Biology subjects

Christensen, C.

Publications and source records attributed to Christensen, C..

12 recordsLinked to original sources

bioRxiv2025

Resource scarcity increases foraging activity despite thermal risk in an arid-adapted bird

Behavioural flexibility is considered key for species to cope with the effects of climate change. Periods of resource scarcity, such as during climate change-driven droughts, may force animals to increase their foraging activity to meet energetic demands. However, doing so may increase the thermal risk inherent to the trade-off between foraging and exposure to higher temperatures. We use biologging data (internal body temperature and activity budgets classified via accelerometers) from a population of wild vulturine guineafowl (Acryllium vulturinum) to quantify this trade-off across varying resource availability (quantified through NDVI) over 2.5 years, including a period of severe drought. We start by linking internal body temperature measurements to external operative temperature to identify a thermal threshold--where body temperature reaches a maximum--at an external temperature of 33.8{degrees}C. We interpret this threshold as the point where birds must prioritise heat dissipation (physiologically and/or behaviourally) to avoid hyperthermia. Relevantly, we find that a larger part of the day exceeds this external thermal threshold as resources decline. We then show that guineafowl feeding activity positively correlates with resource scarcity, suggesting the birds compensate for diminishing resources by increasing foraging time investment, despite thermal risks. However, the compensatory foraging does not appear to buffer the birds against food shortfalls, as birds still lose weight as resource scarcity increases. Sublethal effects (e.g., body mass loss) of compounding environmental stressors have fitness consequences (e.g., postponement of breeding, as was noted in our population). Our results could point to an evolutionary mismatch; the projected intensification of resource scarcity and higher temperatures under climate change may alter trade-offs in such a way that existing physiological and behavioural responses to cyclical dry seasons are no longer adaptive, in vulturine guineafowl, and in other arid-system organisms more broadly.

ecology↗

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

More dominant baboons have less and lower quality sleep

The amount and quality of sleep individuals get can impact various aspects of human and non-human animal health, ultimately affecting fitness. For wild animals that sleep in groups, individuals may disturb one another, influencing sleep quality and quantity, but this aspect of social sleep has been understudied due to methodological challenges. Here, using nighttime rest (absence of bodily movements) as a proxy for sleep, we test the hypothesis that individuals social dominance can affect sleep opportunities by studying a troop of wild chacma baboons (Papio ursinus), a species with a strong hierarchical social structure. First, we show that the troops night-time rest (determined by 40Hz acceleration data) is highly synchronised. Next, we link night-time rest dynamics to daytime spatial networks and dominance hierarchy (from 1Hz GPS data and direct observations). We show that baboon rest synchrony is higher between similarly ranked individuals, and unexpectedly, more dominant baboons experience less and lower-quality rest. We propose that this hierarchy effect is explained by higher-ranked baboons resting closer to more group members, which also leads them exerting greater influence on each others night-time behaviour compared to lower-ranked individuals. Our study provides the first empirical evidence for the impact of social hierarchies on sleep in a wild primate, suggesting that dominance status may impose trade-offs between social rank and the quality and quantity of sleep.

animal behavior and cognition↗

bioRxiv2024

Moving towards more holistic validation of machine learning-based approaches in ecology and evolution

Machine-learning (ML) is revolutionizing field and laboratory studies of animals. However, a challenge when deploying ML for classification tasks is ensuring the models are reliable. Currently, we evaluate models using performance metrics (e.g., precision, recall, F1), but these can overlook the ultimate aim, which is not the outputs themselves (e.g. detected species or individual identities, or behaviour) but their incorporation for hypothesis testing. As improving performance metrics has diminishing returns, particularly when data are inherently noisy (as human-labelled, animal-based data often are), researchers are faced with the conundrum of investing more time in maximising metrics versus doing the actual research. This raises the question: how much noise can we accept in ML models? Here, we start by describing an under-reported factor that can cause metrics to underestimate model performance. Specifically, ambiguity between categories or mistakes in labelling validation data produces hard ceilings that limit performance metrics. This likely widespread issue means that many models could be performing better than their metrics suggest. Next, we argue and show that imperfect models (e.g. low F1 scores) can still be useable. Using a case study on ML-identified behaviour from vulturine guineafowl accelerometer data, we first propose a simulation framework to evaluate robustness of hypothesis testing using models that make classification errors. Second, we show how to determine the utility of a model by supplementing existing performance metrics with biological validations. This involves applying ML models to unlabelled data and using the models outputs to test hypotheses for which we can anticipate the outcome. Together, we show that effects sizes and expected biological patterns can be detected even when performance metrics are relatively low (e.g., F1: 60-70%). In doing so, we provide a roadmap for validation approaches of ML classification models tailored to research in animal behaviour, and other fields with noisy, biological data. HighlightsEvaluating machine learning (ML) models must go beyond performance metrics Mislabels in validation data leads to underestimation of models performance Underestimated metrics can cause research delays despite models being useful We propose simulations and biological validations to evaluate model performance Models with low standard metrics can still be powerful for hypothesis testing

ecology↗

bioRxiv2024

Divergent changes in social stress-induced motivation in male and female mice

Exposure to stressors has been shown to dysregulate motivated behaviors in a bidirectional manner over time. The relationship between stress and motivation is relevant to psychological disorders, including depression, binge eating, and substance abuse; however, this relationship is not well characterized, especially in females, despite their increased risk of these disorders. Social defeat stress is a common model to study stress-induced motivation changes, however, historically this model excluded females due to lack of female-to-female aggression and unreliable male-to-female aggression. Additionally, changes in motivation are often assessed well after stress exposure ends, potentially missing or occluding changes to motivation during stress. Recently, the chronic non-discriminatory social defeat stress (CNSDS) model has demonstrated social defeat of male and female C57BL/6J mice by exposing both mice to an aggressive male CD-1 mouse simultaneously. Here we use this model to directly compare changes in the motivated behavior of male and female mice during and following chronic stress. We hypothesized that motivated behavioral responses would be dysregulated during stress and that the effects would worsen as the stress exposure continued. To monitor motivated behavior, mice had access to a Feeding Experimental Device.3 (FED3), a home cage device for operant responding. Operant responding was monitored prior to, during, and after stress by measuring nose pokes for sucrose pellets on a modified progressive ratio schedule of reinforcement. Our results demonstrated divergent behavioral outcomes between males and female mice in response to stress; where male mice increased motivated behavior during stress only, whereas female mice exhibited a decrease in motivation during and after stress. This study highlights the need to investigate the effects of stress-induced motivation over time, as well as the increased need to understand differences in the stress response in females. HighlightsO_LIOperant behaviors were monitored continuously during and after stress exposure. C_LIO_LIChronic social stress produced opposite effects on motivation in males and females. C_LIO_LISusceptibility to stress only influenced outcomes on female motivated behaviors. C_LI

animal behavior and cognition↗

bioRxiv2024

Worldwide study of the taste of bitter medicines and their modifiers

The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canada immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad- tasting medicines to meet the needs of those most sensitive to them.

physiology↗

bioRxiv2023

The physiological costs of spatial positioning and leadership in collective movements

Individuals can gain substantial benefits from collective actions1-7. However, collective behaviours introduce new challenges, like coordinating actions, maintaining cohesion, and meeting the needs of different individuals. When making collective movements, leaders are typically thought to gain disproportionate benefits through the choice of more beneficial resources3 and/or earlier access to resources8. However, reaping these benefits can also have costs. Being at the front of a group can increase physical exertion4,9,10 and predation risk11,12. Moreover, ending up in a leadership position (i.e., at the front), is a process of negotiation in many animal groups. Within-group differences in directional preferences are typically resolved by some individuals initiating directional movements, after which they are either followed (if they are successful in leading) or return to the group (if they fail)13-30. By combining data on movement initiations (using whole-group GPS tracking31 and individual heart rate from implanted ECG loggers) in wild vulturine guineafowl, we found significant increases in heart rate (and decreases in heart rate variability) during collective movements. We found that attempting--and failing--to initiate directional movement was particularly costly, with the highest costs when consensus among group members was low and when individuals acted against the majority. Increases in heart rate and decreases in its variability can indicate physiological stress, entailing increased energy expenditure and long-term physiological damage. These results suggest that behaviours often thought beneficial to individuals (by influencing group behaviours) are also physiologically costly, representing a constraint on group-living and explaining why sometimes individuals opt out of contributing to leadership.

ecology↗

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

CRISPR-Mediated Generation and Characterization of a Gaa Homozygous c.1935C>A (p.D645E) Pompe Disease Knock-in Mouse Model Recapitulates Human Infantile Onset-Pompe Disease

Pompe disease (PD) is an autosomal recessive disorder caused by deficient lysosomal acid -glucosidase (GAA), leading to reduced degradation and subsequent accumulation of intra-lysosomal glycogen in tissues, especially skeletal and oftentimes cardiac muscle. The c.1935C>A (p.Asp645Glu) variant is the most frequent GAA pathogenic mutation in people of Taiwanese and Southern Chinese ethnicity, causing infantile-onset PD (IOPD), which presents neonatally with severe hypertrophic cardiomyopathy, profound muscle hypotonia, and respiratory failure leading to premature death if untreated. To further investigate the pathogenic mechanism and facilitate development of therapies pertaining to this variant, we applied CRISPR-Cas9 homology-directed repair (HDR) using a novel dual sgRNA approach flanking the target site to generate a GaaEm1935C>A knock-in mouse model as well as a myoblast cell line carrying the Gaa c.1935C>A mutation. Herein we describe the molecular, biochemical, physiological, histological, and behavioral characterization of 3-month-old homozygous GaaEm1935C>A mice. Homozygous GaaEm1935C>A knock-in mice exhibited normal Gaa mRNA expression levels relative to wild-type mice, but GAA enzymatic activity was almost completely abolished, leading to a substantial increase in tissue glycogen storage, and significant concomitant impairment of autophagy. Echocardiography of 3-month-old knock-in mice revealed significant cardiac hypertrophy. The mice also demonstrated skeletal muscle weakness but, paradoxically, not early mortality. Longitudinal studies of this model, including assessment of its immune response to exogenously supplied GAA enzyme, are currently underway. In summary, the GaaEm1935C>A knock-in mouse model recapitulates the molecular, biochemical, histopathologic, and phenotypic aspects of human IOPD caused by the GAA c.1935C>A pathogenic variant. It is an ideal model to assess innovative therapies to treat IOPD, including personalized therapeutic strategies that correct pathogenic variants, restore GAA activity and produce functional phenotypes.

genetics↗

bioRxiv2020

Infralimbic cortical glutamate output is necessary for the neural and behavioral consequences of chronic stress

Exposure to prolonged stress is a major risk-factor for psychiatric disorders such as generalized anxiety and major depressive disorder (MDD). Human imaging studies have identified structural and functional abnormalities in the prefrontal cortex of MDD patients, particularly Brodmanns area 25 (BA25). Further, deep brain stimulation of BA25 reduces symptoms of treatment-resistant depression. The rat homolog of BA25 is the infralimbic cortex (IL), which is critical for cognitive appraisal, executive function, and physiological stress reactivity. Previous studies indicate that the IL undergoes stress-induced changes in excitatory/inhibitory balance culminating in reduced activity of glutamate output neurons. However, the regulatory role of IL glutamate output in mood-related behaviors after chronic variable stress (CVS) is unknown. Here, we utilized a lentiviral-packaged small-interfering RNA to reduce translation of vesicular glutamate transporter 1 (vGluT1 siRNA), thereby constraining IL glutamate output. This viral-mediated gene transfer was used in conjunction with a quantitative anatomical analysis of cells expressing the stable immediate-early gene product {Delta}FosB, which accumulates in response to repeated neural activation. Through assessment of {Delta}FosB-expressing neurons across the frontal lobe in adult male rats, we mapped regions altered by chronic stress and determined the coordinating role of the IL in frontal cortical plasticity. Specifically, CVS-exposed rats had increased density of {Delta}FosB-expressing cells in the IL and decreased density in the anterior insula. The later effect was dependent on IL glutamate output. Next, we examined the interaction of CVS and reduced IL glutamate output in behavioral assays examining coping, anxiety-like behavior, associative learning, and nociception. IL glutamate knockdown decreased immobility during the forced swim test compared to GFP controls, both in rats exposed to CVS as well as rats without previous stress exposure. Further, vGluT1 siRNA prevented CVS-induced avoidance behaviors, while also reducing risk aversion and passive coping. Ultimately, this study identifies the necessity of IL glutamatergic output for regulating frontal cortical neural activity and behavior following chronic stress. These findings also highlight how disruption of excitatory/inhibitory balance within specific frontal cortical cell populations may impact neurobehavioral adaptation and lead to stress-related disorders.

neuroscience↗

bioRxiv2019

Effects of amotosalen treatment on human platelet lysate bioactivity

BackgroundClinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. Due to lack of experience and global diversity in bacterial detection strategies, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. To achieve these aims, we assessed the quality of hPL produced from expired platelet concentrates with pathogen inactivation applied after platelet lysis, as well as its ability to support MSC proliferation and tri-lineage differentiation.\n\nMethodology/principal findingsBone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated human platelet concentrates (hPL-PIPC), with pathogen inactivation applied after soon after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates.\n\nConclusion/significanceThese results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-expiration, pathogen inactivation can provide a valuable tool to further standardize global hPL production methods, increase the pool of starting material, and meet the future demand for animal-free supplements in human cell culturing.

cell biology↗

bioRxiv2017

A Comprehensive Reanalysis Of Publicly Available GWAS Datasets Reveals An X Chromosome Rare Regulatory Variant Associated With High Risk For Type 2 Diabetes.

The reanalysis of publicly available GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics and pathophysiology of complex diseases. We demonstrate this by gathering and reanalyzing public type 2 diabetes (T2D) GWAS data for 70,127 subjects, using an innovative imputation and association strategy based on multiple reference panels (1000G and UK10K). This approach led us replicate and fine map 50 known T2D loci, and identify seven novel associated regions: five driven by common variants in or near LYPLAL1, NEUROG3, CAMKK2, ABO and GIP genes; one by a low frequency variant near EHMT2; and one driven by a rare variant in chromosome Xq23, associated with a 2.7-fold increased risk for T2D in males, and located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a known modulator of insulin sensitivity. We further show that the risk T allele reduces binding of a nuclear protein, resulting in increased enhancer activity in muscle cells. Beyond providing novel insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel analytical approaches.

genetics↗