Nuclear medicine and pediatric nephro-urology: a long-lasting successful partnership.

Congenital anomalies of the kidney and urinary tract, as well as urinary infections, are very frequent in children. After the clinical and laboratory evaluation, the first imaging procedure to be done is a renal and bladder ultrasound, but afterwards, a main contribution comes from nuclear medicine. Through minimally invasive and sedation-free procedures, nuclear medicine allows the evaluation of the functional anatomy of the urinary tract, and the quantification of renal function and drainage. If pediatric dosage cards provided by scientific societies are used, radiation exposure can also be low. In the pediatric conditions previously mentioned, nuclear medicine is used both for initial diagnosis and follow-up, mostly in cases of suspicion of ureteropelvic or ureterovesical junction syndromes, as well as vesicoureteral reflux or renal scars of febrile infectious episodes. Pediatric nephro-urology constitutes a significant workload of pediatric nuclear medicine departments. The following paragraphs are a revision of the renal radiopharmaceuticals, as well as the nuclear nephro-urology procedures - dynamic and static renal scintigraphy, and direct and indirect radionuclide cystography. A summary of the techniques, main indications, interpretation criteria and pitfalls will be provided. Some future directions for the field are also pointed out, among which the most relevant is the need for nuclear medicine professionals to use standardized protocols and integrate multidisciplinary teams with other pediatric and adult health professionals that manage these life-long pediatric pathologies, which are recognized as an important cause of adult chronic kidney disease.

E4-Ubiquitin ligase Ufd2 stabilizes Yap8 and modulates arsenic stress responses independent of the U-box motif.

Adaptation of Saccharomyces cerevisiae cells to arsenic stress is mediated through the activation of arsenic detoxification machinery by the Yap8 transcription factor. Yap8 is targeted by the ubiquitin proteasome system for degradation under physiological conditions, yet it escapes proteolysis in arsenic-injured cells by a mechanism that remains to be elucidated. Here, we show that Ufd2, an E4-Ubiquitin (Ub) ligase, is upregulated by arsenic compounds both at mRNA and protein levels. Under these conditions, Ufd2 interacts with Yap8 mediating its stabilization, thereby controlling expression of ACR3 and capacity of cells to adapt to arsenic injury. We also show that Ufd2 U-box domain, which is associated to the ubiquitination activity of specific ubiquitin ligases, is dispensable for Yap8 stability and has no role in cell tolerance to arsenic stress. Thus, our data disclose a novel Ufd2 role beyond degradation. This finding is further supported by genetic analyses showing that proteins belonging to Ufd2 proteolytic pathways, namely Ubc4, Rad23 and Dsk2, mediate Yap8 degradation.

Arsenic stress elicits cytosolic Ca(2+) bursts and Crz1 activation in Saccharomyces cerevisiae.

Although arsenic is notoriously poisonous to life, its utilization in therapeutics brings many benefits to human health, so it is therefore essential to discover the molecular mechanisms underlying arsenic stress responses in eukaryotic cells. Aiming to determine the contribution of Ca(2+) signalling pathways to arsenic stress responses, we took advantage of the use of Saccharomyces cerevisiae as a model organism. Here we show that Ca(2+) enhances the tolerance of the wild-type and arsenic-sensitive yap1 strains to arsenic stress in a Crz1-dependent manner, thus providing the first evidence that Ca(2+) signalling cascades are involved in arsenic stress responses. Moreover, our results indicate that arsenic shock elicits a cytosolic Ca(2+) burst in these strains, without the addition of exogenous Ca(2+) sources, strongly supporting the notion that Ca(2+) homeostasis is disrupted by arsenic stress. In response to an arsenite-induced increase of Ca(2+) in the cytosol, Crz1 is dephosphorylated and translocated to the nucleus, and stimulates CDRE-driven expression of the lacZ reporter gene in a Cnb1-dependent manner. The activation of Crz1 by arsenite culminates in the induction of the endogenous genes PMR1, PMC1 and GSC2. Taken together, these data establish that activation of Ca(2+) signalling pathways and the downstream activation of the Crz1 transcription factor contribute to arsenic tolerance in the eukaryotic model organism S. cerevisiae.