Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.

Analysis of the regional pattern of sea level change due to ocean dynamics and density changes for 1993-2099 in observations and CMIP5 AOGCMs

Predictions of twenty-first century sea level change show strong regional variation. Regional sea level change observed by satellite altimetry since 1993 is also not spatially homogenous. By comparison with historical and pre-industrial control simulations using the atmosphere–ocean general circulation models (AOGCMs) of the CMIP5 project, we conclude that the observed pattern is generally dominated by unforced (internal generated) variability, although some regions, especially in the Southern Ocean, may already show an externally forced response. Simulated unforced variability cannot explain the observed trends in the tropical Pacific, but we suggest that this is due to inadequate simulation of variability by CMIP5 AOGCMs, rather than evidence of anthropogenic change. We apply the method of pattern scaling to projections of sea level change and show that it gives accurate estimates of future local sea level change in response to anthropogenic forcing as simulated by the AOGCMs under RCP scenarios, implying that the pattern will remain stable in future decades. We note, however, that use of a single integration to evaluate the performance of the pattern-scaling method tends to exaggerate its accuracy. We find that ocean volume mean temperature is generally a better predictor than global mean surface temperature of the magnitude of sea level change, and that the pattern is very similar under the different RCPs for a given model. We determine that the forced signal will be detectable above the noise of unforced internal variability within the next decade globally and may already be detectable in the tropical Atlantic.

Projectile breakup dynamics for (6)Li+(59)Co: Kinematical analysis of alpha-d coincidences

A study of the kinematics of the alpha-d coincidences in the (6)Li + (59)Co system at a bombarding energy of E(lab) = 29.6MeV is presented. With exclusive measurements performed over different angular intervals it is possible to identify the respective contributions of the sequential and direct projectile breakup components. The angular distributions of both breakup components are fairly well described by the Continuum-Discretized Coupled-Channels framework (CDCC). Furthermore, a careful analysis of these processes using a semiclassical approach provides information on both their lifetime and their distance of occurrence with respect to the target. Breakup to the low-lying (near-threshold) continuum is delayed, and happens at large internuclear distances. This suggests that the influence of the projectile breakup on the complete fusion process can be related essentially to the direct breakup to the (6)Li high-lying continuum spectrum.

Structure, Dynamics, and RNA Interaction Analysis of the Human SBDS Protein

Shwachman-Bodian-Diamond syndrome is an autosomal recessive genetic syndrome with pleiotropic phenotypes, including pancreatic deficiencies, bone marrow dysfunctions with increased risk of myelodysplasia or leukemia, and skeletal abnormalities. This syndrome has been associated with mutations in the SBDS gene, which encodes a conserved protein showing orthologs in Archaea and eukaryotes. The Shwachman-Bodian-Diamond syndrome pleiotropic phenotypes may be an indication of different cell type requirements for a fully functional SBDS protein. RNA-binding activity has been predicted for archaeal and yeast SBDS orthologs, with the latter also being implicated in ribosome biogenesis. However, full-length SBDS orthologs function in a species-specific manner, indicating that the knowledge obtained from model systems may be of limited use in understanding major unresolved issues regarding SBDS function, namely, the effect of mutations in human SBDS on its biochemical function and the specificity of RNA interaction. We determined the solution structure and backbone dynamics of the human SBDS protein and describe its RNA binding site using NMR spectroscopy. Similarly to the crystal structures of Archaea, the overall structure of human SBDS comprises three well-folded domains. However, significant conformational exchange was observed in NMR dynamics experiments for the flexible linker between the N-terminal domain and the central domain, and these experiments also reflect the relative motions of the domains. RNA titrations monitored by heteronuclear correlation experiments and chemical shift mapping analysis identified a classic RNA binding site at the N-terminal FYSH (fungal, Yhr087wp, Shwachman) domain that concentrates most of the mutations described for the human SBDS. (C) 2010 Elsevier Ltd. All rights reserved.

Evolutionary dynamics of heterochromatin in the genome of Dichotomius beetles based on chromosomal analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stochastic dynamics in exotic and native blowflies: an analysis combining laboratory experiments and a two-patch metapopulation model

In this study we explored the stochastic population dynamics of three exotic blowfly species, Chrysomya albiceps, Chrysomya megacephala and Chrysomya putoria, and two native species, Cochliomyia macellaria and Lucilia eximia, by combining a density-dependent growth model with a two-patch metapopulation model. Stochastic fecundity, survival and migration were investigated by permitting random variations between predetermined demographic boundary values based on experimental data. Lucilia eximia and Chrysomya albiceps were the species most susceptible to the risk of local extinction. Cochliomyia macellaria, C. megacephala and C. putoria exhibited lower risks of extinction when compared to the other species. The simultaneous analysis of stochastic fecundity and survival revealed an increase in the extinction risk for all species. When stochastic fecundity, survival and migration were simulated together, the coupled populations were synchronized in the five species. These results are discussed, emphasizing biological invasion and interspecific interaction dynamics.

Dynamics of bone healing after osteotomy with piezosurgery or conventional drilling - histomorphometrical, immunohistochemical, and molecular analysis

Background: Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling.Methods: One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5).Results: Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p < 0.05). Immunohistochemical and qRT-PCR analyses didn't detect significant differences in expression of all the proteins and most of the genes tested.Conclusions: Based on the results of our study we conclude that in a rat tibial bone defect model the bone healing dynamics after piezosurgery are comparable to those observed with conventional drilling. © 2013 Esteves et al.; licensee BioMed Central Ltd.

International technological dynamics in production sectors: An empirical analysis

A new methodology is proposed for evaluating the economic development opportunities associated with the different industries making up a country’s economic structure. To this end, neo-Schumpeterian concepts are used to reinterpret the tools afforded by the “product space” literature in an attempt to assess the technological pervasiveness and sophistication of different production sectors. The ultimate objective is to develop a description of today’s techno-productive paradigm and the differential role that the various sectors play in it. An analysis of export data from 113 countries and territories for 2005-2009 indicates that the key sectors in the world economy are: industrial machinery, scientific and medical instruments, and pharmaceuticals. The strong performance of sectors based on mature technologies suggests that key sectors originating in different stages in history can survive and overlap one another, much like geological strata, owing to the persistence of older technological systems.

Dynamics of cell and tissue genesis in the male reproductive system of ticks (Acari: Ixodidae) Amblyomma cajennese (Fabricius, 1787) and Amblyomma aureolatum (Pallas, 1772): a comparative analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A general framework for multi-compartmental analysis of drug chemotherapy dynamics in human immunodeficiency virus type-1 infected individuals

An optimal control strategy for the highly active antiretroviral therapy associated to the acquired immunodeficiency syndrome should be designed regarding a comprehensive analysis of the drug chemotherapy behavior in the host tissues, from major viral replication sites to viral sanctuary compartments. Such approach is critical in order to efficiently explore synergistic, competitive and prohibitive relationships among drugs and, hence, therapy costs and side-effect minimization. In this paper, a novel mathematical model for HIV-1 drug chemotherapy dynamics in distinct host anatomic compartments is proposed and theoretically evaluated on fifteen conventional anti-retroviral drugs. Rather than interdependence between drug type and its concentration profile in a host tissue, simulated results suggest that such profile is importantly correlated with the host tissue under consideration. Furthermore, the drug accumulative dynamics are drastically affected by low patient compliance with pharmacotherapy, even when a single dose lacks. (C) 2012 Elsevier Inc. All rights reserved.

Analysis of energy dissipation in stirred suspension polymerisation reactors using computational fluid dynamics

This work evaluates the spatial distribution of normalised rates of droplet breakage and droplet coalescence in liquidliquid dispersions maintained in agitated tanks at operation conditions normally used to perform suspension polymerisation reactions. Particularly, simulations are performed with multiphase computational fluid dynamics (CFD) models to represent the flow field in liquidliquid styrene suspension polymerisation reactors for the first time. CFD tools are used first to compute the spatial distribution of the turbulent energy dissipation rates (e) inside the reaction vessel; afterwards, normalised rates of droplet breakage and particle coalescence are computed as functions of e. Surprisingly, multiphase simulations showed that the rates of energy dissipation can be very high near the free vortex surfaces, which has been completely neglected in previous works. The obtained results indicate the existence of extremely large energy dissipation gradients inside the vessel, so that particle breakage occurs primarily in very small regions that surround the impeller and the free vortex surface, while particle coalescence takes place in the liquid bulk. As a consequence, particle breakage should be regarded as an independent source term or a boundary phenomenon. Based on the obtained results, it can be very difficult to justify the use of isotropic assumptions to formulate particle population balances in similar systems, even when multiple compartment models are used to describe the fluid dynamic behaviour of the agitated vessel. (C) 2011 Canadian Society for Chemical Engineering

Combinatorial-topological framework for the analysis of global dynamics

We discuss an algorithmic framework based on efficient graph algorithms and algebraic-topological computational tools. The framework is aimed at automatic computation of a database of global dynamics of a given m-parameter semidynamical system with discrete time on a bounded subset of the n-dimensional phase space. We introduce the mathematical background, which is based upon Conley's topological approach to dynamics, describe the algorithms for the analysis of the dynamics using rectangular grids both in phase space and parameter space, and show two sample applications. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4767672]

An in-depth analysis of the HIV-1/AIDS dynamics by comprehensive mathematical modeling

This work presents major results from a novel dynamic model intended to deterministically represent the complex relation between HIV-1 and the human immune system. The novel structure of the model extends previous work by representing different host anatomic compartments under a more in-depth cellular and molecular immunological phenomenology. Recently identified mechanisms related to HIV-1 infection as well as other well known relevant mechanisms typically ignored in mathematical models of HIV-1 pathogenesis and immunology, such as cell-cell transmission, are also addressed. (C) 2011 Elsevier Ltd. All rights reserved.