DENV-2 backbone. Different doses and routes of vaccine administration were used, and viral load and neutralizing antibody titers were measured at different time-points following vaccination. All 30 vaccinated animals developed a neutralizing antibody response to each of the four dengue serotypes, and only 3 of these animals had detectable serum viral RNA after challenge with wild-type dengue virus (DENV), suggesting protection of vaccinated animals to DENV infection. The vaccine induced statistically significant changes in 595 gene transcripts on days 1, 3, 5 and 7 as compared with baseline and placebo-treated animals. Genes involved in the type I interferon (IFN) response, including IFI44, DDX58, MX1 and OASL, exhibited the highest fold-change in transcript abundance, and this response was strongest following double dose and subcutaneous (versus intradermal) vaccine administration. In addition, modules of genes involved in antigen presentation, dendritic cell activation, and T cell activation and signaling were enriched following vaccination. Increased abundance of gene transcripts related to T cell activation on day 5, and the type I IFN response on day 7, were significantly correlated with the development of high neutralizing antibody titers on day 30.
Conclusions/significance: These results suggest that early transcriptional responses may be predictive of development of adaptive immunity to TDV vaccination in cynomolgus macaques, and will inform studies of human responses to dengue vaccines.
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http://dx.doi.org/10.1371/journal.pntd.0004731 | DOI Listing |
New Phytol
December 2024
State Key Laboratory of Wheat Improvement, College of Life Science, Shandong Agricultural University, Tai'an, 271018, China.
Protoderm formation is a crucial step in early embryo patterning in plants, separating the precursors of the epidermis and the inner tissues. Although key regulators such as ARABIDOPSIS THALIANA MERISTEM LAYER1 (ATML1) and PROTODERMAL FACTOR2 (PDF2) have been identified in the model plant Arabidopsis thaliana, the genetic pathways controlling protoderm specification remain largely unexplored. Here, we combined genetic, cytological, and molecular approaches to investigate the regulatory mechanisms of protoderm specification in Arabidopsis thaliana.
View Article and Find Full Text PDFBMC Plant Biol
December 2024
Henan Province Key Laboratory of Germplasm Innovation and Utilization of Eco- economic Woody Plant, Pingdingshan University, Pingdingshan, Henan, 467000, China.
Background: Fruit size is a crucial economic trait that impacts the quality of jujube (Ziziphus jujuba), however, research in this area remains limited. This study utilized two jujube cultivars with similar genetic backgrounds but differing fruit sizes to investigate the regulatory mechanisms affecting fruit size through cytological observations, transcriptome sequencing, and heterologous overexpression.
Results: The findings reveal that variations in mesocarp cell numbers during early fruit development significantly influence final fruit size.
Sci Rep
December 2024
Center for Global Health and Inter-Disciplinary Research, College of Public Health, University of South Florida, Tampa, FL, USA.
Successful transmission of Plasmodium falciparum from one person to another relies on the complete intraerythrocytic development of non-pathogenic sexual gametocytes infectious for anopheline mosquitoes. Understanding the genetic factors that regulate gametocyte development is vital for identifying transmission-blocking targets in the malaria parasite life cycle. Toward this end, we conducted a forward genetic study to characterize the development of gametocytes from sexual commitment to mature stage V.
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December 2024
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.
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December 2024
Centre for Veterinary Systems Transformation and Sustainability, Clinical Department for Farm Animals and Food System Science, University of Veterinary Medicine Vienna, Vienna, Austria.
The early microbial colonization of the porcine gut is an important priming factor for gut and immune development. Nevertheless, little is known about the composition of microbes that translocate into the ileo-cecal lymph nodes (ICLN) in the neonatal phase. This study aimed to characterize age- and nutrition-related changes in the metabolically active bacterial and fungal composition of the ICLN in suckling and newly weaned piglets.
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