Cell leukostasis during organ-targeted chemotherapy in human retinal endothelial cells and rhesus macaques endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE34389 | GEO | 2011/12/13
SECONDARY ACCESSION(S): PRJNA149585
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE34379: Carboplatin-treated human retinal endothelial cells GSE34381: Melphalan-treated human retinal endothelial cells Refer to individual Series
2011-12-13 | E-GEOD-34389 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-06-19 | GSE218271 | GEO
Project description:The mechanisms underlying depletion of CD4 T cells during acute HIV-1 infection are not well understood. Here we show that caspase-1-induced pyroptosis, a highly inflammatory programmed cell death pathway, is the dominant mechanism responsible for the rapid depletion of CD4 T cells in gut-associated lymphatic tissue (GALT), spleen, and lymph nodes during acute simian immunodeficiency virus (SIV) infection in rhesus macaques. Upregulation of interferon-gamma inducible factor 16, a host DNA sensor that triggers pyroptosis, was also observed in tissue-resident CD4 T cells and correlated with viral loads and CD4 T cell loss. In contrast, caspase-3-mediated apoptosis and viral cytotoxicity only accounted for a small fraction of CD4 T cell death. Other programmed cell death mechanisms, including mitochondria-induced caspase-independent cell death, necroptosis, and autophagy, did not significantly contribute to CD4 T cell depletion. These data support a model in which caspase-1-mediated pyroptosis is the principal mechanism that results in CD4 T cell loss in the GALT and lymphoid organs and release of proinflammatory cytokines. These findings contribute to our understanding of the pathogenesis of acute SIV infection and have important implications for the development of therapeutic strategies. IMPORTANCE Different mechanisms for CD4 T cell depletion during acute HIV-1 infection have been proposed. In this study, we demonstrate that in early simian immunodeficiency virus infection, depletion of CD4 T cells is primarily due to pyroptosis. Other mechanisms may also contribute in a minor way to CD4 T cell depletion.
| S-EPMC9472632 | biostudies-literature
Project description:PurposeNon-human primates (NHPs) are useful models for human retinal disease. Chromatic pupillometry has been proposed as a noninvasive method of identifying inherited retinal diseases (IRDs) in humans; however, standard protocols employ time-consuming dark adaptation. We utilized shortened and standard dark-adaptation protocols to compare pupillary light reflex characteristics following chromatic stimulation in rhesus macaques with achromatopsia to wild-type (WT) controls with normal retinal function.MethodsNine rhesus macaques homozygous for the p.R656Q mutation (PDE6C HOMs) and nine WT controls were evaluated using chromatic pupillometry following 1-minute versus standard 20-minute dark adaptations. The following outcomes were measured and compared between groups: pupil constriction latency, peak constriction, pupil constriction time, and constriction velocity.ResultsPupil constriction latency was significantly longer in PDE6C HOMs with red-light (P = 0.0002) and blue-light (P = 0.04) stimulation versus WT controls. Peak constriction was significantly less in PDE6C HOMs with all light stimulation compared to WT controls (P < 0.0001). Pupil constriction time was significantly shorter in PDE6C HOMs versus WT controls with red-light (P = 0.04) and white-light (P = 0.003) stimulation. Pupil constriction velocity was significantly slower in PDE6C HOMs versus WT controls with red-light (P < 0.0001), blue-light (P < 0.0001), and white-light (P = 0.0002) stimulation. Dark adaptation time only significantly affected peak (P = 0.008) and time of pupil constriction (P = 0.02) following blue-light stimulation.ConclusionsChromatic pupillometry following 1- and 20-minute dark adaptation is an effective tool for screening NHPs for achromatopsia.Translational relevanceRapid identification of NHPs with IRDs will provide animal research models to advance research and treatment of achromatopia in humans.
| S-EPMC10289275 | biostudies-literature
Project description:A defining feature of catarrhine primates is uniform trichromacy-the ability to distinguish red (long; L), green (medium; M), and blue (short; S) wavelengths of light. Although the tuning of photoreceptors is conserved, the ratio of L:M cones in the retina is variable within and between species, with human cone ratios differing from other catarrhines. Yet, the sources and structure of variation in cone ratios are poorly understood, precluding a broader understanding of color vision variability. Here, we report a large-scale study of a pedigreed population of rhesus macaques (Macaca mulatta). We collected foveal RNA and analyzed opsin gene expression using cDNA and estimated additive genetic variance of cone ratios. The average L:M ratio and standard error was 1.03:1 ± 0.02. There was no age effect, and genetic contribution to variation was negligible. We found marginal sex effects with females having larger ratios than males. S cone ratios (0.143:1 ± 0.002) had significant genetic variance with a heritability estimate of 43% but did not differ between sexes or age groups. Our results contextualize the derived human condition of L-cone dominance and provide new information about the heritability of cone ratios and variation in primate color vision.
| S-EPMC9544366 | biostudies-literature
Project description:Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5-10 y old were calculated for neutrophils (1.63 ± 0.16 d, 1.42 × 109 cells/l/d), basophils (1.78 ± 0.30 d, 5.89 × 106 cells/l/d), and CD14+CD16- classical monocytes (1.01 ± 0.15 d, 3.09 × 108 cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4-5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.
| S-EPMC6263173 | biostudies-literature
Project description:The emergence of social behaviors early in life is likely crucial for the development of mother-infant relationships. Some of these behaviors, such as the capacity of neonates to imitate adult facial movements, were previously thought to be limited to humans and perhaps the ape lineage. Here we report the behavioral responses of infant rhesus macaques (Macaca mulatta) to the following human facial and hand gestures: lip smacking, tongue protrusion, mouth opening, hand opening, and opening and closing of eyes (control condition). In the third day of life, infant macaques imitate lip smacking and tongue protrusion. On the first day of life, the model's mouth openings elicited a similar matched behavior (lip smacking) in the infants. These imitative responses are present at an early stage of development, but they are apparently confined to a narrow temporal window. Because lip smacking is a core gesture in face-to-face interactions in macaques, neonatal imitation may serve to tune infants' affiliative responses to the social world. Our findings provide a quantitative description of neonatal imitation in a nonhuman primate species and suggest that these imitative capacities, contrary to what was previously thought, are not unique to the ape and human lineage. We suggest that their evolutionary origins may be traced to affiliative gestures with communicative functions.
| S-EPMC1560174 | biostudies-literature
Project description:BackgroundNeuromelanin is mostly located in dopaminergic neurons in the substantia nigra (SN) pars compacta, and can be detected by magnetic resonance imaging (MRI). It is a promising imaging-base biomarker for neurological diseases. We previously developed a melanin-specific probe N-(2-(diethylamino)-ethyl)-18F-5-fluoropicolinamide (18F-P3BZA), which was initially developed for the imaging of melanoma. 18F-P3BZA exhibited high levels of binding to the melanin in vitro and in vivo with high retention and favorable pharmacokinetics. In this study we further investigated whether 18F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques.Results18F-P3BZA exhibited desired hydrophobicity with estimated log Know 5.08 and log D7.4 1.68. 18F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. 18F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. Binding of 18F-P3BZA to B16F10 cells was much higher than to SKOV3 cells at 60 min (6.17 ± 0.53%IA and 0.24 ± 0.05%IA, respectively). In the biodistribution study, 18F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, 18F-P3BZA uptake in B16F10 tumors could be blocked by excess cold 19F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI 18F-P3BZA provided clear visualization of neuromelanin-rich SN at 30-60 min after injection in healthy macaques. The SN to cerebella ratios were 2.7 and 2.4 times higher at 30 and 60 min after injection. In in vitro autoradiography studies 18F-P3BZA exhibited high levels of binding to the SN, and almost no binding to surrounding midbrain tissues.Conclusion18F-P3BZA PET/MRI clearly images neuromelanin in the SN, and may assist in the early diagnosis of neurological diseases associated with abnormal neuromelanin expression.
| S-EPMC11372002 | biostudies-literature
Project description:As natural disasters become more frequent due to climate change, understanding the biological impact of these ecological catastrophes on wild populations becomes increasingly pertinent. Fluctuating asymmetry (FA), or random deviations from bilateral symmetry, is reflective of developmental instability and has long been positively associated with increases in environmental stress. This study investigates craniofacial FA in a population of free-ranging rhesus macaques (Macaca mulatta) that has experienced multiple Category 3 hurricanes since the colony's inception on Cayo Santiago, including 275 individuals from ages 9 months to 31 years (F = 154; M = 121). Using geometric morphometrics to quantify FA and a linear mixed-effect model for analysis, we found that sex, age, and decade of birth did not influence the amount of FA in the individuals included in the study, but the developmental stage at which individuals experienced these catastrophic events greatly impacted the amount of FA exhibited (p = .001). Individuals that experienced these hurricanes during fetal life exhibited greater FA than any other post-natal developmental period. These results indicate that natural disasters can be associated with developmental disruption that results in long-term effects if occurring during the prenatal period, possibly due to increases in maternal stress-related hormones.
| S-EPMC10421717 | biostudies-literature
Project description:Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.
| S-EPMC4671657 | biostudies-literature