HU, the major histone-like protein of E. coli, modulates the binding of IHF to oriC.

HU is one of the most abundant DNA binding proteins of bacteria. Unlike IHF, integration host factor of Escherichia coli, with which HU shares many properties, including a strong sequence homology and similar predicted structure, HU seems to bind non-specifically to DNA whereas IHF binds to specific sites. In this work we compare the binding characteristics of HU and IHF to a DNA fragment containing the minimal origin of replication of E. coli (oriC) and we analyse the effect of HU on the binding capacity of IHF to this oriC fragment. We show that HU interacts randomly and non-specifically with oriC as opposed to the specific binding of IHF to this same DNA sequence. In addition, we show that HU can modulate the binding of IHF to its specific oriC site. Depending on the relative concentrations of HU and IHF, HU is able either to activate or to inhibit the binding of IHF to oriC.     

GPSDB: a new database for synonyms expansion of gene and protein names

SUMMARY: We present a new database, GPSDB (Gene and Protein Synonyms DataBase) which collects gene/protein names, in a species specific way, from 14 main biological resources. A web-based search interface gives access to the database: given a gene/protein name, it retrieves all synonyms for this entity and queries Medline with a set of user-selected terms. AVAILABILITY: GPSDB is freely available from http://biomint.oefai.at/ CONTACT: johann@oefai.at.     

A role for the Plasmodium falciparum RESA protein in resistance against heat shock demonstrated using gene disruption

During erythrocyte invasion, the Plasmodium falciparum Ring-infected erythrocyte surface antigen (RESA) establishes specific interactions with spectrin. Based on analysis of strains with a large chromosome 1 deletion, RESA has been assigned several functions, none of which is firmly established. Analysis of parasites with a disrupted resa1 gene and isogenic parental or resa3-disrupted controls confirmed the critical role of RESA in the surface reactivity of immune adult sera on glutaraldehyde-fixed ring stages. Absence of RESA did not influence merozoite invasion or erythrocyte membrane rigidity, was associated with a modest increase of cytoadhesion to CD36 under conditions of flow, but resulted in marked susceptibility to heat shock. resa1-KO-infected erythrocytes were prone to heat-induced vesiculation like uninfected erythrocytes, whereas parental or resa3-KO infected erythrocytes remained undamaged. Furthermore, a 6 h exposure of ring stages at 41 degrees C resulted in 33% culture inhibition of resa1-KO parasites while marginally impacting parental and resa3-KO parasite growth. This points to a role for RESA in protecting the infected erythrocyte cytoskeleton during febrile episodes. Infection patterns of resa1-KO and parental parasites in Saimiri sciureus indicated that RESA does not, at least on its own, modulate virulence in the squirrel monkey, as had been previously suggested.     

Prenatal and preimplantation genetic diagnosis: decision tree, new practices?

Preimplantation genetic diagnosis (PGD) purpose is to assess the genetic status of 3 day-old embryos. PGD offers thus to couples "at-risk" of a genetic disorder an earlier option to prenatal diagnosis (PND). At the beginning, PGD's indications, patients and law were very closed to PND, but PGD specificities are gradually raising. Particularly, indications vary considerably in countries where the absence of law authorizes all the practices. Some of these applications are moreover raising serious ethical issues. Even in France, where this activity is particularly supervised, the recent modification to the law marks this evolution.     

Mitochondrial translation: elongation factor tu is essential in fission yeast and depends on an exchange factor conserved in humans but not in budding yeast

The translation elongation factor EF-Tu is a GTPase that delivers amino-acylated tRNAs to the ribosome during the elongation step of translation. EF-Tu/GDP is recycled by the guanine nucleotide exchange factor EF-Ts. Whereas EF-Ts is lacking in S. cerevisiae, both translation factors are found in S. pombe and H. sapiens mitochondria, consistent with the known similarity between fission yeast and human cell mitochondrial physiology. We constructed yeast mutants lacking these elongation factors. We show that mitochondrial translation is vital for S. pombe, as it is for human cells. In a genetic background allowing the loss of mitochondrial functions, a block in mitochondrial translation in S. pombe leads to a major depletion of mtDNA. The relationships between EF-Ts and EF-Tu from both yeasts and humans were investigated through functional complementation and coexpression experiments and by a search for suppressors of the absence of the S. pombe EF-Ts. We find that S. cerevisiae EF-Tu is functionally equivalent to the S. pombe EF-Tu/EF-Ts couple. Point mutations in the S. pombe EF-Tu can render it independent of its exchange factor, thereby mimicking the situation in S. cerevisiae.     

Chromosome imbalances in oligodendroglial tumors detected by comparative genomic hybridization

Seven well-differentiated oligodendrogliomas, 16 anaplastic oligodendrogliomas and two cases of oligoastrocytomas were investigated by comparative genomic hybridization (CGH) on frozen tissue samples. The most frequent losses found involved 1p and 19q in 32% of cases. Loss of 9p was observed during malignant progression in 25% of anaplastic oligodendrogliomas. In two anaplastic oligodendrogliomas gain of 1q was found. The frequent losses of chromosome 16 and 22 have not been reported previously. These results underscore that CGH is a powerful tool for the classification of gliomas complementing the traditional histopathological approach.     

A yeast mitochondrial membrane methyltransferase-like protein can compensate for oxa1 mutations

Members of the Oxa1p/Alb3/YidC family mediate the insertion of various organelle or bacterial hydrophobic proteins into membranes. They present at least five transmembrane segments (TM) linked by hydrophilic domains located on both sides of the membrane. To examine how Oxa1p structure relates to its function, we have introduced point mutations and large deletions into various domains of the yeast mitochondrial protein. These mutants allowed us to show the importance of the first TM domain as well as a synergistic interaction between the first loop and the C-terminal tail, which both protrude into the matrix. These mutants also led to the isolation of a high copy suppressor, OMS1, which encodes a member of the methyltransferase family. Overexpression of OMS1 seems to increase the steady-state level of both the mutant and wild-type Oxa1p. We show that Oms1p is a mitochondrial inner membrane protein inserted independently of Oxa1p. Oms1p presents one TM and a N-in C-out topology with the C-terminal domain carrying the methyltransferase-like domain. A conserved motif within this domain is essential for the suppression of oxa1 mutations. We discuss the possible role of Oms1p on Oxa1p intermembrane space domain.