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

Death Caused by Honey Bee Stings: Case Report

A bee sting is always potentially serious. The severity and duration of a reaction can vary from one person to another. In addition, one's own reaction to a bee sting may differ between occurrences. Most persons experience a local non-serious allergic reaction to bee venom. However, depending on the location and number of bee stings received, as well as the ever-present possibility of a severe allergic reaction to bee venom, a serious reaction can be precipitated that can be life-threatening. A 49 years old man having a history of allergic reaction to bee sting was found dead near to 9 nests. There were many dead honey bees on him. External examination of the body showed more than 50 stings all over the body. Upon medico-legal autopsy, pulmonary edema and swelling in laryngeal area were the internal findings. History of allergy, autopsy findings and findings obtained from crime scene investigation were evaluated together and the cause of death was concluded to be anaphylactic shock resulted from bee stings. [Med-Science 2014; 3(2.000): 1305-14

Post-mortem alcohol analysis in synovial fluid: an alternative method for estimation of blood alcohol level in medico-legal autopsies?

WOS: 000268224600007PubMed: 19778215To evaluate the effectiveness of synovial fluid alcohol concentration in prediction of blood alcohol concentration, synovial fluid and blood was studied of 50 autopsy cases and the alcohol levels determined by using Head Space Gas Chromatography method. To exclude the effect of decomposition on alcohol levels, corpses with postmortem intervals less than 24 hours and not showing signs of decomposition were selected. Of 50 cases, alcohol was detected in 15 cases both in blood and in synovial fluid. In 35 cases alcohol analysis was negative both in blood and synovial fluid. No false positive results were seen in terms of synovial fluid. In two of the 15 cases, the alcohol determined was methyl alcohol and in others the alcohol was ethyl alcohol. In these 15 cases, only in one case was SAC level lower than the BAC level, and in 14 cases; SAC levels were higher than those of BAC. BAC (Blood Alcohol Concentration)/SAC (Synovial Fluid Alcohol Concentration) ratios were determined, and in 13 ethanol cases the mean ratio was determined to be 0.95 (0.90 +/- 0.07). The regression analysis showed a fairly linear relationship between the BAC and SAC, with a correlation coefficient of 0.984 (y=0.86x + 10.4). The present study demonstrates that the synovial fluid is a valuable body fluid that can be used in prediction of blood alcohol concentration in forensic autopsy cases in which blood can not be properly obtained

Rabies in Turkey: Three human cases illustrating the importance of suspecting exposure

Rabies, a fatal encephalitis of viral origin, is still a major health problem in the developing world. It begins, after exposure, with centripetal spread of the virus through peripheral nerves to the central nervous system. The virus proliferates there and spreads to the tissues via peripheral nerves. The diagnosis is not difficult when a nonimmunized patient presents with hydrophobia after a bite by a known rabid animal. Failure to identify an exposure and administer postexposure prophylaxis, however, can lead to a fatal outcome. We report 3 fatal cases of rabies in which the risk of developing rabies had not been seriously considered. Two had apparent dog bites, but 1 had a minor abrasion. Because rabies is uniformly fatal, possible exposure should be seriously considered in patients with mammalian bites or scratches

Fatalities Caused by Spherical Bullets Fired from Blank Cartridge Guns in Istanbul, Turkey

Blank cartridge guns are generally regarded as being harmless and are not considered to be firearms in the legal sense in most countries. To show the danger of these guns upon simple modifications, we report 59 fatalities resulting from these simply modified blank cartridge guns in Istanbul, Turkey. The great majority of the victims were males and the age of those ranged from 11 to 61 years. In 55.9% of these cases, homicide was the origin followed by suicide (39%). The right temporal region was detected to be the preferred region in suicidal shots by blank cartridge guns with a frequency of 56.5%. In trial shots, all these guns were detected to discharge steel or lead spherical objects, generally 4 or 5 mm in diameter, successfully. Our findings strongly suggest that these guns should also be considered as handguns in the legal sense

Suicidal hanging in Istanbul, Turkey: 1979-2012 Autopsy results

WOS: 000355681900010PubMed ID: 26048496A retrospective study was carried out on 4549 which is the total number of hanging cases autopsied at Forensic Medicine Institute in Istanbul, Turkey. 4502 hanging cases of suicidal origin were detected and evaluated in terms of demographic features, the type of hanging material used for ligature, internal findings in neck organs, toxicological findings and microscopic findings. Of these suicides, 3295 (73.2%) were males and 1207 (26.8%) were females. The average age of the victims was 37.8 (SD 1.6). Crude suicidal hanging rate is approximately two-fold increase in women, while it is about five-to six-fold increase in men during 33 years. 1424 of the victims committed suicide by hanging themselves at home, and 441 of them in prison and indoor areas. The alcohol in the blood of all autopsy victims was tested and results were positive for 687 people. A drug active agent was detected in 108 (2.4%) victims: 70 (1.5%) of them were antidepressants, 20 (0.5%) of them were analgesic/anti-inflammatory/anti-histaminic and 18 (0.4%) of them were antipsychotic. In the examination of the psychoactive substances in blood and urine, any of such substances was not detected in 4146 of the victims. However, victims' blood and urine contained a sedative-hypnotic-anxiolytic with 74 (1.6%), a cannabinoid with 16 (0.4%) and an opioid with 12 (0.3%). Psychoactive substance examination was not carried out for 243 victims. Of these cases, 4060 (90.2%), ecchymosis in soft tissues and 2800 (62.1%) fracture in neck organs was found. (C) 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved

INFLUENCE OF SEASONALITY ON SUICIDAL HANGING IN ISTANBUL, 1979-2012: ASSOCIATIONS WITH GENDER, AGE, LOCATION AND INSTRUMENTS OF SUICIDE

WOS: 000373721600008Objective: Seasonal variations in deaths by suicide have been reported in many countries. However, in Turkey there is no substantial research on this topic. The aim of this study is to examine the influence of the seasons on suicides by hanging in Istanbul during the period 1979 to 2012 and to assess the associations of seasonal suicide by hanging with gender, age, location and instruments. Material and Method: This paper describes the demographic characteristics of suicidal hanging victims for the past 33 years. A total number of 82871 autopsies were performed in the Council of Forensic Medicine in Istanbul Turkey Morgue Department between 1979 and 2012; 4502 (5.43%) of these deaths occurred as a result of hanging. 4502 suicides by hanging were selected using the study criteria. Results: In this study, most victims were male and the mean age was 37.8 years. Most suicides took place at home but also occurred in prisons, open and built-up areas and workplaces. 455 victims hanged themselves with rope. Inseasonal spring and summer, hangings peaked among total population. The seasonal distribution of the hangings showed a significant difference in both sexes as evidenced by the goodness of the fit test. There were no statistically significant seasonal variations of suicidal hanging for age, location and instrument. Conclusion: The results show that the highest rates were observed in the warmest months. This study is an important source of epidemiological data for suicide by hanging

Contribution of biventricular cardiac blood and pleural effusion strontium concentrations to the diagnosis of drowning

The present study evaluated cardiac blood and pleural effusion strontium (Sr) concentrations in dead bodies found in fresh water or seawater. Eighty cases that had been found in water (59 seawater, 13 fresh water, 8 unknown) were compared with 20 control cases, which had not been found in water and died due to unrelated cause of death, in terms of right ventricle cardiac blood strontium concentration (RVSr), left ventricle cardiac blood strontium concentration (LVSr) and their differences [LVSr-RVSr], as well as pleural effusion strontium concentration (PlSr). The ages of cases were between 2 and 82 years. Seventy one cases were retrieved from water within the first 24 hours. Cause of death was reported as drowning (regardless of Sr concentration) in 68 cases. Whilst 8 cases referred to the supreme board for further investigation, cause of death could not be detected in 3 cases because of advanced decomposition. Of the bodies found in seawater, LVSr and PlSr concentrations were significantly higher than the bodies found in fresh water. LVSr, RVSr and [LVSr-RVSr] concentrations were significantly higher than those of the control group. No difference was determined between the bodies found in fresh water and the control group in terms of [LVSr-RVSr] concentration