Protein Degradation of RNA Polymerase II-Association Factor 1(PAF1) Is Controlled by CNOT4 and 26S Proteasome

The PAF complex (PAFc) participates in various steps of the transcriptional process, from initiation to termination, by interacting with and recruiting various proteins to the proper locus for each step. PAFc is an evolutionarily conserved, multi-protein complex comprising PAF1, CDC73, CTR9, LEO1, yRTF1 and, in humans, hSKI8. These components of PAFc work together, and their protein levels are closely interrelated. In the present study, we investigated the mechanism of PAF1 protein degradation. We found that PAF1 protein levels are negatively regulated by the expression of CNOT4, an ortholog of yNOT4 and a member of the CCR4-NOT complex. CNOT4 specifically controls PAF1 but not other components of PAFc at the protein level by regulating the polyubiquitination of PAF1 and its subsequent degradation by the 26S proteasome. The degradation of PAF1 was found to require nuclear localization, as no PAF1 degradation by CNOT4 and the 26S proteasome was observed with NLS (nucleus localization signal)-deficient PAF1 mutants. However, chromatin binding by PAF1 was not necessary for 26S proteasome- or CNOT4-mediated degradation. Our results suggest that CNOT4 controls the degradation of chromatin-unbound PAF1 via the 26S proteasome.open1184Ysciescopu

Temperature change in pig rib bone during implant site preparation by low-speed drilling

OBJECTIVES: The purpose of this study was to evaluate the temperature change during low-speed drilling using infrared thermography. MATERIAL AND METHODS: Pig ribs were used to provide cortical bone of a similar quality to human mandible. Heat production by three implant drill systems (two conventional drilling systems and one low-speed drilling system) was evaluated by measuring the bone temperature using infrared thermography. Each system had two different bur sizes. The drill systems used were twist drill (2.0 mm/2.5 mm), which establishes the direction of the implant, and finally a 3.0 mm-pilot drill. Thermal images were recorded using the IRI1001 system (Infrared Integrated Systems Ltd.). Baseline temperature was 31±1ºC. Measurements were repeated 10 times, and a static load of 10 kg was applied while drilling. Data were analyzed using descriptive statistics. Statistical analysis was conducted with two-way ANOVA. RESULTS AND CONCLUSIONS: Mean values (n=10 drill sequences) for maximum recorded temperature (Max TºC), change in temperature (ΔTºC) from baseline were as follows. The changes in temperature (ΔTºC) were 1.57ºC and 2.46ºC for the lowest and the highest values, respectively. Drilling at 50 rpm without irrigation did not produce overheating. There was no significant difference in heat production between the 3 implant drill systems (p>;0.05). No implant drill system produced heat exceeding 47ºC, which is the critical temperature for bone necrosis during low-speed drilling. Low-speed drilling without irrigation could be used during implant site preparation

Short-Term Effects of Combined Serial Casting and Botulinum Toxin Injection for Spastic Equinus in Ambulatory Children with Cerebral Palsy

PURPOSE: The purpose of this paper is to test the hypothesis that combination therapy of serial cast and botulinum toxin type A (BTX-A) injection can further enhance the effects of a BTX-A injection in ambulant children with cerebral palsy (CP) who have an equinus foot. MATERIALS AND METHODS: Children in group A (30 legs of 21 children) received a serial casting application after an injection of BTX-A, and children in group B (25 legs of 17 children) received only a BTX-A injection. Assessments were performed before the intervention and 1 month after the intervention. RESULTS: After the intervention, there were significant improvements in tone, dynamic spasticity, and passive range of motion (ROM) in both groups. However, the changes were greater in group A than in group B. Dimension D (standing) in Gross Motor Function Measure (GMFM)-66 was significantly improved in group A but not in group B. On the other hand, there were no significant changes in dimension E (walking, running, jumping) in GMFM-66 in either group. CONCLUSION: The results of our study suggest that a serial casting application after BTX-A injection can enhance the benefits of BTX-A injection in children with cerebral palsy.ope

A Comparative Study on the Efficacy of Covered Metal Stent and Plastic Stent in Unresectable Malignant Biliary Obstruction

Background/AimsThe placement of self expandable metal stent (SEMS) is one of the palliative therapeutic options for patients with unresectable malignant biliary obstruction. The aim of this study was to compare the effectiveness of a covered SEMS versus the conventional plastic stent.MethodsWe retrospectively evaluated 44 patients with unresectable malignant biliary obstruction who were treated with a covered SEMS (21 patients) or a plastic stent (10 Fr, 23 patients). We analyzed the technical success rate, functional success rate, early complications, late complications, stent patency and survival rate.ResultsThere was one case in the covered SEMS group that had failed technically, but was corrected successfully using lasso. Functional success rates were 90.5% in the covered SEMS group and 91.3% in the plastic stent group. There was no difference in early complications between the two groups. Median patency of the stent was significantly prolonged in patients who had a covered SEMS (233.6 days) compared with those who had a plastic stent (94.6 days) (p=0.006). During the follow-up period, stent occlusion occurred in 11 patients of the covered SEMS group. Mean survival showed no significant difference between the two groups (covered SEMS group, 236.9 days; plastic stent group, 222.3 days; p=0.182).ConclusionsThe patency of the covered SEMS was longer than that of the plastic stent and the lasso of the covered SEMS was available for repositioning of the stent

Effects of an internal medicine floor interdisciplinary team on hospital and clinical outcomes of seniors with acute medical illness

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100310/1/ggi12035.pd

Disrupted-in-schizophrenia 1 (DISC1) Regulates Dysbindin Function by Enhancing Its Stability

Dysbindin and DISC1 are schizophrenia susceptibility factors playing roles in neuronal development. Here we show that the physical interaction between dysbindin and DISCI is critical for the stability of dysbindin and for the process of neurite outgrowth. We found that DISCI forms a complex with dysbindin and increases its stability in association with a reduction in ubiquitylation. Furthermore, knockdown of DISCI or expression of a deletion mutant, DISCI lacking amino acid residues 403-504 of DISC1 (DISC1(Delta 403-504)), effectively decreased levels of endogenous dysbindin. Finally, the neurite outgrowth defect induced by knockdown of DISCI was partially reversed by coexpression of dysbindin. Taken together, these results indicate that dysbindin and DISC1 form a physiologically functional complex that is essential for normal neurite outgrowth.X111211Ysciescopu

Effects of mealworm (Tenebrio molitor) larvae hydrolysate on nutrient ileal digestibility in growing pigs compared to those of defatted mealworm larvae meal, fermented poultry by-product, and hydrolyzed fish soluble

Objective: To investigate effect of mealworm (Tenebrio molitor) larvae hydrolysate on nutrient ileal digestibility compared to those of dried mealworm larvae meal, fermented poultry by-product, and hydrolyzed fish soluble in growing pigs. Methods: A total of 12 crossbred ([LandracexYorkshire]xDuroc) growing pigs with average body weight of 28.70 +/- 0.32 kg were surgically equipped with simple T-cannulas. A total of 12 pigs were assigned to individual metabolic crates and allotted to one of four treatments with 3 replicates in a fully randomized design. Results: Apparent ileal digestibility (AID) of dry matter (DM) was the highest in pigs fed HML diet. AIDs of crude protein (CP) were higher in pigs fed HML and DMLM diets than those in pigs fed the other two diets. AID of total amino acid was higher (p = 0.06) in pigs fed HML diet. AIDs of lysine (Lys), methionine (Met), and threonine (Thr) were similar in pigs fed DMLM and HML diets, but were higher (p = 0.05, p<0.05, and p = 0.05, respectively) than those in pigs fed FPBM or HFS diet. Pigs fed HML diet had higher standardized ileal digestibilities (SIDs) of DM and CP (p<0.05 and p<0.05, respectively) compared to pigs fed the other FPBM and HFS diets. SIDs of total amino acid were not different (p = 0.06) between treatments. For SIDs of Lys, Met, and Thr, pigs fed HML and DMLM diets showed higher SIDs (p = 0.05, p<0.05, and p<0.05, respectively) than pigs fed FPBM and HFS diets. SIDs of non-essential amino acids (aspartic acid, glycine, and alanine) were higher (p<0.05, p< 0.05, and p<0.05, respectively) in pigs fed HML, FPBM, and DMLM diets than those in pigs fed the HFS diet. AID and SID of glutamic acid were higher in pigs fed HML and FPBM diets. Conclusion: In conclusion, dietary supplementation of mealworm larvae hydrolysate had higher digestibility in DM, CP, Lys, Met, and Thr compared to dietary supplementation with fermented poultry by-product and hydrolyzed fish soluble.Y