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In forensic anthropology, there is an inherent difficulty in estimating the post-mortem interval (PMI). This study aimed to assess whether there is a correlation between changes in the bone mineral component and the PMI estimation. Samples of femur and humerus from 80 identified individuals with known post-mortem interval were analyzed. Infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR) was applied for this analysis, several indices having been obtained from the infrared bands most representative of the bone's relative contents in carbonate and phosphate. Specific relationships between sex/age and PMI were attained: for larger PMIs, there was an increase in the amount of B-type carbonate (BPI), A-type carbonates (API), and in the carbonate/phosphate (C/P) ratio, and a decrease of the crystallinity index (CI) and in the carbonate ratio (C/C). Two particular infrared indices (CI and C/C) were identified as the most suitable for post-mortem interval estimation, especially in females, controlling the effects of sex and age (in the statistical analysis).
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Antropología Forense , Húmero , Autopsia/métodos , Femenino , Fémur/química , Antropología Forense/métodos , Humanos , Cambios Post Mortem , Espectroscopía Infrarroja por Transformada de Fourier/métodosRESUMEN
Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties. These are strongly dependent on the dynamical behaviour of water, known to play a fundamental role in normal cellular activity and in the maintenance of the three-dimensional architecture of the tissue and the functional state of biopolymers. In this study, quasi-elastic neutron scattering was used to probe the dynamical behaviour of water in human cancer specimens and their respective surrounding normal tissue from breast and tongue, as an innovative approach for identifying particular features of malignancy. This methodology has been successfully used by the authors in human cells and was the first study of human tissues by neutron scattering techniques. A larger flexibility was observed for breast versus tongue tissues. Additionally, different dynamics were found for malignant and non-malignant specimens, depending on the tissue: higher plasticity for breast invasive cancer versus the normal, and an opposite effect for tongue. The data were interpreted in the light of two different water populations within the samples: one displaying bulk-like dynamics (extracellular and intracellular/cytoplasmic) and another with constrained flexibility (extracellular/interstitial and intracellular/hydration layers).
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Neoplasias , Agua , Humanos , Difracción de Neutrones/métodos , NeutronesRESUMEN
Advances in research in Cultural Heritage see increasing application of a multidisciplinary approach and the combined use of physical and chemical characterization of artefacts that can be used to define their structure and their state of conservation, also providing valuable information in selecting the most suitable microclimatic conditions for the exhibition environment. This approach provides a platform for a synergic collaboration amongst researchers, restorers, conservators, and archaeologists. Existing state-of-the-art technologies for neutron-based methods are currently being applied to the study of objects of historical and cultural interest in several neutron-beam facilities around the world. Such techniques are non-invasive and non-destructive and are, therefore, ideal to provide structural information about artefacts, such as their composition, presence of alterations due to the environmental conditions, inclusions, structure of the bulk, manufacturing techniques, and elemental composition, which provide an overall fingerprint of the object's characteristics, thanks to the nature of the interaction of neutrons with matter. Here, we present an overview of the main neutron methods for the characterization of materials of interest in Cultural Heritage and we provide a brief introduction to the sensors and detectors that are used in this framework. We conclude with some case studies underlining the impact of these applications in different archaeological and historical contexts.
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The Sarcocornia genus is an extreme salt-tolerant plant that can be cultivated in saline habitats almost worldwide. To preserve Sarcocornia perennis, convective drying experiments were conducted and their effects on the physico-chemical properties and phenolic content of the plant were studied using conventional and vibrational spectroscopy techniques. The drying process of Sarcocornia perennis at temperatures of 40 °C, 50 °C, 60 °C and 70 °C revealed three periods of convective drying process with drying times ranging between 4.5 and 24.9 h, respectively to higher and lower temperatures. The heating-up period can be neglected as compared with the drying process, and the duration of constant rate period, as a percentage of the total drying time, ranged between 34 and 20% respectively at 40 °C and 70 °C. The Modified Page model was proposed to describe the drying process at the different temperatures. From a nutritional point of view, this halophyte plant may be considered as a good source of fibres, phenolic compounds and natural minerals, such as sodium, potassium, calcium and magnesium. The convective drying, in the temperature range currently used, was found to preserve the colour, nutritional characteristics and phytochemical value of Sarcocornia perennis. These results were confirmed by FTIR-ATR and highlight the potential use of the dried plant in novel food products.
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OBJECTIVES: Vibrational spectroscopy is a valuable tool for the study of burned skeletal remains. Nonetheless, most investigations have been focused on a limited number of samples as well as on faunal bones rather than human bones. Conclusions based on those investigations may lack representativeness, namely about the intrabone, intra- and interskeleton variability of several chemometric indices. We aimed to investigate this issue on a large sample of human bones. MATERIAL AND METHODS: Powder samples were collected from 168 bones from four human skeletons. The sampling targeted 47 long bones, 72 short bones, and 49 tarsal bones as well as different bone regions in a total of 638 powder samples. Bones were experimentally burned in an electric muffle furnace for two hours to maximum temperatures ranging from 400°C to 1000°C. Another 623 burned samples were then collected totaling 1261 samples subjected to FTIR-ATR analysis. The CI, BPI, C/C, and OH/P indices were calculated. RESULTS: An important intrabone, intra- and interskeleton variation was observed, especially for the BPI. The CI, C/C, and OH/P indices revealed much less variation so site-specific sampling may not be as critical in these cases. Clear differences between our results and those from previous investigations were observed, namely on the temperature increment evolution of the CI and C/C indices. DISCUSSION: The relatively large heterogeneity, especially at the intrabone level, is possibly the consequence of microstructural bone differences. The dissimilarities observed between our investigation and other published studies are probably due to the fact that the samples used here came from human rather than faunal bones. Also, our samples were buried previously to the experimental burning so this may also partly explain our contrasting results, since previous research was mostly performed on fresh bone. Future inferences based on vibrational spectroscopy analyses should take into account the possible effect of all these sources.
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Huesos/diagnóstico por imagen , Huesos/fisiología , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Adulto , Femenino , Antropología Forense , Humanos , Masculino , VibraciónRESUMEN
In the present study, we developed a green epoxidation approach for the synthesis of the diastereomers of (-)-isopulegol benzyl ether epoxide using molecular oxygen as the oxidant and a hybrid manganese(III)-porphyrin magnetic reusable nanocomposite as the catalyst. High activity, selectivity, and stability were obtained, with up to four recycling cycles without the loss of activity and selectivity for epoxide. The anticancer effect of the newly synthesized isopulegol epoxide diastereomers was evaluated on a human osteosarcoma cell line (MG-63); both diastereomers showed similar in vitro potency. The measured IC50 values were significantly lower than those reported for other monoterpene analogues, rendering these epoxide isomers as promising anti-tumor agents against low prognosis osteosarcoma.
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Antineoplásicos/farmacología , Biomimética , Fenómenos Magnéticos , Metaloporfirinas/química , Nanocompuestos/química , Osteosarcoma/patología , Antineoplásicos/síntesis química , Antineoplásicos/química , Rastreo Diferencial de Calorimetría , Catálisis , Línea Celular Tumoral , Monoterpenos Ciclohexánicos , Compuestos Epoxi/síntesis química , Compuestos Epoxi/química , Humanos , Manganeso/química , Nanocompuestos/ultraestructura , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Estereoisomerismo , Terpenos/síntesis química , Terpenos/química , Terpenos/farmacología , TermogravimetríaRESUMEN
The first neutron scattering study on human nucleated cells is reported, addressing the subject of solvent-slaving to a drug by probing intracellular water upon drug exposure. Inelastic and quasi-elastic neutron scattering spectroscopy with isotope labelling was applied for monitoring interfacial water response to the anticancer drug cisplatin, in the low prognosis human metastatic breast cancer cells MDA-MB-231. Optical vibrational data were also obtained for lyophilised cells. Concentration-dependent dynamical changes evidencing a progressive mobility reduction were unveiled between untreated and cisplatin-exposed samples, concurrent with variations in the native organisation of water molecules within the intracellular medium as a consequence of drug action. The results thus obtained yielded a clear picture of the intracellular water response to cisplatin and constitute the first reported experimental proof of a drug impact on the cytomatrix by neutron techniques. This is an innovative way of tackling a drug's pharmacodynamics, searching for alternative targets of drug action.
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Cisplatino/metabolismo , Matriz Extracelular/metabolismo , Agua/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/farmacología , Sistemas de Liberación de Medicamentos , Matriz Extracelular/efectos de los fármacos , Humanos , Neutrones , Análisis EspectralRESUMEN
Studies of drug-cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activity and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(ii) and Pd(ii) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2-8 µM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied - mononuclear vs. polynuclear, and Pt(ii) vs. Pd(ii). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(ii) agent having a more significant impact on proteins while its Pt(ii) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of the biochemical impact and physiological reaction of cells to anticancer agents.
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Antineoplásicos/química , Antineoplásicos/farmacología , Cisplatino/farmacología , Espectrofotometría Infrarroja , Espectrometría Raman , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Biomarcadores/metabolismo , Línea Celular Tumoral , Humanos , Espermina/metabolismo , Neoplasias de la Mama Triple Negativas/patología , VibraciónRESUMEN
The presence of plastic debris and organo-brominated compounds in the marine environment poses a concern to wildlife. Plastic can absorb and release chemical compounds, making their ingestion potentially harmful, while chemical compounds have become omnipresent, with a tendency to bioaccumulate in the food web. Seabirds are often used as indicators of marine plastic pollution, yet studies on the exposure of tropical communities to plastic contamination are still scarce. In this study we monitored the amounts of plastics in faeces and organo-brominated compounds ingested/assimilated in feathers by adults and chicks of Cape Verde shearwaters and Bulwer's petrels from Cabo Verde. Anthropogenic pollutants, polybrominated diphenyl ethers (PBDEs), and naturally generated methoxylated-PBDEs (MeO-PBDEs) were among the probed compounds. The frequency of plastic debris ingestion was similar in both species' adults and chicks, although, the characteristics of the ingested plastic differed. Frequency and number of microplastics increased throughout the nestling season for chicks from both species. All species and age groups showed the presence of PBDEs and MeO-PBDEs. Among PBDEs, Bulwer's petrels exhibited higher concentrations than Cape Verde shearwaters, and chicks had higher concentration profiles than adults. Specifically, Bulwer's petrel chicks showed higher concentrations than Cape Verde shearwater chicks. On the contrary, Cape Verde shearwater adults exhibited higher occurrence and concentrations of MeO-PBDEs when compared to Cape Verde shearwater chicks. We found no effect of plastic loadings or loadings of organohalogen contaminants on body condition or size, although harmful effects may be hidden or reveal themselves in a medium- to long-term. Feather samples from both adults and chicks were shown to be useful for comparing intraspecific contamination levels and appear suitable for the long-term assessment of organohalogen contaminants in seabirds. Species-specific foraging and feeding strategies are likely the drivers of the observed variation in organochlorine contamination burdens among seabird species.
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Monitoreo del Ambiente , Éteres Difenilos Halogenados , Plásticos , Contaminantes Químicos del Agua , Animales , Plásticos/análisis , Éteres Difenilos Halogenados/análisis , Contaminantes Químicos del Agua/análisis , Aves/metabolismo , Plumas/química , Masculino , Exposición a Riesgos Ambientales/estadística & datos numéricosRESUMEN
In this study we found that endocrine disrupting chemicals (EDCs) were omnipresent in a tropical seabird community comprising diverse ecological guilds and distinct foraging and trophic preferences. Because EDCs tend to bioaccumulate within the food web and microplastics can absorb and release harmful chemical compounds, our findings draw attention to the potential threats to wildlife. Thus, the goal of this study was to investigate the role of plastic ingestion, trophic and foraging patterns (δ15N and δ13C) of five tropical seabird species breeding in sympatry, on the exposure to EDCs, namely Polybrominated diphenyl ethers (PBDEs), methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and personal care products (PCPs, e.g., musk fragrances and UV-filters). Results indicated that microplastics occurrence and EDCs detection frequency varied among species. Microplastics occurrence was higher in species with dual and coastal foraging strategies. Preen oil had higher levels of MeO-PBDEs and PCPs, while serum had higher levels of PBDEs. In brown boobies, the correlation between microplastics and ∑PBDEs levels was significant, suggesting that microplastics ingestion is a key PBDEs route. Trophic position (δ15N) plays a key role in PBDEs accumulation, particularly in Bulwer's petrel, which occupies a high trophic position and had more specialized feeding ecology than the other species. MeO-PBDEs were linked to foraging habitat (δ13C), although the link to foraging locations deserves further investigation. Overall, our findings not only fill key gaps in our understanding of seabirds' exposure to microplastics and EDCs, but also provide an essential baseline for future research and monitoring efforts. These findings have broader implications for the marine wildlife conservation and pollution management in sensitive environments, such as the tropical regions off West Africa.
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Disruptores Endocrinos , Monitoreo del Ambiente , Animales , Éteres Difenilos Halogenados/análisis , Microplásticos , Plásticos , Animales Salvajes , Aves , Ingestión de AlimentosRESUMEN
Marine plastic contamination is currently considered ubiquitous in aquatic environments. These particles present a resistant and hydrophobic substrate known to promote microbial colonisation and biofilm formation in aquatic ecosystems, the so-called "Plastisphere", raising concerns about its potential ecological risks. The novelty of this topic translates into a relatively low number of studies, including for transitional coastal ecosystems, such as sandy beaches or estuarine habitats. Therefore, a sampling campaign was conducted in two transitional coastal ecosystems - the Mondego estuary (Portugal) - and adjacent sandy beaches (winter 2020). After visual sorting and filtering of suspected particles under sterile conditions DNA extraction and 16S rRNA amplicon high throughput sequencing was used to profile the bacterial communities on the surface of plastic particles and from those found on the water and sediments from the sampled transitional coastal ecosystems. All particles were characterised according to type, colour and size, and the chemical nature of the particles was determined by FTIR-ATR or µ-FTIR spectroscopy after DNA extraction. All samples contained plastics in several sizes (micro and mesoplastics), shapes (higher abundances of fragments on beaches and fibres in the estuarine waters), colours and polymers. Although no significant differences were detected in the α-diversity indexes of the bacterial communities between plastics and their surrounding environments, data showed the occurrence of unique key bacterial groups on plastics from both environments, such as pathogens (e.g., Lactococcus, Staphylococcus and Streptococcus) and groups commonly associated with wastewater treatment plants (e.g., members of the phylum Firmicutes). This highlights the concerns for plastics to act as vectors of transmission and spread of these bacterial groups in transitional coastal ecosystems. Furthermore, it raises the possibility that (micro)plastics entering the estuary from the sea play a substantial contribution to overall dynamics of (micro)plastics and their microbial assemblages in the estuarine system.
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Ecosistema , Contaminantes Químicos del Agua , ARN Ribosómico 16S/genética , Contaminantes Químicos del Agua/análisis , Plásticos , Bacterias , ADNRESUMEN
Acetic acid treatment for an accurate differentiation between ancient and recent human bones was assessed using Raman and FTIR-ATR spectroscopies. Each set of skeletal samples was analysed by these techniques, prior and after chemical washing, in order to determine the variations in bone´s chemical composition and crystallinity. Bone samples were collected from several independent sources: recent bones burned under controlled experimental conditions or cremated, and archaeological (XVII century and Iron Age). The effect of acetic acid, expected to impact mostly on carbonates, was clearly evidenced in the spectra of all samples, particularly in FTIR-ATR, mainly through the bands typical of A- and B-carbonates. Furthermore, as seen for crematoria and archaeological samples, acetic acid was found to remove contaminants such as calcium hydroxide. Overall, acetic acid treatment can be an effective method for removing carbonates (exogenous but possibly also endogenous) and external contaminants from bone. However, these effects are dependent on the skeletal conditions (e.g. post-mortem interval and burning settings). In addition, this chemical washing was shown to be insufficient for an unequivocal discrimination between recent and archaeological skeletal remains. Based on the measured IR indexes, only cremated bones could be clearly distinguished.
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Ácido Acético , Restos Mortales , Humanos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Carbonatos/análisis , Huesos/químicaRESUMEN
Normal-to-cancer (NTC) transition is known to be closely associated to cell´s biomechanical properties which are dependent on the dynamics of the intracellular medium. This study probes different human cancer cells (breast, prostate and lung), concomitantly to their healthy counterparts, aiming at characterising the dynamical profile of water in distinct cellular locations, for each type of cell, and how it changes between normal and cancer states. An increased plasticity of the cytomatrix is observed upon normal-to-malignant transformation, the lung carcinoma cells displaying the highest flexibility followed by prostate and breast cancers. Also, lung cells show a distinct behaviour relative to breast and prostate, with a higher influence from hydration water motions and localised fast rotations upon NTC transformation. Quasielastic neutron scattering techniques allowed to accurately distinguish the different dynamical processes taking place within these highly heterogeneous cellular systems. The results thus obtained suggest that intracellular water dynamics may be regarded as a specific reporter of the cellular conditions-either healthy or malignant.
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Neoplasias , Agua , Humanos , Difracción de Neutrones , NeutronesRESUMEN
Oceans have been considered as an unlimited supply of goods and services, but resource extraction and waste disposal became ubiquitous and have been damaging the health of marine ecosystems. Finding suitable sentinel species of the human impacts on the oceans is thus imperative, since they may work as early warnings of disruptive situations. In this study, we investigated how taxonomy and foraging distribution influenced the occurrence of anthropogenic debris among five seabird species inhabiting the tropical Atlantic region. Occurrence of anthropogenic debris was assessed using faeces of breeding individuals as a proxy of ingestion. A total of 268 particles were extracted from all samples. The categories "fragments" and "fibres", as well as the colour "blue", were the most prevalent characteristics across species. There was a high diversity of polymers from cellulosic particles to synthetic plastics (Anthropogenic Cellulosic 26.9 %; Polyester 7.7 %; Varnish 5.8 %; Polypropylene 1.9 %). Species with a more coastal foraging strategy exhibited higher occurrence and number of anthropogenic debris when compared to species foraging comparably more in pelagic areas. This suggests that anthropogenic debris are more prevalent in coastal foraging areas, where human activities occur in higher number and frequency (e.g., fisheries) and sources of freshwater input from inland are at close distance. These results provide more evidence to the growing perception on the ubiquity and diversity of anthropogenic debris in the marine environment, and further support the usefulness of using seabirds as bio-indicators of anthropogenic pollution in both neritic and oceanic regions.
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Ecosistema , Residuos , Humanos , Animales , Residuos/análisis , Monitoreo del Ambiente/métodos , Plásticos , Aves , Ingestión de AlimentosRESUMEN
The "Hypogeum of the Garlands" is a sepulchral site, recently found in Grottaferrata (Lazio, Italy), dating back to the first-second century AD. Two sarcophagi were discovered inside, hosting the human remains of Aebutia Quarta, a rich Roman woman, and her son Carvilius Gemellus. While the body of Carvilius is exceptionally well-preserved, following its embalming and perfect sealing of the sarcophagus, in the case of Aebutia only the bones were preserved because of the sarcophagus's seal breaking down, although she was covered with perfectly preserved flower garlands. Embalming of the body was a rare ritual in the Imperial Roman times when corpses were more often cremated. The remains of Aebutia showed possible traces of heating. Burned bones from a third individual were discovered on the chamber's floor and preliminary anthropological survey showed that this individual was a male of 40-50 years old. Here, a combination of spectroscopic techniques, including non-destructive inelastic neutron scattering and Raman spectroscopy, and minimally destructive Fourier transform infrared spectroscopy, were applied to the analysis of these bone samples to give information about ancient Roman funerary practices. The temperature and burning conditions were thus determined, showing that Aebutia Quarta was exposed to mild temperatures (200 °C) only in the upper part of the body, while the third individual was likely cremated as its bones were exposed to temperatures up to 900 °C in quasi-anaerobic conditions.
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Huesos , Espectrometría Raman , Adulto , Femenino , Historia Antigua , Humanos , Italia , Masculino , Persona de Mediana Edad , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A SERS study of chromone 3-carboxylic acid adsorbed on silver colloids was undertaken, in order to assess the ability of this compound to accept electrons in charge transfer (CT) processes. Theoretical SERS intensities under photoinduced CT resonant conditions have been carried out for both the neutral and the deprotonated species allowing to conclude, by comparison with the experimental data, that the recorded SER corresponds to the anionic form of the acid linked to the metal. It was shown that the SERS-CT mechanism predominates for this particular compound, thus explaining the strong enhancement of the band at ca. 1600 cm(-1) assigned to the 8a ring stretching mode. The identification of CT processes is of the utmost importance for understanding the mechanism through which these benzopyranes may act as antioxidants.
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Antioxidantes/química , Ácidos Carboxílicos/química , Cromonas/química , Benzopiranos/química , Coloides/química , Electrones , Plata/química , Espectrometría RamanRESUMEN
This study aims to analyse human bones exposed to low/medium temperatures (200-650°C) under experimentally controlled conditions, both oxidizing and reducing, using complementary optical and neutron vibrational spectroscopy techniques. Clear differences were observed between the aerobically and anaerobically heated bones. The organic constituents disappeared at lower temperatures for the former (ca 300°C), while they lingered for higher temperatures in anaerobic environments (ca 450-550°C). Unsaturated non-graphitizing carbon species (chars) were detected mainly for anaerobically heated samples, and cyanamide formation occurred only at 650°C in reducing settings. Overall, the main changes were observed from 300 to 400°C in anaerobic conditions and from 450 to 500°C in aerobic environments. The present results enabled the identification of specific spectroscopic biomarkers of the effect of moderate temperatures (less than or equal to 650°C) on human bone, thus contributing to a better characterization of forensic and archaeological skeletal remains subject to heating under distinct environmental settings. In particular, these data may provide information regarding cannibalism or ancient bone boiling and defleshing rituals.
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Complementary optical and neutron-based vibrational spectroscopy techniques (Infrared, Raman and inelastic neutron scattering) were applied to the study of human bones (femur and humerus) burned simultaneously under either aerobic or anaerobic conditions, in a wide range of temperatures (400 to 1000 °C). This is the first INS study of human skeletal remains heated in an oxygen-deprived atmosphere. Clear differences were observed between both types of samples, namely the absence of hydroxyapatite's OH vibrational bands in bone burned anaerobically (in unsealed containers), coupled to the presence of cyanamide (NCNH2) and portlandite (Ca(OH)2) in these reductive conditions. These results are expected to allow a better understanding of the heat effect on bone´s constituents in distinct environmental settings, thus contributing for an accurate characterisation of both forensic and archaeological human skeletal remains found in distinct scenarios regarding oxygen availability.
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Restos Mortales/química , Fémur/química , Calor , Húmero/química , Humanos , Espectrometría RamanRESUMEN
The interaction of double-stranded DNA with two polynuclear Pd(II) chelates with the biogenic polyamines spermidine (Spd) and spermine (Spm), Pd(II)-Spd and Pd(II)-Spm, as well as with the free ligands Spd and Spm, was studied using atomic force microscopy (AFM) at a highly oriented pyrolytic graphite (HOPG) surface, voltammetry at a glassy carbon (GC) electrode, and gel electrophoresis. The AFM and voltammetric results showed that the interaction of Spd and Spm with DNA occurred even for a low concentration of polyamines and caused no oxidative damage to DNA. The Pd(II)-Spd and Pd(II)-Spm complexes were found to induce greater morphological changes in the dsDNA conformation, when compared with their ligands. The interaction was specific, inducing distortion and local denaturation of the B-DNA structure with release of some guanine bases. The DNA strands partially opened give rise to palladium intra- and interstrand cross-links, leading to the formation of DNA adducts and aggregates, particularly in the case of the Pd(II)-Spd complex.
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Poliaminas Biogénicas/química , Quelantes/química , ADN/metabolismo , Compuestos Organometálicos/química , Compuestos Organometálicos/metabolismo , Paladio/química , Animales , Carbono/química , Bovinos , ADN/química , Electroquímica , Electrodos , Electroforesis , Vidrio/química , Grafito/química , Ligandos , Microscopía de Fuerza Atómica , Modelos Moleculares , Conformación de Ácido Nucleico , Oxidación-Reducción , Propiedades de SuperficieRESUMEN
Polyamines are small cationic molecules required for cellular proliferation and are detected at higher concentrations in most tumour tissues, compared to normal tissues. Agmatine (AGM), a biogenic amine, is able to arrest proliferation in cell lines by depleting intracellular polyamine levels. It enters mammalian cells via the polyamine transport system. Agmatine is able to induce oxidative stress in mitochondria at low concentrations (10 or 100 microM), while at higher concentrations (e.g. 1-2 mM) it does not affect mitochondrial respiration and is ineffective in inducing any oxidative stress. As this effect is strictly correlated with the mitochondrial permeability transition induction and the triggering of the pro-apoptotic pathway, AGM may be considered as a regulator of this type of cell death. Furthermore, polyamine transport is positively correlated with the rate of cellular proliferation. By increasing the expression of antizyme, a protein that inhibits polyamine biosynthesis and transport, AGM also exhibits a regulatory effect on cell proliferation. Methylglyoxal bis(guanylhydrazone) (MGBG), a competitive inhibitor of S-adenosyl-L: -methionine decarboxylase, displaying anticancer activity, is a structural analogue of the natural polyamine spermidine. MGBG has been extensively studied, preclinically as well as clinically, and its anticancer activity has been attributed to the inhibition of polyamine biosynthesis and also to its effect on mitochondrial function. Numerous findings have suggested that MGBG might be used as a chemotherapeutic agent against cancer.