Sequence-structure-function relationships of Tgs1, the yeast snRNA/snoRNA cap hypermethylase

The Saccharomyces cerevisiae Tgs1 methyltransferase (MTase) is responsible for conversion of the m⁷G caps of snRNAs and snoRNAs to a 2,2,7- trimethylguanosine structure. To learn more about the evolutionary origin of Tgs1 and to identify structural features required for its activity, we performed a structure–function study. By using sequence comparison and phylogenetic analysis, we found that Tgs1 shows strongest similarity to Mj0882, a protein related to a family comprised of bacterial rRNA:m²G MTases RsmC and RsmD. The structural information of Mj0882 was used to build a homology model of Tgs1p which allowed us to predict the range of the minimal globular MTase domain and the localization of other residues that may be important for enzyme function. To further characterize functional domains of Tgs1, mutants were constructed and tested for their effects on cell viability, subcellular localization and binding to the small nuclear ribonucleoproteins (snRNPs) and small nucleolar RNPs (snoRNPs). We found that the N-terminal domain of the hypermethylase is dispensable for binding to the common snRNPs and snoRNPs proteins but essential for correct nucleolar localization. Site- directed mutagenesis of Tgs1 allowed also the identification of the residues likely to be involved in the formation of the m7G-binding site and the catalytic center.     

RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization

Mitogen activation of mRNA decay pathways likely involves specific endoribonucleases, such as G3BP, a phosphorylation-dependent endoribonuclease that associates with RasGAP in dividing but not quiescent cells. G3BP exclusively cleaves between cytosine and adenine (CA) after a specific interaction with RNA through the carboxyl-terminal RRM-type RNA binding motif. Accordingly, G3BP is tightly associated with a subset of poly(A)(+) mRNAs containing its high-affinity binding sequence, such as the c-myc mRNA in mouse embryonic fibroblasts. Interestingly, c-myc mRNA decay is delayed in RasGAP-deficient fibroblasts, which contain a defective isoform of G3BP that is not phosphorylated at serine 149. A G3BP mutant in which this serine is changed to alanine remains exclusively cytoplasmic, whereas a glutamate for serine substitution that mimics the charge of a phosphorylated serine is translocated to the nucleus. Thus, a growth factor-induced change in mRNA decay may be modulated by the nuclear localization of a site-specific endoribonuclease such as G3BP.     

Tumeur testiculaire bilatérale synchrone à cellules de Leydig: à propos d’un cas

Testicular Leydig cell tumours are rare, representing between 1% and 3% of all testicular tumours. Synchronous bilateral tumours are extremely unusual. Found in 20% of cases in under ten year olds, it appears in all age groups and 25% of cases are diagnosed in the over fifties. It should be suspected in cases of secretory abnormality concerning the sexual hormones and is confirmed by histology. We report the case of a 25-year-old patient who presented a synchronous bilateral Leydig cell tumour treated by unilateral orchidectomy and contralateral tumorectomy.     

Pure choriocarcinoma of the testis presenting with jaundice: a case report and review of the literature

ABSTRACT: INTRODUCTION: Testicular cancer is the most common malignancy in men 15- to 35-years-old. The North American standard classification divides testicular cancers into germ cell tumors and non-germ cell tumors. The lymphatic spread of germ cell tumors usually involves the retroperitoneal lymph nodes. However, this spread to the retroperitoneum rarely involves the hepatic hilum. We describe an unusual case of metastatic choriocarcinoma of the testis that was clinically mimicked by a cholestatic jaundice. This is an unusual presentation of testicular cancer and, to the best of our knowledge, the first report of this kind in the literature. CASE PRESENTATION: A 28-year-old Moroccan man presented with a four-week history of progressive obstructive jaundice, and weight loss to our emergency department. Abdominal ultrasound showed a dilatation of the biliary ducts due to pathologically enlarged lymph nodes of the hepatic hilum. A complete clinical and radiologic assessment to discover the primary tumor was negative except for pulmonary metastasis. In the laboratory findings at admission there were signs of cholestasis with an abnormal increase in the rate of testicular tumor markers (serum beta-human chorionic gonadotropin level was 11,000IU/ml), which subsequently led to the suspicion of a testicular tumor. Further evaluation included testicular palpation and ultrasound which revealed a testicular nodule. The patient underwent an inguinal orchidectomy of the right testis and histopathological examination confirmed a pure choriocarcinoma. The prognosis was poor due to lymph node involvement at the hepatic hilum. He died one month later, despite general chemotherapy. CONCLUSIONS: The clinical presentation of the disease and the rarity of this entity are two remarkable characteristics described in this case report which are rarely reported in literature.     

Place de la scintigraphie dans le diagnostic de l’embolie pulmonaire chez la femme enceinte – À propos de 17 cas

IntroductionPulmonary embolism in pregnant women is a deadly disease; its diagnosis is based on specific algorithms. The lung scan is one of the recommended diagnostic suspicion in further investigations.Material and methodsRetrospective study of a series of cases of pulmonary embolism in the period pre-partum and post-partum pregnant women collected during 3 years, from January 2010 to January 2013, at the reanimation department maternity Souissi in Rabat.ResultsSeventeen cases of pulmonary embolism pre- and post-partum. The age ranged between 21 and 37 years (mean age 30 years). Four EP post-partum were recorded with 13 cases of EP pre-partum whose mean gestational age was 30SA. Several risk factors were found: 7 cases obesity, 4 cases cesarean section, 3 cases of varicose veins, 2 cases of endometritis, 1 case of twin pregnancy, 1 case of gestational hypertension and 1 case of alitement. The first reason for consultation was respiratory distress (12 cases), followed by chest pain (9 cas) and palpitations (6 cas). Lung scintigraphy performed in 14 patients’ objective 9 cases of perfusion defect, 4 cases of normal scan and 1 case of massive PE. No deaths or recurrences have been reported.ConclusionPregnancy and the post-partum period are at high risk of thromboembolic events due to physiological changes. The diagnostic approach is now well codified with scores of clinical and paraclinical probability. The lung scintigraphy can be a method of choice. Hybrid imaging is a good alternative for diagnostic performance.