Post-mortem CT: A Useful Tool to Confirm a Case of Suspected Sudden Cardiac Death.

Sudden cardiac death (SCD) is defined as the unexpected death of an individual, not due to any extracardiac cause, occurring within one hour of symptom onset or within 24 hours of last being seen in good health if the death is unwitnessed. Forensic pathologists routinely encounter several SCD cases in their practice. The presentation of such cases can be of two types; firstly, with typical signs and symptoms suggestive of cardiac pathology, and secondly, devoid of any presentation history. This history helps forensic pathologists look for relevant findings during the autopsy examination. The authors intend to explore the feasibility of using advanced radiological techniques like post-mortem CT (PMCT) in determining the cause of death through a minimally invasive approach. In the present case, a 65-year-old male was found unresponsive at his residence on the morning of his death. He had a history of dull chest pain for the past two days, which had resolved after he self-prescribed a few medications. The presenting complaint of chest pain had started the intervening night prior to his death. The deceased was a known case of hypertension and was not compliant with treatment, as stated by the relatives. He was declared as brought dead by the treating emergency medicine physician at the Fortis Flt. Lt. Rajan Dhall Hospital and the body was sent by the authorities to the mortuary of the Department of Forensic Medicine, AIIMS, New Delhi for autopsy examination since an autopsy should be conducted by a government hospital or institute by law. PMCT depicted an alternate hyperdense and hypodense region circumferentially surrounding the heart, indicating hemopericardium. It was followed by a traditional autopsy and histopathology examination, which confirmed the presence of hemopericardium and left ventricular rupture associated with acute coronary insufficiency. Such cases with an indicative history, circumstantial evidence, and PMCT findings can be considered for minimal invasive autopsy. If the external findings indicate the application of physical force, then an explorative dissection could be done. Therefore, we conclude that PMCT can be used as a reliable tool for determining the cause of death in SCDs on a case-to-case basis.

Dithiothreitol causes toxicity in C. elegans by modulating the methionine-homocysteine cycle.

The redox reagent dithiothreitol (DTT) causes stress in the endoplasmic reticulum (ER) by disrupting its oxidative protein folding environment, which results in the accumulation and misfolding of the newly synthesized proteins. DTT may potentially impact cellular physiology by ER-independent mechanisms; however, such mechanisms remain poorly characterized. Using the nematode model Caenorhabditis elegans, here we show that DTT toxicity is modulated by the bacterial diet. Specifically, the dietary component vitamin B12 alleviates DTT toxicity in a methionine synthase-dependent manner. Using a forward genetic screen, we discover that loss-of-function of R08E5.3, an S-adenosylmethionine (SAM)-dependent methyltransferase, confers DTT resistance. DTT upregulates R08E5.3 expression and modulates the activity of the methionine-homocysteine cycle. Employing genetic and biochemical studies, we establish that DTT toxicity is a result of the depletion of SAM. Finally, we show that a functional IRE-1/XBP-1 unfolded protein response pathway is required to counteract toxicity at high, but not low, DTT concentrations.

Animal and plant cells synthesize a significant fraction of their proteins on a structure known as the endoplasmic reticulum. Researchers often use the molecule dithiothreitol to specifically target this compartment and learn more about its role. The toxin works by disturbing the complex chemical environment present in the reticulum, which is required for the proteins to assemble properly. However, it is important to clarify whether dithiothreitol could also affect other parts of the cell, as this could give rise to misleading results. To explore this possibility, Gokul G and Jogender Singh studied the effects of dithiothreitol on the millimetre-long roundworm Caenorhabditis elegans. Their experiments revealed that vitamin B12 could protect against dithiothreitol toxicity via a complex cascade of molecular events which reduced the levels of an important regulatory molecule known as S-adenosylmethionine. Crucially, the chemical reactions that dithiothreitol targeted took place outside the reticulum, suggesting that the toxin impairs processes in the wider cell. These results suggest that dithiothreitol should be reconsidered for use in endoplasmic reticulum studies. However, they also imply that this toxin could be beneficial in small doses, as a reduced concentration of S-adenosylmethionine increases lifespan and health in a variety of organisms.

Extracellular Proteostasis: Laying Siege to Pathogens.

How protein homeostasis is maintained in the extracellular space remains poorly studied. A recent study employed a Caenorhabditis elegans model to carry out a systematic analysis of the extracellular proteostasis network and uncovered its role in combating a pathogenic attack.