Expression of alpha-synuclein is increased in the hippocampus of rats with high levels of innate anxiety

A genomic region neighboring the alpha-synuclein gene, on rat chromosome 4, has been associated with anxiety- and alcohol-related behaviors in different rat strains. In this study, we have investigated potential molecular and physiological links between alpha-synuclein and the behavioral differences observed between Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rats, a genetic model of anxiety. As expected, LEW rats appeared more fearful than SHR rats in three anxiety models: open field, elevated plus maze and light/dark box. Moreover, LEW rats displayed a higher preference for alcohol and consumed higher quantities of alcohol than SHR rats. alpha-Synuclein mRNA and protein concentrations were higher in the hippocampus, but not the hypothalamus of LEW rats. This result inversely correlated with differences in dopamine turnover in the hippocampus of LEW and SHR rats, supporting the hypothesis that alpha-synuclein is important in the downregulation of dopamine neurotransmission. A novel single nucleotide polymorphism was identified in the 30-untranslated region (3`-UTR) of the alpha-synuclein cDNA between these two rat strains. Plasmid constructs based on the LEW 3`-UTR sequence displayed increased expression of a reporter gene in transiently transfected PC12 cells, in accordance with in-vivo findings, suggesting that this nucleotide exchange might participate in the differential expression of alpha-synuclein between LEW and SHR rats. These results are consistent with a novel role for alpha-synuclein in modulating rat anxiety- like behaviors, possibly through dopaminergic mechanisms. Since the behavioral and genetic differences between these two strains are the product of independent evolutionary histories, the possibility that polymorphisms in the alpha-synuclein gene may be associated with vulnerability to anxiety- related disorders in humans requires further investigation. Molecular Psychiatry (2009) 14, 894-905; doi: 10.1038/mp.2008.43; published online 22 April 2008

Crop rotation scheduling with adjacency constraints

In this article we propose a 0-1 optimization model to determine a crop rotation schedule for each plot in a cropping area. The rotations have the same duration in all the plots and the crops are selected to maximize plot occupation. The crops may have different production times and planting dates. The problem includes planting constraints for adjacent plots and also for sequences of crops in the rotations. Moreover, cultivating crops for green manuring and fallow periods are scheduled into each plot. As the model has, in general, a great number of constraints and variables, we propose a heuristics based on column generation. To evaluate the performance of the model and the method, computational experiments using real-world data were performed. The solutions obtained indicate that the method generates good results.

Sustainable vegetable crop supply problem

We consider an agricultural production problem, in which one must meet a known demand of crops while respecting ecologically-based production constraints. The problem is twofold: in order to meet the demand, one must determine the division of the available heterogeneous arable areas in plots and, for each plot, obtain an appropriate crop rotation schedule. Rotation plans must respect ecologically-based constraints such as the interdiction of certain crop successions, and the regular insertion of fallows and green manures. We propose a linear formulation for this problem, in which each variable is associated with a crop rotation schedule. The model may include a large number of variables and it is, therefore, solved by means of a column-generation approach. We also discuss some extensions to the model, in order to incorporate additional characteristics found in field conditions. A set of computational tests using instances based on real-world data confirms the efficacy of the proposed methodology. (C) 2009 Elsevier B.V. All rights reserved.

Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response

Components of the DNA mismatch repair (MMR) pathway are major players in processes known to generate genetic diversity, such as mutagenesis and DNA recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas disease has a highly heterogeneous population, composed of a pool of strains with distinct characteristics. Studies with a number of molecular markers identified up to six groups in the T. cruzi population, which showed distinct levels of genetic variability. To investigate the molecular basis for such differences, we analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed the existence of distinct isoforms of this protein. Here we compared cell survival rates after exposure to genotoxic agents and levels of oxidative stress-induced DNA in different parasite strains. Analyses of msh2 mutants in both T. cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the response to various DNA damaging agents. The results suggest that the distinct MSH2 isoforms have differences in their activity. More importantly, they also indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite response to oxidative stress through a novel mitochondrial function that may be conserved in T. brucei. (C) 2010 Elsevier B.V. All rights reserved.