Relaxin gene family in teleosts: phylogeny, syntenic mapping, selective constraint, and expression analysis

<p>Abstract</p> <p>Background</p> <p>In recent years, the relaxin family of signaling molecules has been shown to play diverse roles in mammalian physiology, but little is known about its diversity or physiology in teleosts, an infraclass of the bony fishes comprising ~ 50% of all extant vertebrates. In this paper, 32 relaxin family sequences were obtained by searching genomic and cDNA databases from eight teleost species; phylogenetic, molecular evolutionary, and syntenic data analyses were conducted to understand the relationship and differential patterns of evolution of relaxin family genes in teleosts compared with mammals. Additionally, real-time quantitative PCR was used to confirm and assess the tissues of expression of five relaxin family genes in <it>Danio rerio </it>and <it>in situ </it>hybridization used to assess the site-specific expression of the insulin 3-like gene in <it>D. rerio </it>testis.</p> <p>Results</p> <p>Up to six relaxin family genes were identified in each teleost species. Comparative syntenic mapping revealed that fish possess two paralogous copies of human <it>RLN3</it>, which we call <it>rln3a </it>and <it>rln3b</it>, an orthologue of human <it>RLN2</it>, <it>rln</it>, two paralogous copies of human <it>INSL5</it>, <it>insl5a and insl5b</it>, and an orthologue of human <it>INSL3</it>, <it>insl3</it>. Molecular evolutionary analyses indicated that: <it>rln3a, rln3b </it>and <it>rln </it>are under strong evolutionary constraint, that <it>insl3 </it>has been subject to moderate rates of sequence evolution with two amino acids in <it>insl3/INSL3 </it>showing evidence of positively selection, and that <it>insl5b </it>exhibits a higher rate of sequence evolution than its paralogue <it>insl5a </it>suggesting that it may have been neo-functionalized after the teleost whole genome duplication. Quantitative PCR analyses in <it>D. rerio </it>indicated that <it>rln3a </it>and r<it>ln3b </it>are expressed in brain, <it>insl3 </it>is highly expressed in gonads, and that there was low expression of both <it>insl5 </it>genes in adult zebrafish. Finally, <it>in situ </it>hybridization of <it>insl3 </it>in <it>D. rerio </it>testes showed highly specific hybridization to interstitial Leydig cells.</p> <p>Conclusions</p> <p>Contrary to previous studies, we find convincing evidence that teleosts contain orthologues of four relaxin family peptides. Overall our analyses suggest that in teleosts: 1) <it>rln3 </it>exhibits a similar evolution and expression pattern to mammalian <it>RLN3</it>, 2) <it>insl3 </it>has been subject to positive selection like its mammalian counterpart and shows similar tissue-specific expression in Leydig cells, 3) <it>insl5 </it>genes are highly represented and have a relatively high rate of sequence evolution in teleost genomes, but they exhibited only low levels of expression in adult zebrafish, 4) <it>rln </it>is evolving under very different selective constraints from mammalian <it>RLN</it>. The results presented here should facilitate the development of hypothesis-driven experimental work on the specific roles of relaxin family genes in teleosts.</p

Pollination Biology and Adaptive Radiation of Agavaceae, with Special Emphasis on the Genus Agave

Agavaceae are an American family that comprises nine genera and ca. 300 species distributed in arid and semiarid environments, mainly in Mexico. The family is very successful and displays a wide array of ecological, reproductive, and morphological adaptations. Many of its members play important roles as keystone species, because they produce abundant resources during the reproductive season. In this paper we analyze the current knowledge about the pollination ecology of the different genera in the family and the role that pollination systems have played in the ecological and phylogenetic success of the group. After providing an overview of each of the genera in the family, we discuss in detail aspects of the reproductive ecology of species in the genus Agave s.l., which is composed of ca. 208 species and includes subgenera of Agave (Agave and Littaea), Manfreda, Polianthes, and Prochnyanthes. Finally, we describe the results of analyses to test the hypothesis that there has been an adaptive radiation in the genus Agave. Using chloroplast and nuclear DNA sequences we estimate the age of the Agavaceae family and the genus Agave to be 12-26 millions of years ago (MYA) and 10 MYA, respectively, and show that mean rates of diversification were higher in the genus Agave than the genus Yucca. The values we report for rates of diversification in Agave s.l. are high when compared to other radiations in plants and animals. We suggest that the desertification of North America, which started ca. 15 MY A was critical in the radiation of agaves and that the generalist pollination system of Agave has been more successful in generating new species than the extreme specialization of Yucca

PSORIASIS IS ASSOCIATED WITH ELEVATED GUT IL-1Α AND INTESTINAL MICROBIOME ALTERATIONS

Psoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut

Acupuncture, Counseling, and Usual care for Depression (ACUDep): study protocol for a randomized controlled trial

Background: The evidence on the effect of acupuncture or counseling for depression is not conclusive yet is sufficient to warrant further research. Our aim is to conduct a full-scale RCT to determine the clinical and cost effectiveness of acupuncture and counseling compared to usual care alone. We will explore the experiences and perspectives of patients and practitioners. Methods/Design: Randomized controlled trial with three parallel arms: acupuncture plus usual care, counseling plus usual care, and usual care alone, in conjunction with a nested qualitative study using in-depth interviews with purposive samples of trial participants. Participants: Patients aged over 18 years diagnosed with depression or mood disorder by their GP and with a score of 20 or above on the Beck Depression Inventory (BDI-II). Randomization: Computer randomization by York Trials Unit to acupuncture, counseling, and usual care alone in proportions of 2:2:1, respectively, with secure allocation concealment. Interventions: Patients allocated to acupuncture and counseling groups receive the offer of up to 12 weekly sessions. Both interventions allow flexibility to address patient variation, yet are constrained within defined protocols. Acupuncture is based on traditional Chinese medicine and counseling is non-directive within the humanistic tradition. Outcome: The PHQ-9 is the primary outcome measure, collected at baseline, 3, 6, 9, and 12 months. Also measured is BDI-II, SF-36 Bodily pain subscale, and EQ-5D. Texted mood scores are collected weekly over the first 15 weeks. Health-related resource use is collected over 12 months. Analysis: The sample size target was for 640 participants, calculated for an effect size of 0.32 on the PHQ-9 when comparing acupuncture with counseling given 90% power, 5% significance, and 20% loss to follow-up. Analysis of covariance will be used on an intention-to-treat basis. Thematic analysis will be used for qualitative data. We will compare incremental cost-effectiveness of the three treatment options at 12 months. Discussion: Ethical approval was obtained in October 2009. There were six subsequent protocol amendments, the last of which was approved in January 2012. Recruitment of 755 participants took place over 18 months. Data collection will be completed by June 2012. No interim analyses have been conducted

New Insights into Alzheimer's Disease Progression: A Combined TMS and Structural MRI Study

BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas. METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness. CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD

The relaxin family peptide receptors and their ligands : new developments and paradigms in the evolution from jawless fish to mammals

Relaxin family peptide receptors (Rxfps) and their ligands, relaxin (Rln) and insulin-like (Insl) peptides, are broadly implicated in the regulation of reproductive and neuroendocrine processes in mammals. Most placental mammals harbour genes for four receptors, namely rxfp1, rxfp2, rxfp3 and rxfp4. The number and identity of rxfps in other vertebrates are immensely variable, which is probably attributable to intraspecific variation in reproductive and neuroendocrine regulation. Here, we highlight several interesting, but greatly overlooked, aspects of the rln/insl-rxfp evolutionary history: the ancient origin, recruitment of novel receptors, diverse roles of selection, differential retention and lineage-specific loss of genes over evolutionary time. The tremendous diversity of rln/insl and rxfp genes appears to have arisen from two divergent receptors and one ligand that were duplicated by whole genome duplications (WGD) in early vertebrate evolution, although several genes, notably relaxin in mammals, were also duplicated via small scale duplications. Duplication and loss of genes have varied across lineages: teleosts retained more WGD-derived genes, dominated by those thought to be involved in neuroendocrine regulation (rln3, insl5 and rxfp 3/4 genes), while eutherian mammals witnessed the diversification and rapid evolution of genes involved in reproduction (rln/insl3). Several genes that arose early in evolutionary history were lost in most mammals, but retained in teleosts and, to a lesser extent, in early diverging tetrapods. To elaborate on their evolutionary history, we provide updated phylogenies of the Rxfp1/2 and Rxfp3/4 receptors and their ligands, including new sequences from early diverging vertebrate taxa such as coelacanth, skate, spotted gar, and lamprey. We also summarize the recent progress made towards understanding the functional biology of Rxfps in non-mammalian taxa, providing a new conceptual framework for research on Rxfp signaling across vertebrates

The relaxin family peptide receptors and their ligands: new developments and paradigms in the evolution from jawless fish to mammals

Relaxin family peptide receptors (Rxfps) and their ligands, relaxin (Rln) and insulin-like (Insl) peptides, are broadly implicated in the regulation of reproductive and neuroendocrine processes in mammals. Most placental mammals harbour genes for four receptors, namely rxfp1, rxfp2, rxfp3 and rxfp4. The number and identity of rxfps in other vertebrates are immensely variable, which is probably attributable to intraspecific variation in reproductive and neuroendocrine regulation. Here, we highlight several interesting, but greatly overlooked, aspects of the rln/insl-rxfp evolutionary history: the ancient origin, recruitment of novel receptors, diverse roles of selection, differential retention and lineage-specific loss of genes over evolutionary time. The tremendous diversity of rln/insl and rxfp genes appears to have arisen from two divergent receptors and one ligand that were duplicated by whole genome duplications (WGD) in early vertebrate evolution, although several genes, notably relaxin in mammals, were also duplicated via small scale duplications. Duplication and loss of genes have varied across lineages: teleosts retained more WGD-derived genes, dominated by those thought to be involved in neuroendocrine regulation (rln3, insl5 and rxfp 3/4 genes), while eutherian mammals witnessed the diversification and rapid evolution of genes involved in reproduction (rln/insl3). Several genes that arose early in evolutionary history were lost in most mammals, but retained in teleosts and, to a lesser extent, in early diverging tetrapods. To elaborate on their evolutionary history, we provide updated phylogenies of the Rxfp1/2 and Rxfp3/4 receptors and their ligands, including new sequences from early diverging vertebrate taxa such as coelacanth, skate, spotted gar, and lamprey. We also summarize the recent progress made towards understanding the functional biology of Rxfps in non-mammalian taxa, providing a new conceptual framework for research on Rxfp signaling across vertebrates

Data from: Rethinking refugia: tree topology, divergence dates, and demographic history trace the distribution of the endangered Plymouth gentian (Sabatia kennedyana) from the Pleistocene glaciation to present day

Premise of study: Molecular population genetics is a powerful tool to infer how species responded to past environmental change. In the northern hemisphere, interest is increasing in how species responded to changes in ice coverage and temperature during the last glaciation maximum (LGM, between 18000–21000 yr ago) with a common assumption that glacial refugia were located at the southern edge of a species range. Methods: We reconstructed the glacial and postglacial phylogeography of Sabatia kennedyana, a member of the Atlantic Coastal Plains Flora with a current distribution from Nova Scotia (NS) to South Carolina, using both cpDNA and nuclear markers. We also examined clinal variation in morphological traits, in particular relative investment in asexual vs sexual growth. Key results: We find strong evidence that the species did not reside in southern glacial refugia, but rather in primary glacial refugia off the exposed continental shelf extending from Cape Cod and that this area was responsible for the founding of modern populations across the range from Nova Scotia (NS) to the United States. Additionally, based on the finding of higher cpDNA diversity and older cpDNA lineages in NS, we propose that multiple founder events occurred in NS, while only a single lineage gave rise to current populations in the United States. Conclusions: By understanding how S. kennedyana responded to past shifts in climate and by identifying areas of high genetic diversity in the northern range edge, we discuss the potential response of the species to future climate change scenarios