Enzymatic System of Metabolism and Detoxication of Xenobiotics as a Basis of Metabolic Portraiting during Prognostication of Risk of Pathological Processes

We studied intraspecific features of the main enzymes of metabolism and detoxication of xenobiotics on mice (eight inbred lines) and rats (five lines) for estimation of possible variants of complete or incomplete metabolic equality. Significant genetically determined intraspecific differences for activities of the enzymes of metabolism and detoxication of xenobiotics were described. Generalized criteria for comparison of the metabolic status were proposed on the basis of activities of the main enzymes: cytochrome P-450 (hydroxylation and epoxidation), epoxyhydrolase, glutathione-S-transferase, UDP-glucuronosyl transferase, and sulfotransferase. The proposed criteria for estimation of the metabolic parameters of an individual can serve as a basis of metabolic portraiting.     

A new species of Galearis (Orchidinae: Orchidaceae) from Sichuan,China

A new species, Galearis huanglongensis Q.W.Meng & Y.B.Luo, is described and illustrated. It is similar to Galearis cyclochila (Franch. & Sav.) Soó and Galearis diantha (Schltr.) P.F.Hunt, but differs in having a short spur, two elliptical lateral stigma lobes and distinctly separated bursicles. This new species is known only from the type locality, the Huanglong Valley, Songpan County, western Sichuan, China, growing amongst mosses under alpine shrubs at an elevation of about 3000 m. Based on two years of observations of its population size, the species was categorized as critically endangered CR (B1a, B2a) according to the World Conservation Union (IUCN) Red List Categories and Criteria, Version 3.1. The micromorphology of pollinia and seeds was observed by scanning electron microscopy and compared with that of G. cyclochila and G. diantha. The results supported G. huanglongensis Q.W.Meng & Y.B.Luo as a new species. © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society, 2008, 158 , 689–695.     

Human P301L-Mutant Tau Expression in Mouse Entorhinal-Hippocampal Network Causes Tau Aggregation and Presynaptic Pathology but No Cognitive Deficits

Accumulation of hyperphosphorylated tau in the entorhinal cortex (EC) is one of the earliest pathological hallmarks in patients with Alzheimer’s disease (AD). It can occur before significant Aβ deposition and appears to “spread” into anatomically connected brain regions. To determine whether this early-stage pathology is sufficient to cause disease progression and cognitive decline in experimental models, we overexpressed mutant human tau (hTauP301L) predominantly in layer II/III neurons of the mouse EC. Cognitive functions remained normal in mice at 4, 8, 12 and 16 months of age, despite early and extensive tau accumulation in the EC. Perforant path (PP) axon terminals within the dentate gyrus (DG) contained abnormal conformations of tau even in young EC-hTau mice, and phosphorylated tau increased with age in both the EC and PP. In old mice, ultrastructural alterations in presynaptic terminals were observed at PP-to-granule cell synapses. Phosphorylated tau was more abundant in presynaptic than postsynaptic elements. Human and pathological tau was also detected within hippocampal neurons of this mouse model. Thus, hTauP301L accumulation predominantly in the EC and related presynaptic pathology in hippocampal circuits was not sufficient to cause robust cognitive deficits within the age range analyzed here.     

Simulation of protein misfolding using a lattice model

The structure of the tightly bound complex of the globular myosin head with F-actin is the key to understanding important details of the mechanism of how the actin-myosin motor functions. The current notion on this complex is based on the docking of known atomic structures of constituent proteins into low-resolution electron-density maps. The atomic structure of the complex was refined by the molecular mechanics method, which consists in minimizing the energy of molecular interaction and which makes it possible to optimize not only the relative position of protein backbones as rigid bodies, but also the position of side chains on the protein interface. The structure calculated using ICM-Pro software, on the one hand, is close to the model obtained using electron microscopy; on the other hand, it ensures the best calculated interaction energy and accounts for the results of mutagenesis experiments. On the basis of the structure obtained, we can suggest the molecular mechanisms underlying the actin-activated release of ATP hydrolysis products from myosin and the decrease in the affinity of myosin for actin upon binding of nucleotides.     

cDNA sequence and predicted primary structure of the gamma subunit from the ATP synthase from Chlamydomonas reinhardtii

The 1701-base nucleotide sequence (not including the poly(A) tail) of a cDNA for the gamma subunit of the ATP synthase from Chlamydomonas reinhardtii was determined. A start translation sequence, 23 bases in from the 5' end, initiates an 1074-base-long open reading frame. The sequence of the first 21 amino acids at the amino-terminal end of the mature gamma subunit from C. reinhardtii was determined and compared to the deduced amino acid sequence of the open reading frame. From this it was determined that the mature protein contains 323 amino acids, with the first 35 amino acids probably being part of the transit peptide. The length of the mature protein is the same as that for the mature gamma subunit from spinach, for which only a few of the amino acids of the transit peptide are known. The similarity of the two mature proteins at the nucleotide level is 56% while at the amino acid level it is 77%. In addition, the 3 cysteines, which in spinach are involved in the energy-linked catalytic functions of the ATP synthase, are conserved in the predicted amino acid sequence for the gamma subunit from C. reinhardtii. In contrast, the mature C. reinhardtii gamma subunit contains 3 additional cysteine residues not found in the spinach gamma subunit.