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.
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.
Introduction:The radiological investigations that will be performed after the hemodynamic stabilization of trauma cases presenting to the emergency room are of vital importance when deciding on the treatment to be administered to the patient. Posteroanterior chest radiography was not applied in the proper position, to include all the soft tissues of the chest and shoulder, after an injury caused by a sharp object in our case. Therefore, a radiopaque foreign object retained within the body was not detected. Case Report: Our case was brought to the emergency room because of a stabbing injury, but no pathological findings were determined at the initial examination or based on the X-graphs taken. Approximately 1 year after discharge, the patient presented to another hospital because of a persistent swelling and pain in the left armpit. A metallic image consistent with a knife point 7-8 cm in length was determined to be under the left armpit. Conclusion: The radiographs not taken in the proper position may lead to undesirable consequences. Therefore, we recommend that great attention should be paid while taking the radiographs, ensuring the proper position and careful evaluation.
esep tayininde STR analizi uzun bir süredir kullanılmakta ve bu analizi yapan birçok firmaya ait onlarca ticari kit piyasada bulunmaktadır. A An na ah ht ta ar r K Ke el li im me el le er r: : Babalık; adli genetik A AB BS ST TR RA AC CT T In our paternity case, two alleged fathers who are father and the son were analyzed with using ESSplex and also IDplex STR (Short Tandem Repeat) kits. Analysis performed on blood examples from mother, two alleged fathers (father and son) and boy. Analysis performed with ESSplex kit based on 15 STR loci; however, no exclusions could be achieved. Then IDplex kit analysis was performed and the paternity of father was rejected only on 2 STR loci (D13S317-TPOX). According to results of analysis with both STR kits, sons paternity index was calculated as 20. 438.967.205,199 and the probability of exclusion is calculated as 99,99999999% of compatible allele inheritance between the child was detected. While no tests were performed on mother, the analysis of 20 STR loci; however, no exclusions could be achieved. So paternity index was calculated as 5.723.409,271 the probability of exclusion is calculated as 99,9999%. To avoid false acceptance in paternity cases, where individuals are close relatives to each other, it may be necessary to evaluate mother, father and son's DNA profile and more than one STR kits must be used.
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