Low acclimation capacity of narrow‐ranging thermal specialists exposes susceptibility to global climate change

Thermal acclimation is hypothesized to offer a selective advantage in seasonal habitats and may underlie disparities in geographic range size among closely‐related species with similar ecologies. Understanding this relationship is also critical for identifying species that are more sensitive to warming climates. Here, we study North American plethodontid salamanders to investigate whether acclimation ability is associated with species’ latitudinal extents and the thermal range of the environments they inhabit. We quantified variation in thermal physiology by measuring standard metabolic rate (SMR) at different test and acclimation temperatures for 16 species of salamanders with varying latitudinal extents. A phylogenetically‐controlled Markov chain Monte Carlo generalized linear mixed model (MCMCglmm) was then employed to determine whether there are differences in SMR between wide‐ and narrow‐ranging species at different acclimation temperatures. In addition, we tested for a relationship between the acclimation ability of species and the environmental temperature ranges they inhabit. Further, we investigated if there is a trade‐off between critical thermal maximum (CTMax) and thermal acclimation ability. MCMCglmm results show a significant difference in acclimation ability between wide and narrow‐ranging temperate salamanders. Salamanders with wide latitudinal distributions maintain or slightly increase SMR when subjected to higher test and acclimation temperatures, whereas several narrow‐ranging species show significant metabolic depression. We also found significant, positive relationships between acclimation ability and environmental thermal range, and between acclimation ability and CTMax. Wide‐ranging salamander species exhibit a greater capacity for thermal acclimation than narrow‐ranging species, suggesting that selection for acclimation ability may have been a key factor enabling geographic expansion into areas with greater thermal variability. Further, given that narrow‐ranging salamanders are found to have both poor acclimation ability and lower tolerance to warm temperatures, they are likely to be more susceptible to environmental warming associated with anthropogenic climate change.     

Ciliary neurotrophic factor upregulates ubiquitin-proteasome components in a rat model of neuronal injury

Neuronal injury triggers the release of ciliary neurotrophic factor (CNTF), promoting local neuronal repair but producing systemic effects of anorexia and lean body weight loss. Due to the rapid rate of systemic protein loss stimulated by CNTF, we hypothesized involvement of the hepatic ubiquitin-proteasome proteolytic (UPP) pathway in CNTF-induced proteolysis. To assess the role of central CNTF in systemic UPP regulation, we measured hepatic UPP mRNA and proteasome activity in a rat model of neuronal injury and determined alterations induced by intracerebroventricular (ICV) administration of CNTF-neutralizing antibody or additional exogenous CNTF. We also assessed proteolytic parameters and nutritional status by measuring caloric intake, body weight, and protein levels. We produced neuronal injury by implanting a lateral ventricle cannula and giving daily ICV saline bolus injections, which increased hepatic 20S proteasome mRNA and enzymatic activity while reducing caloric intake, body weight, and protein levels compared to controls. Administration of ICV anti-CNTF antibodies (but not control antibodies) prevented these effects. Addition of exogenous CNTF augmented the weight loss along with the increases in 20S proteasome mRNA and proteolytic activity induced by neuronal injury. We conclude that CNTF decreases lean body weight through a combination of appetite inhibition and UPP pathway activation.     

Behavioral coping strategies in a cichlid fish: the role of social status and acute stress response in direct and displaced aggression

The African cichlid fish, Astatotilapia burtoni, has a complex social system with a sophisticated social hierarchy that offers unique opportunities to understand how social rank and its physiological substrates relate to behavioral strategies. In A. burtoni, a small fraction of the males are dominant (T, territorial), as distinguished by being large, brightly colored, reproductively active, and aggressively defending territories. In contrast, the majority of males are non-dominant (NT, non-territorial), being smaller, drably colored, sexually immature, and typically schooling with females. The social system is regulated by aggressive interactions between males and behavioral responses to aggression can be direct or displaced with respect to the animal that acts. To determine whether direct and displaced behaviors are differentially exhibited by T and NT males, individuals were shown a video presentation of a dominant male displaying aggressively. Analysis of aggressive acts toward the video display and displaced activity toward a tank mate revealed that T males exhibited more direct behavior (toward the video display), while NT males engaged in more displaced behavior (toward tank mates). Because similar experiments with primates suggest that shifts in behavioral strategies are linked to changes in the stress response (as measured by circulating cortisol levels), we measured cortisol levels of T and NT males following exposure to the aggressive stimulus. Although in some animals subordinate males are reported to have higher cortisol levels, here we show that in A. burtoni the endocrine response to specific situations can vary considerably even among animals of the same status. Interestingly, NT males with intermediate cortisol levels showed more directed behavior while NT males with both high and low cortisol levels showed more displaced. This suggests an optimal physiological stress response in NT males that predisposes them to challenge aggressors perhaps making it more likely for them to ascend in status.     

Receptor Tyrosine Kinase-like Orphan Receptor 2 (Ror2) Expression Creates a Poised State of Wnt Signaling in Renal Cancer

Expression of the receptor tyrosine kinase-like orphan receptor 2 (Ror2) has been identified in an increasing array of tumor types and is known to play a role as an important mediator of Wnt signaling cascades. In this study, we aimed to clarify Ror2 interactions with the Wnt pathways within the context of renal cell carcinoma (RCC). An examination of Ror2 expression in primary human RCC tumors showed a significant correlation with several Wnt signaling genes, including the classical feedback target gene Axin2. We provide evidence that Ror2 expression results in a partially activated state for canonical Wnt signaling through an increased signaling pool of β-catenin, leading to an enhancement of downstream target genes following Wnt3a stimulation in both renal and renal carcinoma-derived cells. Additionally, inhibition of low-density lipoprotein receptor-related protein 6 (LRP6) with either siRNA or dickkopf decreased the response to Wnt3a stimulation, but no change was seen in the increased β-catenin pool associated with Ror2 expression, suggesting that LRP6 cofactor recruitment is necessary for a Wnt3a-induced signal but that it does not participate in the Ror2 effect on β-catenin signaling. These results highlight a new role for Ror2 in conveying a tonic signal to stabilize soluble β-catenin and create a poised state of enhanced responsiveness to Wnt3a exogenous signals in RCC.     

Identification and structure-activity relationships of a new series of Melanocortin-4 receptor antagonists

The identification and optimization of a series of acylguanidine-based melanocortin-4 receptor antagonists is discussed.     

The association between blood coagulation activity and lung function: a population-based study

Background

Increased in susceptibility to thrombotic disease may be associated with lower lung function. If causal, this association may suggest an area for development of new interventions for lung disease. The aim of this study was to investigate the association between blood coagulation activation as measured by plasma d-dimers and lung function.

Methodology/Principal Findings

We conducted a cross-sectional study on 2463 randomly selected adults in 1991 and followed up 1252 of these individuals in 2000. Plasma D-dimer levels, a marker of activity of blood coagulation pathways, were analysed in the baseline 1991 samples. There was an inverse cross-sectional association between plasma D-dimer and Forced Expiratory Volume in one second, with a decrease of 71 ml per µg FEU/ml increment in plasma D-dimer (95% confidence intervals CI: −135 to −6), and a decrease in Forced Vital Capacity (97 ml per µg FEU/ml increase in D-dimer, 95%CI: −170 to −24). These associations were attenuated after adjustment for serum highly sensitive CRP. No association was observed between plasma D-dimer and the decline in lung function between 1991 and 2000.

Conclusions/Significance

The cross-sectional findings are consistent with the hypothesis that activation of blood coagulation pathways is associated with decreased lung function, and that systemic inflammation may contribute to this relation. However, the lack of an association with decline in lung function suggests that clotting pathways that involve d-dimers may not be a promising therapeutic target for new interventions for respiratory disease.     

Partitioning of anthropogenic watering sites by desert carnivores

We investigated the role of water features as focal attractors for gray foxes (Urocyon cinereoargenteus), coyotes (Canis latrans), and bobcats (Felis rufus) in west Texas to determine if they were foci for interspecific interaction. Mixed effects models indicated that species partitioned use of water features spatially and temporally. Linear models indicated factors influencing relative activity at water features varied by species. For coyotes and bobcats, the water availability model, containing days since last rainfall and nearest-neighbor distance to water was best supported by the data, with relative activity increasing with time between rainfall and distance between waters. For gray foxes, the best approximating model indicated that relative activity was inversely correlated to coyote and bobcat activity indices, and positively correlated to topographical complexity. Encounters between carnivore species were low, with most occurring between coyotes and gray foxes, followed by coyotes and bobcats, and bobcats and gray foxes. These findings suggest a behavioral-environmental mechanism that may function to modulate resource partitioning by carnivores in the arid West. © 2011 The Wildlife Society.