MITF-MIR211 axis is a novel autophagy amplifier system during cellular stress

Macroautophagy (autophagy) is an evolutionarily conserved recycling and stress response mechanism. Active at basal levels in eukaryotes, autophagy is upregulated under stress providing cells with building blocks such as amino acids. A lysosome-integrated sensor system composed of RRAG GTPases and MTOR complex 1 (MTORC1) regulates lysosome biogenesis and autophagy in response to amino acid availability. Stress-mediated inhibition of MTORC1 results in the dephosphorylation and nuclear translocation of the TFE/MITF family of transcriptional factors, and triggers an autophagy- and lysosomal-related gene transcription program. The role of family members TFEB and TFE3 have been studied in detail, but the importance of MITF proteins in autophagy regulation is not clear so far. Here we introduce for the first time a specific role for MITF in autophagy control that involves upregulation of MIR211. We show that, under stress conditions including starvation and MTOR inhibition, a MITF-MIR211 axis constitutes a novel feed-forward loop that controls autophagic activity in cells. Direct targeting of the MTORC2 component RICTOR by MIR211 led to the inhibition of the MTORC1 pathway, further stimulating MITF translocation to the nucleus and completing an autophagy amplification loop. In line with a ubiquitous function, MITF and MIR211 were co-expressed in all tested cell lines and human tissues, and the effects on autophagy were observed in a cell-type independent manner. Thus, our study provides direct evidence that MITF has rate-limiting and specific functions in autophagy regulation. Collectively, the MITF-MIR211 axis constitutes a novel and universal autophagy amplification system that sustains autophagic activity under stress conditions.No sponso

ANALYSIS OF A CENTRAL MAXILLARY INCISOR BY USING A 3-DIMENSIONAL FINITE-ELEMENT METHOD

An attempt is made for determining the stress distribution in a maxillary central incisor by using a three-dimensional finite element model. The tooth is assumed isotropic, homogeneous, elastic and unsymmetrical. A load of 450 N, 26-degrees to the longitudinal axis is applied on the incisal margin of the tooth. The distribution of compressive, tensile and shear stresses were plotted for the whole tooth structure. It is found that cracks or fractures occur under thc given load

Anomalous origin of circumflex coronary artery from the right pulmonary artery associated with subaortic stenosis and coarctation of the aorta

Anomalous origin of the circumflex coronary artery is extremely rare and may cause acute cardiac decompensation associated with correction of coexisting congenital malformations. We describe a 10-year-old female patient who underwent surgical repair of the aortic coarctation at 4 years of age. Six years later, she presented with chest pain during exercise. Cardiac catheterization demonstrated 25 mmHg subaortic systolic gradient and retrograde filling of the circumflex coronary artery from the left anterior descending and right coronary artery, with drainage into the right pulmonary artery. Reimplantation of the anomalous circumflex coronary artery to the aorta and resection of subaortic fibrous membrane was performed. Her postoperative course was uneventful, with complete relief of symptoms. (C) 1997 Elsevier Science B.V

How does neonatal thymectomy affect the immune system?

Background - The aim of this study was to determine the effects of neonatal thymectomy on the immune system in later life

A New Proximal Anastomosis Technique In Two Patients With Severely Calcified Aorta

A severely calcified aorta carries a high risk of atheroemboli and bleeding for cardiac surgery with an incidence range of 14% to 29%. Various techniques were described avoiding cannulation and clamping of the aorta. Nowadays, the no-touch beating heart technique seems to be the best alternative in patients with calcific aorta. Herein, we present a closed proximal anastomosis technique in this high-risk patient group. (Ann Thorac Surg 2011;92:1914-6) (C) 2011 by The Society of Thoracic Surgeon

A rare case of mixed type total anomalous pulmonary venous connection and its surgical treatment

In the mixed types of total anomalous pulmonary venous connection, pulmonary veins frequently show an opening at the supracardiac and cardiac level. Rarely, some other combinations of mixed type cases have been reported in the literature. In the present case the right and left pulmonary veins formed two distinct venous chambers and showed supracardiac and intracardiac openings. Anastomosis of each of these common venous chambers was performed to the left atrium, separate from each other, by extracardiac approach. The patient had no hemodynamic problems in the postoperative period and showed no pulmonary venous obstruction in a control angiography performed after 9 months. He has not needed medication and has shown no limitation of activity during a follow-up of 6 years

Current Status of the Use of Single-Nucleotide Polymorphisms in Forensic Practices

Forensic geneticists often use short tandem repeats (STRs) to solve cases. However, STRs can be insufficient when DNA samples are degraded due to environmental exposure and mass disasters, alleged and real relatives are genetically related in paternity or kinship analyses, or a suspect is lacking. In such cases, single-nucleotide polymorphisms (SNPs) can provide valuable information and thus should be seriously considered as a tool to help resolve challenging cases. In this review, the current status of SNP analyses in forensic applications and the comparative advantages and disadvantages of SNPs with other biomarkers are discussed

Current Status of the Use of Single-Nucleotide Polymorphisms in Forensic Practices

Forensic geneticists often use short tandem repeats (STRs) to solve cases. However, STRs can be insufficient when DNA samples are degraded due to environmental exposure and mass disasters, alleged and real relatives are genetically related in paternity or kinship analyses, or a suspect is lacking. In such cases, single-nucleotide polymorphisms (SNPs) can provide valuable information and thus should be seriously considered as a tool to help resolve challenging cases. In this review, the current status of SNP analyses in forensic applications and the comparative advantages and disadvantages of SNPs with other biomarkers are discussed

Early and moderate long-term results of a new surgical technique for repair of aortic coarctation

Objective. From June 1987 to September 1995, 53 patients underwent a new technique of coarctation repair. This technique consists of complete mobilization of the left subclavian artery so that it can be pulled down as far as possible