A Hypothesis for the Composition of the Tardigrade Brain and its Implications for Panarthropod Brain Evolution

Incredibly disparate brain types are found in Metazoa, which raises the question of how this disparity evolved. Ecdysozoa includes representatives that exhibit ring-like brains-the Cycloneuralia-and representatives that exhibit ganglionic brains-the Panarthropoda (Euarthropoda, Onychophora, and Tardigrada). The evolutionary steps leading to these distinct brain types are unclear. Phylogenomic analyses suggest that the enigmatic Tardigrada is a closely related outgroup of a Euarthropoda + Onychophora clade; as such, the brains of tardigrades may provide insight into the evolution of ecdysozoan brains. Recently, evolutionarily salient questions have arisen regarding the composition of the tardigrade brain. To address these questions, we investigated brain anatomy in four tardigrade species-Hypsibius dujardini, Milnesium n. sp., Echiniscus n. sp., and Batillipes n. sp.-that together span Tardigrada. Our results suggest that general brain morphology is conserved across Tardigrada. Based on our results we present a hypothesis that proposes direct parallels between the tardigrade brain and the segmental trunk ganglia of the tardigrade ventral nervous system. In this hypothesis, brain neuropil nearly circumscribes the tardigrade foregut. We suggest that the tardigrade brain retains aspects of an ancestral cycloneuralian brain, while exhibiting ganglionic structure characteristic of euarthropods and onychophorans

Wheels within wheels: Hamiltonian dynamics as a hierarchy of action variables

In systems where one coordinate undergoes periodic oscillation, the net displacement in any other coordinate over a single period is shown to be given by differentiation of the action integral associated with the oscillating coordinate. This result is then used to demonstrate that the action integral acts as a Hamiltonian for slow coordinates providing time is scaled to the ``tick-time'' of the oscillating coordinate. Numerous examples, including charged particle drifts and relativistic motion, are supplied to illustrate the varied application of these results.Comment: 7 pages, 3 figure

Transcriptome profiling with focus on potential key genes for wing development and evolution in Megaloprepus caerulatus, the damselfly species with the world's largest wings

The evolution, development and coloration of insect wings remains a puzzling subject in evolutionary research. In basal flying insects such as Odonata, genomic research regarding bauplan evolution is still rare. Here we focus on the world’s largest odonate species—the “forest giant” Megaloprepus caerulatus, to explore its potential for looking deeper into the development and evolution of wings. A recently discovered cryptic species complex in this genus previously considered monotypic is characterized by morphological differences in wing shape and color patterns. As a first step toward understanding wing pattern divergence and pathways involved in adaptation and speciation at the genomic level, we present a transcriptome profiling of M. caerulatus using RNA-Seq and compare these data with two other odonate species. The de novo transcriptome assembly consists of 61,560 high quality transcripts and is approximately 93% complete. For almost 75% of the identified transcripts a possible function could be assigned: 48,104 transcripts had a hit to an InterPro protein family or domain, and 28,653 were mapped to a Gene Ontology term. In particular, we focused on genes related to wing development and coloration. The comparison with two other species revealed larva-specific genes and a conserved ‘core’ set of over 8,000 genes forming orthologous clusters with Ischnura elegans and Ladona fulva. This transcriptome may provide a first point of reference for future research in odonates addressing questions surrounding the evolution of wing development, wing coloration and their role in speciation

Advancing the Frontier of Peacekeeping Research

The impact of United Nations (UN) peacekeeping on conflict has received a sustained amount of attention in the empirical literature. The advent of new data on UN peacekeeping and new temporal units of analysis have enabled researchers to expand the frontiers of peacekeeping research and undertake a more nuanced examination of peacekeeping effectiveness. In this special section, a series of articles examine how UN peacekeeping affects different types of violence within conflicts and leads to different types of peaceful outcomes. Factors such as the cultural affinity between peacekeepers and local communities, the size of peacekeeping operations and the specific composition of UN forces are shown to be important variables associated with lower levels of casualties and violence and also a higher likelihood of mediation and timely peaceful settlements in civil wars. In the aggregate, these articles suggest that robust peacekeeping is associated with better outcomes in many stages of conflict

Multi-transmission-line-beam interactive system

We construct here a Lagrangian field formulation for a system consisting of an electron beam interacting with a slow-wave structure modeled by a possibly non-uniform multiple transmission line (MTL). In the case of a single line we recover the linear model of a traveling wave tube (TWT) due to J.R. Pierce. Since a properly chosen MTL can approximate a real waveguide structure with any desired accuracy, the proposed model can be used in particular for design optimization. Furthermore, the Lagrangian formulation provides for: (i) a clear identification of the mathematical source of amplification, (ii) exact expressions for the conserved energy and its flux distributions obtained from the Noether theorem. In the case of uniform MTLs we carry out an exhaustive analysis of eigenmodes and find sharp conditions on the parameters of the system to provide for amplifying regimes

Genomic and geographical structure of human cytomegalovirus

Human cytomegalovirus (CMV) has infected humans since the origin of our species and currently infects most of the world’s population. Variability between CMV genomes is the highest of any human herpesvirus, yet large portions of the genome are conserved. Here, we show that the genome encodes 74 regions of relatively high variability each with 2 to 8 alleles. We then identified two patterns in the CMV genome. Conserved parts of the genome and a minority (32) of variable regions show geographic population structure with evidence for African or European clustering, although hybrid strains are present. We find no evidence that geographic segregation has been driven by host immune pressure affecting known antigenic sites. Forty-two variable regions show no geographical structure, with similar allele distributions across different continental populations. These “nongeographical” regions are significantly enriched for genes encoding immunomodulatory functions suggesting a core functional importance. We hypothesize that at least two CMV founder populations account for the geographical differences that are largely seen in the conserved portions of the genome, although the timing of separation and direction of spread between the two are not clear. In contrast, the similar allele frequencies among 42 variable regions of the genome, irrespective of geographical origin, are indicative of a second evolutionary process, namely balancing selection that may preserve properties critical to CMV biological function. Given that genetic differences between CMVs are postulated to alter immunogenicity and potentially function, understanding these two evolutionary processes could contribute important information for the development of globally effective vaccines and the identification of novel drug targets

A surrogate-based approach for post-genomic partner identification

BACKGROUND: Modern drug discovery is concerned with identification and validation of novel protein targets from among the 30,000 genes or more postulated to be present in the human genome. While protein-protein interactions may be central to many disease indications, it has been difficult to identify new chemical entities capable of regulating these interactions as either agonists or antagonists. RESULTS: In this paper, we show that peptide complements (or surrogates) derived from highly diverse random phage display libraries can be used for the identification of the expected natural biological partners for protein and non-protein targets. Our examples include surrogates isolated against both an extracellular secreted protein (TNFβ) and intracellular disease related mRNAs. In each case, surrogates binding to these targets were obtained and found to contain partner information embedded in their amino acid sequences. Furthermore, this information was able to identify the correct biological partners from large human genome databases by rapid and integrated computer based searches. CONCLUSIONS: Modified versions of these surrogates should provide agents capable of modifying the activity of these targets and enable one to study their involvement in specific biological processes as a means of target validation for downstream drug discovery

Differential expression of glycoproteins containing [alpha]--galactosyl groups on normal human breast epithelial cells and MCF-7 human breast carcinoma cells

Cell surface glycoproteins were isolated from the lysates of 125I-labeled normal human mammary epithelial cells (NHMEC) and from the human breast carcinoma cell line MCF-7, of blood-group O phenotype, by affinity chromatography on Griffonia simplicifolia I lectin-Sepharose. Specific elution of glycoproteins from the column with methyl [alpha]--galactoside suggests the presence of [alpha]--galactosyl groups on these moieties. SDS-PAGE analysis of isolated glycoproteins revealed both quantitative and qualitative differences between glycoproteins from normal and malignant cells. Three major glycoproteins of Mr 180 kDa, 85 kDa and the 44 kDa were obtained from MCF-7 cells. The 180-kDa glycoprotein was absent in NHMEC and the 44-kDa glycoprotein was very weakly expressed in these cells. The only glycoprotein which was found in almost equal amount in the lysate from both normal and malignant cells was the 85-kDa glycoprotein. These results indicate differences between normal human mammary epithelial cells and one kind of malignant human mammary epithelial cells, in the expression of glycoproteins containing [alpha]--galactosyl groups, irrespective of blood-group phenotype; they also demonstrate that [alpha]--galactosyl group are expressed in a very restrictive manner on the surface of this tumor cell line.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29093/1/0000129.pd

Peptides identify multiple hotspots within the ligand binding domain of the TNF receptor 2

BACKGROUND: Hotspots are defined as the minimal functional domains involved in protein:protein interactions and sufficient to induce a biological response. RESULTS: Here we describe the use of complex and high diversity phage display libraries to isolate peptides (called Hotspot Ligands or HSPLs) which sub-divide the ligand binding domain of the tumor necrosis factor receptor 2 (TNFR2; p75) into multiple hotspots. We have shown that these libraries could generate HSPLs which not only subdivide hotspots on protein and non-protein targets but act as agonists or antagonists. Using this approach, we generated peptides which were specific for human TNFR2, could be competed by the natural ligands, TNFα and TNFβ and induced an unexpected biological response in a TNFR2-specific manner. CONCLUSIONS: To our knowledge, this is the first report describing the dissection of the TNFR2 into biologically active hotspots with the concomitant identification of a novel and unexpected biological activity

After the RCT: who comes to a family-based intervention for childhood overweight or obesity when it is implemented at scale in the community?

Background: When implemented at scale, the impact on health and health inequalities of public health interventions depends on who receives them in addition to intervention effectiveness. Methods: The MEND 7–13 (Mind, Exercise, Nutrition…Do it!) programme is a family-based weight management intervention for childhood overweight and obesity implemented at scale in the community. We compare the characteristics of children referred to the MEND programme (N=18 289 referred to 1940 programmes) with those of the population eligible for the intervention, and assess what predicts completion of the intervention. Results: Compared to the MEND-eligible population, proportionally more children who started MEND were: obese rather than overweight excluding obese; girls; Asian; from families with a lone parent; living in less favourable socioeconomic circumstances; and living in urban rather than rural or suburban areas. Having started the programme, children were relatively less likely to complete it if they: reported ‘abnormal’ compared to ‘normal’ levels of psychological distress; were boys; were from lone parent families; lived in less favourable socioeconomic circumstances; and had participated in a relatively large MEND programme group; or where managers had run more programmes. Conclusions: The provision and/or uptake of MEND did not appear to compromise and, if anything, promoted participation of those from disadvantaged circumstances and ethnic minority groups. However, this tendency was diminished because programme completion was less likely for those living in less favourable socioeconomic circumstances. Further research should explore how completion rates of this intervention could be improved for particular groups