A new simulation-based model for calculating post-mortem intervals using developmental data for Lucilia sericata (Dipt.: Calliphoridae)

Homicide investigations often depend on the determination of a minimum post-mortem interval (PMI$_{min}$) by forensic entomologists. The age of the most developed insect larvae (mostly blow fly larvae) gives reasonably reliable information about the minimum time a person has been dead. Methods such as isomegalen diagrams or ADH calculations can have problems in their reliability, so we established in this study a new growth model to calculate the larval age of \textit{Lucilia sericata} (Meigen 1826). This is based on the actual non-linear development of the blow fly and is designed to include uncertainties, e.g. for temperature values from the crime scene. We used published data for the development of \textit{L. sericata} to estimate non-linear functions describing the temperature dependent behavior of each developmental state. For the new model it is most important to determine the progress within one developmental state as correctly as possible since this affects the accuracy of the PMI estimation by up to 75%. We found that PMI calculations based on one mean temperature value differ by up to 65% from PMIs based on an 12-hourly time temperature profile. Differences of 2\degree C in the estimation of the crime scene temperature result in a deviation in PMI calculation of 15 - 30%.Comment: 14 pages, 5 figures, 1 tabl

Estimating the age of Calliphora vicina eggs (Diptera: Calliphoridae): determination of embryonic morphological landmarks and preservation of egg samples

ORCID No. 0000-0002-8917-9646© The Author(s) 2016. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The attached file is the published version of the article

Mouse Model of Mutated in Colorectal Cancer Gene Deletion Reveals Novel Pathways in Inflammation and Cancer

© 2019 The Authors Background & Aims: The early events by which inflammation promotes cancer are still not fully defined. The MCC gene is silenced by promoter methylation in colitis-associated and sporadic colon tumors, but its functional significance in precancerous lesions or polyps is not known. Here, we aimed to determine the impact of Mcc deletion on the cellular pathways and carcinogenesis associated with inflammation in the mouse proximal colon. Methods: We generated knockout mice with deletion of Mcc in the colonic/intestinal epithelial cells (MccΔIEC) or in the whole body (MccΔ/Δ). Drug-induced lesions were analyzed by transcriptome profiling (at 10 weeks) and histopathology (at 20 weeks). Cell-cycle phases and DNA damage proteins were analyzed by flow cytometry and Western blot of hydrogen peroxide–treated mouse embryo fibroblasts. Results: Transcriptome profiling of the lesions showed a strong response to colon barrier destruction, such as up-regulation of key inflammation and cancer-associated genes as well as 28 interferon γ–induced guanosine triphosphatase genes, including the homologs of Crohn's disease susceptibility gene IRGM. These features were shared by both Mcc-expressing and Mcc-deficient mice and many of the altered gene expression pathways were similar to the mesenchymal colorectal cancer subtype known as consensus molecular subtype 4 (CMS4). However, Mcc deletion was required for increased carcinogenesis in the lesions, with adenocarcinoma in 59% of MccΔIEC compared with 19% of Mcc-expressing mice (P =.002). This was not accompanied by hyperactivation of β-catenin, but Mcc deletion caused down-regulation of DNA repair genes and a disruption of DNA damage signaling. Conclusions: Loss of Mcc may promote cancer through a failure to repair inflammation-induced DNA damage. We provide a comprehensive transcriptome data set of early colorectal lesions and evidence for the in vivo significance of MCC silencing in colorectal cancer

Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum

Abstract Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095–246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria.Abstract Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095–246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria

Fructose stimulated de novo lipogenesis is promoted by inflammation

Benign hepatosteatosis, affected by lipid uptake, de novo lipogenesis and fatty acid (FA) oxidation, progresses to non-alcoholic steatohepatitis (NASH) on stress and inflammation. A key macronutrient proposed to increase hepatosteatosis and NASH risk is fructose. Excessive intake of fructose causes intestinal-barrier deterioration and endotoxaemia. However, how fructose triggers these alterations and their roles in hepatosteatosis and NASH pathogenesis remain unknown. Here we show, using mice, that microbiota-derived Toll-like receptor (TLR) agonists promote hepatosteatosis without affecting fructose-1-phosphate (F1P) and cytosolic acetyl-CoA. Activation of mucosal-regenerative gp130 signalling, administration of the YAP-induced matricellular protein CCN1 or expression of the antimicrobial peptide Reg3b (beta) peptide counteract fructose-induced barrier deterioration, which depends on endoplasmic-reticulum stress and subsequent endotoxaemia. Endotoxin engages TLR4 to trigger TNF production by liver macrophages, thereby inducing lipogenic enzymes that convert F1P and acetyl-CoA to FA in both mouse and human hepatocytes

The importance of carcass volatiles as attractants for the hide beetle Dermestes maculatus (De Geer)

A decaying cadaver emits volatile organic compounds that are used by necrophilous and necrophagous insects in order to find their brood substrate. Although volatile organic compounds (VOCs) that are released by carcasses have been identified, little is known about the specific compounds that are used by these insects while searching for a brood substrate. Therefore, we have investigated the chemical ecology involved in the attraction of the necrophagous hide beetle Dermestes maculatus, which feeds as an adult and larva upon decomposing carcasses. Our aims have been to identify the responsible compounds in the odours of the carcass that are important for the attraction of the beetles. Furthermore, we have studied sex-and age-related differences in beetle attraction and tested whether the hide beetle can distinguish between various stages of decomposition by means of the emitted odours. Headspace collection of volatiles released from piglet carcasses (bloated stage, post-bloating stage, advanced decay and dry remains), coupled gas chromatography-mass spectrometry (GC-MS), gas chromatography with electroantennographic detection (GC-EAD) and bioassays were conducted to identify the volatiles responsible for the attraction of the beetles. Freshly emerged male beetles were attracted by the odour of piglets in the post-bloating stage (9 days after death; T(mean) = 27 degrees C) and the EAD-active compound benzyl butyrate. Statistical analysis revealed a higher relative proportion of benzyl butyrate in the odour bouquet of the post-bloating stage in comparison with the other stages. We therefore conclude that this compound plays an important role in the attraction of hide beetles to carcass odour. This underlines the potential use of D. maculatus for the estimation of the post mortem interval. The decomposition stage at which the female beetles are attracted to the odour of a cadaver remains unknown, as does the nature of this attraction. Pheromones (sexual or aggregation pheromones) might play an essential role correlated with their attraction to carrion and consequently with their attraction to the substrate for mating and ovipositioning. (C) 2011 Elsevier Ireland Ltd. All rights reserved