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Rabbits raised on mechanically challenging diets have significantly increased bone volume fraction relative to controls fed a less challenging diet. The postweaning timing of the introduction of mechanically challenging foods also influences architectural properties suggesting that bone plasticity can extend well into adulthood and that bony responses to changes in loading may be rapid. These findings demonstrate that bony architecture of the mandibular condyle in rabbits responds to variation in mechanical loading during an organism's lifetime and has the potential to track dietary variation within and among species. © 2020. Published by The Company of Biologists Ltd.Mosquitoes spread deadly diseases that impact millions of people every year. Understanding mosquito physiology and behavior is vital for public health and disease prevention. However, many important questions remain unanswered in the field of mosquito neuroethology, particularly in our understanding of the larval stage. In this study, we investigate the innate exploration behavior of six different species of disease vector mosquito larvae. We show that these species exhibit strikingly different movement paths, corresponding to a wide range of exploration behaviors. We also investigate the response of each species to an appetitive food cue, aversive cue or neutral control. By contrast to the large differences in exploration behavior, all species appeared to gather near preferred cues through random aggregation rather than directed navigation and exhibited slower speeds once encountering food patches. Our results identify key behavioral differences among important disease vector species, and suggests that navigation and exploration among even closely related mosquito species may be much more distinct than previously thought. © 2020. Published by The Company of Biologists Ltd.High temperatures can negatively impact performance and survival of organisms, particularly ectotherms. While an organism's response to high temperature stress clearly depends on current thermal conditions, its response may also be affected by the temporal pattern and duration of past temperature exposures. We used RNA sequencing of Manduca sexta larvae fat body tissue to evaluate how diurnal temperature fluctuations during development affected gene expression both independently and in conjunction with subsequent heat stress. Additionally, we compared gene expression between two M. sexta populations, a lab colony and a genetically related field population that have been separated for>300 generations and differ in their thermal sensitivities. Lab-adapted larvae were predicted to show increased expression responses to both single and repeated thermal stress, whereas recurrent exposure could decrease later stress responses for field individuals. We found large differences in overall gene expression patterns between the two populations across all treatments, as well as population-specific transcriptomic responses to temperature; most differentially expressed genes were upregulated in the field compared with lab larvae. Developmental temperature fluctuations alone had minimal effects on long-term gene expression patterns, with the exception of a somewhat elevated stress response in the lab population. Fluctuating rearing conditions did alter gene expression during exposure to later heat stress, but this effect depended on both the population and the particular temperature conditions. This study contributes to increased knowledge of molecular mechanisms underlying physiological responses of organisms to temperature fluctuations, which is needed for the development of more accurate thermal performance models. Selleck Wnt inhibitor © 2020. Published by The Company of Biologists Ltd.Variation in joint shape and soft tissue can alter range of motion (ROM) and create trade-offs between stability and flexibility. The shape of the distinctive zygosphene-zygantrum joint of snake vertebrae has been hypothesized to prevent axial torsion (twisting), but its function has never been tested experimentally. We used experimental manipulation of morphology to determine the role of the zygosphene-zygantrum articulation by μCT-scanning and 3D printing two mid-body vertebrae with unaltered shape and with the zygosphene digitally removed for four species of phylogenetically diverse snakes. We recorded the angular ROM while manipulating the models in yaw (lateral bending), pitch (dorsoventral bending), and roll (axial torsion). Removing the zygosphene typically increased yaw and dorsal pitch ROM. In the normal vertebrae, roll was less then 2.5 deg for all combinations of pitch and yaw. Roll increased in altered vertebrae but only for combinations of high yaw and ventral pitch that were near or beyond the limits of normal vertebra ROM. In the prairie rattlesnake and brown tree snake, roll in the altered vertebrae were always limited by bony processes other than the zygosphene, whereas in the altered vertebrae of the corn snake and boa constrictor roll ROM was unconstrained when the pre- and post-zygapophyses no longer overlapped. The zygosphene acts as a bony limit for yaw and dorsal pitch, indirectly preventing roll by precluding most pitch and yaw combinations where roll could occur and potentially allowing greater forces to be applied across the vertebral column than would be possible with only soft-tissue constraints. © 2020. Published by The Company of Biologists Ltd.Antoni Ribas, MD, PhD, discusses the biological discoveries that have led to new therapies for melanoma-and the future of treatment for the disease. ©2020 American Association for Cancer Research.In vitro approaches for predicting drug-drug interactions (DDIs) caused by alterations in transporter protein regulation are not well established. However, reports of transporter regulation via nuclear receptor (NR) modulation by drugs are increasing. This study examined alterations in transporter protein levels in sandwich-cultured human hepatocytes (SCHH; n = 3 donors) measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis after treatment with T0901317, the first described synthetic liver X receptor (LXR) agonist. T0901317 treatment (10 μM, 48 h) decreased the levels of organic cation transporter (OCT) 1 (0.22-, 0.43- and 0.71-fold of control) and organic anion transporter (OAT) 2 (0.38-, 0.38- and 0.53-fold of control), and increased multidrug resistance protein (MDR) 1 (1.37-, 1.48 and 1.59-fold of control). The induction of NR downstream gene expression support the hypothesis that T0901317 off-target effects on farnesoid X receptor (FXR) and pregnane X receptor (PXR) activation are responsible for the unexpected changes in OCT1, OAT2 and MDR1.