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Santana, S.

Publications and source records attributed to Santana, S..

5 recordsLinked to original sources

Severely lipoatrophic mice are hypermetabolic and hyperthermic under thermoneutral conditions in part due to an enhanced liver de novo lipogenesis

White, beige and brown adipocytes store energy as lipids, secrete hormones and produce heat, playing an important role in the regulation of energy balance through not completely defined mechanisms. We investigate herein the impact of the almost complete absence of mature adipocytes (severe lipoatrophy) in the determination of energy balance (energy intake and expenditure) and homeothermy in mice. For this, mice with severe lipoatrophy induced by adipocyte deletion of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) (PPAR{gamma} flox adiponectin-Cre) and littermate controls (PPAR{gamma} flox) were evaluated for energy balance, thermoneutral zone, core body temperature, locomotor activity, and gene expression profiles at different ambient temperatures. Severely lipoatrophic mice are heavier, hypermetabolic and hyperphagic and feature a widened thermoneutral zone, lower ambulatory activity, and metabolic inflexibility at both 23 and 17{degrees}C, along with unstable thermal behavior characterized by hyperthermia at 30{degrees}C, normothermia at 23{degrees}C, and bouts of hypothermia at 17{degrees}C. Noteworthy, lipoatrophic mice hypermetabolism at 30{degrees}C is not due to thyroid hormones, impaired insulation or increased body and lean masses and is not altered by pharmacological blockade of either {beta}-adrenergic receptor signaling with propranolol or skeletal muscle sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCA) and sarcolipin (SLN)-mediated calcium cycling with dantrolene, but is partially attenuated by pharmacological inhibition of acetyl-CoA carboxylase (ACC) and de novo lipogenesis with ND-630. In conclusion, severe lipoatrophy causes hypermetabolism and hyperthermia at 30{degrees}C partly through the activation of liver de novo fatty acid synthesis.

physiology↗

On the cusp of adaptive change: the hierarchical radiation of phyllostomid bats

Adaptive radiations are bursts in biodiversity that lead to the origin of new evolutionary lineages and phenotypes. However, adaptive radiations typically occur over millions of years and it is unclear how the macroevolutionary dynamics that underpin them vary through time and among groups of organisms. Phyllostomid bats radiated extensively for diverse diets -from insects to vertebrates, fruit, nectar, and blood- and we use their molars as a model system to examine the dynamics of adaptive radiations. Three-dimensional shape analyses of lower molars of Noctilionoidea (Phyllostomidae and close relatives) indicate that different diet groups exhibit distinct morphotypes. Comparative analyses further reveal that phyllostomids are a striking example of a hierarchical radiation; their initial, higher-level diversification involved an early burst in molar morphological disparity as lineages invaded new diet-affiliated adaptive zones, followed by subsequent lower-level diversifications within adaptive zones involving less dramatic morphological changes. We posit that strong selective pressures related to initial shifts to derived diets may have freed molars from morpho-functional constraints associated with the ancestral molar morphotype. Then, lineages with derived diets (frugivores and nectarivores) diversified considerably within broad adaptive zones, likely reflecting finer-scale niche partitioning. The observed early burst pattern is only evident when examining molar traits that are strongly linked to diet, highlighting the importance of ecomorphological traits in comparative studies. Our results support the hypothesis that adaptive radiations are commonly hierarchical and involve different tempos and modes at different phylogenetic scales, with early bursts being more common at broader scales. SIGNIFICANCE STATEMENTMany groups of organisms are exceptionally diverse in their ecology, morphology, and number of species. But there is debate as to whether these groups commonly achieved this diversity through bursts in diversification early in their history. Phyllostomid bats are one of the most ecologically diverse mammalian families and a classic example of an adaptive radiation. We use their molar shapes, which correlate with diet, as a model for examining macroevolutionary patterns during diversifications. We find that phyllostomids experienced a two-step process of diversification; the first step involved a rapid burst, whereas the second involved finer-scale changes as lineages filled ecological niches. We posit that this is a common, yet underappreciated, pattern during the early histories of many diverse clades.

evolutionary biology↗

Growth rate as a modulator of tooth patterning during adaptive radiations

Tooth classes are a mammalian innovation that has contributed to the evolutionary success of mammals. However, our understanding of how tooth classes have evolved and diversified remains limited. Here, we use the evolutionary radiation of noctilionoid bats, the most diverse clade of mammals in terms of diet type, as a model system to show how the tooth developmental program evolved during the adaptation to new diet types. We combined morphological, developmental, cellular, and modeling approaches, to investigate the developmental differences between two tooth classes, molars and premolars and the mechanisms driving their diversification. We demonstrate that tooth classes develop through independent developmental cascades that deviate from classical models. Then we showed that the dramatic diversification of tooth number and size is driven by the modulation of the growth rate of the jaw, explaining the rapid gain/loss of teeth during the evolution of this clade. Finally, we propose a mathematical model that recapitulates the successive appearance of tooth buds and supports the hypothesis that growth acts as a key driver of the evolution of tooth number and size by tinkering with reaction/diffusion processes. Our results demonstrate developmental independence between mammalian tooth classes and provide a mechanism to explain their rapid diversification. More broadly, these results reveal how simple modifications of one developmental mechanism by another can drive the evolution of repeated structures during adaptive radiations.

evolutionary biology↗

Sensory neuron-derived Nav1.7 contributes to dorsal horn neuron excitability

Expression of the voltage-gated sodium channel Nav1.7 in sensory neurons is required for pain sensation. We examined the role of Nav1.7 in the dorsal horn of the spinal cord using an epitope-tagged knock-in mouse. Immuno-electron microscopy showed the presence of Nav1.7 in dendrites of lamina II neurons, despite the absence of mRNA. Peripheral nervous system-specific Nav1.7 KO mice showed central deficits with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Nav1.7 blocker PF05089771 diminished excitability in dorsal horn neurons, but had no effect on Nav1.7 KO mice. These data demonstrate an unsuspected functional role of peripherally generated Nav1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

neuroscience↗

Insights on the assembly rules of a continent-wide multilayer network

Introductory paragraphHow are ecological systems assembled? Here, we aim to contribute to answering this question by harnessing the framework of a novel integrative hypothesis. We shed light on the assembly rules of a multilayer network formed by frugivory and nectarivory interactions between bats and plants in the Neotropics. Our results suggest that, at a large scale, phylogenetic trade-offs separate species into different layers and modules. At an intermediate scale, the modules are also shaped by geographic trade-offs. And at a small scale, the network shifts to a nested structure within its modules, probably as a consequence of resource breadth processes. Finally, once the topology of the network is shaped, morphological traits related to consuming fruits or nectar determine which species are central or peripheral. Our results help understand how different processes contribute to the assemblage of ecological systems at different scales, resulting in a compound topology.

ecology↗