Proteomic analysis of plasma from patients with systemic lupus erythematosus: increased presence of haptoglobin alpha2 polypeptide chains over the alpha1 isoforms

In the present study plasma samples from 15 systemic lupus erythematosus (SLE) patients and 16 healthy controls of initially unknown haptoglobin (Hp) phenotype were separated by 2-DE, and tryptic digests of the excised Hpalpha polypeptide chain spots were analyzed by MALDI-TOF-MS. Selected tryptic peptides were sequenced by nano-(n)ESI-IT MS/MS. The six major Hp phenotypes were present, although with distinct frequencies in controls and SLE patients. Thus, there were an increased proportion of SLE patients with Hp 2-2, or Hp 2-1S phenotypes. The Hp phenotype distribution resulted in allele frequencies of 0 625 (Hp(2)), 0.281 (Hp(1S)), and 0.093 (Hp(1F)) in healthy controls, correlating fairly well with the allele frequencies of European populations. In contrast, the Hp allele frequencies of the SLE patients were 0.733 (Hp(2)), 0.233 (Hp(1S)), and 0.033 (Hp1(1F)), which clearly indicated an increased frequency of Hp(2), a similar proportion of Hp(1S) and a diminished proportion of Hp(1F) in SLE patients compared with that in healthy controls. Preferential Hpalpha2 expression in SLE patients may contribute to some of the clinical manifestations of the disease such as hypergammaglobulinemia, systemic vasculitis, and cardiovascular disorders.     

Tools for kinetic modeling of biochemical networks

The number of software packages for kinetic modeling of biochemical networks continues to grow. Although most packages share a common core of functionality, the specific capabilities and user interfaces of different packages mean that choosing the best package for a given task is not trivial. We compare 12 software packages with respect to their functionality, reliability, efficiency, user-friendliness and compatibility. Although most programs performed reliably in all numerical tasks tested, SBML compatibility and the set-up of multicompartmentalization are problematic in many packages. For simple models, GEPASI seems the best choice for non-expert users. For large-scale models, environments such as Jarnac/JDesigner are preferable, because they allow modular implementation of models. Virtual Cell is the most versatile program and provides the simplest and clearest functionality for setting up multicompartmentalization.     

From the rye Alt3 and Alt4 aluminum tolerance loci to orthologous genes in other cereals

The major limit to plant growth in acid soils is the presence of toxic aluminum (Al) cations, which limit growth by inhibiting root elongation. Aluminum tolerance in rye is controlled by (at least) four independent loci (Alt1, Alt2, Alt3 and Alt4) located on chromosome arms 6RS, 3RS, 4RL and 7RS, respectively. In this work, we analyzed several F₂ populations in which two different Alt loci were segregating. We constructed a map of chromosome 7R, which contains the Alt4 locus and microsatellite and PCR-markers (B1, B4, B11, B26 and BCD1230). These markers were mapped to the S arm of 7R using wheat-rye addition lines. Our results show that all these markers are linked to the Alt4 locus already known to be on 7RS. In addition, the OPS14 ₇₀₅ RAPD marker was linked to the Alt3 locus using bulked segregant analysis. This RAPD marker was transformed into a SCAR (ScOPS14 ₇₀₅ ) and was localized to arm 4RL using wheat-rye addition lines. Finally, this SCAR was linked to the Alt3 locus at a genetic distance of 23.4 cM. In light of the current findings, and taking into account the synteny relationships in cereals, we propose candidate Alt3 and Alt4 orthologues in other cereals.     

Lipid second messengers and related enzymes in vertebrate rod outer segments

Rod outer segments (ROSs) are specialized light-sensitive organelles in vertebrate photoreceptor cells. Lipids in ROS are of considerable importance, not only in providing an adequate environment for efficient phototransduction, but also in originating the second messengers involved in signal transduction. ROSs have the ability to adapt the sensitivity and speed of their responses to ever-changing conditions of ambient illumination. A major contributor to this adaptation is the light-driven translocation of key signaling proteins into and out of ROS. The present review shows how generation of the second lipid messengers from phosphatidylcholine, phosphatidic acid, and diacylglycerol is modulated by the different illumination states in the vertebrate retina. Findings suggest that the light-induced translocation of phototransduction proteins influences the enzymatic activities of phospholipase D, lipid phosphate phosphatase, diacylglyceride lipase, and diacylglyceride kinase, all of which are responsible for the generation of the second messenger molecules.     

A new species of Empruthotrema (Monogenea: Monocotylidae) from Pteromylaeus bovinus (Myliobatidae) from the Western Mediterranean

Empruthotrema chisholmae n. sp. is described from specimens recovered from a bull ray Pteromylaeus bovinus (Geoffroy Saint-Hilaire, 1817) at the Oceanogràfic Aquarium in Valencia, Spain. The bull ray was caught in the Spanish Mediterranean (Puerto de Mazarrón, Murcia). The new species resembles 4 others of the same genus ( Empruthotrema dasyatidis Whittington and Kearn, 1992, Empruthotrema kearni Whittington, 1990, Empruthotrema stenophallus Chisholm and Whittington, 2005, and Empruthotrema tasmaniensis Chisholm and Whittington, 1999) in having a haptor with 13 marginal loculi, the posteriormost loculus single and medial. The new species can be distinguished from these other species of the genus by the morphology of the sclerotized male copulatory organ, which is the shortest described. The new species also differs from the other species by the following combination of features: haptor with 13 marginal loculi, the presence of eyespots, the absence of an accessory piece associated with the male copulatory organ, and a long egg appendage (more than 150 μm). Empruthotrema chisholmae is the first species of the genus reported from the Mediterranean.     

Structure of Dimeric F1F0-ATP Synthase

The structure of the dimeric ATP synthase from yeast mitochondria was analyzed by transmission electron microscopy and single particle image analysis. In addition to the previously reported side views of the dimer, top view and intermediate projections served to resolve the arrangement of the rotary c₁₀ ring and the other stator subunits at the F₀-F₀ dimeric interface. A three-dimensional reconstruction of the complex was calculated from a data set of 9960 molecular images at a resolution of 27 Å. The structural model of the dimeric ATP synthase shows the two monomers arranged at an angle of ∼45°, consistent with our earlier analysis of the ATP synthase from bovine heart mitochondria (Minauro-Sanmiguel, F., Wilkens, S., and Garcia, J. J. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 12356–12358). In the ATP synthase dimer, the two peripheral stalks are located near the F₁-F₁ interface but are turned away from each other so that they are not in contact. Based on the three-dimensional reconstruction, a model of how dimeric ATP synthase assembles to form the higher order oligomeric structures that are required for mitochondrial cristae biogenesis is discussed.     

Dosimetric characterization of an 192Ir brachytherapy source with the Monte Carlo code PENELOPE

Monte Carlo calculations are highly spread and settled practice to calculate brachytherapy sources dosimetric parameters. In this study, recommendations of the AAPM TG-43U1 report have been followed to characterize the Varisource VS2000 ¹⁹²Ir high dose rate source, provided by Varian Oncology Systems.In order to obtain dosimetric parameters for this source, Monte Carlo calculations with PENELOPE code have been carried out. TG-43 formalism parameters have been presented, i.e., air kerma strength, dose rate constant, radial dose function and anisotropy function. Besides, a 2D Cartesian coordinates dose rate in water table has been calculated. These quantities are compared to this source reference data, finding results in good agreement with them.The data in the present study complement published data in the next aspects: (i) TG-43U1 recommendations are followed regarding to phantom ambient conditions and to uncertainty analysis, including statistical (type A) and systematic (type B) contributions; (ii) PENELOPE code is benchmarked for this source; (iii) Monte Carlo calculation methodology differs from that usually published in the way to estimate absorbed dose, leaving out the track-length estimator; (iv) the results of the present work comply with the most recent AAPM and ESTRO physics committee recommendations about Monte Carlo techniques, in regards to dose rate uncertainty values and established differences between our results and reference data.The results stated in this paper provide a complete parameter collection, which can be used for dosimetric calculations as well as a means of comparison with other datasets from this source.     

The inter-generic fungicidal activity of <Emphasis Type="Italic">Xanthophyllomyces dendrorhous</Emphasis>

In this study, the existence of intra-specific and inter-generic fungicidal activity in Xanthophyllomyces dendrorhous and Phaffia rhodozyma strains isolated from different regions of the earth was examined. Assays were performed under several culture conditions, showing that all the analyzed X. dendrorhous and P. rhodozyma strains have killing activity against Kloeckera apiculata, Rhodotorula sloffiae, and R. minuta. This activity was greater in rich media at a pH from 4.6 to 5.0. Extracellular protein extracts with fungicidal activity were obtained from cultures of all strains, and their characterization suggested that a protein of 33 kDa is the antifungal factor. According to peptide mass fingerprinting and an analysis of the results with the MASCOT search engine, this protein was identified as an aspartic protease. Additionally, extrachromosomal double-stranded DNA elements (dsDNAs) were observed in all X. dendrorhous and P. rhodozyma strains. Although there is a high variability, two dsDNAs of 5.4 and 6.8 kb are present in all strains.     

Early Origin for Human-Like Precision Grasping: A Comparative Study of Pollical Distal Phalanges in Fossil Hominins

Background

The morphology of human pollical distal phalanges (PDP) closely reflects the adaptation of human hands for refined precision grip with pad-to-pad contact. The presence of these precision grip-related traits in the PDP of fossil hominins has been related to human-like hand proportions (i.e. short hands with a long thumb) enabling the thumb and finger pads to contact. Although this has been traditionally linked to the appearance of stone tool-making, the alternative hypothesis of an earlier origin—related to the freeing of the hands thanks to the advent of terrestrial bipedalism—is also possible given the human-like intrinsic hand proportion found in australopiths.

Methodology/Principal Findings

We perform morphofunctional and morphometric (bivariate and multivariate) analyses of most available hominin pollical distal phalanges, including Orrorin, Australopithecus, Paranthropous and fossil Homo, in order to investigate their morphological affinities. Our results indicate that the thumb morphology of the early biped Orrorin is more human-like than that of australopiths, in spite of its ancient chronology (ca. 6 Ma). Moreover, Orrorin already displays typical human-like features related to precision grasping.

Conclusions

These results reinforce previous hypotheses relating the origin of refined manipulation of natural objects–not stone tool-making–with the relaxation of locomotor selection pressures on the forelimbs. This suggests that human hand length proportions are largely plesiomorphic, in the sense that they more closely resemble the relatively short-handed Miocene apes than the elongated hand pattern of extant hominoids. With the advent of terrestrial bipedalism, these hand proportions may have been co-opted by early hominins for enhanced manipulative capabilities that, in turn, would have been later co-opted for stone tool-making in the genus Homo, more encephalized than the previous australopiths. This hypothesis remains may be further tested by the finding of more complete hands of unequivocally biped early hominins.