MADAM - An open source meta-analysis toolbox for R and Bioconductor

Background  

Meta-analysis is a major theme in biomedical research. In the present paper we introduce a package for R and Bioconductor that provides useful tools for performing this type of work. One idea behind the development of MADAM was that many meta-analysis methods, which are available in R, are not able to use the capacities of parallel computing yet. In this first version, we implemented one meta-analysis method in such a parallel manner. Additionally, we provide tools for combining the results from a set of methods in an ensemble approach. Functionality for visualization of results is also provided.     

Inferring the biogeographic origins of inter‐continental disjunct endemics using a Bayes‐DIVA approach

The arcto‐Tertiary relictual flora is comprised of many genera that occur non‐contiguously in the temperate zones of eastern Asia, Europe, eastern North America, and western North America. Within each distributional area, species are typically endemic and may thus be widely separated from closely related species within the other areas. It is widely accepted that this common pattern of distribution resulted from of the fragmentation of a once more‐continuous arcto‐Tertiary forest. The historical biogeographic events leading to the present‐day disjunction have often been investigated using a phylogenetic approach. Limitations to these previous studies have included phylogenetic uncertainty and uncertainty in ancestral range reconstructions. However, the recently described Bayes‐DIVA method handles both types of uncertainty. Thus, we used Bayes‐DIVA analysis to reconstruct the stem lineage distributions for 185 endemic lineages from 23 disjunct genera representing 17 vascular plant families. In particular, we asked whether endemic lineages within each of the four distributional areas more often evolved from (1) widespread ancestors, (2) ancestors dispersed from other areas, or (3) endemic ancestors. We also considered which of these three biogeographic mechanisms may best explain the origins of arcto‐Tertiary disjunct endemics in the neotropics. Our results show that eastern Asian endemics more often evolved from endemic ancestors compared to endemics in Europe and eastern and western North America. Present‐day endemic lineages in the latter areas more often arose from widespread ancestors. Our results also provide anecdotal evidence for the importance of dispersal in the biogeographic origins of arcto‐Tertiary species endemic in the neotropics.     

The very early evolution of protein translocation across membranes

In this study, we used a computational approach to investigate the early evolutionary history of a system of proteins that, together, embed and translocate other proteins across cell membranes. Cell membranes comprise the basis for cellularity, which is an ancient, fundamental organizing principle shared by all organisms and a key innovation in the evolution of life on Earth. Two related requirements for cellularity are that organisms are able to both embed proteins into membranes and translocate proteins across membranes. One system that accomplishes these tasks is the signal recognition particle (SRP) system, in which the core protein components are the paralogs, FtsY and Ffh. Complementary to the SRP system is the Sec translocation channel, in which the primary channel-forming protein is SecY. We performed phylogenetic analyses that strongly supported prior inferences that FtsY, Ffh, and SecY were all present by the time of the last universal common ancestor of life, the LUCA, and that the ancestor of FtsY and Ffh existed before the LUCA. Further, we combined ancestral sequence reconstruction and protein structure and function prediction to show that the LUCA had an SRP system and Sec translocation channel that were similar to those of extant organisms. We also show that the ancestor of Ffh and FtsY that predated the LUCA was more similar to FtsY than Ffh but could still have comprised a rudimentary protein translocation system on its own. Duplication of the ancestor of FtsY and Ffh facilitated the specialization of FtsY as a membrane bound receptor and Ffh as a cytoplasmic protein that could bind nascent proteins with specific membrane-targeting signal sequences. Finally, we analyzed amino acid frequencies in our ancestral sequence reconstructions to infer that the ancestral Ffh/FtsY protein likely arose prior to or just after the completion of the canonical genetic code. Taken together, our results offer a window into the very early evolutionary history of cellularity.     

Proteomic analysis of endothelial cold-adaptation

Background

Milkweeds (Asclepias L.) have been extensively investigated in diverse areas of evolutionary biology and ecology; however, there are few genetic resources available to facilitate and compliment these studies. This study explored how low coverage genome sequencing of the common milkweed (Asclepias syriaca L.) could be useful in characterizing the genome of a plant without prior genomic information and for development of genomic resources as a step toward further developing A. syriaca as a model in ecology and evolution.

Results

A 0.5× genome of A. syriaca was produced using Illumina sequencing. A virtually complete chloroplast genome of 158,598 bp was assembled, revealing few repeats and loss of three genes: accD, clpP, and ycf1. A nearly complete rDNA cistron (18S-5.8S-26S; 7,541 bp) and 5S rDNA (120 bp) sequence were obtained. Assessment of polymorphism revealed that the rDNA cistron and 5S rDNA had 0.3% and 26.7% polymorphic sites, respectively. A partial mitochondrial genome sequence (130,764 bp), with identical gene content to tobacco, was also assembled. An initial characterization of repeat content indicated that Ty1/copia-like retroelements are the most common repeat type in the milkweed genome. At least one A. syriaca microread hit 88% of Catharanthus roseus (Apocynaceae) unigenes (median coverage of 0.29×) and 66% of single copy orthologs (COSII) in asterids (median coverage of 0.14×). From this partial characterization of the A. syriaca genome, markers for population genetics (microsatellites) and phylogenetics (low-copy nuclear genes) studies were developed.

Conclusions

The results highlight the promise of next generation sequencing for development of genomic resources for any organism. Low coverage genome sequencing allows characterization of the high copy fraction of the genome and exploration of the low copy fraction of the genome, which facilitate the development of molecular tools for further study of a target species and its relatives. This study represents a first step in the development of a community resource for further study of plant-insect co-evolution, anti-herbivore defense, floral developmental genetics, reproductive biology, chemical evolution, population genetics, and comparative genomics using milkweeds, and A. syriaca in particular, as ecological and evolutionary models.     

Trapped in a vicious loop: Toll-like receptors sustain the spontaneous cytokine production by rheumatoid synovium

Synovial tissue of patients with rheumatoid arthritis (RA) spontaneously produces several cytokines, of which a fundamental role in joint inflammation and destruction has been established. However, the factors sustaining this phenomenon remain poorly understood. In a recent report, blockade of Toll-like receptor 2 (TLR2) was found to inhibit the spontaneous release of inflammatory cytokines by intact RA synovial explant cultures. Adding to the recent evidence implicating other TLRs (in particular, TLR4), this observation highlights the potential of TLRs as therapeutic targets to suppress the local production of multiple cytokines and to control the chronic inflammatory loop in RA.     

Quantitative study on the inferior vena cava between the renal vein and diaphragm

50 dissections of the human inferior V. cava have been performed in order to measure its right renal vein - diaphragm, retrohepatic, and suprahepatic segments. We conclude that some individual parameters as skin type, age, height, weight did not influence the magnitude of the studied segments. The average measurements of the different parameters proposed for the inferior V. cava are: 1. The distances between the right renal vein and the diaphragm and between the right renal vein and the right atrium are 113.94 mm and 135.16 mm, respectively; 2. the length of the retrohepatic portion of the inferior V. cava and the suprahepatic one were 78.34 mm and 19.34 mm respectively; 3. the valve of the inferior V. cava is present in 46% of the observations; its length and width averages are 31 mm and 10.22 mm, respectively.     

Local texture convergence: a new approach to seeking assembly rules

Much of community-ecology theory describes (or even assumes) constraints on the coexistence of species. These constraints are often described using functional characters as an index to the niche of the species. The hypothesis/assumption is that those species which are too similar in functional characters, and hence in niche, cannot coexist. However, this body of theory is rarely tested. We attempted a test by making a prediction of texture convergence that follows logically from the theory, yet is simple enough to test – one based on similarity of ecological assembly between the patches of a community. We used replicate quadrats within twelve herbaceous communities. Eleven characters were measured, that were intended to reflect the functional above-ground niche of the species. We examined each character in turn, to test for ecological convergence to a similar mean within each community, with species either weighted equally (i.e. using species presence) or weighted by their biomass. Convergence with species weighted by their biomass was seen in chlorophyll content, indicating a significant tendency for each patch in a community to comprise a rather constant mixture of species types in terms of their different chlorophyll contents. In terms of species presence, texture divergence occurred in leafiness (LAR), specific leaf area (SLA) and leaf inclination, i.e. there was more variation between quadrats within a site than expected at random. However, significant results were sparse: the bulk of evidence is for no significant departure from a null model, i.e. no support for a widespread body of ecological theory.