Publications by authors named "Kimberly Zaldana"

Persistent viral infections are associated with long-term health issues and prolonged transmission. How external perturbations after initial exposure affect the duration of infection is unclear. We discovered that murine astrovirus, an enteric RNA virus, persists indefinitely when mice remain unperturbed but is cleared rapidly after cage change.

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Unlabelled: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that continues to have poor prognosis despite recent therapeutic advances. Venetoclax (Ven), a BCL2-inhibitor has shown a high response rate in AML; however, relapse is invariable due to mitochondrial dysregulation that includes upregulation of the antiapoptotic protein MCL1, a central mechanism of Ven resistance (Ven-res). We have previously demonstrated that the transcription factor STAT3 is upregulated in AML hematopoietic stem and progenitor cells (HSPCs) and can be effectively targeted to induce apoptosis of these aberrant cells.

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Article Synopsis
  • - The study investigates how genetics and environment together affect immune responses in mice, focusing on three different inbred strains (C57BL/6, 129S1, PWK/PhJ) in an outdoor setting and infected with a specific parasite.
  • - It finds that while the overall structure of immune cells is influenced by both genetics and the environment, the variation in certain immune responses, like cytokine levels, is mainly determined by genetics, affecting how many parasites the mice carry.
  • - Additionally, the expression of immune markers like CD44 shows different influences: on T cells, it’s mostly genetic, while on B cells, it’s more environmental; and importantly, the impact of genetics appears to lessen when the mice
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Environmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individual's interaction with its environment. We therefore tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including associations measured from spatiotemporal co-occurrences, to immune phenotypes.

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Plasma cells (PCs) are essential for humoral immunity, as they are responsible for the production of antibodies and contribute to immunological memory. Despite their importance, differentiating between long-lived and short-lived PCs remains a challenge due to a lack of specific markers to distinguish these populations. Addressing this gap, our study introduces a novel J-chain CreERT2 GFP allele (IgJ) for precise genetic studies of PCs.

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The paucity of blood granulocyte populations such as neutrophils in laboratory mice is a notable difference between this model organism and humans, but the cause of this species-specific difference is unclear. We previously demonstrated that laboratory mice released into a seminatural environment, referred to as rewilding, display an increase in blood granulocytes that is associated with expansion of fungi in the gut microbiota. Here, we find that tonic signals from fungal colonization induce sustained granulopoiesis through a mechanism distinct from emergency granulopoiesis, leading to a prolonged expansion of circulating neutrophils that promotes immunity.

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The relative and synergistic contributions of genetics and environment to inter-individual immune response variation remain unclear, despite its implications for understanding both evolutionary biology and medicine. Here, we quantify interactive effects of genotype and environment on immune traits by investigating three inbred mouse strains rewilded in an outdoor enclosure and infected with the parasite, . Whereas cytokine response heterogeneity was primarily driven by genotype, cellular composition heterogeneity was shaped by interactions between genotype and environment.

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Chromosomal instability (CIN) is a hallmark of many cancers. Restricting the localization of centromeric histone H3 variant CENP-A to centromeres prevents CIN. CENP-A overexpression (OE) and mislocalization have been observed in cancers and correlate with poor prognosis; however, the molecular consequences of CENP-A OE on CIN and aneuploidy have not been defined.

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