Alkylphospholipids (APLs) represent a new class of drugs which do not interact directly with DNA but act on the cell membrane where they accumulate and interfere with lipid metabolism and signalling pathways. This review summarizes the mode of action at the molecular level of these compounds. In this sense, a diversity of mechanisms has been suggested to explain the actions of clinically-relevant APLs, in particular, in cancer treatment. One consistently reported finding is that APLs reduce the biosynthesis of phosphatidylcholine (PC) by inhibiting the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT). APLs also alter intracellular cholesterol traffic and metabolism in human tumour-cell lines, leading to an accumulation of cholesterol inside the cell. An increase in cholesterol biosynthesis associated with a decrease in the synthesis of choline-containing phospholipids and cholesterol esterification leads to a change in the free-cholesterol:PC ratio in cells exposed to APLs. Akt phosphorylation status after APL exposure shows that this critical regulator for cell survival is modulated by changes in cholesterol levels induced in the plasma membrane by these lipid analogues. Furthermore, APLs produce cell ultrastructural alterations with an abundant autophagic vesicles and autolysosomes in treated cells, indicating an interference of autophagy process after APL exposure. Thus, antitumoural APLs interfere with the proliferation of tumour cells via a complex mechanism involving phospholipid and cholesterol metabolism, interfere with lipid-dependent survival-signalling pathways and autophagy. Although APLs also exert antiparasitic, antibacterial, and antifungal effects, in this review we provide a summary of the antileishmanial activity of these lipid analogues. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
The trafficking of human beings is one of the most heinous crimes on earth. Shamefully, human trafficking remains a lucrative business in 2020, just as it was thousands of years ago. The estimated astonishing number of victims would most likely surprise nonexperts. The prosecution of human trafficking is often difficult and requires the identification of victims. The fields of forensic anthropology and forensic odontology are of the highest value for this purpose. Forensic genetics is also of interest and can be applied not only to solving crimes but also to preventing them. At the University of Granada, we aim to pioneer the application of these technologies to both solve and prevent human trafficking. In 1999, we introduced the first national missing persons genetic identification program, the Spanish Phoenix Program; in 2004, we created and launched DNA-PROKIDS, designed to deter child trafficking; and in 2016, we created DNA-ProORGAN, a program that is currently being developed to identify transplanted organs, by obtaining DNA samples from the donor, the transplanted organ, and the recipient, to track transplants and identify illegal activities. Several tasks remain, despite existing technological advances and international cooperation. National missing persons databases must be enlarged, and new ones must be created, to facilitate the generation of reliable data. Specific legislation, at the national level, can be enacted to support database development and promote international interactions. These advances would help solve crimes and prevent them, representing the primary challenge faced by forensic science community in the 21st century. This article is categorized under: Forensic Biology > DNA Databases and Biometrics K E Y W O R D S DNA, forensic science, genetic identification, human rights, human trafficking 1 | INTRODUCTION Human trafficking remains an immense problem and a heinous crime that has been perpetrated by humanity since its origins. The coronavirus disease 2019 (COVID-19) pandemic and the anticipated worldwide economic crisis will, most
Skeletal remains are the only biological material that remains after long periods; however, environmental conditions such as temperature, humidity, and pH affect DNA preservation, turning skeletal remains into a challenging sample for DNA laboratories. Sample selection is a key factor, and femur and tooth have been traditionally recommended as the best substrate of genetic material. Recently, petrous bone (cochlear area) has been suggested as a better option due to its DNA yield. This research aims to evaluate the efficiency of petrous bone compared to other cranium samples (tooth) and postcranial long bones (femur and tibia). A total amount of 88 samples were selected from 38 different individuals. The samples were extracted by using an organic extraction protocol, DNA quantification by Quantifiler Trio kit and amplified with GlobalFiler kit. Results show that petrous bone outperforms other bone remains in quantification data, yielding 15–30 times more DNA than the others. DNA profile data presented likeness between petrous bone and tooth regarding detected alleles; however, the amount of DNA extracted in petrous bones allowed us to obtain more informative DNA profiles with superior quality. In conclusion, petrous bone or teeth sampling is recommended if DNA typing is going to be performed with environmentally degraded skeletal remains.
Forensic microbiomics is a promising tool for crime investigation. Geolocation, which connects an individual to a certain place or location by microbiota, has been fairly well studied in the literature, and several applications have been found. The aim of this review is to highlight the main findings in this field, including the current sample storage, DNA extraction, sequencing and data analysis techniques that are being used, and its potential applications in human trafficking and ancient DNA studies. Second, the challenges and limitations of forensic microbiomics and geolocation are emphasised, providing recommendations for the establishment of this tool in the forensic science community.
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