Biology subjects

Ross, C. N.

Publications and source records attributed to Ross, C. N..

8 recordsLinked to original sources

bioRxiv2026

Development of immunological reagents for the identification of biomarkers of inflammation in the common marmoset

Marmosets (MAR, Callithrix jacchus) are nonhuman primates extensively studied in a broad array of preclinical biomedical research areas. However, the limited number of available immunological reagents remains a critical shortcoming of these models. We successfully developed monoclonal antibodies (mAbs) pairs that can be used in immunoassays for the identification and quantification of the biomarkers of inflammation C-reactive protein (CRP), CXCL-10 (IP-10), interleukin (IL)-4, IL-6, and IL-10. Recombinant MAR protein variants were produced in mammalian cells, purified and used for mice immunization. Hybridoma clones were selected first for their capacity to bind the recombinant proteins. All possible pair combinations of these mAbs were then tested for their capacity to identify their targets in MAR-derived samples. These MAR samples consisted of supernatant of PBMCs exposed ex vivo to different stimulants, and plasma samples from animals stimulated in vivo with a low-dose intravenous LPS inoculation. The majority of the mAbs that recognized the recombinant proteins failed to bind to the MAR-derived homologs. However, we found MAR-derived reactive mAbs and selected pairs with optimal sensitivity and signal-to-noise ratio for immunoassays that included Luminex multiplexing assays, ELISA, and ELISpot assays. These immunoreagents and assays will improve the translational value of different MAR biomedical models.

immunology↗

bioRxiv2026

An Aging Risk-Factor Scale: Biomarkers of Renal Disease and Anemia are Primary Predictors of Three-Year Survival in Common Marmosets (Callithrix jacchus)

Valid animal models are needed to evaluate how age-related changes in kidney function influence healthspan. Aging marmosets frequently develop renal insufficiency with anemia and exhibit reductions in body mass and metabolic rate. However, it remains unclear which age-related changes predict survival and which thresholds indicate increased mortality risk. We prospectively evaluated age, body composition, resting energy expenditure, hematology, and blood chemistry as predictors of 3-year survival in female and male marmosets (n = 66), 2-16 years of age. Objectives were to identify prognostic markers, define high-risk thresholds, and to develop and test a composite risk-factor scale for mortality screening in captivity. A 10-variable model showed the best predictive performance in multivariable Cox proportional hazards modeling, and was retained for further analysis (concordance = 0.881, p < 0.001). ROC curves using Youdens Index and AUC identified high-risk thresholds for predictors in the multivariable model, and threshold-defined categories were evaluated by Kaplan-Meier survival analysis. The 10 binary risk-factors were combined into a composite scale scored from 0 to 10 and tested with Cox regression. The scale explained approximately 42% of variance in survival and each additional risk factor increased mortality risk 1.75-fold (95% CI: 1.43-2.14, p < 0.001). Marmosets with [≥]7 risk factors exhibited a 19-month reduction in survival, and this high-risk threshold predicted 3-year survival with 89.4% accuracy. Results support the scale as a screening tool for mortality risk and highlight the high prevalence of age-associated renal disease and anemia in marmosets.

physiology↗

bioRxiv2025

Aging Leads to Altered Physiological Reactivity in Response to Repeated Social Separation Stress in a Nonhuman Primate Model

Social relationships are critical for maintaining physical health and psychological wellbeing. Since nearly 1 in 4 adults aged 65 years or older are socially isolated, there is a strong need to understand how repeated social stress negatively impacts health outcomes. Using a nonhuman primate model of social aging (i.e., marmosets), we examined whether individuals transitioning into old age ("peri-geri") or individuals who were already geriatric ("very-geri") showed differences in measures of hypothalamic-pituitary axis (HPA) activity, markers of metabolic and immune function, and reunion social behavior in response to repeated social separation challenges (SSC). We found female marmosets, especially peri-geri females, had higher HPA reactivity and better HPA recovery than male marmosets, but this difference diminished in older, very-geri marmosets. HPA activity was correlated with multiple outcomes including locomotive behavior and grooming, changes in blood glucose levels, and neutrophil counts. Moreover, marmosets who approached their partner more and were groomed less during reunions had higher cortisol levels the following day. Interestingly, we found two distinct HPA profiles among our marmosets with half showing strong HPA responses (reactors) and the other half showing little or no HPA response (non-reactors). Non-reactors had less weight gain/more weight loss; elevated levels of calcium, phosphorus, and white blood cells; and received less grooming and social contact time during reunion. Overall, old-aged marmosets who show attenuated HPA responses may have different vulnerabilities to negative health and behavioral outcomes during social stress, and male marmosets appear more likely to present with this HPA non-reactor phenotype earlier in aging.

physiology↗

bioRxiv2025

The genomic legacy of selectively breeding rhesus macaques for HIV/AIDS-related research

BackgroundRhesus macaques are the preferred non-human primate model for HIV/AIDS-related research. Specific major histocompatibility complex (MHC) haplotypes and genetic ancestry are linked to slow disease progression of Simian Immunodeficiency Virus (SIV) infections in macaques. To maximize their utility for HIV/AIDS research, the Southwest National Primate Research Center (SNPRC) has introduced targeted breeding strategies to reduce the prevalence of SIV-refractory MHC haplotypes and levels of admixture between Indian- and Chinese-origin macaques. ResultsWe characterized the MHC region in SNPRC macaques by targeted deep sequencing of 1,458 animals born over a ten-year period. Following the implementation of MHC management strategies, the prevalence of SIV-refractory MHC haplotypes reduced significantly while overall haplotype diversity was maintained. We investigated the impact of management strategies on admixture, population genetic structure, genetic diversity and inbreeding using whole exome sequencing of founding and colony-born animals (n=488). Admixture analysis of founders showed some Chinese ancestry, though population substructure more closely reflected primate research center source than geographical origin. The levels of Chinese ancestry declined significantly over time, though genetic diversity remains high. Finally, we performed genome-wide scans for genetic selection over time. We identify numerous genomic regions where allele frequencies have shifted significantly, supporting the presence of short-term adaptation within the colony. ConclusionsWe show that colony management strategies have been successful without reducing genetic diversity of the MHC or exonic regions. We also show that colony genetic substructure is related to animal colony source and that mergers and migrations have reduced inbreeding and increased overall genetic diversity.

genomics↗

bioRxiv2025

Validation of Body Condition Scoring as a Screening Test for Low Body Condition and Obesity in Common Marmosets (Callithrix jacchus)

Assessing body weight is common practice for monitoring health in common marmosets (Callithrix jacchus). Body composition analysis via quantitative magnetic resonance (QMR) is a more in-depth assessment allowing measurements of lean and fat mass, but it is expensive and remains unavailable to most. Alternatively, body condition scoring (BCS) is an instrument-free method for visually inspecting and palpating lean and fat tissue. Animals are rated for lean and fat mass abundance, using an ordinal scale with species-specific descriptions as reference. However, modified BCS systems developed for other species are being used, because no BCS system has been fully validated for marmosets. The accuracy of BCS in identifying marmosets with poor body condition or obesity remains unknown. We assessed an adapted BCS for marmosets (n=68, 2-16 years). Objectives were to 1) determine whether BCS predicts body weight and body composition, and 2) evaluate the performance of BCS as a screening test for low body condition and obesity in marmosets, in comparison to QMR body composition analysis. BCS predicted body weight and body composition (F(15, 166)=7.51, Wilks {Lambda}=0.240, p<0.001), and was better at predicting low lean mass and obesity, than at predicting low adiposity. Marmosets with low BCS had higher odds of low lean mass (B=3.37, (95% CI, 0.95-5.78), OR=29.0, p=0.006). Marmosets with excessively high BCS had higher odds of obesity (B=2.72, (95% CI, 1.07-4.38), OR=15.23, p=0.001). The accuracy of BCS suggests it can serve as an instrument-free method to screen for low body condition (79.4%-91.2%) and obesity (77.9%) in marmosets. Research highlightsO_LIWe evaluated body condition scoring (BCS) as a screening tool for detecting low body condition and obesity in marmosets by comparing it to diagnoses based on quantitative magnetic resonance, the gold-standard method for body composition analysis. C_LIO_LIBCS was more accurate at detecting low lean mass and obesity than low adiposity, with marmosets having low BCS showing higher odds of low lean mass and those with excessively high BCS having higher odds of obesity. C_LIO_LIResults suggest that BCS can serve as an instrument-free method to screen for low body condition and obesity in marmosets, enabling early detection of health decline and guiding the need for further diagnostic testing and treatment. C_LI

physiology↗

bioRxiv2023

Genetic characterization of a captive marmoset colony using genotype-by-sequencing

The marmoset is a fundamental non-human primate model for the study of aging, neurobiology, and many other topics. Genetic management of captive marmoset colonies is complicated by frequent chimerism in the blood and other tissues, a lack of tools to enable cost-effective, genome-wide interrogation of variation, and historic mergers and migrations of animals between colonies. We implemented genotype-by-sequencing (GBS) of hair follicle derived DNA (a minimally chimeric DNA source) of 82 marmosets housed at the Southwest National Primate Research Center (SNPRC). Our primary goals were the genetic characterization of our marmoset population for pedigree verification and colony management and to inform the scientific community of the functional genetic makeup of this valuable resource. We used the GBS data to reconstruct the genetic legacy of recent mergers between colonies, to identify genetically related animals whose relationships were previously unknown due to incomplete pedigree information, and to show that animals in the SNPRC colony appear to exhibit low levels of inbreeding. Of the >99,000 single-nucleotide variants (SNVs) that we characterized, >9,800 are located within gene regions known to harbor pathogenic variants of clinical significance in humans. Overall, we show the combination of low-resolution (sparse) genotyping using hair follicle DNA is a powerful strategy for the genetic management of captive marmoset colonies and for identifying potential SNVs for the development of biomedical research models.

genetics↗

bioRxiv2022

Efficient generation of marmoset primordial germ cell-like cells using induced pluripotent stem cells

Reconstitution of germ cell fate from pluripotent stem cells provides an opportunity to understand the molecular underpinnings of germ cell development. Here, we established robust methods for pluripotent stem cells (iPSCs) culture in the common marmoset (Callithrix jacchus, cj), which stably propagate in an undifferentiated state. Notably, iPSCs cultured on a feeder layer in the presence of a WNT signaling inhibitor upregulated genes related to ubiquitin-dependent protein catabolic processes and enter a permissive state that enables differentiation into primordial germ cell-like cells (PGCLCs) bearing immunophenotypic and transcriptomic similarities to pre-migratory cjPGCs in vivo. Induction of cjPGCLCs is accompanied by transient upregulation of mesodermal genes culminating in the establishment of a primate specific germline transcriptional network. Moreover, cjPGCLCs can be expanded in monolayer while retaining the germline state. Upon co-culture with mouse testicular somatic cells, these cells acquire an early prospermatogonia-like phenotype. Our findings provide a framework for understanding and reconstituting marmoset germ cell development in vitro, thus providing a comparative tool and foundation for a preclinical modeling of human in vitro gametogenesis.

developmental biology↗

bioRxiv2020

SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species

There are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.

immunology↗