Biology subjects

Russell, G.

Publications and source records attributed to Russell, G..

4 recordsLinked to original sources

bioRxiv2023

In vitro and in vivo effects of zoledronate on senescence and senescence-associated secretory phenotype markers

In addition to reducing fracture risk, zoledronate has been found in some studies to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple co-morbidities, the non-skeletal actions of zoledronate could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype [SASP]) actions. To test this, we first performed in vitro senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronate killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronate or vehicle for 8 weeks, zoledronate significantly reduced circulating SASP factors, including CCL7, IL-1{beta}, TNFRSF1A, and TGF{beta}1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronate demonstrated a significant downregulation of senescence/SASP genes (SenMayo). To establish that these cells are potential senolytic/senomorphic targets of zoledronate, we used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronate significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. Collectively, our findings demonstrate that zoledronate has senolytic effects in vitro and modulates senescence/SASP biomarkers in vivo. These data point to the need for additional studies testing zoledronate and/or other bisphosphonate derivatives for senotherapeutic efficacy.

physiology↗

bioRxiv2022

Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling - the ANXA1 gene and retrograde endocannabinoid signaling - show top differential expression and the most significant enrichment. Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

neuroscience↗

bioRxiv2021

Ecological habitat partitioning and feeding specialisations of coastal minke whales (Balaenoptera acutorostrata) using a designated MPA in northeast Scotland

In the design of protected areas for cetaceans, spatial maps rarely take account of the life-history and behaviour of protected species relevant to their spatial ambit, which may be important when modelling population trends or assessing susceptibility to anthropogenic threats. In the present study, we examined the distribution and feeding behaviours of minke whales by age-class (adults versus juveniles) from long-term studies in the Moray Firth in northeast Scotland, where a Marine Protected Area (MPA) has recently been designated. Data were collected from dedicated boat surveys between 2000 and 2019, during which 657 encounters with 774 whales of confirmed age-class (444 juveniles and 330 adults) were recorded from 50,041 km of survey effort, resulting in 224 individual follows. Feeding/foraging whales were documented in 84% of the encounters. Adults and juveniles were occasionally seen together, but their distributions were not statistically correlated, and GIS revealed spatial separation by age-class[-]with juveniles preferring shallow, inshore waters with sandy-gravel sediments and adults preferring deeper, offshore waters with steep benthic slope. Whilst adult minkes employed a range of "active" prey-entrapment specialisations, showing seasonal flexibility in their targeted prey with interindividual variation, juveniles almost exclusively used "passive" (low energy) feeding methods, targeting low-density patches of inshore prey. These findings corroborate the need to incorporate demographic/behavioural data into spatial models when identifying priority areas for protected cetaceans and may be important to adaptive management objectives for the species in the Moray Firth MPA.

ecology↗

bioRxiv2020

Simulated poaching affects connectedness and efficiency in social networks of African savanna elephants

Selective harvest, such as poaching, impacts group-living animals directly through mortality of individuals with desirable traits, and indirectly by altering the structure of their social networks. Understanding the relationship between the structural network changes and group performance in wild animals remains an outstanding problem. To address this knowledge gap, we evaluate the immediate effect of disturbance on group sociality in African savanna elephants -- an example, group-living species threatened by poaching. Drawing on static association data from one free ranging population, we constructed 100 virtual networks; performed a series of experiments poaching the oldest, socially central or random individuals; and quantified the immediate change in the theoretical indices of network connectivity and efficiency of social diffusion. Although the virtual networks never broke down, targeted elimination of the socially central conspecifics, regardless of age, decreased network connectivity and efficiency. These findings hint at the need to further study resilience by modeling network reorganization and interaction-mediated socioecological learning, empirical data permitting. Our work is unique in quantifying connectivity together with global efficiency in multiple virtual networks that represent the sociodemographic diversity of elephant populations likely found in the wild. The basic design of our simulation platform makes it adaptable for hypothesis testing about the consequences of anthropogenic disturbance or lethal management on social interactions in a variety of group-living species with limited, real-world data. Author SummaryWe consider the immediate response of animal groups to human disturbance by using the African savanna elephant as an example of a group-living species threatened by poaching. Previous research in one elephant population showed that poaching-induced mortality reduced social interaction among distantly related elephants, but not among close kin. Whether this type of resilience indicates that affected populations function similarity before and after poaching is an open problem. Understanding it is important because poaching often targets the largest and most socially and ecologically experienced group members. Drawing on empirical association data, we simulated poaching in 100 virtual elephant populations and eliminated the most senior or sociable members. Targeted poaching of sociable conspecifics was more impactful. Although it did not lead to population breakdown, it hampered theoretical features of interspecific associations that in other systems have been associated with group cohesion and the efficiency of transferring social information. Our findings suggest that further inquiry into the relationship between resilience to poaching and group performance is warranted. In addition, our simulation platform offers a generalizable basis for hypothesis testing in other social species, wild or captive, subject to exploitation by humans.

animal behavior and cognition↗