Pre- and post-mating reproductive isolation evolve independently during rapid adaptation to high temperature

Ambient temperature is one major ecological factor driving adaptation in natural populations, but its impact on the emergence of new species is not yet clear. Here, we explored the evolution of reproductive isolation during temperature adaptation by exposing 10 replicate Drosophila simulans populations to a hot temperature regime. Within less than 200 generations, both pre- and post-mating reproductive isolation evolved. The altered lipid metabolism of evolved flies also affected the cuticular hydrocarbon (CHCs) profiles. Different CHC profiles could explain the emerged assortative mating between ancestral and evolved populations. Hence, we identified the hallmark of ecological speciation driven by temperature adaptation. While this pre-mating isolation occurred only between ancestral and evolved replicate populations, post-mating reproductive isolation was observed among evolved replicate populations. We propose that epistatic interactions of reproduction-related genes between males and females resulted in adaptive co-evolution. Incompatibilities between different gene combinations favored in each replicate could explain the observed post-mating reproductive isolation. We anticipate that this mutation-order-like speciation from standing genetic variation, a new speciation process, is widespread in nature when highly polygenic traits are involved in adaptation.

Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites.

Perturbations of the Proteome and of Secreted Metabolites in Primary Astrocytes from the hSOD1(G93A) ALS Mouse Model

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose pathophysiology is largely unknown. Despite the fact that motor neuron (MN) death is recognized as the key event in ALS, astrocytes dysfunctionalities and neuroinflammation were demonstrated to accompany and probably even drive MN loss. Nevertheless, the mechanisms priming astrocyte failure and hyperactivation are still obscure. In this work, altered pathways and molecules in ALS astrocytes were unveiled by investigating the proteomic profile and the secreted metabolome of primary spinal cord astrocytes derived from transgenic ALS mouse model overexpressing the human (h)SOD1(G93A) protein in comparison with the transgenic counterpart expressing hSOD1(WT) protein. Here we show that ALS primary astrocytes are depleted of proteins—and of secreted metabolites—involved in glutathione metabolism and signaling. The observed increased activation of Nf-kB, Ebf1, and Plag1 transcription factors may account for the augmented expression of proteins involved in the proteolytic routes mediated by proteasome or endosome–lysosome systems. Moreover, hSOD1(G93A) primary astrocytes also display altered lipid metabolism. Our results provide novel insights into the altered molecular pathways that may underlie astrocyte dysfunctionalities and altered astrocyte–MN crosstalk in ALS, representing potential therapeutic targets to abrogate or slow down MN demise in disease pathogenesis.