Up-regulation of tRNA biosynthesis affects translational readthrough in maf1-delta mutant of Saccharomyces cerevisiae

Maf1p is a negative effector of RNA polymerase III in yeast. The maf1-delta mutation caused an increase in the level of cellular tRNAs, but a decrease of translational readthrough at nonsense codons. Using the lacZ- luc dual gene reporter system, we detected an almost twofold diminution of UAA and UAG readthrough in maf1-delta compared with the parental strain. The maf1-delta mutation did not affect the rate of protein biosynthesis and growth at standard conditions, but resulted in temperature-sensitive growth on non-fermentable carbon sources. We examined the correlation of the temperature sensitive and antisuppression phenotypes of maf1- Delta using a colour phenotype assay in the ade2-1 SUP11 strain. Antisuppression, but not the temperature-sensitive growth defect, was compensated either by increased dosage of SUP11or by [PSI(+)], the prion form of the translation termination factor Sup35p. Summarizing, the elevated tRNA levels in maf1- Delta increase translational fidelity and, independently, affect growth under special conditions.     

Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes

While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).     

Topoisomerase IIalpha expression in ductal carcinoma in situ of the breast: a preliminary study

Ductal carcinoma in situ (DCIS) of the breast, a precursor lesion of invasive breast cancer, is a heterogeneous disease in terms of histomorphologic features and biologic behavior. Our aim was to assess the proliferative activity, expressed as topoisomerase IIalpha (Topo IIalpha) immunoreactivity and c-erbB-2 expression in relation to morphologic features and architectural pattern of DCIS. The study included 26 DCIS, which were reclassified according to the recommendations of Consensus Conference. Topo-IIalpha and c-erbB-2 immunoreactivity were detected on paraffin sections. Topo IIalpha was consistently negative in normal ductal epithelium. Topo IIalpha-labeling index (Topo IIalpha-LI) was 0.7+/-0.6% for grade I, 4.3+/-3.9% for grade II, and 13.4+/-8.9 for grade III lesions (P<.01). For mixed nuclear grade DCIS, Topo IIalpha-LI was 6.8+/-4.8. There was no difference in Topo IIalpha-LI between different architectural patterns in low- and intermediate-grade lesions. In high nuclear grade DCIS, there was a progressive increase in Topo IIalpha-LI from solid toward cribriform and comedo-type DCIS. Positive c-erbB-2 immunoreactivity was found in 46% of DCIS, being highest in DCIS with high nuclear grade (78%) and in lesions with extensive necrosis. Topo IIalpha-LI was significantly higher in c-erbB-2-positive lesions (Topo IIalpha-LI- 12.4+/-8.5) as compared with negative lesions (Topo IIalpha-LI- 3.9+/-4.5, P<. 0001). Overexpression of c-erbB-2 and Topo IIalpha is associated with poorly differentiated lesions. Proliferative activity in individual ducts of DCIS depended primarily on the nuclear grade and was independent of architectural patterns of individual ducts in architecturally heterogeneous lesions.     

Bacteremia caused by an undescribed species of Janibacter

A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated from the blood of a patient with acute myeloid leukemia. It was identified by 16S rRNA gene sequencing as a previously undescribed species of Janibacter. The isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and glycopeptides.     

Estimation of the parameters of the relationship between power and time to exhaustion from a single ramp test.

This study aimed to estimate the power/time relationship from a single ramp test (RT) assuming critical power (Pc) from ventilatory threshold (VT) and energy reserve (W') from total work during RT These estimates from single RT were compared to those from a series of 4 constant power exercises (CPT) and from a series of 4 RT. Only W' from CPT was higher than from the series of RT and from single RT using VT (p < 0.05).     

A new form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly

We report two patients, born of consanguineous parents, affected by a disorder resulting in mild growth retardation. Hallmarks are amelogenesis imperfecta (absence of the enamel cap) associated with brachyolmia-like anomalies: platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping and herniation of the nuclei, and broad femoral necks. Inheritance appears to be autosomal recessive.     

Monomères acryliques à fonction carbonate cyclique, 2 Modification chimique de copolymères à groupements carbonate cyclique lateraux

Acrylic monomers with a cyclic carbonate function, their synthesis having been described previously, are used to synthesize copolymers with pendent cyclic carbonate side groups. Their chemical modification by ring opening addition reactions provides a convenient method for preparing functional polymers. The study of reactions with amines, on model compounds and on polymers, shows the possibility of obtaining a macromolecular network with crosslinking groups of carbamate type.     

Actions of some transmitters and their antagonists on salivary secretion in a tick

Cholinomimetics (pilocarpine, carbachol, physostigmine, acetylcholine, acetyl-beta-methylcholine) and sympathomimetics (dopamine, epinephrine), when injected into the hemolymph, provoked salivary fluid secretion in the female ixodid tick Amblyomma hebraeum Koch. Atropine, but not tubocurarine or toxiferine, abolished pilocarpine-induced secretion without reducing the response to dopamine. Reserpine and guanethidine likewise selectively attenuated pilocarpine-induced secretion. Following extirpation of the synganglion, pilocarpine no longer provoked a secretory response whereas dopamine did. Thus, the salivary gland appears to be innervated directly by catecholaminergic rather than cholinergic secretory nerves. It is suggested that pilocarpine elicits salivation by interacting with muscarinic-type cholinergic receptors situated either on the cell bodies of the secretory nerves, or alternatively in the integrative or sensory pathway.     

Expression of the CD7 Ligand K-12 in Human Thymic Epithelial Cells: Regulation by IFN-γ

CD7 is an immunoglobulin superfamily molecule expressed on T, NK, and pre-B lymphocytes. Previous studies have demonstrated a role for CD7 in T- and NK-cell activation and cytokine production. Recently, an epithelial cell secreted protein, K12, was identified as a CD7 ligand. Although CD7 is expressed intrathymically, it is not known if K12 is produced in human thymus. To determine roles that K12 might play in the human thymus, we analyzed expression of K12 in human thymocytes, thymic epithelial cells (TE), and thymic fibroblasts. We found that recombinant human K12 bound strongly to soluble hCD7, with a K_eq of 37.6×10^–9M, and this interaction was inhibited by a novel antihuman K12 monoclonal antibody (K12-A1). K12 mRNA was detected by RT–PCR and northern analysis in human TE and thymic fibroblasts, but not in human thymocytes. Expression of K12 in TE cells was upregulated by IFN- . Taken together, these data demonstrated that K12 is produced by human TE cells and thymic fibroblasts, and is regulated in thymus by IFN- . These data suggest a role for thymic microenvironment-produced K12 in regulation of thymocyte signaling and cytokine release, particularly in the setting of thymus pathology where IFN- is upregulated such as myasthenia gravis.     

A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndrome

We report a family heterozygous for a newly identified mutation in the tyrosine kinase I domain of the FGFR2 gene (1576A > G, encoding the missense substitution Lys526Glu), associated with variable expressivity of Crouzon syndrome, including clinical nonpenetrance. Our observations expand both the clinical and molecular spectrum of this unusual subset of FGFR2 mutations.