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

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

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Discovery and insights from DSX mission's high-power VLF wave transmission experiments in the radiation belts.

Space weather phenomena can threaten space technologies. A hazard among these is the population of relativistic electrons in the Van Allen radiation belts. To reduce the threat, artificial processes can be introduced by transmitting very-low-frequency (VLF) waves into the belts. The resulting wave-particle interactions may deplete these harmful electrons. However, when transmitting VLF waves in space plasma, the antenna, plasma, and waves interact in a manner that is not well-understood. We conducted a series of VLF transmission experiments in the radiation belts and measured the power and radiation impedance under various frequencies and conditions. The results demonstrate the critical role played by the plasma-antenna-wave interaction around high-voltage space antennae and open the possibility to transmit high power in space. The physical insight obtained in this study can provide guidance to future high-power space-borne VLF transmitter developments, laboratory whistler-mode wave injection experiments, and the interpretation of various astrophysical and optical phenomena

The Photospheric Convection Spectrum

Abstract. Spectra of the cellular photospheric flows are determined from observations acquired by the MDI instrument on the SOHO spacecraft. Spherical harmonic spectra are obtained from the full-disk observations. Fourier spectra are obtained from the high-resolution observations. The p-mode oscillation signal and instrumental artifacts are reduced by temporal filtering of the Doppler data. The resulting spectra give power (kinetic energy) per wave number for effective spherical harmonic degrees from 1 to over 3000. Significant power is found at all wavenumbers, including the small wavenumbers representative of giant cells. The time evolution of the spectral coefficients indicates that these small wavenumber components rotate at the solar rotation rate and thus represent a com-ponent of the photospheric cellular flows. The spectra show distinct peaks representing granules and supergranules but no distinct features at wavenumbers representative of mesogranules or giant cells. The observed cellular patterns and spectra are well represented by a model that includes two distinct modes – granules and supergranules. 1

Snudging cheapskates and magnificent profusion : the conceptual baggage of ‘mean’ and ‘generous’

The way people behave with money communicates a great deal about their character. In this chapter, we examine the ‘conceptual baggage’ (McConnell-Ginet, Language, 84(3), 497–527, 2008) for synonyms of ‘mean’ and ‘generous’. Drawing data from The Historical Thesaurus, we show that generosity is connected to positive assessments across a range of fields, including appearance, morality and space, while meanness is similarly widely disparaged. Drawing out the ideological connections between the lexical items and their cultural baggage, we argue that ‘wealth’ operates as a synonym for goodness, while ‘poverty’ functions as a synonym of badness. In order to challenge this, we suggest that attention be paid to ‘relative generosity’ and demonstrate how results from data analysis can be used to critically assess the prevailing economic orthodoxy