Novel oxidative stress-responsive gene ERS25 functions as a regulator of the heat-shock and cell death response

Members of the yeast p24 family, including Emp24p and Erv25p, exist as heteromeric complexes that have been proposed to cycle between the endoplasmic reticulum (ER) and Golgi compartments. The specific functions and sites of action of p24 proteins are still unknown. Here we identified a human homolog of the yeast p24 family of proteins, named ERS25 (endoplasmic reticulum stress-response protein 25), and investigated its role in stress response. ERS25 is predicted to have an ER localization signal peptide, a GOLD (Golgi dynamics) domain, which is found in several eukaryotic Golgi and lipid-trafficking proteins, a coiled-coil region, and a transmembrane domain. We demonstrate that ERS25 is localized to the ER and is induced by ER-specific stress, heat shock, and oxidative stress. The selective induction of ERS25 by brefeldin A, but not tunicamycin, implicates the involvement of ERS25 in protein trafficking between the ER and the Golgi. Small interfering RNA-mediated inhibition of ERS25 results in a significant decrease in apoptosis as well as a reduction of reactive oxygen species induced by oxidative stress. Moreover, ERS25 depletion results in a significant increase in the levels of the ER chaperone HSP70 in response to heat-shock stress through increased levels of HSF-1. We also found that inhibition of ERS25 induction in response to heat shock enhanced the binding of HSP70 to Apaf-1, which is likely to interfere in stress-mediated apoptosis. Together, the data presented here demonstrate that ERS25 may play a critical role in regulation of heat-shock response and apoptosis.     

Reproductive development and maternal effects in the pine weevil Hylobius abietis

1. In a laboratory study of maturation feeding of female pine weevil Hylobius abietis on current and 1‐year‐old stem bark of transplants of Scots and Corsican pine, Norway and Sitka spruce, Douglas fir, and hybrid larch, the length of the pre‐oviposition period was influenced by the species on which weevils fed. The shortest pre‐oviposition period was on hybrid larch (11.8 days) and the longest on Douglas fir (15.5 days). 2. The species on which weevils fed also affected fecundity but there was evidence of a species–year interaction. Over a period of 36 days, most eggs were laid by weevils feeding on current stem of Norway spruce and Corsican and Scots pine and fewest on current stem of Sitka spruce. 3. Significant maternal effects on egg size were observed both in relation to female size and conifer species. The largest eggs were laid on Corsican pine and the smallest on Douglas fir, with no evidence of a trade‐off between number of eggs laid and their size. 4. There was a positive relationship between egg and larval size and between larval size and survival on logs of four conifer species. Residual resistance mechanisms in the bark of recently cut stumps and larval competition are discussed briefly in relation to the importance of the observed maternal effects on weevil population dynamics.     

Mutations in a newly identified Drosophila melanogaster gene, mago nashi, disrupt germ cell formation and result in the formation of mirror-image symmetrical double abdomen embryos.

The mago nashi (mago) locus is a newly identified strict maternal effect, grandchildless-like, gene in Drosophila melanogaster. In homozygous mutant mago females reared at 17 degrees C, mago+ function is reduced, the inviable embryos lack abdominal segments and 84-98% of the embryos die. In contrast, at 25 degrees C, some mago alleles produce a novel gene product capable of inducing the formation of symmetrical double abdomen embryos. Reciprocal temperature-shift experiments indicate that the temperature-sensitive period is during oogenetic stages 7-14. Furthermore, embryos collected from mago1 homozygous females contain no apparent functional posterior determinants in the posterior pole. In viable F1 progeny from mago mutant females, regardless of genotype and temperature, polar granules are reduced or absent and germ cells fail to form (the grandchildless-like phenotype). Thus, we propose that the mago+ product is a component of the posterior determinative system, required during oogenesis, both for germ cell determination and delineation of the longitudinal axis of the embryo.     

Interaction of GABA and volatile anesthetics in the nematode Caenorhabditis elegans

The authors tested whether mutant strains of Caenorhabditis elegans with altered sensitivity to volatile anesthetics have altered responses to GABA or GABA-agonists. They determined the ED50s of the wild-type strain N2 and two mutant strains of C. elegans to a GABA-mimetic ivermectin (IVM) and to GABA. unc-79, a strain with increased sensitivity to halothane, was more sensitive than N2 to IVM and GABA. unc-9, a strain that suppresses the increased sensitivity of unc-79 to halothane, was less sensitive than N2 to IVM and GABA. The authors also tested whether doses of GABA or IVM and volatile anesthetics were additive in their effects on C. elegans. Halothane (2.1%) did not shift the ED50 of IVM, but was antagonistic to GABA. Enflurane (4%) was antagonistic to both IVM and GABA. However, ED50s of halothane and enflurane were unchanged in the presence of IVM (35 nM) or GABA (150 mM). The authors conclude that GABA by itself does not appear to mediate halothane or enflurane sensitivity in C. elegans.     

Sequence analysis of sub-genotype D hepatitis B surface antigens isolated from Jeddah,Saudi Arabia

Little is known about the prevalence of HBV genotypes/sub-genotypes in Jeddah province, although the hepatitis B virus (HBV) was identified as the most predominant type of hepatitis in Saudi Arabia. To characterize HBV genotypes/sub-genotypes, serum samples from 15 patients with chronic HBV were collected and subjected to HBsAg gene amplification and sequence analysis. Phylogenetic analysis of the HBsAg gene sequences revealed that 11 (48%) isolates belonged to HBV/D while 4 (18%) were associated with HBV/C. Notably, a HBV/D sub-genotype phylogenetic tree identified that eight current isolates (72%) belonged to HBV/D1, whereas three isolates (28%) appeared to be more closely related to HBV/D5, although they formed a novel cluster supported by a branch with 99% bootstrap value. Isolates belonging to D1 were grouped in one branch and seemed to be more closely related to various strains isolated from different countries. For further determination of whether the three current isolates belonged to HBV/D5 or represented a novel sub-genotype, HBV/DA, whole HBV genome sequences would be required. In the present study, we verified that HBV/D1 is the most prevalent HBV sub-genotype in Jeddah, and identified novel variant mutations suggesting that an additional sub-genotype designated HBV/DA should be proposed. Overall, the results of the present HBsAg sequence analyses provide us with insights regarding the nucleotide differences between the present HBsAg/D isolates identified in the populace of Jeddah, Saudi Arabia and those previously isolated worldwide. Additional studies with large numbers of subjects in other areas might lead to the discovery of the specific HBV strain genotypes or even additional new sub-genotypes that are circulating in Saudi Arabia.     

IDENTIFYING ASSESSOR DIFFERENCES IN WEIGHTING THE UNDERLYING SENSORY DIMENSIONS

In a previous paper Kunert and Qannari (1999) discussed a simple alternative to Generalized Procrustes Analysis to analyze data derived from a sensory profiling study. After simple pretreatments of the individual data matrices, they propose to merge the data sets together and undergo Principal Components Analysis of the matrix thus formed. On the basis of two data sets, it was shown that the results slightly differ from those obtained by means of Generalized Procrustes Analysis.
In this paper we give a mathematical justification to this approach by relating it to a statistical regression model. Furthermore, we obtain additional information from this method concerning the dimensions used by the assessors as well as the contribution of each assessor to the determination of these dimensions. This information may be useful to characterize the performance of the assessors and single out those assessors who downweight or overweight some dimensions. In particular, those assessors who overweight the last dimensions should arouse suspicion regarding their performance as, in general, the last dimensions in a principal components analysis are deemed to reflect random fluctuations.