Comparison of metal ion-induced conformational changes in parvalbumin and oncomodulin as probed by the intrinsic fluorescence of tryptophan 102.

The calcium-induced conformational changes of the 108-amino acid residue proteins, cod III parvalbumin and oncomodulin, were compared using tryptophan as a sensitive spectroscopic probe. As native oncomodulin is devoid of tryptophan, site-specific mutagenesis was performed to create a mutant protein in which tryptophan was placed in the identical position (residue 102) as the single tryptophan residue in cod III parvalbumin. The results showed that in the region probed by tryptophan-102, cod III parvalbumin experienced significantly greater changes in conformation upon decalcification compared to the oncomodulin mutant, F102W. Addition of 1 eq of Ca2+ produced greater than 90% of the total fluorescence response in F102W, while in cod III parvalbumin, only 74% of the total was observed. Cod III parvalbumin displayed a negligible response upon Mg2+ addition. In contrast, F102W did respond to Mg2+, but the response was considerably less when compared to Ca2+ addition. Time-resolved fluorescence showed that the tryptophan in both proteins existed in at least two conformational states in the presence of Ca2+ and at least three conformational states in its absence. Comparison with quantum yield measurements indicated that the local electronic environment of the tryptophan was significantly different in the two proteins. Collectively, these results demonstrate that both cod III parvalbumin and oncomodulin undergo Ca2(+)-specific conformational changes. However, oncomodulin is distinct from cod III parvalbumin in terms of the electronic environment of the hydrophobic core, the magnitude of the Ca2(+)-induced conformational changes, and the number of calcium ions required to modulate the major conformational changes

Identity threat and identity multiplicity among minority youth: Longitudinal relations of perceived discrimination with ethnic, religious, and national identification in Germany

The notion that ethnic and religious minority identities are inherently incompatible with the national identities of European immigrant‐receiving societies is popular in public discourse. Although findings documenting such negative associations seemingly support this claim, other research shows that the intergroup context matters for the extent to which minorities’ ethnic and religious identities are conflicting (i.e., negatively associated) or compatible (i.e., positively associated) with European national identities. However, previous research relied on cross‐sectional data and therefore could not capture the dynamic process through which minority youth come to develop compatible or conflicting identification patterns. We extend this work with a longitudinal approach by capturing developmental trajectories of identity multiplicity among ethnic minority early adolescents in Germany over three waves with 9‐month intervals. At each measurement point, participants reported their ethnic, religious, and (German) national identification and their experiences with discriminatory treatment. We estimate a cross‐lagged panel model to study how identification relates to perceived discrimination and how this affects (changes in) associations between ethnic, religious, and national identification of minority youth. Our results show prevalent positive associations between ethnic, religious, and national identification across minority youth in the sample. Those who report more frequent discrimination, however, lower their (German) national identification over time, which in turn predicts increased minority identification. We conclude that identity threat indeed triggers a development of more conflicting identification patterns

Delineating ethnic and religious identities in research with British South Asians

The present essay presents a rationale for delineating ethnic and religious identities in empirical research into self-identification among British South Asians. It is argued that the delineation of these identities is important in order to (i) predict and explain the identificatory possibilities available to these individuals; (ii) explore the differential values attributed to these identities; (iii) the level of psychological 'connectedness' between the identities; and (iv) the inter-relations between these identities, particularly in relation to psychological coherence. It is argued that a systematic delineation of these identities may have favourable theoretical, empirical and practical outcomes

Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future

The key clinical attributes of preserved dorzolamide/timolol fixed combination (DTFC) and the emerging potential of preservative-free (PF) DTFC are reviewed with published evidence and clinical experience. The indications and role of DTFC in current glaucoma management are critically discussed. Preserved DTFC became the first intraocular pressure (IOP)-lowering fixed combination (FC) approved by the US Food and Drug Administration (FDA) and remains one of most commonly used medications worldwide. The pharmacological properties of DTFC reflect those of its two time-tested constituents, i.e., the carbonic anhydrase inhibitor dorzolamide and the non-selective beta-blocker timolol. In regulatory studies DTFC lowers IOP on average by 9 mmHg (32.7%) at peak and by 7.7 mmHg (27%) at trough. In trials DTFC shows equivalence to unfixed concomitant therapy, but in real-life practice it may prove superior owing to enhanced convenience, elimination of the washout effect from the second drop, improved tolerability, and better adherence. PF DTFC became the first PF FC approved, first in unit-dose pipettes, and more recently in a multidose format. Cumulative evidence has confirmed that PF DTFC is at least equivalent in efficacy to preserved DTFC and provides a tangible clinical benefit to patients with glaucoma suffering from ocular surface disease by improving tolerability and adherence. Finally, we identify areas that warrant further investigation with preserved and PF DTF