The lipolytic enzyme phospholipase A2 (PLA2) is involved in the degradation of high‐molecular weight phospholipid aggregates in vivo. The enzyme has very high catalytic activities on aggregated substrates compared with monomeric substrates, a phenomenon called interfacial activation. Crystal structures of PLA2s in the absence and presence of inhibitors are identical, from which it has been concluded that enzymatic conformational changes do not play a role in the mechanism of interfacial activation. The high‐resolution NMR structure of porcine pancreatic PLA2 free in solution was determined with heteronuclear multidimensional NMR methodology using doubly labeled 13C, 15N‐labeled protein. The solution structure of PLA2 shows important deviations from the crystal structure. In the NMR structure the Ala1 alpha‐amino group is disordered and the hydrogen bonding network involving the N‐terminus and the active site is incomplete. The disorder observed for the N‐terminal region of PLA2 in the solution structure could be related to the low activity of the enzyme towards monomeric substrates. The NMR structure of PLA2 suggests, in contrast to the crystallographic work, that conformational changes do play a role in the interfacial activation of this enzyme.
Up to 4 years after the disaster, symptoms were more prevalent among survivors than controls. Although medical disorders cannot be excluded, the reported symptoms showed several features similar to those of medically unexplained symptoms in the general population.
BackgroundDisaster experiences have been associated with higher prevalence rates of (mental) health problems. The objective of this study was to examine the independent relation between a series of single disaster experiences versus the independent predictive value of a accumulation of disaster experiences, i.e. a sum score of experiences and symptoms of distress and post-traumatic stress disorder (PTSD).MethodsSurvivors of a fireworks disaster participated in a longitudinal study and completed a questionnaire three weeks (wave 1), eighteen months (wave 2) and four years post-disaster (wave 3). Ten years post-disaster (wave 4) the respondents consisted of native Dutch survivors only. Main outcome measures were general distress and symptoms of PTSD.ResultsDegree of disaster exposure (sum score) and some disaster-related experiences (such as house destroyed, injured, confusion) were related to distress at waves 2 and 3. This relation was mediated by distress at an earlier point in time. None of the individual disaster-related experiences was independently related to symptoms of distress. The association between the degree of disaster exposure and symptoms of PTSD at waves 2 and 3 was still statistically significant after controlling for symptoms of distress and PTSD at earlier point in time. The variable ‘house destroyed’ was the only factor that was independently related to symptoms of PTSD at wave 2. Ten years after the disaster, disaster exposure was mediated by symptoms of PTSD at waves 2 and 3. Disaster exposure was not independently related to symptoms of PTSD ten years post-disaster.ConclusionsUntil 4 years after the disaster, degree of exposure (a sum score) was a risk factor for PTSD symptoms while none of the individual disaster experiences could be identified as an independent risk factor. Ten years post-disaster, disaster exposure was no longer an independent risk factor for symptoms of PTSD. Since symptoms of PTSD and distress at earlier waves perpetuate the symptoms at later waves, health care workers should aim their resources at those who still have symptoms after one and a half year post-disaster, to prevent health problems at medium and long-term.
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