Macromolecular crystallography radiation damage research: what’s new?

An introductory overview of the special issue papers on radiation damage in this issue.

The Ratio of ADP- to TRAP-Induced Platelet Aggregation Quantifies P2Y(12)-Dependent Platelet Inhibition Independently of the Platelet Count

Objective This study aimed to assess the association of clinical factors with P2Y(12)-dependent platelet inhibition as monitored by the ratio of ADP-to TRAP-induced platelet aggregation and conventional ADP-induced aggregation, respectively. Background Controversial findings to identify and overcome high platelet reactivity (HPR) after coronary stent-implantation and to improve clinical outcome by tailored anti-platelet therapy exist. Monitoring anti-platelet therapy ex vivo underlies several confounding parameters causing that ex vivo platelet aggregation might not reflect in vivo platelet inhibition. Methods In a single centre observational study, multiple electrode aggregometry was performed in whole blood of patients after recent coronary stent-implantation. Relative ADP-induced aggregation (r-ADP-agg) was defined as the ratio of ADP-to TRAP-induced aggregation reflecting the individual degree of P2Y(12)-mediated platelet reactivity. Results Platelet aggregation was assessed in 359 patients. Means (+/- SD) of TRAP-, ADP-induced aggregation and r-ADP-agg were 794 +/- 239 AU* min, 297 +/- 153 AU* min and 37 +/- 14%, respectively. While ADP-and TRAP-induced platelet aggregation correlated significantly with platelet count (ADP: r = 0.302;p< 0.001;TRAP: r = 0.509 p< 0.001), r-ADP-agg values did not (r = -0.003;p = 0.960). These findings were unaltered in multivariate analyses adjusting for a range of factors potentially influencing platelet aggregation. The presence of an acute coronary syndrome and body weight were found to correlate with both ADP-induced platelet aggregation and r-ADP-agg. Conclusion The ratio of ADP-to TRAP-induced platelet aggregation quantifies P2Y(12)-dependent platelet inhibition independently of the platelet count in contrast to conventional ADP-induced aggregation. Furthermore, r-ADP-agg was associated with the presence of an acute coronary syndrome and body weight as well as ADP-induced aggregation. Thus, the r-ADP-agg is a more valid reflecting platelet aggregation and potentially prognosis after coronary stent-implantation in P2Y(12)-mediated HPR than conventional ADP-induced platelet aggregation

Colouring cryo-cooled crystals: online microspectrophotometry

A portable and readily aligned online microspectrophotometer that can be easily installed on macromolecular crystallography beamlines is described. It allows measurement of the spectral characteristics of macromolecular crystals prior, during, and after the X-ray diffraction experiment

Photochemical mechanism of an atypical algal phytochrome

International audiencePhytochromes are bilin-containing photoreceptors that are typically sensitive to the red/far-red region of the visible spectrum. Recently, phytochromes from certain eukaryotic algae have become attractive targets for optogenetic applications because of their unique ability to respond to multiple wavelengths of light. Herein, a combination of time-resolved spectroscopy and structural approaches across picosecond to second timescales have been used to map photochemical mechanisms and structural changes in this atypical group of phytochromes. The photochemistry of an orange/far-red light-sensitive algal phytochrome from Dolihomastix tenuilepis has been investigated by using a combination of visible, IR and X-ray scattering probes. The entire photocycle, correlated with accompanying structural changes in the cofactor/protein, are reported. This study identifies a complex photocycle for this atypical phytochrome. It also highlights a need to combine outcomes from a range of biophysical approaches to unravel complex photochemical and macromolecular processes in multi-domain photoreceptor proteins that are the basis of biological light-mediated signalling

Structure and function of an insect α-carboxylesterase (α Esterase 7) associated with insecticide resistance

Insect carboxylesterases from the αEsterase gene cluster, such as αE7 (also known as E3) from the Australian sheep blowfly Lucilia cuprina (LcαE7), play an important physiological role in lipid metabolism and are implicated in the detoxification of or

Potenziale einer Multikuppelbarkeit im Schienenpersonennahverkehr

DE: Ein Großteil der Triebzüge im deutschen Schienenpersonennahverkehr besitzt die Scharfenbergkupplung Typ 10, die meist mechanisches und pneumatisches Kuppeln ermöglicht. Elektro-Kupplungen und Leittechnik sind aufgrund fehlender Normung größtenteils inkompatibel, sodass ein gekuppelter Betrieb unterschiedlicher Fahrzeugbaureihen nicht oder nur eingeschränkt möglich ist. Eine uneingeschränkte Kuppelbarkeit der Triebzüge könnte große Potenziale im täglichen Betrieb erschließen. Für diese Analyse wurde untersucht, welche technischen Maßnahmen eine Multikuppelbarkeit erfordert, wie regulatorische Anpassungen gestaltet werden könnten und welche betrieblichen Auswirkungen hierdurch zu erwarten sind. Erste Ergebnisse zeigen, dass durch eine Multikuppelbarkeit die Zahl an Direktverbindungen erhöht werden kann. Darüber hinaus kann die betriebliche Flexibilität durch den wechselseitigen Einsatz von Fahrzeugen gesteigert werden. Eine große Herausforderung stellt jedoch die Kuppelzeit innerhalb der Bahnhöfe und die damit verbundene Gleisbelegungszeit des Zuges dar. EN: The majority of multiple units in the German local rail passenger transport system have the Scharfenberg coupler type 10, which mostly allows mechanical and pneumatic coupling. Due to a lack of standardization, electric couplers and control technology are largely incompatible, so that coupled operation of different vehicle series is not possible or only possible to a limited extent. Unrestricted couplability of multiple units could open up great potential in daily operation. For this analysis, the technical measures required for multi-couplability were investigated, as well as how regulatory adjustments could be designed and what operational effects can be expected as a result. Initial results show that multicouplability can increase the number of direct connections. In addition, operational flexibility can be increased through the alternating use of vehicles. However, the coupling time within the stations and the associated track occupation time of the train pose a major challenge

Temperature-dependent macromolecular X-ray crystallography

The dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed