Schistosoma mansoni: Activation of the alternative pathway of human complement by schistosomula

Schistosomula of Schistosoma mansoni newly transformed from cercariae by either the mechanical or skin penetration procedures, as well as 5-day-old schistosomula recovered from the lungs of mice, were tested for their ability to activate the human alternative complement pathway. Newly transformed larvae prepared by both methods, although less active than cercariae, were found to activate the pathway to a comparable degree as judged by the consumption of fluid phase C3 and factor B and the conversion of native C3 into a component with a more anodal electrophoretic mobility. The alternative pathway activating capacity could not be blocked or enhanced by pretreating the larvae with purified IgG or F(ab′)₂ fragments prepared from human sera containing antibodies directed against schistosomula. In contrast to newly transformed parasites, 5-day-old schistosomula recovered from mouse lungs failed to activate the alternative pathway as judged by either the C3 or B consumption assays or the C3 conversion assay. This developmental change could not be reversed by treating lung stage larvae with neuraminidase and heparinase, enzymes which are known to alter the activating capacity of other particulate substances or with chondroitinase ABC or trypsin.     

EVOLUTIONARILY STABLE SELFING RATES OF HERMAPHRODITIC PLANTS IN COMPETING AND DELAYED SELFING MODES WITH ALLOCATION TO ATTRACTIVE STRUCTURES

I present a resource-allocation model to analyze how patterns of allocation to reproductive structures influence the evolution of selfing rates in hermaphrodites subject to competing and delayed forms of self-fertilization. The evolutionarily stable state does not depend on the mode of pollination. In contrast to previous models in which the number and the size of flowers were not considered, intermediate selfing is not evolutionarily stable with linear constraints on flower number and size. In contrast, intermediate selfing can be evolutionarily stable with nonlinear constraints on flower number and size. Optimal allocations to attractive structures increase and selfing rates decrease in the presence of inbreeding depression. In particular, stable intermediate levels of selfing may be favored when flower number is strongly constrained. Thus, nonlinear constraints on flower number and size could favor the evolution of intermediate selfing in either the delayed or the competing modes of selfing. Outcrossing is not favored in the absence of inbreeding depression, a result inconsistent with Holsinger's results in which allocation to attractive structures was not considered.     

Investigating proline puckering states in diproline segments in proteins

In the current study, the puckering states of the Proline ring occurring in diproline segments (^LPro‐^LPro) in proteins has been investigated with a segregation made on the basis of cis and trans states for the Pro‐Pro peptide bond and the conformational states for the diproline segment to investigate the effects of conformation of the diproline segment on the corresponding puckering state of the Proline ring in the segment if any. The value of the endocyclic ring torsional angles of the pyrrolidine ring has been used for calculating and visualizing various puckering states using a proposed new sign convention (+/?) nomenclature. The results have been compared to that obtained in a previous study on peptides from this group. In this study, quite interestingly, the Planar (G) conformation that was present in 14.3% of the cases in peptides, appears to be nearly a rare conformation in the case of proteins (1.9%). The present study indicates that the (C^γ‐exo/C^γ‐exo), (C^γ‐exo/Twisted C^γ‐exo‐C^β‐endo) and (Twisted C^γ‐endo‐C^β‐exo/Twisted C^γ‐endo‐C^β‐exo) categories are the most preferred combinations. For Proline rings in proteins, the states C^γ‐exo, Twisted C^γ‐exo‐C^β‐endo and Twisted C^γ‐endo‐C^β‐exo are the most preferred states. Within diproline segments, the pyrrolidine ring conformations do not show a strong co‐relation to the backbone conformation in which they are observed. It is likely that five‐membered rings have a considerable plasticity of structure and are readily deformed to accommodate a variety of energetically preferred backbone conformations. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 605–610, 2013.     

Synthesis of Stable Isotope Labeled Analogs of the Anti-Hepatitis C Virus Nucleotide Prodrugs PSI-7977 and PSI-352938

In order to support bioanalytical LC/MS method development and plasma sample analysis in preclinical and clinical studies of the anti-hepatitis C-virus nucleotides, PSI-7977 and PSI-352938, the corresponding stable isotope labeled forms were prepared. These labeled compounds were prepared by addition reaction of the freshly prepared Grignard reagent ¹³CD₃MgI to the corresponding 2 ′-ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2 ′-C-(trideuterated-¹³C-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones.     

NMR characterization of conformational fluctuations and noncovalent interactions of SUMO protein from Drosophila melanogaster (dSmt3)

Structural heterogeneity in the native-state ensemble of dSmt3, the only small ubiquitin-like modifier (SUMO) in Drosophila melanogaster, was investigated and compared with its human homologue SUMO1. Temperature dependence of amide proton's chemical shift was studied to identify amino acids possessing alternative structural conformations in the native state. Effect of small concentration of denaturant (1M urea) on this population was also monitored to assess the ruggedness of near-native energy landscape. Owing to presence of many such amino acids, especially in the β₂-loop-α region, the native state of dSmt3 seems more flexible in comparison to SUMO1. Information about backbone dynamics in ns-ps timescale was quantified from the measurement of ¹⁵N-relaxation experiments. Furthermore, the noncovalent interaction of dSmt3 and SUMO1 with Daxx12 (Daxx⁷²⁹DPEEIIVLSDSD⁷⁴⁰), a [V/I]-X-[V/I]-[V/I]-based SUMO interaction motif, was characterized using Bio-layer Interferometery and NMR spectroscopy. Daxx12 fits itself in the groove formed by β₂-loop-α structural region in both dSmt3 and SUMO1, but the binding is stronger with the former. Flexibility of β₂-loop-α region in dSmt3 is suspected to assist its interaction with Daxx12. Our results highlight the role of native-state flexibility in assisting noncovalent interactions of SUMO proteins especially in organisms where a single SUMO isoform has to tackle multiple substrates single handedly.     

Are diminutive turtles miniaturized? The ontogeny of plastron shape in emydine turtles

Miniaturization, or the evolution of a dramatically reduced body size compared to related lineages, is an extraordinarily widespread phenomenon among metazoans. Evolutionary biologists have been fascinated by miniaturization because this transition has occurred numerous times, often among close relatives, providing a model system for studying convergent evolution and its underlying mechanisms. Much of the developmental work describing the ontogeny of miniature species suggests that paedomorphosis is the predominant avenue of miniaturization. Nevertheless, specific alterations to ontogeny appear highly variable, so that even related lineages with similar miniaturized traits produce those similarities via distinct ontogenetic paths. One major vertebrate group that has been overlooked in research on miniaturization is turtles. In the present study, we examined patterns of shape change in the plastron (the ventral part of the shell) over the course of ontogeny in a small clade of turtles (Emydinae) aiming to investigate whether two independently evolved diminutive members of the clade (Glyptemys muhlenbergii and Clemmys guttata) should be considered as miniaturized. We employ geometric morphometric methods to quantify the patterns of shape change these potentially miniaturized species and their relatives undergo during ontogeny, and use molecular phylogenetic trees to reconstruct ancestral conditions and provide information on the polarity of shape changes. We find that differing changes in ontogenetic parameters relative to ancestral conditions accompany the evolution of small size in emydines: G. muhlenbergii changes the duration of ontogeny and rate of shape change, whereas C. guttata changes growth rate. The observed ontogenetic repatterning of these species is reminiscent of changes in ontogeny and life history often found in miniaturized taxa. However, we conclude that C. guttata and G. muhlenbergii are not truly miniaturized because they still produce typical adult shell morphologies, and larger emydines display comparable ontogenetic flexibility. Because no emydines carry juvenile shell features forward into adulthood, we speculate that few, if any turtles, will show paedomorphic shell traits without corresponding changes in defensive strategy because such shells may offer insufficient protection. © 2013 The Linnean Society of London     

Stable isotopes as tracers of trophic interactions in marine mutualistic symbioses

Mutualistic nutritional symbioses are widespread in marine ecosystems. They involve the association of a host organism (algae, protists, or marine invertebrates) with symbiotic microorganisms, such as bacteria, cyanobacteria, or dinoflagellates. Nutritional interactions between the partners are difficult to identify in symbioses because they only occur in intact associations. Stable isotope analysis (SIA) has proven to be a useful tool to highlight original nutrient sources and to trace nutrients acquired by and exchanged between the different partners of the association. However, although SIA has been extensively applied to study different marine symbiotic associations, there is no review taking into account of the different types of symbiotic associations, how they have been studied via SIA, methodological issues common among symbiotic associations, and solutions that can be transferred from one type of association with another. The present review aims to fill such gaps in the scientific literature by summarizing the current knowledge of how isotopes have been applied to key marine symbioses to unravel nutrient exchanges between partners, and by describing the difficulties in interpreting the isotopic signal. This review also focuses on the use of compound‐specific stable isotope analysis and on statistical advances to analyze stable isotope data. It also highlights the knowledge gaps that would benefit from future research.