Nug1 is a potassium-stimulated GTPase affecting the association of early 60S assembly factors in ribosome biogenesis

Ribosomes are complex macromolecular machineries responsible for protein synthesis (translation) in all living cells. In yeast, they are composed of four rRNA species assembled with 79 ribosomal proteins to form the small (40S) and the large (60S) subunit. To reach their final translation-competent form, they go through a complex, highly dynamic and coordinated process termed ribosome biogenesis. In eukaryotes, more than 180 transiently associating non-ribosomal factors (assembly factors) and 70 small nucleolar RNAs (snoRNAs) are involved in rRNA processing and modifications, as well as in the assembly of r-proteins (Henras et al., 2008; Lafontaine and Tollervey, 2001; Staley and Woolford, 2009). Several of the 60S ribosome biogenesis factors belong to the superfamily of GTPases, including Nug1. Nug1 is a circularly permuted GTPase and an essential trans-acting factor in ribosome biogenesis. It co-purifies with various nucleolar and nucleoplasmic pre-ribosomal particles and exhibits RNA-binding properties (Bassler et al., 2001; Bassler et al., 2006). However, several questions remained open regarding the exact role of Nug1 in ribosome biogenesis, including the regulation of its enzymatic GTPase activity, its binding site on the pre-ribosome, as well as a possible role in the recruitment and/or release of other 60S assembly factors. During my PhD studies, I performed a series of in vitro GTPase and nucleotide binding assays using the C. thermophilum (CtNug1) orthologue to address Nug1’s enzymatic activity. With these, I showed that CtNug1 exhibits a low intrinsic GTPase activity that can be stimulated by potassium ions, rendering Nug1 a cation-dependent GTPase. I’ve also generated a series of point mutations in the G-domain that specifically inhibit GTP hydrolysis or nucleotide binding. The orthologous mutations in the yeast Nug1 GTPase domain were subsequently tested for their effects on ribosome biogenesis. Early 60S assembly factors including Dbp10, Spb1, Nop2 and Mrt4 associated less with affinity purified pre-ribosomal particles, when the Nug1 nucleotide-binding mutant (D446N) was expressed or when Nug1 was depleted. Interestingly, no growth defects or biochemical differences in pre-ribosomal particle composition were observed for the catalytic (G339A) mutant, suggesting that the GTP hydrolysis is not essential for Nug1’s function. From the early assembly factors affected, only the essential RNA helicase Dbp10 was genetically linked to Nug1 (Bassler et al., 2001). In collaboration with Dr. Emma Thomson, we identified the binding sites of Nug1 and Dbp10 onto the pre-ribosome using the CRAC technique. Both proteins were found to bind in close proximity to each other on the interface of the 60S subunit at the PTC area. Further, in vitro binding assays confirmed a physical interaction between Nug1 and Dbp10. Together the findings from my PhD thesis show that Nug1 affects the dynamic interplay of assembly factors including those localizing to the PTC area (Dbp10, Sbp1, Nop2, Nsa2), as well as factors involved in the P-stalk formation (Mrt4, Yvh1, Rpp0, Rpl12). In this interplay, the Nug1 binds at the base of helix 89 and may act as a molecular GTPase switch that mediates the crosstalk between the maturation of PTC and the P-stalk, two distinct and essential hallmarks of the 60S subunit

An improved StarGAN for emotional voice conversion: enhancing voice quality and data augmentation

Emotional Voice Conversion (EVC) aims to convert the emotional style of a source speech signal to a target style while preserving its content and speaker identity information. Previous emotional conversion studies do not disentangle emotional information from emotion-independent information that should be preserved, thus transforming it all in a monolithic manner and generating audio of low quality, with linguistic distortions. To address this distortion problem, we propose a novel StarGAN framework along with a two-stage training process that separates emotional features from those independent of emotion by using an autoencoder with two encoders as the generator of the Generative Adversarial Network (GAN). The proposed model achieves favourable results in both the objective evaluation and the subjective evaluation in terms of distortion, which reveals that the proposed model can effectively reduce distortion. Furthermore, in data augmentation experiments for end-to-end speech emotion recognition, the proposed StarGAN model achieves an increase of 2% in Micro-F1 and 5% in Macro-F1 compared to the baseline StarGAN model, which indicates that the proposed model is more valuable for data augmentation.Comment: Accepted by Interspeech 202

Rupture of totally implantable central venous access devices (Intraports) in patients with cancer: report of four cases

BACKGROUND: Totally implantable central venous access devices (intraports) are commonly used in cancer patients to administer chemotherapy or parenteral nutrition. Rupture of intraport is a rare complication. PATIENTS AND METHODS: During 3 years period, a total of 245 intraports were placed in cancer patients for chemotherapy. Four of these cases (two colon cancer and one each of pancreas and breast cancer) had rupture of the intraport catheter, these forms the basis of present report. RESULTS: Mean time insitu for intraports was 164∀35 days. Median follow-up time was 290 days and total port time in situ was 40180 days. The incidence of port rupture was 1 per 10,000 port days. Three of the 4 cases were managed by successful removal of catheters. In two of these the catheter was removed under fluoroscopic control using femoral route, while in the third patient the catheter (partial rupture) was removed surgically. One of the catheters could not be removed and migrated to right ventricle on manipulations. CONCLUSION: Port catheter rupture is a rare but dreaded complication associated with subcutaneous port catheter device placement for chemotherapy. In case of such an event the patient should be managed by an experienced vascular surgeon and interventional radiologist, as in most cases the ruptured catheter can be retrieved by non operative interventional measures

Desmoid tumor in Gardner's Syndrome presented as acute abdomen

BACKGROUND: Gardner's syndrome can occasionally be complicated with intra-abdominal desmoid tumor. These tumors usually remain asymptomatic but can exhibit symptoms due to intestinal, vascular and ureteral compression and obstruction. CASE PRESENTATION: A rare case of a 41-year-old male patient with Gardner's syndrome complicated with intra-abdominal desmoid tumor, which first presented as acute abdomen, is presented. CONCLUSION: Extra-abdominal manifestations of Gardner's syndrome along with a palpable abdominal mass would raise suspicion for the presence of a desmoid tumor in the majority of cases. In life-threatening cases, surgical treatment should be considered as a palliative approach, though the extent of excision remains debatabl

Carcinoid tumour of the appendix in children: a case report

Carcinoids are the most common tumours of the appendix. These tumours show prevalence in white children. The clinical presentation of the appendiceal carcinoids is similar to that of acute appendicitis, although in many cases the tumour is diagnosed incidentally during an operation. The diagnosis should be confirmed histologically. The prognosis in patients with local disease is excellent. In small lesions isolated appendicectomy is considered as the most appropriate treatment, while in larger lesions right colectomy should be performed. We report a case of a carcinoid tumour in the tip of the appendix of a thirteen year old girl which was diagnosed intraoperatively. The patient received isolated appendicectomy due to the small size of the lesion. Ten years after the operation there is no evidence of recurrence or metastases, and the patient is considered free of disease

Integrable extensions of the Adler map via Grassmann algebras

We study certain extensions of the Adler map on Grassmann algebras Γ(n) of order n. We consider a known Grassmann-extended Adler map and under the assumption that n =1, obtain a commutative extension of the Adler map in six dimensions. We show that the map satisfies the Yang–Baxter equation, admits three invariants, and is Liouville integrable. We solve the map explicitly by regarding it as a discrete dynamical system

Cecal epiploica appendix torsion in a female child mimicking acute appendicitis: a case report

Acute appendicitis is the most common cause of the right lower quadrant acute abdominal pain in children. Some other conditions including cecal epiploica appendix torsion, can simulate acute abdomen. Epiploica appendix torsion usually occurs in the sigmoid colon and rarely in the cecum of adult males. In children, this entity is extremely rare and may represent a diagnostic and therapeutic dilemma. We report a case of an 8-year-old Greek girl, presented with signs and symptoms mimicking acute abdomen. Our patient is the younger one among the other four with cecal epiploica appendix torsion that had been reported in the literature

Torsion of an intrahydrocelic sac in a child: A case report

We report the case of a 3-yr-old boy who presented an acute right hydrocele. A rapid scrotal swelling under tension developed the first hours and the child complained for discomfort especially during palpation of the scrotum. Three days later, surgical exploration revealed an incomplete torsion of a communicated and pedunculated peritoneal sac arising from the tunica vaginalis testis

Pelvic plastron secondary to acute appendicitis in a child presented as appendiceal intussusception. A case report

We report an unusual case of an 11-year-old Greek girl with complicated acute appendicitis. The pelvic plastron that had been formatted secondary to appendix perforation was mimicking appendiceal intussusception in the preoperative ultrasound and computed tomography images. Although acute complicated appendicitis and appendiceal intussusception may represent possible causes of acute abdomen no similar cases have reported in the literature