Biology subjects

Cox, A. R.

Publications and source records attributed to Cox, A. R..

12 recordsLinked to original sources

bioRxiv2025

Divergent climate impacts despite similar response to temperature in a widespread aerial insectivore

Climate change is shifting when animals breed1,2, but it is still not clear why some populations keep pace with warming while others fall behind3,4. Differences could arise from variation in sensitivity to temperature3 or constraints on the ability to respond to temperature. Without knowing whether populations differ in sensitivity--or in their ability to act on that sensitivity--we cannot identify which are most at risk. Using 1,555 population-years from 123 populations of tree swallows (Tachycineta bicolor), we show that populations have similar sensitivity to local temperature, advancing breeding by about one day per degree of warming. However, northern populations face tighter time constraints and greater exposure to recent warming. Northern populations have advanced laying dates the most, but still experience stronger selection for earlier breeding, especially in warm years; they have also declined most in breeding abundance. These findings show that vulnerability to climate change can arise not just from different sensitivity to warming, but from when and where populations can respond effectively. By disentangling sensitivity from timing constraints, our results support a general mechanism by which even uniformly responsive species can show uneven impacts of climate change across their ranges.

ecology↗

bioRxiv2025

Legal Harvest of Shorebirds and Resident Game Birds on a Caribbean island: A Martinique Case Study

Legal hunting practiced under regulatory frameworks is not always assessed for its sustainability. The lack of harvest data is of particular concern in the case of birds occurring on islands. Resident species on islands often exhibit limited geographic ranges and inherently small population sizes, rendering them particularly susceptible to environmental and anthropogenic threats. Islands also support seasonally fluctuating populations of migratory species, providing essential habitats for stopovers and non-breeding periods. Within this context, the sustainability of gamebird harvest practiced on islands within a regulatory framework needs to be evaluated to inform management and prevent negative impacts on populations. Here, we present a case study of an island-wide assessment of bird hunting estimates, based on data available from a legal hunting program, in Martinique, a tropical oceanic island part of the Caribbean biodiversity hotspot. Our objectives were to determine the magnitude of gamebird harvest, track changes in harvest levels over time, and assess harvest sustainability. Our assessment, which is based on hunting logbooks and hunter surveys between the 2012-2013 and 2021-2022 hunting seasons, provides harvest estimates for two groups of migratory species, shorebirds (Charadriidae, Scolopacidae) and teals (Anatidae), and two groups of resident species (Columbidae and Mimidae). In Martinique, harvest management measures, combined with increased hunters engagement and enforcement of regulations, has led more stringent harvest regulations, improved compliance from hunters, and a reduction of Martiniques national shorebird harvest. However, considering continued and rapid shorebirds population declines across the Western Atlantic flyway, shorebird harvest assessment at the flyway level remains a priority.

ecology↗

bioRxiv2025

Beige fat appearance during lipoatrophy reveals trade-offs between metabolic homeostasis and female fertility

White adipose tissue (WAT) meets the energetic demands required for estrous cycle regularity, ovulation, and reproductive success in women. Here, we report WAT loss and subsequent female-specific compensatory beige fat recruitment impact metabolic and reproductive outcomes in mice. Female mice that undergo progressive lipoatrophy ( fat-less) displayed disrupted estrous cycles, reduced ovarian reserve, and subfertility. These effects were attributable to an accumulation of thermogenic beige fat cells in residual subcutaneous WAT depots and greater energy expenditure. Conversely, high-fat diet lowered energy expenditure and rescued estrous cycle regularity among fat-less mice compared to littermate controls, despite profound insulin resistance and metabolic dysfunction. Together, these findings provide evidence of trade-offs between the maintenance of metabolic homeostasis and reproduction, where increased energy expenditure and beige fat cell emergence compensate for fat loss but occur at the expense of fecundity in female mice.

cell biology↗

bioRxiv2025

A national assessment of waterbird hunting in coastal wetlands of Suriname, south America

The central northern coast of South America has extensive wetlands critical for waterbird conservation. While waterbird harvest occurs in the region, the impact on species population dynamics remains unclear. This study assesses waterbird hunting in the coastal wetlands of Suriname, addressing: (i) the extent of waterbird harvest, (ii) changes in harvest magnitude over time, and (iii) the motivations and methods used by hunters. We collected data via a national survey of licensed hunters in 2006 and 2016 using structured interviews. A Bayesian hierarchical model was used to analyze the data. We estimated harvest levels for 11 species and three groups (small herons, small shorebirds, large shorebirds). For most species, mean harvest per hunter significantly decreased from 2006 to 2016, except for blue-winged teal and migratory shorebirds. Most hunting was for non-commercial purposes (personal consumption and recreational). This is the first national assessment of waterbird hunting in Suriname. Harvest levels vary by species, and the sustainability of these levels remains uncertain. Managing hunting in Suriname requires addressing both legal and illegal hunting. Given Surinames importance for waterbirds, particularly species like the scarlet ibis and migratory shorebirds, it should be a priority for conservation efforts.

ecology↗

bioRxiv2024

A Comprehensive Atlas of AAV Tropism in the Mouse

Gene therapy with Adeno-Associated Viral (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence. Cre-driven activation of tdTomato fluorescence offered superior sensitivity for transduced cells. All serotypes except AAV3B and AAV4 had high liver tropism. Fluorescence activation revealed transduction of unexpected tissues, including adrenals, testes and ovaries. Rare transduced cells within tissues were also readily visualized. Biodistribution of AAV genomes correlated with fluorescence, except in immune tissues. AAV4 was found to have a pan-endothelial tropism while also targeting pancreatic beta cells. This public resource enables selection of the best AAV serotypes for basic science and preclinical applications in mice.

molecular biology↗

bioRxiv2022

Vitamin B2 enables peroxisome proliferator-activated receptor α regulation of fasting glucose availability

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrophy. In our study, depleting FAD pools in mice with a vitamin B2 deficient diet (B2D) caused phenotypes associated with organic acidemias and other IEMs, including reduced body weight, hypoglycemia, and fatty liver disease. Integrated discovery approaches revealed B2D tempered fasting activation of target genes for the nuclear receptor PPAR, including those required for gluconeogenesis. Treatment with the PPAR agonist fenofibrate activated the integrated stress response and refilled amino acid substrates to rescue fasting glucose availability and overcome B2D phenotypes. Overall, these findings reveal PPAR governs metabolic responses to FAD availability and nominate its pharmacologic activation as strategies for organic acidemias.

physiology↗

bioRxiv2021

Constitutive loss of DNMT3A causes morbid obesity through misregulation of adipogenesis

DNA Methyltransferase 3A (DNMT3A) is an important facilitator of differentiation of both embryonic and hematopoietic stem cells. Heterozygous germline mutations in DNMT3A lead to Tatton-Brown-Rahman Syndrome (TBRS), characterized by obesity and excessive height. While DNMT3A is known to impact feeding behavior via the hypothalamus, here we investigated a role in adipocyte progenitors utilizing heterozygous knockout mice that recapitulate cardinal TBRS phenotypes. These mice become morbidly obese due to adipocyte enlargement and tissue expansion. Adipose tissue in these mice exhibited defects in preadipocyte maturation and precocious activation of inflammatory gene networks, including interleukin-6 signaling. Adipocyte progenitor cell lines lacking DNMT3A exhibited aberrant differentiation. Furthermore, mice in which Dnmt3a was specifically ablated in adipocyte progenitors showed enlarged fat depots and increased progenitor numbers, partly recapitulating the TBRS obesity phenotypes. Loss of DNMT3A led to constitutive DNA hypomethylation, such that the DNA methylation landscape of young adipocyte progenitors resemble that of older wild-type mice. Together, our results demonstrate that DNMT3A coordinates both the central and local control of energy storage required to maintain normal weight and prevent inflammatory obesity.

cell biology↗

bioRxiv2021

Accumulation of auranofin in white adipose tissues lowers leptin levels and exerts anti-diabetic effects

Low-grade, sustained inflammation in white adipose tissue (WAT) characterizes obesity and frequently coincides with insulin resistance and type 2 diabetes (T2D). However, pharmacological targeting of WAT inflammation lacks durable therapeutic effects. Through a computational screen, we identified the FDA-approved rheumatoid arthritis drug auranofin is a putative small molecule for obesity treatment. We discovered that allometrically scaled safe auranofin doses homed to WAT and improved insulin sensitivity in obese wild-type mice. Auranofin treatment also normalized other obesity-associated abnormalities, including hepatic steatosis and hyperinsulinemia. Surprisingly, the anti-diabetic effects of auranofin required leptin lowering and beta-adrenergic receptors in WAT. These metabolic benefits of leptin reduction were superior to any immune impacts of auranofin in WAT. Our studies reveal important metabolic properties of anti-inflammatory treatments and contribute to the notion that leptin reduction in the periphery can be accomplished to treat obesity and T2D.

physiology↗

bioRxiv2020

Ubc9 deletion in adipocytes causes lipoatrophy in mice

ObjectiveWhite adipose tissue (WAT) expansion regulates energy balance and overall metabolic homeostasis. WAT absence or loss occurring through lipodystrophy and lipoatrophy contributes to the development of dyslipidemia, hepatic steatosis, and insulin resistance. We previously demonstrated the sole small ubiquitin-like modifier (SUMO) E2-conjuguating enzyme Ubc9 represses human adipocyte differentiation. Germline and other tissue-specific deletions of Ubc9 frequently cause lethality in mice. As a result, the role of Ubc9 during WAT development remains unknown. MethodsTo determine how Ubc9 impacts body composition and energy balance, we generated adipocyte-specific Ubc9 knockout mice (Ubc9a-KO). CRISPR/Cas9 gene editing inserted loxP sites flanking exons 3 and 4 at the Ubc9 locus. Subsequent genetic crosses to AdipoQ-Cre transgenic mice allowed deletion of Ubc9 in white and brown adipocytes. We measured multiple metabolic endpoints that describe energy balance and carbohydrate metabolism in Ubc9a-KO and littermate controls during postnatal growth. ResultsTo our surprise, Ubc9a-KO mice developed hyperinsulinemia and hepatic steatosis. Global energy balance defects emerged from dysfunctional WAT marked by pronounced local inflammation, loss of serum adipokines, hepatomegaly, and near absence of major adipose tissue depots. We observed progressive lipoatrophy that commences in the early adolescent period. ConclusionsOur results demonstrate that Ubc9 expression in mature adipocytes is essential for maintaining WAT expansion. Deletion of Ubc9 in fat cells compromised and diminished adipocyte function that provoked WAT inflammation and ectopic lipid accumulation in the liver. Our findings reveal an indispensable role for Ubc9 during white adipocyte expansion and endocrine control of energy balance.

developmental biology↗

bioRxiv2020

STAT1 dissociates adipose tissue inflammation from insulin sensitivity in obesity

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes mellitus (T2DM). However, the causal relationship of these events remains unclear. The established dominance of signal transducer and activator of transcription 1 (STAT1) function in the immune response suggests an obligate link between inflammation and the co-morbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1 fKO) enhanced mitochondrial function and accelerated TCA cycle flux coupled with subcutaneous WAT hyperplasia. STAT1 fKO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFN{gamma}) activity enhanced insulin sensitivity in diet-induced obesity. Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.

immunology↗

bioRxiv2019

Tamoxifen Suppresses Pancreatic β-Cell Proliferation in Mice

Tamoxifen is a mixed agonist/antagonist estrogen analogue that is frequently used to induce conditional gene deletion in mice using Cre-loxP mediated gene recombination. Tamoxifen is routinely employed in extremely high-doses relative to typical human doses to induce efficient gene deletion in mice. Although tamoxifen has been widely assumed to have no influence upon {beta}-cells, the acute developmental and functional consequences of high-dose tamoxifen upon glucose homeostasis and adult {beta}-cells are largely unknown. We tested if tamoxifen influences glucose homeostasis in male mice of various genetic backgrounds. We then carried out detailed histomorphometry studies of mouse pancreata. We also performed gene expression studies with islets of tamoxifen-treated mice and controls. Tamoxifen had modest effects upon glucose homeostasis of mixed genetic background (F1 B6129SF1/J) mice, with fasting hyperglycemia and improved glucose tolerance but without overt effects on fed glucose levels or insulin sensitivity. Tamoxifen inhibited proliferation of {beta}-cells in a dose-dependent manner, with dramatic reductions in {beta}-cell turnover at the highest dose (decreased by 66%). In sharp contrast, tamoxifen did not reduce proliferation of pancreatic acinar cells. {beta}-cell proliferation was unchanged by tamoxifen in 129S2 mice but was reduced in C57Bl6 genetic background mice (decreased by 59%). Gene expression studies revealed suppression of RNA for cyclins D1 and D2 within islets of tamoxifen-treated mice. Tamoxifen has a cytostatic effect on {beta}-cells, independent of changes in glucose homeostasis, in mixed genetic background and also in C57Bl6 mice. Tamoxifen should be used judiciously to inducibly inactivate genes in studies of glucose homeostasis.

developmental biology↗

bioRxiv2018

The Case For and Against Double-blind Reviews

To date, the majority of authors on scientific publications have been men. While much of this gender bias can be explained by historic sexism and discrimination, there is concern that women may still be disadvantaged by the peer review process if reviewers unconscious biases lead them to reject publications with female authors more often. One potential solution to this perceived gender bias in the reviewing process is for journals to adopt double-blind reviews whereby neither the authors nor the reviewers are aware of each others identities and genders. To test the efficacy of double-blind reviews, we assigned gender to every authorship of every paper published in 5 different journals with different peer review processes (double-blind vs. single blind) and subject matter (birds vs. behavioral ecology) from 2010-2018 (n = 4865 papers). While female authorships comprised only 35% of the total, the double-blind journal Behavioral Ecology did not have more female authorships than its single-blind counterparts. Interestingly, the incidence of female authorship is higher at behavioral ecology journals (Behavioral Ecology and Behavioral Ecology and Sociobiology) than in the ornithology journals (Auk, Condor, Ibis), for papers on all topics as well as those on birds. These analyses suggest that double-blind review does not currently increase the incidence of female authorship in the journals studied here. We conclude, at least for these journals, that double-blind review does not benefit female authors and may, in the long run, be detrimental.

scientific communication and education↗