Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis.

Histone acetylation affects many nuclear processes including transcription, chromatin assembly, and DNA damage repair. Acetylation of histone H3 lysine 56 (H3 K56ac) in budding yeast occurs during mitotic S phase and persists during DNA damage repair. Here, we show that H3 K56ac is also present during premeiotic S phase and is conserved in fission yeast. Furthermore, the H3 K56ac modification is not observed in the absence of the histone chaperone Asf1. asf1delta and H3 K56R mutants exhibit similar sensitivity to DNA damaging agents. Mutational analysis of Asf1 demonstrates that DNA damage sensitivity correlates with (i) decreased levels of H3 K56ac and (ii) a region implicated in histone binding. In contrast, multiple asf1 mutants that are resistant to DNA damage display WT levels of K56ac. These data suggest that maintenance of H3 K56 acetylation is a primary contribution of Asf1 to genome stability in yeast.

Glycopeptidolipid acetylation affects sliding motility and biofilm formation in Mycobacterium smegmatis.

The absence of glycopeptidolipids (GPLs) abolishes the ability of mycobacteria both to slide over the surface of motility plates and to form biofilms on polyvinyl chloride. In a screen for biofilm-defective mutants of Mycobacterium smegmatis mc(2)155, a new mutant was obtained that resulted in partial inhibition of both processes and also showed an intermediate rough colony morphology. The mariner transposon insertion mapped to a GPL biosynthesis gene (atf1) which encodes a putative acetyltranferase involved in the transfer of acetyl groups to the glycopeptide core. Physical characterization of the GPLs from the atf1 mutant demonstrated that they were not acetylated.

[Sliding motility and biofilm formation in mycobacteria]. / Movilidad por deslizamiento y formación de biofilms en las micobacterias.

Using as a model Mycobacterium smegmatis, a non-motile microorganism, we have studied for the first time in mycobacteria the phenomenon known as sliding motility, as well as the process of biofilm formation. A screen of random transposon mutants was performed in order to identify the genes required for mycobacterial sliding over the surface of motility plates. The genetic analysis described here has been published recently. The genes required for sliding and for biofilm formation (mps and tmtpC) are involved in the biosynthesis of the glycopeptidolipids (GPLs) and their transport to the mycobacterial capsule. Based on our results, we suggest a model for the role of the GPLs in both phenomena.

Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review.

OBJECTIVE: To assess the effectiveness and safety of pramipexole as an adjunctive medication in refractory bipolar and unipolar depression in a naturalistic setting. METHODS: Retrospective chart review by psychiatrists on staff at a university hospital identified all patients who had received pramipexole. Response was based on moderate to marked improvement in the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: Pramipexole (mean dose 0.70 mg/d, mean duration 24.4 weeks) was effective in 6/12 (50.0%) of patients with bipolar depression, and 8/20 (40%) of patients with unipolar depression, mean duration of follow-up of 24.4 weeks. One case of transient hypomania was noted. Eight patients discontinued pramipexole due to lack of response and four due to side effects. CONCLUSIONS: Pramipexole, used as an adjunct to antidepressants or mood stabilizers, appeared to be effective and safe in the treatment of unipolar and bipolar depression. These uncontrolled, retrospective, naturalistic pilot data require confirmation by controlled research before conclusions can be made.

Genetic analysis of sliding motility in Mycobacterium smegmatis.

A screen for nonsliding mutants of Mycobacterium smegmatis yielded 20 mutants with transposon insertions in the mps gene, which is involved in glycopeptidolipid biosynthesis. One mutant had an insertion in a gene predicted to encode a membrane transport protein. All mutants lacked glycopeptidolipids and were unable to form biofilms on polyvinyl chloride.

Rad6-dependent ubiquitination of histone H2B in yeast.

Although ubiquitinated histones are present in substantial levels in vertebrate cells, the roles they play in specific biological processes and the cellular factors that regulate this modification are not well characterized. Ubiquitinated H2B (uH2B) has been identified in the yeast Saccharomyces cerevisiae, and mutation of the conserved ubiquitination site is shown to confer defects in mitotic cell growth and meiosis. uH2B was not detected in rad6 mutants, which are defective for the ubiquitin-conjugating enzyme Ubc2, thus identifying Rad6 as the major cellular activity that ubiquitinates H2B in yeast.

Mutations in both the structured domain and N-terminus of histone H2B bypass the requirement for Swi-Snf in yeast.

The chromatin elements targeted by the ATPdependent, Swi-Snf nucleosome-remodeling complex are unknown. To address this question, we generated mutations in yeast histone H2B that suppress phenotypes associated with the absence of Swi-Snf. Sin- (Swi-Snf-independent) mutations occur in residues involved in H2A-H2B dimer formation, dimer- tetramer association, and in the H2B N-terminus. The strongest and most pleiotropic Sin- mutation removed 20 amino acid residues from the H2B N-terminus. This mutation allowed active chromatin to be formed at the SUC2 locus in a snf5Delta mutant and resulted in hyperactivated levels of SUC2 mRNA under inducing conditions. Thus, the H2B N-terminus may be an important target of Swi-Snf in vivo. The GCN5 gene product, the catalytic subunit of several nuclear histone acetytransferase complexes that modify histone N-termini, was also found to act in conjunction with Swi-Snf. The phenotypes of double gcn5Deltasnf5Delta mutants suggest that histone acetylation may play both positive and negative roles in the activity of the Swi-Snf-remodeling factor.

Functional analysis of histones H2A and H2B in transcriptional repression in Saccharomyces cerevisiae.

The presence of H2A-H2B dimers in nucleosomes can inhibit the binding of transcription factors to chromatin templates. To study the roles of histones H2A and H2B in transcriptional repression in vivo, mutant forms of these histones were analyzed in two different assay systems. Two repression domains were identified in H2A. One domain includes residues that fall in the beginning of the H2A-H2B dimerization region, and the second is in the H2A N terminus, a region of potential interactions with nonhistone proteins. The function of H2A and H2B in one repression assay was found to be dependent on three SPT (suppressor of Ty) genes whose products are important for chromatin-mediated repression. These results suggest that repressive chromatin structure may be established through the interactions of the Spt proteins with these histones. In contrast, other proteins, the products of the HIR (histone regulation) genes, may function to direct H2A and H2B to specific promoters.

Freeze-dried allograft versus autograft bone in scoliosis surgery. A retrospective comparative study.

Two groups of 36 patients who underwent posterior vertebral fusion for scoliosis were compared retrospectively; the postoperative follow-up was 2 years. Autogenous bone taken from the iliac crest was used in group A, whereas the patients in group B received freeze-dried allograft from our bone bank. There was no significant difference between the two groups in maintenance of the curve correction after the same delay, nor in incidence of complications. A reduction of blood loss or operating time, however, could not be demonstrated in our study.

[Ischemic necrosis of the femoral head following osteosynthesis of an extracapsular fracture]. / Nécrose ischémique de la tête fémorale après ostéosynthèse d'une fracture extracapsulaire.

The authors have reviewed 6 cases of avascular necrosis of the femoral head which occurred after internal fixation of an extracapsular fracture in the adult. This is a rare and poorly described complication. Several pathogenic hypotheses are discussed, but none could be retained formally. The aim of this article is to point out this type of complication, which still lacks a satisfactory explanation.

[Avulsion-fracture of the subscapular muscle]. / Avulsion-fracture du muscle sous-scapulaire.

The authors report a case of avulsion-fracture of the humeral insertion of the subscapularis muscle, treated by surgery. They discuss this lesion and review the literature.

[Treatment of fractures of the carpal scaphoid with Herbert's bone screw. Review of 21 clinical cases]. / Traitement des fractures du scaphoïde carpien par vis de Herbert. Revue de 21 cas cliniques.

Twenty-one patients with scaphoid fractures treated by internal fixation with the Herbert screw are reviewed. Nine patients presented acute fractures and twelve had fractures with delayed or non-union. The results of these two kinds of lesions are analyzed following the criteria established by Herbert and Fisher in 1984. This type of internal fixation gives excellent results in isolated lesions of the scaphoid provided it is correctly executed.