Single crystals of V-amylose complexed with alpha-naphthol

Lamellar square single crystals of V-amylose were obtained by adding alpha-naphthol to metastable dilute aqueous solutions of synthetic amylose chains with an average degree of polymerization of 100. The morphology and structure of the crystals were studied using low-dose transmission electron microscopy including high-resolution imaging, as well as electron and X-ray diffraction. The crystals are crystallized in a tetragonal P4(1)2(1)2 or P4(3)2(1)2 space group with unit cell parameters, calculated from X-ray diffraction data, a = b = 2.2844 nm (+/-0.0005) and c = 0.7806 nm (+/-0.001), implying the presence of two amylose chains per unit cell. High-resolution lattice images of the crystals confirmed that the amylose chains were crystallized as 8-fold helices corresponding to the repeat of four maltosyl units.     

Mitochondrial Dysfunction and Redox Homeostasis Impairment as Pathomechanisms of Brain Damage in Ethylmalonic Encephalopathy: Insights from Animal and Human Studies

Cellular and Molecular Neurobiology - Ethylmalonic encephalopathy (EE) is a severe intoxication disorder caused by mutations in the ETHE1 gene that encodes a mitochondrial sulfur dioxygenase...     

Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25

The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4⁺ T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma.     

Phylogeographical patterns in Coenosia attenuata (Diptera: Muscidae): a widespread predator of insect species associated with greenhouse crops

The tiger‐fly Coenosia attenuata is a globally widespread predatory fly which is not only associated with greenhouse crops, but also occurs in open fields. It is a potential control agent against some of the more common pests in these crops. Assessing the genetic structure and gene flow patterns may be important for planning crop protection strategies and for understanding the historical processes that led to the present distribution of genetic lineages within this species. In the present study, the phylogeographical patterns of this species, based on mitochondrial cytochrome oxidase I and nuclear white and elongation factor‐1α genes, are described, revealing relatively low genetic diversity and weak genetic structure associated with a recent and sudden population expansion of the species. The geographical distribution of mitochondrial haplotypes indicates the Mediterranean as the most likely region of origin of the species. Some dispersal patterns of the species are also revaled, including at least three independent colonizations of North and South America: one from Middle East to North America with a strong bottleneck event, another from Europe to South America (Chile), with both likely to be a result of unintentional introduction, and a third one of still undetermined origin to South America (Ecuador). © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114 , 308–326.     

Evolution and molecular mechanisms of adaptive developmental plasticity

Aside from its selective role in filtering inter-individual variation during evolution by natural selection, the environment also plays an instructive role in producing variation during development. External environmental cues can influence developmental rates and/or trajectories and lead to the production of distinct phenotypes from the same genotype. This can result in a better match between adult phenotype and selective environment and thus represents a potential solution to problems posed by environmental fluctuation. The phenomenon is called adaptive developmental plasticity. The study of developmental plasticity integrates different disciplines (notably ecology and developmental biology) and analyses at all levels of biological organization, from the molecular regulation of changes in organismal development to variation in phenotypes and fitness in natural populations. Here, we focus on recent advances and examples from morphological traits in animals to provide a broad overview covering (i) the evolution of developmental plasticity, as well as its relevance to adaptive evolution, (ii) the ecological significance of alternative environmentally induced phenotypes, and the way the external environment can affect development to produce them, (iii) the molecular mechanisms underlying developmental plasticity, with emphasis on the contribution of genetic, physiological and epigenetic factors, and (iv) current challenges and trends, including the relevance of the environmental sensitivity of development to studies in ecological developmental biology, biomedicine and conservation biology.     

Worker demography in a large-colony,swarm-founding wasp

Neotropical swarm-founding wasps build nests enclosed in a covering envelope, which makes it difficult to count individual births and deaths. Thus, knowledge of worker demography is very limited for swarm-founding species compared with that for independent-founding species. In this study, we explored the worker demography of the swarm-founding wasp Polybia paulista, the colony size of which usually exceeds several thousand adults. We considered each wasp colony as an open-population and estimated the survival probability, recruitment rate, and population size of workers using the developments of the Cormack–Jolly–Seber model. We found that capture probability varied considerably among the workers, probably due to age polyethism and/or task specialization. The daily survival rate of workers was high (around 0.97) throughout the season and was not related to the phase of colony development. On the other hand, the recruitment rate ranged from 0 to 0.37, suggesting that worker production was substantially less important than worker survival in determining worker population fluctuations. When we compared survival rates among worker groups of one colony, the mean daily survival rate was lower for founding workers than for progeny workers and tended to be higher in progeny workers that emerged in winter. These differences in survivorship patterns among worker cohorts would be related to worker foraging activity and/or level of parasitism.     

The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a "total ancestry" estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries--a phenomenon described and intended as the "whitening of Brazil"--is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations.     

Kinetics of double-chain reversals bridging contiguous quartets in tetramolecular quadruplexes

Repetitive 5'GGXGG DNA segments abound in, or near, regulatory regions of the genome and may form unusual structures called G-quadruplexes. Using NMR spectroscopy, we demonstrate that a family of 5'GCGGXGGY sequences adopts a folding topology containing double-chain reversals. The topology is composed of two bistranded quadruplex monomeric units linked by formation of G:C:G:C tetrads. We provide a complete thermodynamic and kinetic analysis of 13 different sequences using absorbance spectroscopy and DSC, and compare their kinetics with a canonical tetrameric parallel-stranded quadruplex formed by TG4T. We demonstrate large differences (up to 10(5)-fold) in the association constants of these quadruplexes depending on primary sequence; the fastest samples exhibiting association rate equal or higher than the canonical TG4T quadruplex. In contrast, all sequences studied here unfold at a lower temperature than this quadruplex. Some sequences have thermodynamic stability comparable to the canonical TG4T tetramolecular quadruplex, but with faster association and dissociation. Sequence effects on the dissociation processes are discussed in light of structural data.     

Influence of different mucosal resiliency and denture reline on stress distribution in peri-implant bone tissue during osseointegration. A three-dimensional finite element analysis

doi: 10.1111/j.1741‐2358.2011.00569.x Influence of different mucosal resiliency and denture reline on stress distribution in peri‐implant bone tissue during osseointegration. A three‐dimensional finite element analysis Objective: The aim of this study was to evaluate the influence of mucosal properties and relining material on the stress distribution in peri‐implant bone tissue during masticatory function with a conventional complete denture during the healing period through finite element analysis. Materials and Methods: Three‐dimensional models of a severely resorbed mandible with two recently placed implants in the anterior region were created and divided into the following situations: (i) conventional complete denture and (ii) relined denture with soft lining material. The mucosal tissue properties were divided into soft, resilient and hard. The models were exported to mechanical simulation software; two simulations were carried out with a load at the lower right canine (35 N) and the lower right first molar (50 N). Data were qualitatively evaluated using Maximum Principal Stress, in MPa, given by the software. Results: All models showed stress concentrations in the cortical bone corresponding to the cervical part of the implant. The mucosal properties influenced the stress in peri‐implant bone tissue showing a different performance according to the denture base material. The simulations with relined dentures showed lower values of stress concentration than conventional ones. Conclusions: It seems that the mucosal properties and denture reline have a high influence on the stress distribution in the peri‐implant bone during the healing period.     

Echinococcus granulosus antigen B structure: subunit composition and oligomeric states

Background

Antigen B (AgB) is the major protein secreted by the Echinococcus granulosus metacestode and is involved in key host-parasite interactions during infection. The full comprehension of AgB functions depends on the elucidation of several structural aspects that remain unknown, such as its subunit composition and oligomeric states.

Methodology/Principal Findings

The subunit composition of E. granulosus AgB oligomers from individual bovine and human cysts was assessed by mass spectrometry associated with electrophoretic analysis. AgB8/1, AgB8/2, AgB8/3 and AgB8/4 subunits were identified in all samples analyzed, and an AgB8/2 variant (AgB8/2v8) was found in one bovine sample. The exponentially modified protein abundance index (emPAI) was used to estimate the relative abundance of the AgB subunits, revealing that AgB8/1 subunit was relatively overrepresented in all samples. The abundance of AgB8/3 subunit varied between bovine and human cysts. The oligomeric states formed by E. granulosus AgB and recombinant subunits available, rAgB8/1, rAgB8/2 and rAgB8/3, were characterized by native PAGE, light scattering and microscopy. Recombinant subunits showed markedly distinct oligomerization behaviors, forming oligomers with a maximum size relation of rAgB8/3>rAgB8/2>rAgB8/1. Moreover, the oligomeric states formed by rAgB8/3 subunit were more similar to those observed for AgB purified from hydatid fluid. Pressure-induced dissociation experiments demonstrated that the molecular assemblies formed by the more aggregative subunits, rAgB8/2 and rAgB8/3, also display higher structural stability.

Conclusions/Significance

For the first time, AgB subunit composition was analyzed in samples from single hydatid cysts, revealing qualitative and quantitative differences between samples. We showed that AgB oligomers are formed by different subunits, which have distinct abundances and oligomerization properties. Overall, our findings have significantly contributed to increase the current knowledge on AgB expression and structure, highlighting issues that may help to understand the parasite adaptive response during chronic infection.