Comparative Fibroblast Physiology Identifies High-Altitude Specializations in Gelada

Physiology · 2026-05-01

Mammals occupy diverse environments and face many physiological challenges, such as hypoxia. Several species, including certain human populations, have acclimated to high-altitude, chronically low-oxygen conditions. However, human high-altitude populations arose roughly 46,000 years ago, whereas other species, including primates like the gelada (Theropithecus gelada), have lived at elevations of 2,350-4,550m in the Ethiopian Highlands for at least 1 million years. Geladas exhibit a combination of morphological and physiological traits associated with altitude adaptation, including larger chest dimensions, reduced hemoglobin concentrations, and increased selection in hypoxia-related genes. To investigate the cellular mechanisms underlying hypoxia tolerance in geladas, we isolated dermal fibroblasts from ear biopsies collected from wild individuals (n = 25) in Ethiopia as part of the Simien Mountains Gelada Research Project. These cells were compared to dermal fibroblasts from sea-level humans (ATCC), and we also included fibroblasts from fat-tailed dwarf lemurs. Using an Amplex Red assay, we measured reactive oxygen species (ROS) production across species. Under baseline normoxic conditions (21% O 2 ), gelada fibroblasts generated 91% less ROS than human fibroblasts, suggesting a mechanism to limit hypoxia-induced cellular damage. Under hypoxic conditions (0.5% O 2 ), gelada fibroblasts produced 39% less ROS than humans (n=2) and 72% less than lemurs (n=1). We also assessed HIF1α accumulation by western blot following 6 hours of hypoxia (0.5% O 2 ) and found that gelada HIF1α accumulation was ~⅓ human levels, consistent with enhanced hypoxia tolerance. Future work will expand biological replication and incorporate additional comparison groups, including lowland baboons and high-altitude human populations. Funded by NSF 2022046 & NSF SBE-2010309. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Best practices for genotype imputation from low‐coverage sequencing data in natural populations

UNC Libraries · 2026-04-14

Monitoring genetic diversity in wild populations is a central goal of ecological and evolutionary genetics and is critical for conservation biology. However, genetic studies of nonmodel organisms generally lack access to species-specific genotyping methods (e.g. array-based genotyping) and must instead use sequencing-based approaches. Although costs are decreasing, high-coverage whole-genome sequencing (WGS), which produces the highest confidence genotypes, remains expensive. More economical reduced representation sequencing approaches fail to capture much of the genome, which can hinder downstream inference. Low-coverage WGS combined with imputation using a high-confidence reference panel is a cost-effective alternative, but the accuracy of genotyping using low-coverage WGS and imputation in nonmodel populations is still largely uncharacterized. Here, we empirically tested the accuracy of low-coverage sequencing (0.1-10×) and imputation in two natural populations, one with a large (n = 741) reference panel, rhesus macaques (Macaca mulatta), and one with a smaller (n = 68) reference panel, gelada monkeys (Theropithecus gelada). Using samples sequenced to coverage as low as 0.5×, we could impute genotypes at >95% of the sites in the reference panel with high accuracy (median r²  ≥ 0.92). We show that low-coverage imputed genotypes can reliably calculate genetic relatedness and population structure. Based on these data, we also provide best practices and recommendations for researchers who wish to deploy this approach in other populations, with all code available on GitHub (https://github.com/mwatowich/LoCSI-for-non-model-species). Our results endorse accurate and effective genotype imputation from low-coverage sequencing, enabling the cost-effective generation of population-scale genetic datasets necessary for tackling many pressing challenges of wildlife conservation.

Postoperative inflammatory responses and association with in‐hospital mortality after general surgery

ANZ Journal of Surgery · 2025-04-03

BACKGROUND: The relationship between postoperative in-hospital mortality and inflammatory markers has not been well described. This study aimed to characterize the association between specific clinical markers of inflammation and in-hospital mortality in the early postoperative period in general surgical patients. METHODS: This study included consecutive general surgery admissions at two tertiary hospitals in South Australia over a 2-year period. Collected data included patient demographics, Charlson comorbidity index, in-hospital mortality, vital signs, and laboratory tests. In particular, temperature, neutrophil count, lymphocyte count, platelet count, albumin level, and C-reactive protein (CRP) were collected for the 48 h after surgery. Multivariable logistic regression was conducted to examine the association between clinical inflammatory markers and in-hospital mortality in the first 24 h postoperatively and 24-48 h postoperatively. RESULTS: /L were significantly associated with an increased likelihood of in-hospital mortality, whereas platelets, albumin, and CRP during were not. Between 24 and 48 h postoperatively, increases in maximum neutrophil counts, lymphocyte counts, and platelet counts were significantly associated with an increased likelihood of in-hospital mortality, whereas changes in temperature, albumin, and CRP were not. CONCLUSIONS: This is the first study to characterize the inflammatory response using specific clinical laboratory markers, and their relative association with in-hospital mortality, in the first 2 days after general surgery.

Evidence for deceptive fertility in a wild primate

Current Biology · 2025-11-19 · 1 citations

Intestivirid Acquisition Increases Across Infancy in a Wild Primate Population

Molecular Ecology · 2025-05-22 · 2 citations

Intestivirids (order Crassvirales, family Intestiviridae), viruses that infect Bacteroidales bacteria in the mammalian gastrointestinal tract, have been identified as a highly abundant component of the healthy human virome that may shape patterns of human health and disease through direct action on the microbiome. While double-stranded DNA bacteriophages called crAssphages (Carjivirus communis) that infect bacteria in the Bacteroidales order have been identified in humans within the first month of life, the enormous variation in post-parturition infant environments and diets has inhibited a robust understanding of the physiological and environmental factors that govern acquisition patterns. We turned to a wild population of graminivorous nonhuman primates (geladas, Theropithecus gelada) under long-term study in the Simien Mountains National Park, Ethiopia, analysing faecal samples from infants and mothers in this population across the infancy period for richness and presence of crAssphage-like viruses (family Intestiviridae). Eight intestivirid genomes were identified based on terminal redundancy representing six unique variants (< 98% intergenomic similarity) closely related to the human crAssphage. The prevalence of intestivirids in gelada faecal samples begins to rise at about 10 months of age, peaks in the months surrounding weaning (~18 months), and somewhat decreases but maintains high levels into adulthood. We found a strong association between cumulative rainfall and intestivirid detection, with a higher likelihood accompanying wetter seasons with higher grass availability. In this population, the months prior to weaning have been found to be accompanied by a shift in the microbiome characterised by a decrease in glycan degrader Bacteroidales taxa and an increase in fermentative Bacteroidales taxa, and wetter seasons when the vast majority of the gelada diet comprises grasses are associated with an increase in fermentative Bacteroidales taxa. In the context of these microbiome shifts, our results suggest that the intestivirid-bacterial host relationship may interact with major developmental and seasonal dietary shifts in the mammalian host.

Author response for "Conditional benefits of social integration in wild female geladas"

2025-04-22

Angiotensin II decreases autophagy and recruits double FYVE domain-containing protein 1 in the mitochondria of vascular smooth muscle cells

Physiology · 2025-05-01

Autophagy, an intracellular degradation process crucial for maintaining cellular homeostasis, is regulated by angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs). However, the role of Double FYVE Domain Containing Protein 1 (DFCP1), an early autophagosome protein that inhibits autophagy, particularly in VSMCs, is still largely unknown. We investigated the role of DFCP1 on Ang II-mediated autophagy in VSMCs and found that Ang II (100 nM) decreased beclin-1 and LC3II (a late autophagosome maker) protein expressions. The Ang II-mediated decrease in beclin-1 and LC3-II was attenuated by an AT 1 R antagonist, losartan (10 µM), indicating that Ang II decreased autophagy in the autophagosome formation stage through AT 1 R. Ang II had no effect on the protein expression of Unc-51-like autophagy activating kinase 1 (ULK1) and phospho-ULK1, which are important in the early stages of autophagosome formation. By contrast, Ang II increased DFCP1 and decreased LC3 protein expressions in a concentration (10 nM-1 mM) and time-dependent manner. Ang II (1 nM, 15 min) increased the DFCP1 puncta fluorescence intensity and the colocalization of DFCP1 with Hsp60 (Veh: 5.7±3.1% vs. Ang II: 11.6±6.7%, N=5, p&lt;0.05, Student’s t -test), a heat shock chaperonin in mitochondria that plays a critical role in mitochondria dynamics and homeostasis. We conclude that in VSMCs, Ang II increases DFCP1 protein expression and decreases non-selective autophagy, which is associated with the initiation of mitophagy, a subtype of selective autophagy. National Institutes of Health DK119652 and DK134574. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Maternal glucocorticoids and behavior shape offspring developmental trade-offs in wild baboons

bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-18

Abstract Mammalian mothers provide behavioral and physiological signals that offspring use to calibrate development in relation to maternal resources and environmental cues. Infants respond selectively as they prioritize certain developmental systems over others, creating developmental tradeoffs between competing biological systems. Here, we investigate the influence of maternal capital (“investment capacity”) on the growth and development of their infants in wild olive baboons ( Papio anubis ) from Laikipia, Kenya. We posit that maternal capital is influenced by a mother’s own early life experiences (e.g., drought, maternal loss) and her current life experiences (e.g., dominance rank, food availability), and is signaled to offspring via maternal effort (i.e., nursing and carrying time) and glucocorticoids. We used behavioral data on 40 infants (43% female) in the first year of life to quantify maternal effort, infant play, and infant independence (i.e., frequency of infant departures from mother). We matched these behavioral data with maternal fecal glucocorticoid measures from lactating mothers, and infant growth measures assessed via photogrammetry. Signals of low maternal capital predicted lower rates of infant play, less behavioral independence, and slower growth. There was a negative relationship between the rate of social contact play and growth rate, indicating a developmental tradeoff. Males were more sensitive than females to some of the maternal signals measured in our study. These results add to a growing body of evidence demonstrating that maternal behavioral and physiological signals shape infant development.

Disparate social structures are underpinned by distinct social rules across a primate radiation

Proceedings of the National Academy of Sciences · 2025-07-31

ABSTRACT Over six decades of research on wild baboons and their close relatives (collectively, the African papionins) have uncovered substantial variation in their behavior and social systems. While most papionins form discrete social groups (single-level societies), a few others form small social units that are nested within larger supergroups (multi-level societies). These two systems are generally thought to be qualitatively distinct, but data from wild populations increasingly suggest that there may be areas of overlap. To quantify this potential gradient in social structure, a more systematic, comparative analysis is needed. Here, we constructed a database of behavioral and demographic records spanning 135 group-years, 28 social groups, 13 long-term field studies, and 11 species to quantify variation in grooming network structure, and identify the individual and dyadic properties (e.g., kinship and social status effects) that underlie this variation. Consistent with accumulating observations in the field, the single-level species could be divided into two categories: cohesive and cliquish . Cohesive single-level networks were dense, kin-biased, and moderately rank-structured, while cliquish single-level networks were more differentiated, slightly more kin-biased, and strongly rank-structured. As expected, multi-level networks were very modular and shaped by females’ ties to specific dominant males but varied in their kin biases. Taken together, these data suggest that (i) kin and rank biases are widespread but vary in their strength; (ii) male-centered subgroups are exclusive to multi-level systems; and (iii) increases in network modularity can emerge in response to heightened nepotism and male-centered clustering. SIGNIFICANCE STATEMENT What forces explain variation in primate societies? While kinship and dominance shape the social lives of many of our close relatives, it is unclear how their effects differ across species. Using a new database comprising decades of field research, we found that baboons and their close relatives fell into three general patterns: one in which groups were cohesive, kin-biased, and moderately rank-biased, another in which groups were more cliquish and nepotistic, and a third in which groups were divided into clusters centered on dominant males. Distinct primate societies may thus reflect differences in the strength of females’ nepotistic biases and the degree of males’ social influence.

For <scp>CPR</scp> or Not‐For‐<scp>CPR</scp>? Demographic Factors Predict Resuscitation Order Documentation and <scp>CPR</scp> Status in General Surgery Patients

ANZ Journal of Surgery · 2025-06-26

BACKGROUND: To improve healthcare equity, this study aimed to determine which demographic factors are associated with resuscitation order documentation and not-for-cardiopulmonary resuscitation (CPR) status in general surgery patients. METHODS: A retrospective cohort study was conducted including patients admitted under general surgical services of two hospitals in South Australia over 2 years. Logistic regression evaluated associations between demographic factors, and resuscitation order documentation and not-for-CPR status. RESULTS: 12 846 patients were included, with 1853 (14.4%) having documented resuscitation orders. Of those with resuscitation orders, 964 (52.0%) were for CPR in cardiac arrest. Increased age (OR 1.05, 95% CI 1.04-1.05, p < 0.001), increased Charlson comorbidity index (OR 1.15, 95% CI 1.13-1.17, p < 0.001) and lower socioeconomic status (OR 0.997, 95% CI 0.995-0.999, p = 0.008) were associated with a greater likelihood of having a resuscitation order documented. Female sex (OR 0.76, 95% CI 0.60-0.95, p = 0.016), increased age (OR 0.92, 95% CI 0.91-0.93, p < 0.001), and Charlson comorbidity index (OR 0.89, 95% CI 0.86-0.92, p < 0.001) were significantly associated with being not-for-CPR. Having a resuscitation order documented (OR 18.0, 95% CI 10.9-29.7, p < 0.001) and being not-for-CPR (OR 20.7, 95% CI 10.0-42.8, p < 0.001) were significantly associated with increased in-hospital mortality. Having a specified religion was associated with an OR of 1.29 for being for CPR (95% CI 1.02-1.62, p = 0.032). CONCLUSION: This study demonstrated that multiple demographic factors predict resuscitation order documentation and content in general surgery patients, including which patients are not-for-CPR. These findings may improve equity in care for general surgery patients in clinical deterioration and end-of-life situations.