Cun Li

University of Wyoming

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Peter W. Nathanielsz

University of Wyoming

Laura A. Cox

Wake Forest University

Hillary F. Huber

Texas Biomedical Research Institute

Geoffrey D. Clarke

Royal Bolton Hospital

Anderson H. Kuo

Midland College

Adam B. Salmon

The University of Texas Health Science Center at San Antonio

Thomas J. McDonald

Texas A&M University

Susan L. Jenkins

Texas Biomedical Research Institute

Mark J. Nijland

University of the Incarnate Word

Thomas Jansson

University of Colorado Anschutz Medical Campus

Cooperative Institutions

The University of Texas Health Science Center at San Antonio

Texas Biomedical Research Institute

Huazhong University of Science and Technology

Wake Forest University

Tongji Hospital

China Agricultural University

The University of Texas at San Antonio

Texas Tech University

Ministry of Agriculture and Rural Affairs

Cornell University

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Research on Rural Elderly Sex Offence——the Investigation Results of Two Prisons in Chongqing

Journal of Hunan Police Academy (2012)

Cun Li

Rural elderly sex offence which has great harmfulness to society is often easily overlooked.Through the investigation on this phenomenon in two prisons in Chongqing,it is found that rural elderly sex offence is serious,and the cause of which is not only the satisfaction of sexual desire but also the deep social factors.This paper deeply analyses the causes and predicts the development trends of this problem and then draws a conclusion that it is a synthesis governing project of the whole society,and that prevention should be its main countermeasure.

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Social phenomenon

Rural Society

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Multi-omics Analysis of Aging Liver Reveals Changes in Endoplasmic Stress and Degradation Pathways in Female Nonhuman Primates

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Sobha Puppala Jeannie Chan Kip D. Zimmerman Zeeshan Hamid Isaac Ampong

The liver is critical for functions that support metabolism, immunity, digestion, detoxification, and vitamin storage. Aging is associated with severity and poor prognosis of various liver diseases such as nonalcoholic fatty liver disease (NAFLD). Previous studies have used multi-omic approaches to study liver diseases or to examine the effects of aging on the liver. However, to date, no studies have used an integrated omics approach to investigate aging-associated molecular changes in the livers of healthy female nonhuman primates. The goal of this study was to identify molecular changes associated with healthy aging in the livers of female baboons (

Omics

10.1101/2023.08.21.554149

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Testing Cellular Proliferation Responses to Oxidative, Glucocorticoid and Metabolic Challenges in the Baboon

Innovation in Aging (2020)

Daniel Adekunbi Cun Li Peter W. Nathanielsz Adam B. Salmon

Abstract Aging is associated with progressive loss of cellular homeostasis which results from intrinsic and extrinsic challenges. Testing how such challenges relate to the aging process is often limited by the available model systems. We use primary cells (fibroblasts) isolated from baboons as a non-human primate cellular model to address how stressful challenges affect resilience. Using a real-time live-cell imaging system, we characterized a protocol for testing the effects of pro-oxidant compounds (e.g hydrogen peroxide (H2O2), paraquat and thapsigargin), dexamethasone and low glucose environment on cellular proliferation in fibroblasts derived from baboons across the life-course. The inhibitory effect of H2O2 (50 and 100µM), an oxidative stress, on cell proliferation was dose-dependent, with a higher impact in old males (age 14.52-14.80 years; average life span 21 years) compared to young males (6.35-6.39 years). Exposure to a different oxidative stress, paraquat (100 and 200µM) tended to reduce cell proliferation rate with age in males but not females. Inhibitory effects of thapsigargin, an endoplasmic reticulum stress inducer, on cell proliferation were dependent on challenge duration (2 vs 24h), concentration (0.1 and 1µM) and donor age, with greater resilience in young males than young females (4.33-6.70 years). Dexamethasone (100 and 500µM), a glucocorticoid, reduced cell proliferation dose-dependently, with older males exhibiting more resilience than females. In response to low glucose (1mM), cell proliferation reduced with age. Donor’s chronological age and sex are important variables in cellular response to challenge compounds faced during aging, which will guide our on-going studies on the cellular transcriptome and proteome.

Thapsigargin

10.1093/geroni/igaa057.3283

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A first case of hepatocellular carcinoma in the baboon (Papio spp.) placenta

Journal of Medical Primatology (2018)

Natalia Schlabritz‐Loutsevitch Maira Carrillo Cun Li Peter W. Nathanielsz Christopher Maguire

We present a case of hepatocellular carcinoma (HCC) in the placenta of healthy baboon (Papio spp.). Grossly, the fetal, maternal, and placental tissues were unremarkable. Histologically, the placenta contained an unencapsulated, poorly demarcated, infiltrative, solidly cellular neoplasm composed of cells that resembled hepatocytes. The neoplastic cells were diffusely positive for vimentin and focally positive for Ae1/Ae3, Arginase -1, glutamine synthetase, and CD10, and negative for ER, vascular markers (CD31 and D240), S100, glypican, C-reactive protein, FABP, desmin, and beta-catenin; INI1 positivity was similar to non-neoplastic tissues. The case likely represents a unique subtype of HCC.

CD31

Desmin

10.1111/jmp.12382

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Antenatal Synthetic Glucocorticoid Exposure at Human Therapeutic Equivalent Doses Predisposes Middle-Age Male Offspring Baboons to an Obese Phenotype That Emerges With Aging

Reproductive Sciences (2018)

Hillary F. Huber Anderson H. Kuo Cun Li Susan L. Jenkins Ken Gerow

10.1177/1933719118778794

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325 Blood pressure and the kidney cortex transcriptome response to high sodium diet challenge in female nonhuman primates

Journal of Clinical and Translational Science (2022)

Angelica M. Riojas Kimberly D. Spradling‐Reeves Robert E. Shade Sobha Puppala Clinton L. Christensen

OBJECTIVES/GOALS: The goal of this study was to understand the impact of a high sodium diet on gene networks in the kidney that correlate with blood pressure in female primates, and translating findings to women. METHODS/STUDY POPULATION: Sodium-naÃ¯ve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 beta-estradiol, and ultrasound-guided kidney biopsies for RNA-Seq were collected at the end of each diet. Blood pressure was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. Weighted gene coexpression network analysis was performed on RNA-Seq data to identify transcripts correlated with blood pressure on each diet. Network analysis was performed on transcripts highly correlated with BP, and in silico findings were validated by immunohistochemistry of kidney tissues. RESULTS/ANTICIPATED RESULTS: On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP. Cell type composition of renal biopsies was consistent among all animals for both diets. Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. DISCUSSION/SIGNIFICANCE: Previous studies in primates to identify molecular networks dysregulated by HS diet focused on males. Current clinical guidelines do not offer sex-specific treatment plans for sodium sensitive hypertension. This study leveraged variation in BP as a first step to identify correlated kidney regulatory gene networks in female primates after a HS diet.

10.1017/cts.2022.182

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Moderate maternal nutrient reduction in pregnancy alters fatty acid oxidation and RNA splicing in the nonhuman primate fetal liver

Journal of Developmental Origins of Health and Disease (2023)

Kip D. Zimmerman Jeannie Chan Jeremy P. Glenn Shifra Birnbaum Cun Li

Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Differentially expressed transcripts were enriched for fatty acid oxidation and RNA splicing-related pathways. Increased RNA splicing activity in MNR was reflected in greater abundances of transcript splice variant isoforms in the MNR group. It can be hypothesized that the increase in splice variants is deployed in an effort to adapt to the poor in utero environment and ensure near-normal development and energy metabolism. This study is the first to study developmental programming across four critical gestational stages during primate fetal liver development and reveals a potentially novel cellular response mechanism mediating fetal programming in response to MNR.

10.1017/s204017442300003x

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A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging

Aging (2017)

Shanshan Yang Ken Gerow Hillary F. Huber McKenna M. Considine Cun Li

Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years. We identified significant age-related 1) linear fall in cortisol and PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and mineralocorticoid receptors; 3) increased PVN 11β-hydroxysteroid dehydrogenase 1 and 2, regulators of local cortisol production, and 4) decreased pituitary proopiomelanocortin. Our data identify increased age-related negative feedback and local PVN cortisol production as potential mechanisms decreasing PVN drive to hypothalamo-pituitary-adrenal axis activity that result in the age-related circulating cortisol fall. Further studies are needed to determine whether the cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an epiphenomenon unrelated to aging processes. We conclude that aging processes are best studied by linear life-course analysis beginning early in life.

Proopiomelanocortin

Mineralocorticoid

10.18632/aging.101235

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Glucocorticoid exposure at the dose used clinically alters cytoskeletal proteins and presynaptic terminals in the fetal baboon brain

The Journal of Physiology (2003)

Iwa Antonow‐Schlorke Matthias Schwab Cun Li Peter W. Nathanielsz

Graphical Abstract Abstract figure legend HCN channels play an evolutionarily conserved pacemaker role in renal pelvic smooth muscle (RPSM) of lower and higher order mammals. The function of hyperpolarization-activated cation (HCN) channels in smooth muscle pacemakers remains controversial. Renal pelvic smooth muscle pacemakers trigger smooth muscle contractions that expel waste from the kidney, and HCN channels have been localized to these pacemaker tissues. To date, however, the mechanisms underlying RPSM pacemaker activity remain elusive. RPSM pacemaker activity was investigated in both lower (top left) and higher order (bottom left) mammalian models, which exhibit divergent upper urinary tract anatomies. We performed morphological and functional studies from the single-molecule to the whole-organ level and showed that HCN channels drive RPSM pacemaker activity. RPSM pacemakers (boxed regions) integrated into the muscular syncytium, expressed HCN channels on their plasmalemma and exhibited the Ih ‘funny’ pacemaker current conducted by HCN channels. Critically, HCN channel block abolished electrical pacemaker activity and peristaltic smooth muscle contractions in both lower and higher order mammalian upper urinary tracts. Thus, HCN channels play an evolutionarily conserved pacemaker role in RPSM pacemakers.

10.1111/j.1469-7793.2003.00117.x

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Female baboon adrenal zona fasciculata and zona reticularis regulatory and functional proteins decrease across the life course

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Hillary F. Huber Cun Li Dongbin Xie Ken Gerow Thomas C. Register

ABSTRACT Debate exists on life-course adrenocortical zonal function trajectories. Rapid, phasic blood steroid concentration changes, such as circadian rhythms and acute stress responses, complicate quantification. To avoid pitfalls and account for life-stage changes in adrenocortical activity indices, we quantified zonae fasciculata (ZF) and reticularis (ZR) across the life-course, by immunohistochemistry of key regulatory and functional proteins. In 28 female baboon adrenals (7.5-22.1 years), we quantified 12 key proteins involved in cell metabolism, division, proliferation, steroidogenesis (including steroid acute regulatory protein, StAR), oxidative stress, and glucocorticoid and mitochondrial function. Life-course abundance of ten ZF proteins decreased with age. Cell cycle inhibitor and oxidative stress markers increased. Seven of the 12 proteins changed in the same direction for ZR and ZF. Importantly, ZF StAR decreased while ZR StAR was unchanged. Findings indicate ZF function decreased, and less markedly ZR function, with age. Causes and aging consequences of these changes remain to be determined.

Zona fasciculata

Zona reticularis

10.1101/2023.09.06.556552

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