Multiple Continental Radiations and Correlates of Diversification in Lupinus (Leguminosae): Testing for Key Innovation with Incomplete Taxon Sampling

Replicate radiations provide powerful comparative systems to address questions about the interplay between opportunity and innovation in driving episodes of diversification and the factors limiting their subsequent progression. However, such systems have been rarely documented at intercontinental scales. Here, we evaluate the hypothesis of multiple radiations in the genus Lupinus (Leguminosae), which exhibits some of the highest known rates of net diversification in plants. Given that incomplete taxon sampling, background extinction, and lineage-specific variation in diversification rates can confound macroevolutionary inferences regarding the timing and mechanisms of cladogenesis, we used Bayesian relaxed clock phylogenetic analyses as well as MEDUSA and BiSSE birth-death likelihood models of diversification, to evaluate the evolutionary patterns of lineage accumulation in Lupinus. We identified 3 significant shifts to increased rates of net diversification (r) relative to background levels in the genus (r = 0.18-0.48 lineages/myr). The primary shift occurred approximately 4.6 Ma (r = 0.48-1.76) in the montane regions of western North America, followed by a secondary shift approximately 2.7 Ma (r = 0.89-3.33) associated with range expansion and diversification of allopatrically distributed sister clades in the Mexican highlands and Andes. We also recovered evidence for a third independent shift approximately 6.5 Ma at the base of a lower elevation eastern South American grassland and campo rupestre clade (r = 0.36-1.33). Bayesian ancestral state reconstructions and BiSSE likelihood analyses of correlated diversification indicated that increased rates of speciation are strongly associated with the derived evolution of perennial life history and invasion of montane ecosystems. Although we currently lack hard evidence for "replicate adaptive radiations” in the sense of convergent morphological and ecological trajectories among species in different clades, these results are consistent with the hypothesis that iteroparity functioned as an adaptive key innovation, providing a mechanism for range expansion and rapid divergence in upper elevation regions across much of the New Worl

Quantitative allele-specific expression and DNA methylation analysis of H19, IGF2 and IGF2R in the human placenta across gestation reveals H19 imprinting plasticity

Extent: 11p.Imprinted genes play important roles in placental differentiation, growth and function, with profound effects on fetal development. In humans, H19 and IGF2 are imprinted, but imprinting of IGF2R remains controversial. The H19 non-coding RNA is a negative regulator of placental growth and altered placental imprinting of H19-IGF2 has been associated with pregnancy complications such as preeclampsia, which have been attributed to abnormal first trimester placentation. This suggests that changes in imprinting during the first trimester may precede aberrant placental morphogenesis. To better understand imprinting in the human placenta during early gestation, we quantified allele-specific expression for H19, IGF2 and IGF2R in first trimester (6–12 weeks gestation) and term placentae (37–42 weeks gestation) using pyrosequencing. Expression of IGF2R was biallelic, with a mean expression ratio of 49:51 (SD = 0.07), making transient imprinting unlikely. Expression from the repressed H19 alleles ranged from 1–25% and was higher (P<0.001) in first trimester (13.5±8.2%) compared to term (3.4±2.1%) placentae. Surprisingly, despite the known co-regulation of H19 and IGF2, little variation in expression of the repressed IGF2 alleles was observed (2.7±2.0%). To identify regulatory regions that may be responsible for variation in H19 allelic expression, we quantified DNA methylation in the H19-IGF2 imprinting control region and H19 transcription start site (TSS). Unexpectedly, we found positive correlations (P<0.01) between DNA methylation levels and expression of the repressed H19 allele at 5 CpG’s 2000 bp upstream of the H19 TSS. Additionally, DNA methylation was significantly higher (P<0.05) in first trimester compared with term placentae at 5 CpG’s 39–523 bp upstream of the TSS, but was not correlated with H19 repressed allele expression. Our data suggest that variation in H19 imprinting may contribute to early programming of placental phenotype and illustrate the need for quantitative and robust methodologies to further elucidate the role of imprinted genes in normal and pathological placental development.Sam Buckberry, Tina Bianco-Miotto, Stefan Hiendleder and Claire T. Robert

Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

Aim: To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age. Materials & methods: Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays. Results & conclusion: We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from early onset preeclampsia cases, but not term preeclampsia, compared with their chronological age. Therefore, early onset preeclampsia is associated with placental aging. Gestational age acceleration prediction from DNA methylation array data may provide insight into the molecular mechanisms of pregnancy disorders.Benjamin T Mayne, Shalem Y Leemaqz, Alicia K Smith, James Breen, Claire T Roberts, Tina Bianco-Miott

MassiR: A method for predicting the sex of samples in gene expression microarray datasets

UNLABELLED: High-throughput gene expression microarrays are currently the most efficient method for transcriptome-wide expression analyses. Consequently, gene expression data available through public repositories have largely been obtained from microarray experiments. However, the metadata associated with many publicly available expression microarray datasets often lacks sample sex information, therefore limiting the reuse of these data in new analyses or larger meta-analyses where the effect of sex is to be considered. Here, we present the massiR package, which provides a method for researchers to predict the sex of samples in microarray datasets. Using information from microarray probes representing Y chromosome genes, this package implements unsupervised clustering methods to classify samples into male and female groups, providing an efficient way to identify or confirm the sex of samples in mammalian microarray datasets. AVAILABILITY AND IMPLEMENTATION: massiR is implemented as a Bioconductor package in R. The package and the vignette can be downloaded at bioconductor.org and are provided under a GPL-2 license.Sam Buckberry, Stephen J. Bent, Tina Bianco-Miotto and Claire T. Robert

Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.Benjamin T. Mayne, Tina Bianco-Miotto, Sam Buckberry, James Breen, Vicki Clifton, Cheryl Shoubridge and Claire T. Robert

Local variation of hashtag spike trains and popularity in Twitter

We draw a parallel between hashtag time series and neuron spike trains. In each case, the process presents complex dynamic patterns including temporal correlations, burstiness, and all other types of nonstationarity. We propose the adoption of the so-called local variation in order to uncover salient dynamics, while properly detrending for the time-dependent features of a signal. The methodology is tested on both real and randomized hashtag spike trains, and identifies that popular hashtags present regular and so less bursty behavior, suggesting its potential use for predicting online popularity in social media.Comment: 7 pages, 7 figure

Placental transcriptome co-expression analysis reveals conserved regulatory programs across gestation

Background: Mammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. Results: In this study, we performed a comprehensive analysis of human placental co-expression using RNA sequencing and intergrated multiple transcriptome datasets spanning human gestation. We identified modules of co-expressed genes that are preserved across human gestation, and also identifed modules conserved in the mouse indicating conserved molecular networks involved in placental development and gene expression patterns more specific to late gestation. Analysis of co-expressed gene flanking sequences indicated that conserved co-expression modules in the placenta are regulated by a core set of transcription factors, including ZNF423 and EBF1. Additionally, we identified a gene co-expression module enriched for genes implicated in the pregnancy pathology preeclampsia. By using an independnet transcriptome dataset, we show that these co-expressed genes are differentially expressed in preeclampsia. Conclusions: This study represents a comprehensive characterisation of placental co-expression and provides insight into potential transcriptional regulators that govern conserved molecular programs fundamental to placental development.Sam Buckberry, Tina Bianco-Miotto, Stephen J. Bent, Vicki Clifton, Cheryl Shoubridge, Kartik Shankar and Claire T. Robert

Alkaloids in Erythrina

Erythrina species are used in popular medicine as sedative, anxiolytic, anti-inflammatory, and antihypertensive. In this work, we investigated the chemical composition of extracts obtained from leaves of E. falcata and E. crista-galli. The hypotensive potential of E. falcata and the mechanism of action were also studied. The extracts were obtained by maceration and infusion. The total content of phenolic compounds and flavonoids was estimated by spectrophotometric methods. The chemical constituents were studied performing a chromatographic analysis by UPLC-ESI-MS. For in vivo protocols, blood pressure and heart rate were measured by the invasive hemodynamic monitoring method. Different concentrations of extracts and drugs such as L-NAME, losartan, hexamethonium, and propranolol were administrated i.v. The results of total phenolic contents for E. falcata and E. crista-galli were 1.3193–1.4989 mgGAE/mL for maceration and 0.8771–0.9506 mgGAE/mL for infusion. In total flavonoids, the content was 7.7829–8.1976 mg RE/g for maceration and 9.3471–10.4765 RE mg/g for infusion. The chemical composition was based on alkaloids, suggesting the presence of erythristemine, 11β-methoxyglucoerysodine, erysothiopine, 11β-hydroxyerysodine-glucose, and 11-hydroxyerysotinone-rhamnoside. A potent dose-dependent hypotensive effect was observed for E. falcata, which may be related to the route of β-adrenergic receptors

Evolução da maturação da uva 'BRS Clara' sob cultivo protegido durante a safra fora de época.

A produção de uvas para mesa vem passando por alguns desafios que demandam alterações nas tecnologias de produção, devido, principalmente, à intensa necessidade de controle de doenças fúngicas. O objetivo deste trabalho foi avaliar o comportamento da evolução da maturação da uva 'BRS Clara' enxertada sobre o porta-enxerto IAC 766 'Campinas', sob cultivo protegido produzida em safra fora de época. Os experimentos foram realizados em Uraí e Marialva (PR). Foram avaliadas semanalmente as características químicas das bagas, como teor de sólidos solúveis, acidez titulável, índice de maturação e pH, a partir do início da maturação até a colheita, em dois sistemas de cultivo protegido: cobertura plástica e sombrite. O delineamento experimental adotado em ambas as áreas foi o inteiramente casualizado com sete repetições. A evolução da maturação nos dois sistemas de cultivo protegido foi comparada por meio da análise de regressão. Em ambas as áreas experimentais, a cobertura plástica possibilitou a antecipação da colheita das uvas em seis dias em relação ao sombrite, considerando o teor de sólidos solúveis. Não houve influência da cobertura plástica sobre o índice de maturação das uvas