The cis-regulatory sequences required for expression of the Drosophila melanogaster adult cuticle gene ACP65A.

Post-embryonic development in insects requires successive molts. Molts are triggered by ecdysteroids, and the nature of the molt (larval, pupal or adult) is determined by juvenile hormones. The genes encoding cuticle proteins are targets of both classes of hormones, and therefore are interesting models to study hormone action at the molecular level. The Drosophila ACP65A cuticle gene is expressed exclusively during the synthesis of the adult exoskeleton, in epidermal domains synthesising flexible cuticle. We have examined the cis-regulatory sequences of ACP65A using phylogenetic comparisons and functional analysis, and find that only about 180 bp are essential, including an 81 bp intron. The restriction of ACP65A expression appears to depend on a strong repression mechanism.

Impact of preemptive reduction of immunosuppression with serial monitoring for BK virus replication in renal transplant recipients undergoing short-term evaluation.

The aim of this preliminary, prospective, longitudinal study was to evaluate the effects on graft function and viral loads of modulation of immunosuppressive therapy based upon serial noninvasive monitoring of urine and serum viral loads with real-time polymerase chain reaction among unselected renal transplant recipients. Thirty-nine renal transplant recipients with follow-up times of 7.8 +/- 4.3 months were monitored monthly with urine and serum samples to measure BK viral load. Interventions such as gradual reductions of mycophenolate mofetil and/or tacrolimus were performed when repeated urine and serum viral loads were >10(5) and >10(3) copies/mL, respectively. Among 271 samples, the patients were divided into 6 groups: negative urine (group = 1; n = 10) and negative serum (group 2; n = 25) versus BK viral loads that were intermittent (urine: group 3; n = 24 and serum: group 4; n = 11) versus persistent (urine: group 5; n = 5 and serum: group 6; n = 3). In groups 3-4 we observed the higher viral loads in the urine than in the serum (10(3): 21; 10(4): 1; 10(5): 1; 10(6): 1 vs 10(2): 8; 10(3): 2; 10(4): 1). The timing of resolution of viremia was more rapid than viruria. In groups 5-6 we observed the greatest viral load and greater number in urine. The overall incidences of viruria and viremia were 74.3% and 35.9%, respectively. The overall rates of clearance of viruria were 26/29 recipients (89%) and viremia, 11/14 recipients (78%). Only 10 patients (25.6%) needed extensive reduction of immunosuppression. No modifications of serum creatinine levels and no rejection episodes were observed. In conclusion this preliminary analysis suggested that serial, noninvasive monitoring of viral load allows gradual premptive reduction of immunosuppression with consequent strong reduction in viral load.

[Cytomegalovirus and BK polyomavirus infection after renal transplantation]. / Infezione da citomegalovirus (CMV) e da polioma BK virus (BKV) dopo trapianto di rene.

Cytomegalovirus (CMV) and BK polyomavirus (BKV) infections have been described in a high percentage of renal transplant patients and are known to cause various complications in renal transplantation. They are closely related to immunosuppressive therapy and implicated in the progression of graft failure. This review focuses on the clinical aspects of CMV and BKV infection after renal transplantation, optimal monitoring, and recent preventive measures and interventions to improve graft function and recipient survival.

The Drosophila ACP65A cuticle gene: deletion scanning analysis of cis-regulatory sequences and regulation by DHR38.

The regulatory sequences of the Drosophila ACP65A cuticle gene were analyzed in vivo in transgenic flies, using both fusion genes constructs and transposase-mediated deletions within a P element containing ACP65A regulatory sequences fused to the lacZ gene (deletion scanning). The sequences located between -594 and +161 are sufficient to confer both temporal and spatial expression specificities, indicating the presence of tissue-specific enhancers and response elements to hormone-induced factors. In addition, timing of expression and tissue-specificity appear to be controlled by distinct cis-regulatory elements, which suggests the existence of independent hormonal and tissue-specific signaling pathways. Gain and loss of function studies also implicate DHR38, the Drosophila homolog of the vertebrate NGFI-B-type nuclear receptors, as an important activator of the ACP65A gene.