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Frataxin (FXN) deficiency is responsible for Friedreich's ataxia (FRDA) in which, besides the characteristic features of spinocerebellar ataxia, two thirds of patients develop hypertrophic cardiomyopathy that often progresses to heart failure and premature death. Different mechanisms might underlie FRDA pathogenesis. Among them, the role of miRNAs deserves investigations. We carried out an miRNA PCR-array analysis of plasma samples of early-, intermediate- and late-onset FRDA groups, defining a set of 30 differentially expressed miRNAs. Hsa-miR223-3p is the only miRNA shared between the three patient groups and appears upregulated in all of them. The up-regulation of hsa-miR223-3p was further validated in all enrolled patients (n = 37, Fc = +2.3; P < 0.0001). Using a receiver operating characteristic curve analysis, we quantified the predictive value of circulating hsa-miR223-3p for FRDA, obtaining an area under the ROC curve value of 0.835 (P < 0.0001) for all patients. Interestingly, we found a significant positive correlation between hsa-miR223-3p expression and cardiac parameters in typical FRDA patients (onset < 25 years). Moreover, a significant negative correlation between hsa-miR223-3p expression and HAX-1 (HCLS1-associated protein X-1) at mRNA and protein level was observed in all FRDA patients. In silico analyses suggested HAX-1 as a target gene of hsa-miR223-3p. Accordingly, we report that HAX-1 is negatively regulated by hsa-miR223-3p in cardiomyocytes (AC16) and neurons (SH-SY5Y), which are critically affected cell types in FRDA. This study describes for the first time the association between hsa-miR223-3p and HAX-1 expression in FRDA, thus supporting a potential role of this microRNA as non-invasive epigenetic biomarker for FRDA.

Frataxin deficiency, responsible for Friedreich's ataxia (FRDA), is crucial for cell survival since it critically affects viability of neurons, pancreatic beta cells and cardiomyocytes. In FRDA, the heart is frequently affected with typical manifestation of hypertrophic cardiomyopathy, which can progress to heart failure and cause premature death. A microarray analysis performed on FRDA patient's lymphoblastoid cells stably reconstituted with frataxin, indicated HS-1-associated protein X-1 (HAX-1) as the most significantly upregulated transcript (FC = +2, P < 0.0006). quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot analysis performed on (I) HEK293 stably transfected with empty vector compared to wild-type frataxin and (II) lymphoblasts from FRDA patients show that low frataxin mRNA and protein expression correspond to reduced levels of HAX-1. Frataxin overexpression and silencing were also performed in the AC16 human cardiomyocyte cell line. HAX-1 protein levels are indeed regulated through frataxin modulation. Moreover, correlation between frataxin and HAX-1 was further evaluated in peripheral blood mononuclear cells (PBMCs) from FRDA patients and from non-related healthy controls. A regression model for frataxin which included HAX-1, group membership and group∗ HAX-1 interaction revealed that frataxin and HAX-1 are associated both at mRNA and protein levels. Additionally, a linked expression of FXN, HAX-1 and antioxidant defence proteins MnSOD and Nrf2 was observed both in PBMCs and AC16 cardiomyocytes. Our results suggest that HAX-1 could be considered as a potential biomarker of cardiac disease in FRDA and the evaluation of its expression might provide insights into its pathogenesis as well as improving risk stratification strategies.

The analyses of the insect species found on decomposing remains may provide useful information for the estimation of the minimum time elapsed since death and other parameters, such as causes and circumstances of death. The majority of research has focused on the early colonizing species, typically blowflies, while research concerning late colonizing insects is currently sparse. Dermestid beetles of the genus Dermestes L. (Coleoptera: Dermestidae) are one of the predominant insect species associated with decomposing remains during dry decay and skeletal stages of decomposition. In some dry environments, Dermestes species are likely to be the only necrophagous insects feeding on the decomposing remains. Furthermore, Dermestes species (immature and adults), their remains (cast skins and fecal material), and their artifacts (pupal chambers) are frequently found associated with ancient remains (e.g., mummies, fossils). Dermestes species have a worldwide distribution and are considered important in decomposition processes, forensic investigations, and economically as a known pest of stored products. Despite their recognized forensic importance, there is limited data documenting the ecology, biology, and the growth rates of the forensically relevant species. The aim of this review is to provide a comprehensive synopsis on the available literature concerning Dermestes species associated with forensic cases. In particular, aspects of colonization behavior, growth rates for forensic taxa and potential best practice guidelines for forensic casework encompassing late colonizing Dermestes species are discussed.

In addition to estimating the postmortem interval (PMI) insects that feed on carcasses may also represent a reliable specimen for toxicological analyses (entomotoxicology). This is especially so in the absence of tissues and fluids normally taken for such purposes. There are many studies involving the extraction of drugs and chemicals from blowfly larvae (Diptera: Calliphoridae) associated with a corpse, but only a few papers have focused on the analyses of gunshot residues (GSR, generally lead (Pb), barium (Ba) and antimony (Sb)) detection in blowfly larvae. Mostly the detection of GSR elements in blowfly larvae has been conducted using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The focus of these studies was on the detection of Pb, Ba and Sb in larvae as pure chemical elements. The aim of this study was to determine if there are any chemical and/or morphological changes of Pb, Ba and Sb following the uptake of GSR by larvae of Calliphora vomitoria (L.) (Diptera: Calliphoridae). Five pieces of swine meat (500g and 16x16x7cm cm each) were shot using a Beretta 98f gun. One piece was not shot (control). The ammunitions used were 9x21mm Winchester with Pb contained in the primer and 9x21mm Fiocchi Leadless no Pb in the primer, and two shooting distances of 2 and 40 cm. 200 C. vomitoria eggs were placed on each piece of meat as close as possible to the shot hole and allowed to develop until the third instar. 500mg of larvae were analysed by ICP-MS while a total amount of 50 stubs each one prepared with the stomach contain of a single larva of each experimental groups were analysed using two different SEMs (Leica StereoScan 420 and Zeiss EVO 50XVP with variable pressure) both coupled with Energy Dispersive X-ray microanalysis (SEM-EDX). The gloves and the hands of the gunman were also analysed. This study demonstrated the presence of actual GSR particles which was obtained by using variable pressure SEM. The EDX analyses showed that GRS particles were in the

On October 2013, in a small city in the North of Italy an old woman (R.) died after a long illness. The woman was known to have a long friendship with her daughter-in-law’s mother (G.), insomuch as the women lived together. Furthermore, G. was known to be a sage, able to predict the future and to bless people. Even though people did not see her for many years, they continued to bring offerings to obtain her blessings. When R. died, G. unexpectedly failed to attend the funeral of her best friend. Worried about the well-being of G. her relatives together with law enforcement forcibly entered into her apartment. The corpse of G. was found in a room of the apartment, seated on an armchair, completely mummified and covered with a linen sheet. Further investigations confirmed that balms had been used to preserve the corpse and to protect it from the colonization of insects. Despite this, on the mummified corpse Dermestes frischii Kugelann (Coleoptera: Dermestidae) larva exuviae, frass and artifacts were found. Dermestid beetles are unpredictable colonisers as they have been reported arriving at a corpse between 24h to 3-6 months after death, depending on the environmental situation. Dermestid frass has been found between 1 month and 10 years after death. In the present case the date the death of G. was estimated to be between 16 and 18 years before discovery.