The blueprint for stress can be found in invertebrates

Through an extremely complicated equilibrium called homeostasis, all living organisms maintain their survival in the face of both externally and internally generated "stimuli". This apparent harmony is constantly challenged. Survival through successful adaptation is maintained as close to steady state as possible by adaptive responses, which may also be called perturbation responses since they have a constitutively defined dynamic capacity, i.e., an immediate limit, in a series of balancing and feedback activities reflecting an astounding array of biological, psychological and sociological behaviors. The broad spectrum of stimuli capable of engaging this protective response is remarkable. We define stress as a type of stimulation that is stronger and lasts for a longer duration, upsetting a typical perturbation response given its dynamic parameters. The stress response, which evolves out of the perturbation response, involves inducible signal molecules, i.e., cytokines. We surmise that the ability to exist in an ever-changing environment was a requirement for all life forms, including invertebrates and single celled organisms. It would be expected that these organisms exhibit both perturbation and stress responses. In this regard, we demonstrate that these organisms have mammalian-like signal molecule systems, i.e., opioid, and corresponding behaviors that are similar to those found in mammals with regard to both perturbation and stress responses. Thus, it would appear that these responses evolved first in simpler organisms and were then maintained and enhanced during evolution.     

Enhanced low oxygen survival in Arabidopsis through increased metabolic flux in the fermentative pathway

We manipulated the enzyme activity levels of the alcohol fermentation pathway, pyruvate decarboxylase (PDC), and alcohol dehydrogenase (ADH) in Arabidopsis using sense and antisense overexpression of the corresponding genes (PDC1, PDC2, and ADH1). Transgenic plants were analyzed for levels of fermentation and evaluated for changes in hypoxic survival. Overexpression of either Arabidopsis PDC1 or PDC2 resulted in improved plant survival. In contrast, overexpression of Arabidopsis ADH1 had no effect on flooding survival. These results support the role of PDC as the control step in ethanol fermentation. Although ADH1 null mutants had decreased hypoxic survival, attempts to reduce the level of PDC activity enough to see an effect on plant survival met with limited success. The combination of flooding survival data and metabolite analysis allows identification of critical metabolic flux points. This information can be used to design transgenic strategies to improve hypoxic tolerance in plants.     

Unexpected presence of fructan 6-exohydrolases (6-FEHs) in non-fructan plants: characterization, cloning, mass mapping and functional analysis of a novel "cell-wall invertase-like" specific 6-FEH from sugar beet (Beta vulgaris L.)

About 15% of flowering plant species synthesize fructans. Fructans serve mainly as reserve carbohydrates and are subject to breakdown by plant fructan exohydrolases (FEHs), among which 1-FEHs (inulinases) and 6-FEHs (levanases) can be differentiated. This paper describes the unexpected finding that 6-FEHs also occur in plants that do not synthesize fructans. The purification, characterization, cloning and functional analysis of sugar beet (Beta vulgaris L.) 6-FEH are described. Enzyme activity measurements during sugar beet development suggest a constitutive expression of the gene in sugar beet roots. Classical enzyme purification followed by in-gel trypsin digestion and mass spectrometry (quadruple-time-of-flight mass spectrometry (Q-TOF) MS) led to peptide sequence information used in subsequent RT-PCR based cloning. Levan-type fructans (beta-2,6) are the best substrates for the enzyme, while inulin-type fructans (beta-2,1) and sucrose are poorly or not degraded. Sugar beet 6-FEH is more related to cell wall invertases than to vacuolar invertases and has a low iso-electric point (pI), clearly different from typical high pI cell wall invertases. Poor sequence homology to bacterial or fungal FEHs makes an endophytic origin highly unlikely. The functionality of the 6-FEH cDNA was further demonstrated by heterologous expression in Pichia pastoris. As fructans are absent in sugar beet, the role of 6-FEH in planta is not obvious. Like chitinases and beta-glucanases hydrolysing cell-surface components of fungal plant pathogens, a straightforward working hypothesis for further research might be that plant 6-FEHs participate in hydrolysis (or prevent the formation) of levan-containing slime surrounding endophytic or phytopathogenic bacteria.     

eIF2B-related disorders: antenatal onset and involvement of multiple organs

Leukoencephalopathy with vanishing white matter, also called "childhood ataxia with central nervous system hypomyelination," is the first human disease related to mutations in any of the five genes encoding subunits of eukaryotic initiation factor eIF2B or any translation factor at all. eIF2B is essential in all cells of the body for protein synthesis and the regulation of this protein synthesis under different stress conditions. It is surprising that mutations in the eIF2B genes have been reported to lead to abnormalities of the white matter of the brain only, although it has been shown recently that ovarian failure may accompany the leukoencephalopathy. Another surprising observation is that the onset of the disease varies from early childhood to adulthood, with the exception of Cree leukoencephalopathy, a disease related to a particular mutation in one of the eIF2B genes, which invariably has its onset within the first year of life. We analyzed the eIF2B genes of nine patients with an antenatal- or early-infantile-onset encephalopathy and an early demise and found mutations in eight of the patients. In addition to signs of a serious encephalopathy, we found oligohydramnios, intrauterine growth retardation, cataracts, pancreatitis, hepatosplenomegaly, hypoplasia of the kidneys, and ovarian dysgenesis. Until now, no evidence had been found for a genotype-phenotype correlation, but the consistently severe phenotype in affected siblings among our patients and in Cree encephalopathy patients suggests an influence of the genotype on the phenotype.     

Meta-analysis of genetic-linkage analysis of quantitative-trait loci

Meta-analysis is an important tool in linkage analysis. The pooling of results across primary linkage studies allows greater statistical power to detect quantitative-trait loci (QTLs) and more-precise estimation of their genetic effects and, hence, yields conclusions that are stronger relative to those of individual studies. Previous methods for the meta-analysis of linkage studies have been proposed, and, although some methods address the problem of between-study heterogeneity, most methods still require linkage analysis at the same marker or set of markers across studies, whereas others do not result in an estimate of genetic variance. In this study, we present a meta-analytic procedure to evaluate evidence from several studies that report Haseman-Elston statistics for linkage to a QTL at multiple, possibly distinct, markers on a chromosome. This technique accounts for between-study heterogeneity and estimates both the location of the QTL and the magnitude of the genetic effect more precisely than does an individual study. We also provide standard errors for the genetic effect and for the location (in cM) of the QTL, using a resampling method. The approach can be applied under other conditions, provided that the various studies use the same linkage statistic.     

Syntheses, structures and electrochemistry of two complexes containing quadruply bonded dimolybdenum atoms

The syntheses, electrochemistry and structures of Mo₂(O₂CCH₂-p-C₆H₄OH)₄, (1·2THF), and Mo₂(O₂CC(OH)(C₆H₅)₂)₄, (2·4THF), as determined by single-crystal X-ray diffraction, are reported. Both molecules crystallized with two axially coordinated THF molecules and 2 contained two additional THF molecules hydrogen bonded to two of the OH groups on the benzilato ligands. Complex 1 crystallized in an extended geometric arrangement involving hydrogen bonds between layers of molecules. The MoMo distance in 1 at 2.0972(8) Å is shorter than that in 2 at 2.1044(10) Å. There was also a large difference in the oxidation potentials of these two compounds with 1 and 2 exhibiting E_1/2 (ox) of 526 and 820 mV, respectively. These effects are attributed to differences in the electron donation ability in the ligands (p-hydroxy phenylacetic and benzilic acids) as assessed by their pK_a values.