Quantitative analysis of protein S-acylation site dynamics using site-specific acyl-biotin exchange (ssABE).

Protein S-acylation (palmitoylation) is a reversible lipid modification that is increasingly recognized as an important regulator of protein function, including membrane association, trafficking, and subcellular localization. Most proteomic methods to study palmitoylation allow characterization of putative palmitoylated proteins but do not permit identification of individual sites of palmitoylation. We have recently adapted the Acyl-Biotin Exchange (ABE) method that is routinely used for palmitoyl-proteome characterization, to permit global S-acylation site analysis. This site-specific ABE (ssABE) protocol, when combined with SILAC-based quantification, allows both the large-scale identification of palmitoylation sites and quantitative profiling of palmitoylation site changes. This approach enables palmitoylation to be studied at a systems level comparable to other more intensively studied post-translational modifications

Sub-space approximations for MDO problems with disparate disciplinary variable dependence

The research leading to these results have been funded by the European Union Seventh Framework Programme FP7-PEOPLE-2012-ITN under grant agreement 316394, Aerospace Multidisciplinarity Enabling DEsign Optimization (AMEDEO) Marie Curie Initial Training Network

Towards Better Integration of Surrogate Models and Optimizers

Surrogate-Assisted Evolutionary Algorithms (SAEAs) have been proven to be very effective in solving (synthetic and real-world) computationally expensive optimization problems with a limited number of function evaluations. The two main components of SAEAs are: the surrogate model and the evolutionary optimizer, both of which use parameters to control their respective behavior. These parameters are likely to interact closely, and hence the exploitation of any such relationships may lead to the design of an enhanced SAEA. In this chapter, as a first step, we focus on Kriging and the Efficient Global Optimization (EGO) framework. We discuss potentially profitable ways of a better integration of model and optimizer. Furthermore, we investigate in depth how different parameters of the model and the optimizer impact optimization results. In particular, we determine whether there are any interactions between these parameters, and how the problem characteristics impact optimization results. In the experimental study, we use the popular Black-Box Optimization Benchmarking (BBOB) testbed. Interestingly, the analysis finds no evidence for significant interactions between model and optimizer parameters, but independently their performance has a significant interaction with the objective function. Based on our results, we make recommendations on how best to configure EGO

Dynamics of a Quantum Phase Transition and Relaxation to a Steady State

We review recent theoretical work on two closely related issues: excitation of an isolated quantum condensed matter system driven adiabatically across a continuous quantum phase transition or a gapless phase, and apparent relaxation of an excited system after a sudden quench of a parameter in its Hamiltonian. Accordingly the review is divided into two parts. The first part revolves around a quantum version of the Kibble-Zurek mechanism including also phenomena that go beyond this simple paradigm. What they have in common is that excitation of a gapless many-body system scales with a power of the driving rate. The second part attempts a systematic presentation of recent results and conjectures on apparent relaxation of a pure state of an isolated quantum many-body system after its excitation by a sudden quench. This research is motivated in part by recent experimental developments in the physics of ultracold atoms with potential applications in the adiabatic quantum state preparation and quantum computation.Comment: 117 pages; review accepted in Advances in Physic

A Wnt-Frz/Ror-Dsh Pathway Regulates Neurite Outgrowth in Caenorhabditis elegans

One of the challenges to understand the organization of the nervous system has been to determine how axon guidance molecules govern axon outgrowth. Through an unbiased genetic screen, we identified a conserved Wnt pathway which is crucial for anterior-posterior (A/P) outgrowth of neurites from RME head motor neurons in Caenorhabditis elegans. The pathway is composed of the Wnt ligand CWN-2, the Frizzled receptors CFZ-2 and MIG-1, the co-receptor CAM-1/Ror, and the downstream component Dishevelled/DSH-1. Among these, CWN-2 acts as a local attractive cue for neurite outgrowth, and its activity can be partially substituted with other Wnts, suggesting that spatial distribution plays a role in the functional specificity of Wnts. As a co-receptor, CAM-1 functions cell-autonomously in neurons and, together with CFZ-2 and MIG-1, transmits the Wnt signal to downstream effectors. Yeast two-hybrid screening identified DSH-1 as a binding partner for CAM-1, indicating that CAM-1 could facilitate CWN-2/Wnt signaling by its physical association with DSH-1. Our study reveals an important role of a Wnt-Frz/Ror-Dsh pathway in regulating neurite A/P outgrowth

The Immature Heart: The Roles of Bone Marrow Stromal Stem Cells in Growth and Myocardial Repair

Studies have shown that adult bone marrow derived stem cells (MSCs) can participate in repair of myocardial injury in adult hearts, as well as in cardiac growth during fetal development in utero. Yet, no studies have evaluated the role of MSCs with respect to normal growth or tissue repair in immature hearts after birth. The present study examines whether MSCs may participate in the myocardial growth and injury in the post-natal immature hearts. MSCs were isolated from adult Lewis rats and labeled with Lac-Z gene using retroviral vectors. These MSCs were injected systemically into groups of neonatal (NB=2days-old), immature (B=30days-old) and adult (A=>3months-old) isogeneic Lewis rats. Additionally, left coronary artery ligation was carried out in subgroups of immature (BL) and adult (AL) rats one week after MSCs injection. The hearts were harvested serially from 2-days to 6-weeks, stained with X-Gal for labeled MSCs. Cardiomyocyte phenotypic expression was evaluated by immunohistological staining for Troponin I-C and Connexin-43. Labeled MSCs were found to home into the bone marrow in all rats of different developmental stages. They could be recruited from bone marrow into the infarcted site of myocardium only in groups AL and BL. They were also capable of differentiating into cardiomyocyte phenotype after myocardial injury. In contrast to that reported in the developing fetus, MSCs did not appear to contribute to the growth of non-injured hearts after birth. However, they can be recruited from the bone marrow and regenerate damaged myocardium both in the adult and in the immature hearts

Glutamate-Gated Chloride Channels of Haemonchus contortus Restore Drug Sensitivity to Ivermectin Resistant Caenorhabditis elegans

Anthelmintic resistance is a major problem in livestock farming, especially of small ruminants, but our understanding of it has been limited by the difficulty in carrying out functional genetic studies on parasitic nematodes. An important nematode infecting sheep and goats is Haemonchus contortus; in many parts of the world this species is resistant to almost all the currently available drugs, including ivermectin. It is extremely polymorphic and to date it has proved impossible to relate any sequence polymorphisms to its ivermectin resistance status. Expression of candidate drug-resistance genes in Caenorhabditis elegans could provide a convenient means to study the effects of polymorphisms found in resistant parasites, but may be complicated by differences between the gene families of target and model organisms. We tested this using the glutamate-gated chloride channel (GluCl) gene family, which forms the ivermectin drug target and are candidate resistance genes. We expressed GluCl subunits from C. elegans and H. contortus in a highly resistant triple mutant C. elegans strain (DA1316) under the control of the avr-14 promoter; expression of GFP behind this promoter recapitulated the pattern previously reported for avr-14. Expression of ivermectin-sensitive subunits from both species restored drug sensitivity to transgenic worms, though some quantitative differences were noted between lines. Expression of an ivermectin-insensitive subunit, Hco-GLC-2, had no effect on drug sensitivity. Expression of a previously uncharacterised parasite-specific subunit, Hco-GLC-6, caused the transgenic worms to become ivermectin sensitive, suggesting that this subunit also encodes a GluCl that responds to the drug. These results demonstrate that both orthologous and paralogous subunits from C. elegans and H. contortus are able to rescue the ivermectin sensitivity of mutant C. elegans, though some quantitative differences were observed between transgenic lines in some assays. C. elegans is a suitable system for studying parasitic nematode genes that may be involved in drug resistance

Forest biodiversity, ecosystem functioning and the provision of ecosystem services

Forests are critical habitats for biodiversity and they are also essential for the provision of a wide range of ecosystem services that are important to human well-being. There is increasing evidence that biodiversity contributes to forest ecosystem functioning and the provision of ecosystem services. Here we provide a review of forest ecosystem services including biomass production, habitat provisioning services, pollination, seed dispersal, resistance to wind storms, fire regulation and mitigation, pest regulation of native and invading insects, carbon sequestration, and cultural ecosystem services, in relation to forest type, structure and diversity. We also consider relationships between forest biodiversity and multifunctionality, and trade-offs among ecosystem services. We compare the concepts of ecosystem processes, functions and services to clarify their definitions. Our review of published studies indicates a lack of empirical studies that establish quantitative and causal relationships between forest biodiversity and many important ecosystem services. The literature is highly skewed; studies on provisioning of nutrition and energy, and on cultural services, delivered by mixed-species forests are under-represented. Planted forests offer ample opportunity for optimising their composition and diversity because replanting after harvesting is a recurring process. Planting mixed-species forests should be given more consideration as they are likely to provide a wider range of ecosystem services within the forest and for adjacent land uses. This review also serves as the introduction to this special issue of Biodiversity and Conservation on various aspects of forest biodiversity and ecosystem services

Additional records of metazoan parasites from Caribbean marine mammals, including genetically identified anisakid nematodes

Studies of marine mammal parasites in the Caribbean are scarce. An assessment for marine mammal endo- and ectoparasites from Puerto Rico and the Virgin Islands, but extending to other areas of the Caribbean, was conducted between 1989 and 1994. The present study complements the latter and enhances identification of anisakid nematodes using molecular markers. Parasites were collected from 59 carcasses of stranded cetaceans and manatees from 1994 to 2006, including Globicephala macrorhynchus, Kogia breviceps, Kogia sima, Lagenodelphis hosei, Mesoplodon densirostris, Peponocephala electra, Stenella longirostris, Steno bredanensis, Trichechus manatus. Tursiops truncatus, and Ziphius cavirostris. Sixteen species of endoparasitic helminthes were morphologically identified, including two species of acanthocephalans (Bolbosoma capitatum, Bolbosoma vasculosum), nine species of nematodes (Anisakis sp., Anisakis brevispiculata, Anisakis paggiae, Anisakis simplex, Anisakis typica, Anisakis ziphidarium, Crassicauda anthonyi, Heterocheilus tunicatus, Pseudoterranova ceticola), two species of cestodes (Monorygma grimaldi, Phyllobothrium delphini), and three species of trematodes (Chiorchis groschafti, Pulmonicola cochleotrema, Monoligerum blairi). The nematodes belonging to the genus Anisakis recovered in some stranded animals were genetically identified to species level based on their sequence analysis of mitochondrial DNA (629 bp of mtDNA cox 2). A total of five new host records and six new geographic records are presented.L'articolo è disponibile sul sito dell'editore http://www.springerlink.com