Further progress in the study of epsilon iron oxide in archaeological baked clays

The occurrence of ε-Fe2O3 in archaeological samples that have been subjected to high temperatures is gradually being detected by the use of micrometric structural characterization techniques. This work provides new information by revealing that the ε-Fe2O3 is formed as a response to temperature, the aggregation state and the position within the baked clay with respect to the nearest heat source. In addition, depending mainly on the atmospheric environment, the temperature reached by the combustion structure, the distance from the heating source and the particle aggregation, other iron oxide magnetic phases are produced. In the baked clay studied here, hematite is found over the whole range of samples studied but its magnetic contribution is negligible. Magnetite is observed at the sample surface, probably due to local atmospheric environment closest to the combustion source. Maghemite is found at all depths up to 6 cm below the sample surface. ε-Fe2O3 has a limited distribution, found within 2–3 cm of the sample surface. Furthermore, the viability of this compound as a palaeofield marker has been evaluated in both archaeological and synthetic samples. The results indicate that ε-Fe2O3 is able to register the direction of the magnetic field. Linear palaeointensity plots have been obtained in synthetic samples, although the value of the palaeofield could be, sometimes, overestimated

On the reliability of archaeomagnetic dating in Iberia: two case studies from Portugal and Zamora

Archaeomagnetic investigations have been carried out on 22 combustion structures from Portugal and Spain, along the Duero River Valley at the archaeological sites of Crestelos and Olival Poço da Barca (NE Portugal) and at El Castillón (NW Spain). The age of most of the investigated structures at Portuguese sites ranges from the 3rd century BC up to Roman times according to archaeological information. At El Castillón the investigated kilns are considered to cover the 5th – 7th centuries AD. Stepwise thermal and alternating field demagnetization isolated a single, stable, characteristic remanence component with very well defined directions. Mean site directions were well grouped in most sites. Only the two most poorly preserved structures showed a relatively high directional dispersion. Classical Thellier paleointensity experiments were conducted on pilot specimens. Successful results were obtained in specimens from el Castillón and from Olival Poço da Barca. In contrast, alterations occurred during thermal treatment at Crestelos kilns and hearths. Archaeomagnetic dating was conducted in all sites by using six reference Palaeosecular Variation (PSV) curves provided by local studies (from Iberia and France) and by regional (SCHA.DIF.3k) and global models (ARCH3k.1 and SHA.DIF.14k). The best PSV master curves for dating purposes on the investigated structures are the French curve for the old structures (older than 200 AD) and the regional SCHA.DIF.3k model for the younger structures. The new archaeomagnetic dating results suggest that the Crestelos site was active since 265±87 BC up to 252±138 AD, with a mean occupation period between 198 BC-43 AD. There could have been a previous occupation of the site but it could not be precisely dated. Distributions of the directions from Crestelos describe a PSV trend consistent with the French curve, suggesting that the archaeomagnetic dating tool could be improved in the near future by dating selected structures by independent methods. Archaeomagnetic dating at El Castillón site provide two phases of occupation of the site, at 441±12 AD and 488±53 AD, consistent with recent radiocarbon ages from the site. The effect of TRM anisotropy on directions has been evaluated, with the results highlighting the necessity for TRM anisotropy corrections if accurate dating is to be obtained

Role of low-density lipoprotein receptor in the hepatitis C virus life cycle.

Hepatitis C virus (HCV) particles are known to be in complex with lipoproteins. As a result of this interaction, the low-density lipoprotein (LDL) receptor (LDLR) has been proposed as a potential entry factor for HCV; however, its implication in virus entry remains unclear. Here, we reinvestigated the role of the LDLR in the HCV life cycle by comparing virus entry to the mechanism of lipoprotein uptake. A small interfering RNA targeting the LDLR in Huh-7 cells reduced HCV infectivity, confirming that this receptor plays a role in the life cycle of HCV generated in cell culture. However, kinetics of internalization were much faster for lipoproteins than for infectious HCV particles. Furthermore, a decrease in HCV RNA replication was observed by blocking the LDLR with a specific antibody, and this was associated with an increase in the ratio of phosphatidylethanolamine to phosphatidylcholine in host cells. Nevertheless, a soluble form of the LDLR inhibited both HCV entry into the hepatocytes and its binding to the LDLR expressed on Chinese hamster ovary cells, suggesting a direct interaction between the HCV particle and the LDLR. Finally, we showed that modification of HCV particles by lipoprotein lipase (LPL) reduces HCV infectivity and increases HCV binding to LDLR. Importantly, LPL treatment also induced an increase in RNA internalization, suggesting that LDLR, at least in some conditions, leads to nonproductive internalization of HCV. Conclusion: The LDLR is not essential for infectious HCV particle entry, whereas the physiological function of this receptor is important for optimal replication of the HCV genome.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Heparin Enhances Serpin Inhibition of the Cysteine Protease Cathepsin L*

The glycosaminoglycan heparin is known to possess antimetastatic activity in experimental models and preclinical studies, but there is still uncertainty over its mechanism of action in this respect. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III, but a similar cofactor role has not been previously investigated for proteases linked to metastasis. The squamous cell carcinoma antigens (serpins B3 and B4) are tumor-associated proteins that can inhibit papain-like cysteine proteases, including cathepsins L, K, and S. In this study, we show that SCCA-1 (B3) and SCCA-2 (B4) can bind heparin as demonstrated by affinity chromatography, native PAGE gel shifts, and intrinsic fluorescence quenching. Binding was specific for heparin and heparan sulfate but not other glycosaminoglycans. The presence of heparin accelerated inhibition of cathepsin L by both serpins, and in the case of SCCA-1, heparin increased the second order inhibition rate constant from 5.4 × 105 to >108, indicating a rate enhancement of at least 180-fold. A templating mechanism was shown, consistent with ternary complex formation. Furthermore, SCCA-1 inhibition of cathepsin L-like proteolytic activity secreted from breast and melanoma cancer cell lines was significantly enhanced by heparin. This is the first example of glycosaminoglycan enhancement of B-clade serpin activity and the first report of heparin acting as a cofactor in serpin cross-class inhibition of cysteine proteases. Most importantly, this finding raises the possibility that the anticancer properties of heparin may be due, at least partly, to enhanced inhibition of prometastatic proteases

Photo-isomerisation of alkenyl complexes of platinum(ii) : structural, spectroscopic, kinetic and computational investigations

In this work UVA and blue light have been used to study photo-isomerisation about the C[double bond, length as m-dash]C double bond in complexes of the type [PtCl(–CH[double bond, length as m-dash]CHAr)(tmeda)] [Ar = C6H5, (E)-2a; 4-CH3O–C6H4, (E)-2b; 3-NO2–C6H4, (E)-2c; and 3-CH3O–C6H4, (E)-2d]. The progress of the reaction has been monitored by NMR spectroscopy following irradiation of the NMR sample. The NMR data have been complemented with X-ray diffractometric analysis of compounds (E)-2a–c and (Z)-2a. The kinetic data clearly indicate that a monomolecular mechanism is operating with the energy of the irradiating light influencing the rate of isomerisation but not the equilibrium composition, which is only slightly in favour of the Z isomer. DFT and TD-DFT theoretical investigations have been carried out to elucidate the nature of the main electronic transitions in the UV-Vis region and the mechanism of the photo-isomerisation reaction appears to proceed through a C[double bond, length as m-dash]C bond twist process similar to that involved in purely organic molecules such as stilbene. In the Z isomer, one ortho proton of the phenyl group can come close to platinum (PtHortho distance of 2.632 Å in (Z)-2a). In the case of 2c, the difference in chemical shift between the two ortho protons varies from 3.30 ppm in the Z isomer, where interaction with Pt is possible, to 0.60 ppm in the E isomer, where such interaction cannot take place. The analysis of the DFT orbitals indicates that the most shifted Hortho is that with a greater positive charge, pointing to an H-bond type of interaction

Abnormal Gamma Oscillations in N-Methyl-D-Aspartate Receptor Hypofunction Models of Schizophrenia

N-methyl-D-aspartate receptor (NMDAR) hypofunction in parvalbumin-expressing (PV+) inhibitory neurons (INs) may contribute to symptoms in patients with schizophrenia (SZ). This hypothesis was inspired by studies in humans involving NMDAR antagonists that trigger SZ symptoms. Animal models of SZ using neuropharmacology and genetic knockouts have successfully replicated some of the key observations in human subjects involving alteration of gamma band oscillations (GBO) observed in electroencephalography and magnetoencephalography signals. However, it remains to be seen if NMDAR hypofunction in PV+ neurons is fundamental to the phenotype observed in these models. In this review, we discuss some of the key computational models of GBO and their predictions in the context of NMDAR hypofunction in INs. While PV+ INs have been the main focus of SZ studies in animal models, we also discuss the implications of NMDAR hypofunction in other types of INs using computational models for GBO modulation in the visual cortex