Patterns of taxonomic diversity among terrestrial isopods

The publication of the world catalog of terrestrial isopods some ten years ago by Schmalfuss has facilitated research on isopod diversity patterns at a global scale. Furthermore, even though we still lack a comprehensive and robust phylogeny of Oniscidea, we do have some useful approaches to phylogenetic relationships among major clades which can offer additional insights into isopod evolutionary dynamics. Taxonomic diversity is one of many approaches to biodiversity and, despite its sensitiveness to biases in taxonomic practice, has proved useful in exploring diversification dynamics of various taxa. In the present work, we attempt an analysis of taxonomic diversity patterns among Oniscidea based on an updated world list of species containing 3,710 species belonging to 527 genera and 37 families (data till April 2014). The analysis explores species diversity at the genus and family level, as well as the relationships between species per genera, species per families, and genera per families. In addition, we consider the structure of isopod taxonomic system under the fractal perspective that has been proposed as a measure of a taxon’s diversification. Finally, we check whether there is any phylogenetic signal behind taxonomic diversity patterns. The results can be useful in a more detailed elaboration of Oniscidea systematics.     

Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells

Angiopoietin-2 (Ang2) is a Tie-2 ligand that destabilizes vascular structures, allowing for neovascularization or vessel regression depending on local vascular endothelial cell growth factor (VEGF) concentrations. Although various stimuli have been shown to affect Ang2 expression, information on the underlying mechanisms involved in Ang2 production in endothelial cells (EC) is just beginning to emerge. In the present study, we have used adenovirus-mediated gene transfer and pharmacological inhibitors to examine the role of the PTEN/PI3-K/Akt pathway on Ang2 release. Inhibition of PI3-kinase with wortmannin led to a stimulation of basal Ang2 release in EC, while overexpression of an active form of Akt reduced Ang2. In addition, adenovirus-mediated gene transfer of the phosphatase PTEN stimulated Ang2 release. Incubation of the cells with Ang1, an agent that activates the PI3-K/Akt pathway in EC, reduced Ang2 release. This effect of Ang1 could be prevented by wortmannin and LY-294002 pretreatment. Similarly, in VEGF-treated EC the increase in Ang2 production observed was greater in the presence of a PI3-K inhibitor. Our observations that PTEN acts as a positive modulator of Ang2 release, while activation of the PI3-K/Akt pathway downregulates Ang2, reveal an additional mechanism through which the PTEN/PI3-K/Akt pathway could affect the angiogenic process.     

Evaluation of the Possible Transmission of BSE and Scrapie to Gilthead Sea Bream (Sparus aurata)

In transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrP^Sc) of the host-encoded cellular prion protein (PrP^C). While the precise mechanism of the PrP^C to PrP^Sc conversion is not understood, it is clear that host PrP^C expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish. Here we show that while gilthead sea bream (Sparus aurata) orally challenged with brain homogenates prepared either from a BSE infected cow or from scrapie infected sheep developed no clinical prion disease, the brains of TSE-fed fish sampled two years after challenge did show signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs. Remarkably, the deposits developed much more rapidly and extensively in fish inoculated with BSE-infected material than in the ones challenged with the scrapie-infected brain homogenate, with numerous deposits being proteinase K-resistant. These plaque-like aggregates exhibited congophilia and birefringence in polarized light, consistent with an amyloid-like component. The neurodegeneration and abnormal deposition in the brains of fish challenged with prion, especially BSE, raises concerns about the potential risk to public health. As fish aquaculture is an economically important industry providing high protein nutrition for humans and other mammalian species, the prospect of farmed fish being contaminated with infectious mammalian PrP^Sc, or of a prion disease developing in farmed fish is alarming and requires further evaluation.     

Tuning magnetic properties using targeted structural distortion: New additions to a family of Mn6 single-molecule magnets

We report the synthesis and magnetic properties of three hexametallic Mn clusters: [Mn₆O₂(Et-sao)₆(O₂C-Naphth)₂(EtOH)₄(H₂O)₂] (1) (HO₂C-Naphth = 1-naphthoic acid, Et-saoH₂ = 2-hydroxyphenylpropanone oxime), [Mn₆O₂(Et-sao)₆(O₂C-Anthra)₂(EtOH)₄(H₂O)₂] · 0.66EtOH · 0.33H₂O (HO₂C-Anthra = anthracene-9-carboxylic acid) (2 · 0.66EtOH · 0.33H₂O) and [Mn₆O₂(Et-sao)₆(O₂CPhCCH)₂(EtOH)₄(H₂O)₂] · 1.7EtOH · 0.3H₂O (HO₂CPhC  CH = 4-ethynylbenzoic acid) (3 · 1.7EtOH · 0.3H₂O). Clusters 1–3 exhibit ferromagnetic exchange between all six Mn^III centres resulting in S = 12 ground spin states. Ac magnetic susceptibility and single crystal micro-SQUID measurements on 1–3 confirm SMM behaviour with barriers to magnetisation reversal of 60.12 (1), 60.10 (2) and 66.79 (3) K.     

The Drosophila F box protein archipelago regulates dMyc protein levels in vivo

BACKGROUND: The Myc oncoprotein is an important regulator of cellular growth in metazoan organisms. Its levels and activity are tightly controlled in vivo by a variety of mechanisms. In normal cells, Myc protein is rapidly degraded, but the mechanism of its degradation is not well understood. RESULTS: Here we present genetic and biochemical evidence that Archipelago (Ago), the F box component of an SCF-ubiquitin ligase and the Drosophila ortholog of a human tumor suppressor, negatively regulates the levels and activity of Drosophila Myc (dMyc) protein in vivo. Mutations in archipelago (ago) result in strongly elevated dMyc protein levels and increased tissue growth. Genetic interactions indicate that ago antagonizes dMyc function during development. Archipelago binds dMyc and regulates its stability, and the ability of Ago to bind dMyc in vitro correlates with its ability to inhibit dMyc accumulation in vivo. CONCLUSIONS: Our data indicate that archipelago is an important inhibitor of dMyc in developing tissues. Because archipelago can also regulate Cyclin E levels and Notch activity, these results indicate how a single F box protein can be responsible for the degradation of key components of multiple pathways that control growth and cell cycle progression.     

Mean Platelet Volume (MPV) Predicts Middle Distance Running Performance

Background

Running economy and performance in middle distance running depend on several physiological factors, which include anthropometric variables, functional characteristics, training volume and intensity. Since little information is available about hematological predictors of middle distance running time, we investigated whether some hematological parameters may be associated with middle distance running performance in a large sample of recreational runners.

Methods

The study population consisted in 43 amateur runners (15 females, 28 males; median age 47 years), who successfully concluded a 21.1 km half-marathon at 75–85% of their maximal aerobic power (VO₂max). Whole blood was collected 10 min before the run started and immediately thereafter, and hematological testing was completed within 2 hours after sample collection.

Results

The values of lymphocytes and eosinophils exhibited a significant decrease compared to pre-run values, whereas those of mean corpuscular volume (MCV), platelets, mean platelet volume (MPV), white blood cells (WBCs), neutrophils and monocytes were significantly increased after the run. In univariate analysis, significant associations with running time were found for pre-run values of hematocrit, hemoglobin, mean corpuscular hemoglobin (MCH), red blood cell distribution width (RDW), MPV, reticulocyte hemoglobin concentration (RetCHR), and post-run values of MCH, RDW, MPV, monocytes and RetCHR. In multivariate analysis, in which running time was entered as dependent variable whereas age, sex, blood lactate, body mass index, VO₂max, mean training regimen and the hematological parameters significantly associated with running performance in univariate analysis were entered as independent variables, only MPV values before and after the trial remained significantly associated with running time. After adjustment for platelet count, the MPV value before the run (p = 0.042), but not thereafter (p = 0.247), remained significantly associated with running performance.

Conclusion

The significant association between baseline MPV and running time suggest that hyperactive platelets may exert some pleiotropic effects on endurance performance.     

Gene expression is highly correlated on the chromosome level in urinary bladder cancer

Objective: Chromosome correlation maps display correlations between gene expression patterns on the same chromosome. Our goal was to map the genes on chromosome regions and to identify correlations through their location on chromosome regions.

Materials and Methods: Following microarray analysis we used Ingenuity Pathway Analysis (IPA) to construct gene networks of the co-deregulated genes in bladder cancer. Chromosome mapping, mathematical modeling and data simulations were performed using the WebGestalt and Matlab^® softwares.

Results: The top deregulated molecules among 129 bladder cancer samples were implicated in the PI3K/AKT signaling, cell cycle, Myc-mediated apoptosis signaling and ERK5 signaling pathways. Their most prominent molecular and cellular functions were related to cell cycle, cell death, gene expression, molecular transport and cellular growth and proliferation. Chromosome correlation maps allowed us to detect significantly co-expressed genes along the chromosomes. We identified strong correlations among tumors of Tα-grade 1, as well as for those of Tα-grade 2, in chromosomes 1, 2, 3, 7, 12 and 19. Chromosomal domains of gene co-expression were revealed for the normal tissues, as well. The expression data were further simulated, exhibiting an excellent fit (0.7 < R² < 0.9). The simulations revealed that along the different samples, genes on same chromosomes are expressed in a similar manner.

Conclusions: Gene expression is highly correlated on the chromosome level. Chromosome correlation maps of gene expression signatures can provide further information on gene regulatory mechanisms. Gene expression data can be simulated using polynomial functions.     

NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist: structural implications for the MHC II (I-Au)-peptide complex from docking calculations.

Experimental autoimmune encephalomyelitis can be induced in susceptible animals by immunodominant determinants of myelin basic protein (MBP). To characterize the molecular features of antigenic sites important for designing experimental autoimmune encephalomyelitis suppressing molecules, we report structural studies, based on NMR experimental data in conjunction with molecular dynamic simulations, of the potent linear dodecapeptide epitope of guinea pig MBP, Gln74-Lys75-Ser76-Gln77-Arg78-Ser79-Gln80-Asp81-Glu82-Asn83-Pro84-Val85 [MBP(74-85)], and its antagonist analogue Ala81MBP(74-85). The two peptides were studied in both water and Me(2)SO in order to mimic solvent-dependent structural changes in MBP. The agonist MBP(74-85) adopts a compact conformation because of electrostatic interactions of Arg78 with the side chains of Asp81 and Glu82. Arg78 is 'locked' in a well-defined conformation, perpendicular to the peptide backbone which is practically solvent independent. These electrostatic interactions are, however, absent from the antagonist Ala81MBP(74-85), resulting in great flexibility of the side chain of Arg78. Sequence alignment of the two analogues with several species of MBP suggests a critical role for the positively charged residue Arg78, firstly, in the stabilization of the local microdomains (epitopes) of the integral protein, and secondly, in a number of post-translational modifications relevant to multiple sclerosis, such as the conversion of charged arginine residues to uncharged citrullines. Flexible docking calculations on the binding of the MBP(74-85) antigen to the MHC class II receptor site I-A(u) using haddock indicate that Gln74, Ser76 and Ser79 are MHC II anchor residues. Lys75, Arg78 and Asp81 are prominent, solvent-exposed residues and, thus, may be of importance in the formation of the trimolecular T-cell receptor-MBP(74-85)-MHC II complex.     

Raphidiopsis mediterranea Skuja represents non-heterocytous life-cycle stages of Cylindrospermopsis raciborskii (Woloszynska) Seenayya et Subba Raju in Lake Kastoria (Greece), its type locality: Evidence by morphological and phylogenetic analysis

The taxonomical relationship of Cylindrospermopsis raciborskii and Raphidiopsis mediterranea was studied by morphological and 16S rRNA gene diversity analyses of natural populations from Lake Kastoria, Greece. Samples were obtained during a bloom (23,830 trichomes mL⁻¹) in August 2003. A high diversity of apical cell, trichome, heterocyte and akinete morphology, trichome fragmentation and reproduction was observed. Trichomes were grouped into three dominant morphotypes: the typical and the non-heterocytous morphotype of C. raciborskii and the typical morphotype of R. mediterranea. A morphometric comparison of the dominant morphotypes showed significant differences in mean values of cell and trichome sizes despite the high overlap in the range of the respective size values. Additionally, two new morphotypes representing developmental stages of the species are described while a new mode of reproduction involving a structurally distinct reproductive cell is described for the first time in planktic Nostocales. A putative life-cycle, common for C. raciborskii and R. mediterranea is proposed revealing that trichome reproduction of R. mediterranea gives rise both to R. mediterranea and C. raciborskii non-heterocytous morphotypes. The phylogenetic analysis of partial 16S rRNA gene (ca. 920 bp) of the co-existing Cylindrospermopsis and Raphidiopsis morphotypes revealed only one phylotype which showed 99.54% similarity to R. mediterranea HB2 (China) and 99.19% similarity to C. raciborskii form 1 (Australia). We propose that all morphotypes comprised stages of the life cycle of C. raciborkii whereas R. mediterranea from Lake Kastoria (its type locality) represents non-heterocytous stages of Cylindrospermopsis complex life cycle.     

Functional Constraints of 6-Phosphogluconate Dehydrogenase (6-PGD) Based on Sequence and Structural Information

The pentose phosphate cycle is considered as a major source of NADPH and pentose needed for nucleic acid biosynthesis. 6-Phosphogluconate dehydrogenase (6PGD), an enzyme participating in this cycle, catalyzes the oxidative decarboxylation of 6PGD to ribulose 5-phosphate with the subsequent release of CO₂ and the reduction of NADP. We have determined the amino acid sequence of 6PGD of Bactrocera oleae and constructed a three-dimensional model based on the homologous known sheep structure. In a comparative study of 6PGD sequences from numerous species, all the conserved and variable regions of the enzyme were analyzed and the regions of functional importance were localized, in an attempt promoted also by the direct involvement of the enzyme in various human diseases. Thus, analysis of amino acid variability of 37 6PGD sequences revealed that all regions important for the catalytic activity, such as those forming the substrate and coenzyme binding sites, are highly conserved in all species examined. Moreover, several amino acid residues responsible for substrate and coenzyme specificity were also found to be identical in all species examined. The higher percentage of protein divergence is observed at two regions that accumulate mutations, located at the distant parts of the two domains of the enzyme with respect to their interface. These peripheral regions of nonfunctional importance are highly variable and are predicted as antigenic, thus reflecting possible regions for antibody recognition. Furthermore, locating the differences between diptera 6PGD sequences on the three-dimensional model suggests probable positions of different amino acid residues appearing at B. oleae fast, intermediate, and slow allozymic variants. Abbreviations used: 6Pgd, 6-Phosphogluconate dehydrogenase gene; 6PGD, 6-Phosphogluconate dehydrogenase enzyme; NADPH, nicotinamide adenine dinucleotide phosphate; ADP, adenine dinucleotide phosphate; TNBS, 2,4,6 trinitrobenzensulfonic acid.