Sexual Dimorphism of the Fovea Capitis Femoris in a Medieval Population from Gloucester, England

Attempts to develop new methods of sex determination in forensic anthropology are constantly being made by researchers in the field. This paper investigates the potential of using an index of the fovea capitis femoris shape as a method of sex determination. The currently held belief is that variation within the fovea capitis is purely idiosyncratic. The study was carried out on a sample of 19 males and 19 females from the Gloucester skeletal collection housed at Liverpool John Moores University. Measurements of the maximum fovea capitis height and breadth were taken from both the left and right femora and converted into an index. It was found that while there was no significant difference in dimensions alone, there was a significant difference in index values between males and females for both the left (t(34) = 4.294, p < 0.001) and right (t(32) = 3.046. p = 0.05) fovea capitis. This method was found to have 78.1% accuracy in determining the sex of an individual. Therefore, we may now be able to state that variation of the fovea capitis is sexuallydimorphic and not exclusively idiosyncratic as first thought

Isoenzyme- and Allozyme-Specific Inhibitors: 2,20-Dihydroxybenzophenones and Their Carbonyl N-Analogues that Discriminate between Human Glutathione Transferase A1-1 and P1-1 Allozymes

The selectivity of certain benzophenones and their carbonyl N-analogues was investigated towards the human GSTP1-1 allozymes A, B and C involved in MDR. The allozymes were purified from extracts derived from E. coli harbouring the plasmids pEXP5-CT/TOPO-TAhGSTP1* A, pOXO4-hGSTP1*B or pOXO4-hGSTP1*C. Compound screening with each allozyme activity indicated three compounds with appreciable inhibitory potencies, 12 and 13 with P1-1A 62% and 67%, 11 and 12 with P1-1C 51% and 70%, whereas that of 15 fell behind with P1-1B (41%). These findings were confirmed by IC50 values (74–125 lM). Enzyme inhibition kinetics, aided by molecular modelling and docking, revealed that there is competition with the substrate CDNB for the same binding site on the allozyme (Ki(13/ A) = 63.6 +- 3.0 lM, K (15/B) = 198.6 +- 14.3 lM, and Ki(11/ C) = 16.5 +- 2.7 lM). These data were brought into context by an in silico structural comparative analysis of the targeted proteins. Although the screened compounds showed moderate inhibitory potency against hGSTP1-1, remarkably, some of them demonstrated absolute isoenzyme and/or allozyme selectivity

MDR-involved human glutathione transferases (hGSTs) are targets for inhibition by 2,2'-dihydroxybenzophenones and N-carbonyl analogues

Over expression of human GSTA1-1 in tumour cells is part of MDR mechanisms. Substituted 2-hydroxybenzophenones are ubiquitous in naturally occurring and synthetic compounds, exhibiting important biological activities. 2,2’-Dihydroxybenzophenones and N-carbonyl analogues, structurally, are ringopened forms of xanthone analogues which we reported recently as hGSTA1-1 inhibitors. The present study combined GST inhibition screening, in silico molecular docking and enzyme inhibition kinetics, revealing four analogues with strong inhibitory potency (IC50 = 0.18-1.8 μM) and modest cytotoxic activity for Caco2 cell line (LC50 = 35 to > 400 μM), thus being useful as lead structures for the design of new inhibitors against hGSTs

Synthesis and Study of 2‑(Pyrrolesulfonylmethyl)‑N‑arylimines: A New Class of Inhibitors for Human Glutathione Transferase A1‑1

Overexpression of human GSTA1-1 in tumor cells is part of MDR mechanisms. We report on the synthesis of 11 pyrrole derivatives as hGSTA1-1 inhibitors starting from 1-methyl-2-[(2-nitrobenzylsulfanyl]-1H-pyrrole. Molecular modeling revealed two locations in the enzyme H binding site: the catalytic primary one accommodating shorter and longer derivatives and the secondary one, where shorter derivatives can occupy. Derivative 9, displaying the highest inhibition and bearing a p-nitroarylimino moiety, and derivative 4, lacking this moiety, were studied kinetically. Derivative 9 binds (Ki(9) = 71 ± 4 μM) at the primary site competitively vs CDNB. Derivative 4 binds (Ki(4) = 135 ± 27 μM) at the primary and secondary sites, allowing the binding of a second molecule (4 or CDNB) leading to formation of unreactive and reactive complexes, respectively. The arylmethylsulfonylpyrrole core structure is a new pharmacophore for hGSTA1-1, whereas its derivative 9 may serve as a lead structure

Designer Xanthone An Inhibitor Scaffold for MDR-Involved Human Glutathione Transferase Isoenzyme A1-1

Glutathione transferases (GSTs) are cell detoxifiers involved in multiple drug resistance (MDR), hampering the effectiveness of certain anticancer drugs. To our knowledge, this is the first report on well-defined synthetic xanthones as GST inhibitors. Screening 18 xanthones revealed three derivatives bearing a bromomethyl and a methyl group (7) or two bromomethyl groups (8) or an aldehyde group (17), with high inhibition potency (>85%), manifested by low IC50 values (7: 1.59 ± 0.25 μM, 8: 5.30 ± 0.30 μM, and 17: 8.56 ± 0.14 μM) and a competitive modality of inhibition versus CDNB (Ki(7) = 0.76 ± 0.18 and Ki(17) = 1.69 ± 0.08 μM). Of them, derivative 17 readily inhibited hGSTA1-1 in colon cancer cell lysate (IC50 = 10.54 ± 2.41 μM). Furthermore, all three derivatives were cytotoxic to Caco-2 intact cells, with 17 being the least cytotoxic (LC50 = 151.3 ± 16.3 μM). The xanthone scaffold may be regarded as a pharmacophore for hGSTA1-1 and the three derivatives, especially 17, as potent precursors for the synthesis of new inhibitors and conjugate prodrugs for human GSTs

Europe's rare earth element resource potential: an overview of REE metallogenetic provinces and their geodynamic setting

Security of supply of a number of raw materials is of concern for the European Union; foremost among these are the rare earth elements (REE), which are used in a range of modern technologies. A number of research projects, including the EURARE and ASTER projects, have been funded in Europe to investigate various steps along the REE supply chain. This paper addresses the initial part of that supply chain, namely the potential geological resources of the REE in Europe. Although the REE are not currently mined in Europe, potential resources are known to be widespread, and many are being explored. The most important European resources are associated with alkaline igneous rocks and carbonatites, although REE deposits are also known from a range of other settings. Within Europe, a number of REE metallogenetic belts can be identified on the basis of age, tectonic setting, lithological association and known REE enrichments. This paper reviews those metallogenetic belts and sets them in their geodynamic context. The most well-known of the REE belts are of Precambrian to Palaeozoic age and occur in Greenland and the Fennoscandian Shield. Of particular importance for their REE potential are the Gardar Province of SW Greenland, the Svecofennian Belt and subsequent Mesoproterozoic rifts in Sweden, and the carbonatites of the Central Iapetus Magmatic Province. However, several zones with significant potential for REE deposits are also identified in central, southern and eastern Europe, including examples in the Bohemian Massif, the Iberian Massif, and the Carpathians

Manipulating Kondo Temperature via Single Molecule Switching

Two conformations of isolated single TBrPP-Co molecules on a Cu(111) surface are switched by applying +2.2 V voltage pulses from a scanning tunneling microscope tip at 4.6 K. The TBrPP-Co has a spin-active cobalt atom caged at its center and the interaction between the spin of this cobalt atom and free electrons from the Cu(111) substrate can cause a Kondo resonance. Tunneling spectroscopy data reveal that switching from the saddle to a planar molecular conformation enhances spin-electron coupling, which increases the associated Kondo temperature from 130 K to 170 K. This result demonstrates that the Kondo temperature can be manipulated just by changing molecular conformation without altering chemical composition of the molecule.Comment: To appear in Nano Lett (2006

Generalized β\beta-conformal change and special Finsler spaces

In this paper, we investigate the change of Finslr metrics $$L(x,y) \to\bar{L}(x,y) = f(e^{\sigma(x)}L(x,y),\beta(x,y)),$$ which we refer to as a generalized $\beta$-conformal change. Under this change, we study some special Finsler spaces, namely, quasi C-reducible, semi C-reducible, C-reducible, $C_2$-like, $S_3$-like and $S_4$-like Finsler spaces. We also obtain the transformation of the T-tensor under this change and study some interesting special cases. We then impose a certain condition on the generalized $\beta$-conformal change, which we call the b-condition, and investigate the geometric consequences of such condition. Finally, we give the conditions under which a generalized $\beta$-conformal change is projective and generalize some known results in the literature.Comment: References added, some modifications are performed, LateX file, 24 page

2,20-Dihydroxybenzophenones and their carbonyl N-analogues as inhibitor scaffolds for MDR-involved human glutathione transferase isoenzyme A1-1

The MDR-involved human GSTA1-1, an important isoenzyme overexpressed in several tumors leading to chemotherapeutic-resistant tumour cells, has been targeted by 2,2′-dihydroxybenzophenones and some of their carbonyl N-analogues, as its potential inhibitors. A structure-based library of the latter was built-up by a nucleophilic cleavage of suitably substituted xanthones to 2,2′-dihydroxy-benzophenones (5–9) and subsequent formation of their N-derivatives (oximes 11–13 and N-acyl hydrazones 14–16). Screening against hGSTA1-1 led to benzophenones 6 and 8, and hydrazones 14 and 16, having the highest inhibition potency (IC50 values in the range 0.18 ± 0.02 to 1.77 ± 0.10 μM). Enzyme inhibition kinetics, molecular modeling and docking studies showed that they interact primarily at the CDNB-binding catalytic site of the enzyme. In addition, the results from cytotoxicity studies with human colon adenocarcinoma cells showed low LC50 values for benzophenone 6 and its N-acyl hydrazone analogue 14 (31.4 ± 0.4 μM and 87 ± 1.9 μM, respectively), in addition to the strong enzyme inhibition profile (IC50(6) = 1,77 ± 0.10 μM; IC50(14) = 0.33 ± 0.05 μM). These structures may serve as leads for the design of new potent mono- and bi-functional inhibitors and pro-drugs against human GTSs