Effects of exogenous steroid hormones on growth, body color, and gonadal development in the Opsariichthys bidens.

To investigate the effects of exogenous steroid hormones on growth, body color, and gonadal development in the Opsariichthys bidens (O. bidens), synthetic methyltestosterone (MT) and 17ß-estradiol (E2) were used for 28 days' treatment of 4-month-old O. bidens before the breeding season. Our results suggested that MT had a significant growth-promoting effect (P < 0.05), whereas E2 played an inhibitory role. On the body surface, the females in the MT group showed gray stripes, and the fish in other groups showed no obvious stripes. The males with MT treatment displayed brighter blue-green stripes compared to the CK and E2 groups. The histological analysis showed that the MT significantly promoted testes development in males, blocked oocyte development, and caused massive apoptosis in females, whereas the E2 group promoted ovarian development and inhibited testes development. Based on qRT-PCR analysis, in females, the expression of igf-1, dmrt1, and cyp19a1a genes revealed that E2 treatment resulted in down-regulation of igf-1 expression and up-regulation of cyp19a1a expression. In males, igf-1 and dmrt1 were significantly up-regulated after MT treatment, and E2 treatment led to down-regulation of igf-1. Therefore, this study demonstrates that MT and E2 play an important role in reversing the morphological sex characteristics of females and males.

Insights into body size variation in cetaceans from the evolution of body-size-related genes.

BACKGROUND: Cetaceans exhibit an exceptionally wide range of body size, yet in this regard, their genetic basis remains poorly explored. In this study, 20 body-size-related genes for which duplication, mutation, or deficiency can cause body size change in mammals were chosen to preliminarily investigate the evolutionary mechanisms underlying the dramatic body size variation in cetaceans. RESULTS: We successfully sequenced 20 body-size-related genes in six representative species of cetaceans. A total of 46 codons from 10 genes were detected and determined to be under strong positive selection, 32 (69.6%) of which were further found to be under radical physiochemical changes; moreover, some of these sites were localized in or near important functional regions. Interestingly, positively selected genes were well matched with body size evolution: for small cetaceans, strong evidence of positive selection was detected at ACAN, OBSL1, and GRB10, within which mutations or duplications could cause short stature; positive selection was found in large cetaceans at CBS and EIF2AK3, which could promote growth, and at the PLOD1 gene, within which mutations could cause tall stature. Importantly, relationship analyses revealed that the evolutionary rate of CBS was positively related to body length and body mass with statistical significance. Additionally, we identified 32 cetacean-specific amino acid changes in 10 genes. CONCLUSIONS: This is the first study to investigate the molecular basis of dramatic body size variation in cetaceans. Our results provide evidence of the positive selection of several body-size-related genes in cetaceans, as well as divergent selection between large or small cetaceans, which suggest cetacean body size variation possibly associated with these genes. In addition, cetacean-specific amino acid changes might have played key roles in body size evolution after the divergence of cetaceans from their terrestrial relatives. Overall, the evolutionary pattern of these body-size-related genes could provide new insights into genetic mechanisms for the body size variation in cetaceans.

Widespread positive selection on cetacean TLR extracellular domain.

Toll like receptors (TLRs), key members of innate immune system, can recognize a wide diversity of pathogens and initiate both innate and adaptive immune responses in vertebrate. Cetaceans must have faced new challenges of pathogens when their terrestrial relatives transitioned from the terrestrial to aquatic environment. Here, we sequenced the extracellular domain (ECD) of 10 TLRs in cetacean lineages because this region involved in the recognition of pathogens. A total of 148 sites ranging between 5-26 codons (0.01%-4.83%) were identified to be robust candidates of positive selection at the ECD of 10 TLRs. In addition, the majority (90.54%) of these positively selected codons were found to have radical amino acid changes, which strengthen the evidence of positive selection. Importantly, more radical amino acid changes in selected sites were enriched in the period of early evolutionary transition from land to semi-aquatic and from semi-aquatic to full-aquatic habitat, which might endow cetaceans with a faster adaptation to new pathogens as they transitioned into novel habitat. Interestingly, similar selective intensity was detected in both viral and non-viral TLRs in cetaceans, which was not in line with previous studies on primates and birds that reported stronger positive selection in non-viral TLRs than in viral TLRs. This result may be explained by the fact that cetaceans might have faced diversity of bacteria and viruses during its transitions from terrestrial to aquatic environment whereas both primates and birds probably being affected by only a restricted number of related viruses due to their homogeneous habitat.

Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases.

Three members of the peroxisome proliferator-activated receptor (PPAR) family, PPARα, PPARγ, and PPARß/δ, have been investigated widely over the past few decades. Although the roles of these PPARs and their agonists/antagonists were defined in clinical and basic studies, the conflicting results from these studies indicate that more analysis is needed to understand the roles of PPARs. PPARα is a ligand-activated transcription factor that contributes to the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. In this review, we focus on the function and mechanisms of PPARα in the cardiovascular system under various pathological conditions, including vascular and heart injury, blood pressure regulation, and lipid disorder-related cardiovascular injury, as well as its polymorphisms and pharmacogenetic associations with cardiovascular diseases. The anti-inflammatory effect of PPARα in cardiovascular injury is mainly through inhibition of pro-inflammatory signaling pathways and improvement of the lipid profile. Moreover, PPARα also modulates the activity of endothelial nitric oxide synthase and resets the renin-angiotensin system to regulate vascular tone. PPARα gene variants appear to be associated with some cardiovascular risk factors, such as higher plasma lipid levels, cardiac growth, and increased risk of coronary artery disease. Nowadays, novel PPARα drugs with broad safety margins and therapeutic potential for metabolic syndrome and cardiovascular diseases are being developed and applied in the clinical setting. The insights from the current review shed new light on areas of further study and provide a better understanding of the role of PPARα in cardiovascular diseases.