Calcisponges have a ParaHox gene and dynamic expression of dispersed NK homeobox genes

This study was funded by the Sars Centre core budget to M. Adamska. Sequencing was performed at the Norwegian High Throughput Sequencing Centre funded by the Norwegian Research Council. O.M.R. and D.E.K.F. acknowledge support from the BBSRC and the School of Biology, University of St Andrews.Sponges are simple animals with few cell types, but their genomes paradoxically contain a wide variety of developmental transcription factors1,2,3,4, including homeobox genes belonging to the Antennapedia (ANTP) class5,6, which in bilaterians encompass Hox, ParaHox and NK genes. In the genome of the demosponge Amphimedon queenslandica, no Hox or ParaHox genes are present, but NK genes are linked in a tight cluster similar to the NK clusters of bilaterians5. It has been proposed that Hox and ParaHox genes originated from NK cluster genes after divergence of sponges from the lineage leading to cnidarians and bilaterians5,7. On the other hand, synteny analysis lends support to the notion that the absence of Hox and ParaHox genes in Amphimedon is a result of secondary loss (the ghost locus hypothesis)8. Here we analysed complete suites of ANTP-class homeoboxes in two calcareous sponges, Sycon ciliatum and Leucosolenia complicata. Our phylogenetic analyses demonstrate that these calcisponges possess orthologues of bilaterian NK genes (Hex, Hmx and Msx), a varying number of additional NK genes and one ParaHox gene, Cdx. Despite the generation of scaffolds spanning multiple genes, we find no evidence of clustering of Sycon NK genes. All Sycon ANTP-class genes are developmentally expressed, with patterns suggesting their involvement in cell type specification in embryos and adults, metamorphosis and body plan patterning. These results demonstrate that ParaHox genes predate the origin of sponges, thus confirming the ghost locus hypothesis8, and highlight the need to analyse the genomes of multiple sponge lineages to obtain a complete picture of the ancestral composition of the first animal genome.PostprintPeer reviewe

Coarse-Grained Barrier Trees of Fitness Landscapes

Recent literature suggests that local optima in fitness landscapes are clustered, which offers an explanation of why perturbation-based metaheuristics often fail to find the global optimum: they become trapped in a sub-optimal cluster. We introduce a method to extract and visualize the global organization of these clusters in form of a barrier tree. Barrier trees have been used to visualize the barriers between local optima basins in fitness landscapes. Our method computes a more coarsely grained tree to reveal the barriers between clusters of local optima. The core element is a new variant of the flooding algorithm, applicable to local optima networks, a compressed representation of fitness landscapes. To identify the clusters, we apply a community detection algorithm. A sample of 200 NK fitness landscapes suggests that the depth of their coarse-grained barrier tree is related to their search difficulty

From Popularity Prediction to Ranking Online News

International audienceNews articles are an engaging type of online content that captures the attention of a significant amount of Internet users. They are particularly enjoyed by mobile users and massively spread through online social platforms. As a result, there is an increased interest in discovering the articles that will become popular among users. This objective falls under the broad scope of content popularity prediction and has direct implications in the development of new services for online advertisement and content distribution. In this paper, we address the problem of predicting the popularity of news articles based on user comments. We formulate the prediction task as a ranking problem, where the goal is not to infer the precise attention that a content will receive but to accurately rank articles based on their predicted popularity. Using data obtained from two important news sites in France and Netherlands, we analyze the ranking effectiveness of two prediction models. Our results indicate that popularity prediction methods are adequate solutions for this ranking task and could be considered as a valuable alternative for automatic online news ranking

Understanding extreme sea levels for broad-scale coastal impact and adaptation analysis

One of the main consequences of mean sea level rise (SLR) on human settlements is an increase in flood risk due to an increase in the intensity and frequency of extreme sea levels (ESL). While substantial research efforts are directed towards quantifying projections and uncertainties of future global and regional SLR, corresponding uncertainties in contemporary ESL have not been assessed and projections are limited. Here we quantify, for the first time at global scale, the uncertainties in present-day ESL estimates, which have by default been ignored in broad-scale sea-level rise impact assessments to date. ESL uncertainties exceed those from global SLR projections and, assuming that we meet the Paris agreement goals, the projected SLR itself by the end of the century in many regions. Both uncertainties in SLR projections and ESL estimates need to be understood and combined to fully assess potential impacts and adaptation needs

Preterm Birth in Caucasians Is Associated with Coagulation and Inflammation Pathway Gene Variants

Spontaneous preterm birth (<37 weeks gestation—PTB) occurs in ∼12% of pregnancies in the United States, and is the largest contributor to neonatal morbidity and mortality. PTB is a complex disease, potentially induced by several etiologic factors from multiple pathophysiologic pathways. To dissect the genetic risk factors of PTB a large-scale high-throughput candidate gene association study was performed examining 1536 SNP in 130 candidate genes from hypothesized PTB pathways. Maternal and fetal DNA from 370 US Caucasian birth-events (172 cases and 198 controls) was examined. Single locus, haplotype, and multi-locus association analyses were performed separately on maternal and fetal data. For maternal data the strongest associations were found in genes in the complement-coagulation pathway related to decidual hemorrhage in PTB. In this pathway 3 of 6 genes examined had SNPs significantly associated with PTB. These include factor V (FV) that was previously associated with PTB, factor VII (FVII), and tissue plasminogen activator (tPA). The single strongest effect was observed in tPA marker rs879293 with a significant allelic (p = 2.30×10−3) and genotypic association (p = 2.0×10−6) with PTB. The odds ratio (OR) for this SNP was 2.80 [CI 1.77–4.44] for a recessive model. Given that 6 of 8 markers in tPA were statistically significant, sliding window haplotype analyses were performed and revealed an associating 4 marker haplotype in tPA (p = 6.00×10−3). The single strongest effect in fetal DNA was observed in the inflammatory pathway at rs17121510 in the interleukin-10 receptor antagonist (IL-10RA) gene for allele (p = 0.01) and genotype (p = 3.34×10−4). The OR for the IL-10RA genotypic additive model was 1.92 [CI 1.15–3.19] (p = 2.00×10−3). Finally, exploratory multi-locus analyses in the complement and coagulation pathway were performed and revealed a potentially significant interaction between a marker in FV (rs2187952) and FVII (rs3211719) (p<0.001). These results support a role for genes in both the coagulation and inflammation pathways, and potentially different maternal and fetal genetic risks for PTB

Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study

BACKGROUND: Chorioamnionitis is a common underlying cause of preterm birth (PTB). It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. METHODS: Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. RESULTS: Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG) haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype (MOR 0.2, P = 0.04) were negatively associated. CONCLUSION: These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis

Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing

<p>Abstract</p> <p>Background</p> <p>Duchenne and Becker Muscular dystrophies (DMD/BMD) are allelic disorders caused by mutations in the dystrophin gene, which encodes a sarcolemmal protein responsible for muscle integrity. Deletions and duplications account for approximately 75% of mutations in DMD and 85% in BMD. The implementation of techniques allowing complete gene sequencing has focused attention on small point mutations and other mechanisms underlying complex rearrangements.</p> <p>Methods</p> <p>We selected 47 patients (41 families; 35 DMD, 6 BMD) without deletions and duplications in <it>DMD </it>gene (excluded by multiplex ligation-dependent probe amplification and multiplex polymerase chain reaction analysis). This cohort was investigated by systematic direct sequence analysis to study sequence variation. We focused our attention on rare mutational events which were further studied through transcript analysis.</p> <p>Results</p> <p>We identified 40 different nucleotide alterations in DMD gene and their clinical correlates; altogether, 16 mutations were novel. DMD probands carried 9 microinsertions/microdeletions, 19 nonsense mutations, and 7 splice-site mutations. BMD patients carried 2 nonsense mutations, 2 splice-site mutations, 1 missense substitution, and 1 single base insertion. The most frequent stop codon was TGA (n = 10 patients), followed by TAG (n = 7) and TAA (n = 4). We also analyzed the molecular mechanisms of five rare mutational events. They are two frame-shifting mutations in the <it>DMD </it>gene 3'end in BMD and three novel splicing defects: IVS42: c.6118-3C>A, which causes a leaky splice-site; c.9560A>G, which determines a cryptic splice-site activation and c.9564-426 T>G, which creates pseudoexon retention within IVS65.</p> <p>Conclusion</p> <p>The analysis of our patients' sample, carrying point mutations or complex rearrangements in <it>DMD </it>gene, contributes to the knowledge on phenotypic correlations in dystrophinopatic patients and can provide a better understanding of pre-mRNA maturation defects and dystrophin functional domains. These data can have a prognostic relevance and can be useful in directing new therapeutic approaches, which rely on a precise definition of the genetic defects as well as their molecular consequences.</p

Four novel UCP3 gene variants associated with childhood obesity: effect on fatty acid oxidation and on prevention of triglyceride storage

The objective of the study was to look for uncoupling protein 3 (UCP3) gene variants in early-onset severe childhood obesity and to determine their effect on long-chain fatty acid oxidation and triglyceride storage

Specialization Can Drive the Evolution of Modularity

Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations

Immunological Basis for the Gender Differences in Murine Paracoccidioides brasiliensis Infection

This study aimed to investigate the immunological mechanisms involved in the gender distinct incidence of paracoccidioidomycosis (pcm), an endemic systemic mycosis in Latin America, which is at least 10 times more frequent in men than in women. Then, we compared the immune response of male and female mice to Paracoccidioides brasiliensis infection, as well as the influence in the gender differences exerted by paracoccin, a P. brasiliensis component with carbohydrate recognition property. High production of Th1 cytokines and T-bet expression have been detected in the paracoccin stimulated cultures of spleen cells from infected female mice. In contrast, in similar experimental conditions, cells from infected males produced higher levels of the Th2 cytokines and expressed GATA-3. Macrophages from male and female mice when stimulated with paracoccin displayed similar phagocytic capability, while fungicidal activity was two times more efficiently performed by macrophages from female mice, a fact that was associated with 50% higher levels of nitric oxide production. In order to evaluate the role of sexual hormones in the observed gender distinction, we have utilized mice that have been submitted to gonadectomy followed by inverse hormonal reconstitution. Spleen cells derived from castrated males reconstituted with estradiol have produced higher levels of IFN-γ (1291±15 pg/mL) and lower levels of IL-10 (494±38 pg/mL), than normal male in response to paracoccin stimulus. In contrast, spleen cells from castrated female mice that had been treated with testosterone produced more IL-10 (1284±36 pg/mL) and less IFN-γ (587±14 pg/mL) than cells from normal female. In conclusion, our results reveal that the sexual hormones had a profound effect on the biology of immune cells, and estradiol favours protective responses to P. brasiliensis infection. In addition, fungal components, such as paracoccin, may provide additional support to the gender dimorphic immunity that marks P. brasiliensis infection