"Natural cause of death or not?" How do nursing home physicians act when in doubt of natural cause of death?

The objective of the study was to explore if nursing home physicians act by law, when they doubt the natural cause of death. In May 1999, a questionnaire was sent to 153 nursing home physicians in the region of Utrecht and Nijmegen. They were asked if they consult the coroner when they have doubts about the natural cause of death. Eighty-six percent (104) returned the questionnaire. Thirty-two percent of the nursing home physicians always consult the coroner and 52% does so most of the time. Only 12% does not consult the coroner most of the time and 2% never does. The main reasons for not consulting the coroner were that nursing home physicians judge a death after a fall as an incident that fits in the descending lifeline of patients and that some nursing home physicians had bad experiences consulting the coroner. We conclude that this policy may lead to underregistration of unnatural deaths. Changing the definition or changing the law may reduce this problem. Education and information can also contribute to change in physician's attitudes.     

Short telomeres: cause or consequence of aging?

Questions about mechanisms, about the direction of causality, and about cellular heterogeneity complicate interpretation of claims associating short telomeres with adverse health outcomes.     

CD133: holy of grail of neuro‐oncology or promiscuous red‐herring?

The CD133 glycoprotein is a controversial cancer stem cell marker in the field of neuro‐oncology, based largely on the now considerable experimental evidence for the existence of both CD133+ve and CD133?ve populations as tumour‐initiating cells. It is thought that decreasing oxygen tension enhances the complex regulation and phenotype of CD133 in glioma. In light of these ideologies, establishing the precise functional role of CD133 is becoming increasingly critical. In this article, we review the complex regulation of CD133 and its extracellular epitope AC133, and associated alterations, to tumour cell behaviour by hypoxia. Furthermore, its role in functional modulation of tumours, rather than determination of a specific stem cell type is therefore alluded to, while evidence for and against its ability as a cancer stem cell marker in primary brain tumours, is critically evaluated. Thus, the suggestion that CD133 may be a central ‘holy grail’ in identifying core cells for propagation of malignant glial neoplasms seems increasingly less convincing. It remains to be seen, however, whether CD133 is randomly expressed on such brain tumour cell populations or whether it is of major significance to brain biological behaviour.     

Cell size: a matter of life or death?

Proper growth and development of multicellular organisms require the tight regulation of cell growth, cell division and cell death. A recent study has identified a novel regulatory link between two of these processes: cell growth and cell death.     

Daxx: death or survival protein?

The death domain-associated protein (Daxx) was originally cloned as a CD95 (FAS)-interacting protein and modulator of FAS-induced cell death. Daxx accumulates in both the nucleus and the cytoplasm; in the nucleus, Daxx is found associated with the promyelocytic leukaemia (PML) nuclear body and with alpha-thalassemia/mental retardation syndrome protein (ATRX)-positive heterochromatic regions. In the cytoplasm, Daxx has been reported to interact with various proteins involved in cell death regulation. Despite a significant number of studies attempting to determine Daxx function in apoptotic and non-apoptotic cell death, its precise role in this process is only partially understood. Here, we critically review the current understanding of Daxx function and shed new light on this interesting field.     

The hemolymph proteome of the honeybee: Gel‐based or gel‐free?

The honeybee has an invaluable economic impact and is a model for studying immunity, development and social behavior. The recent sequencing and annotation of the honeybee genome facilitates the study of its hemolymph, which reflects the physiological condition and mediates immune responses. We aimed at making a proteomic reference map of honeybee hemolymph and compared gel‐free and gel‐based techniques. One hundered and four 2‐DE spots corresponding to 62 different proteins were identified. Eight identical 2‐DLC experiments resulted in the identification of 32 unique proteins. One repeat was clearly not representative for the potential of the given 2‐DLC setup. Only 27% of the identified hemolymph proteins were found by both techniques. In addition, we found proteins of three different viruses which creates possibilities for biomarker design. Future hemolymph studies will benefit from this work.     

Male genes: X‐pelled or X‐cluded?

Two recent studies by Parisi et al. and Ranz et al., catalogue sex differences in gene expression across the whole genome of the fruit fly Drosophila melanogaster. Both report striking associations of sex-biased gene expression with the X chromosome. Genes with male-biased expression are depauperate on the X chromosome, whereas genes with female-biased expression show weaker evidence of being in excess. A number of evolutionary hypotheses for the expulsion or exclusion of male-biased genes from the X chromosome have been suggested. None is entirely consistent with the available evidence.     

Nitric oxide: promoter or suppressor of programmed cell death?

Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent and-independent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.     

Intermittent hypoxia: cause of or therapy for systemic hypertension?

During acute episodes of hypoxia, chemoreceptor-mediated sympathetic activity increases heart rate, cardiac output, peripheral resistance and systemic arterial pressure. However, different intermittent hypoxia paradigms produce remarkably divergent effects on systemic arterial pressure in the post-hypoxic steady state. The hypertensive effects of obstructive sleep apnea (OSA) vs. the depressor effects of therapeutic hypoxia exemplify this divergence. OSA, a condition afflicting 15-25% of American men and 5-10% of women, has been implicated in the pathogenesis of systemic hypertension and is a major risk factor for heart disease and stroke. OSA imposes a series of brief, intense episodes of hypoxia and hypercapnia, leading to persistent, maladaptive chemoreflex-mediated activation of the sympathetic nervous system which culminates in hypertension. Conversely, extensive evidence in animals and humans has shown controlled intermittent hypoxia conditioning programs to be safe, efficacious modalities for prevention and treatment of hypertension. This article reviews the pertinent literature in an attempt to reconcile the divergent effects of intermittent hypoxia therapy and obstructive sleep apnea on hypertension. Special emphasis is placed on research conducted in the nations of the former Soviet Union, where intermittent hypoxia conditioning programs are being applied therapeutically to treat hypertension in patients. Also reviewed is evidence regarding mechanisms of the pro- and anti-hypertensive effects of intermittent hypoxia.     

Can hyperparasitoids cause large‐scale outbreaks of insect herbivores?

Synchronous population fluctuations occur in many species and have large economic impacts, but remain poorly understood. Dispersal, climate and natural enemies have been hypothesized to cause synchronous population fluctuations across large areas. For example, insect herbivores cause extensive forest defoliation and have many natural enemies, such as parasitoids, that may cause landscape‐scale changes in density. Between outbreaks, parasitoid‐caused mortality of hosts/herbivores is high, but it drops substantially during outbreak episodes. Because of their essential role in regulating herbivore populations, we need to include parasitoids in spatial modelling approaches to more effectively manage insect defoliation. However, classic host‐parasitoid population models predict parasitoid density, and parasitoid density is difficult to relate to host‐level observations of parasitoid‐caused mortality. We constructed a novel model to study how parasitoids affect insect outbreaks at the landscape scale. The model represents metacommunity dynamics, in which herbivore regulation, colonisation and extinction are driven by interactions with the forest, primary parasitoids and hyperparasitoids. The model suggests that parasitoid spatial dynamics can produce landscape‐scale outbreaks. Our results propose the testable prediction that hyperparasitoid prevalence should increase just before the onset of an outbreak because of hyperparasitoid overexploitation. If verified empirically, hyperparasitoid distribution could provide a biotic indicator that an outbreak will occur.     

Trophic control of mesopredators in terrestrial ecosystems: top‐down or bottom‐up?

It has been argued that widespread extinctions of top predators have changed terrestrial ecosystem structures through mesopredator release, where increased abundances of medium-sized predators have detrimental effects on prey communities. This top-down concept has received much attention within conservation biology, but few studies have demonstrated the phenomenon. The concept has been criticized since alternative explanations involving bottom-up impacts from bioclimatic effects on ecosystem productivity and from anthropogenic habitat change are rarely considered. We analyse the response of a mesopredator (the red fox) to declines in top predators (wolf and Eurasian lynx) and agricultural expansion over 90 years in Sweden, taking bioclimatic effects into account. We show a top-down mesopredator release effect, but ecosystem productivity determined its strength. The impacts of agricultural activity were mediated by their effects on top predator populations. Thus, both top-down and bottom-up processes need to be understood for effective preservation of biodiversity in anthropogenically transformed ecosystems.     

NMDA receptor signaling: death or survival?

Glutamate-induced neuronal damage is mainly caused by overactivation of N-methyl-D-aspartate (NMDA) receptors.Conversely,normal physiological brain function and neuronal survival require adequate activ...     

The role of VDAC in cell death: Friend or foe?

As the voltage-dependent anion channel (VDAC) forms the interface between mitochondria and the cytosol, its importance in metabolism is well understood. However, research on VDAC's role in cell death is a rapidly growing field, unfortunately with much confusing and contradictory results. The fact that VDAC plays a role in outer mitochondrial membrane permeabilization is undeniable, however, the mechanisms behind this remain very poorly understood. In this review, we will summarize the studies that show evidence of VDAC playing a role in cell death. To begin, we will discuss the evidence for and against VDAC's involvement in mitochondrial permeability transition (MPT) and attempt to clarify that VDAC is not an essential component of the MPT pore (MPTP). Next, we will evaluate the remaining literature on VDAC in cell death which can be divided into three models: proapoptotic agents escaping through VDAC, VDAC homo- or hetero-oligomerization, or VDAC closure resulting in outer mitochondrial membrane permeabilization through an unknown pathway. We will then discuss the growing list of modulators of VDAC activity that have been associated with induction/protection against cell death. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.     

Virus-induced dysregulation of programmed immunocompetent cell death: pathology or adaptation?

The review summarizes information from recent literature and results of the authors' own investigations concerning dysbalance of programmed cell death in establishment of a long-term virus persistense. The article discusses molecular mechanisms of apoptosis modulation of immune cellls by persistent viruses.     

Morning sickness: adaptive cause or nonadaptive consequence of embryo viability?

"Morning sickness" is the common term for nausea and vomiting in early human pregnancy (NVP). Recent interest in why NVP occurs-that is, in the evolutionary costs and benefits of NVP-has spurred the development of two alternative hypotheses. The "prophylaxis," or "maternal and embryonic protection," hypothesis suggests that NVP serves a beneficial function by expelling foods that may contain harmful toxins and microorganisms and triggering aversions to such foods throughout pregnancy. The alternative "by-product" hypothesis suggests that NVP is a nonfunctional by-product of conflict--over resource allocation--between the pregnant woman and the embryo. The critical predictions of the prophylaxis hypothesis have been developed and tested, whereas the by-product hypothesis has not been subjected to similar scrutiny. To address this gap, we developed a graphical model and used it to derive predictions from the by-product hypothesis under two different assumptions, namely, that NVP is either (i) a by-product of current conflict between a pregnant woman and an embryo or (ii) a by-product of honest signals of viability produced by the embryo. Neither version of the by-product hypothesis is fully consistent with available data. By contrast, the timing of NVP, its variation among societies, and associated patterns of food cravings and aversions are consistent with the prophylaxis hypothesis.