16 research outputs found

    Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins

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    Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD+ tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase β, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care

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    Large-amplitude cycles of Daphnia and its algal prey in enriched environments

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    Ecological theory predicts that stable populations should yield to large-amplitude cycles in richer environments1±3. This does not occur in nature. The zooplankton Daphnia and its algal prey in lakes throughout the world illustrate the problem4±6. Experiments show that this system its the theory's assumptions7±9, yet it is not destabilized by enrichment 6. We have tested and rejected four of ive proposed explanations 10. Here, we investigate the fifth mechanism: inedible algae in nutrient-rich lakes suppress cycles by reducing nutrients available to edible algae. We found three novel results in nutrient-rich microcosms from which inedible algae were excluded. First, as predicted by theory, some Daphniaedible algal systems now display large-amplitude predator-prey cycles. Second, in the same environment, other populations are stable, showing only small-amplitude demographic cycles. Stability is induced when Daphnia diverts energy from the immediate production of young. Third, the system exhibits coexisting attractors -a stable equilibrium and large-amplitude cycle. We describe a mechanism that flips the system between these two states
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