Age-specific reproductive investment in female burying beetles: independent effects of state and risk of death

1.How much should an individual invest in reproduction as it grows older? Answering this question involves determining whether individuals measure their age as the time left for future reproduction or as the rate of deterioration in their state. Theory suggests that in the former case individuals should increase their allocation of resources to reproduction as opportunities for future breeding dwindle, and terminally invest when they breed for the last time. In the latter case they should reduce their investment in reproduction with age, either through adaptive reproductive restraint or as a passive by-product of senescence.
2.Here we present the results of experiments on female burying beetles, Nicrophorus vespilloides, in which we independently manipulated the perceived risk of death (by activating the immune system) and the extent of deterioration in state (by changing age of first reproduction and/or prior investment in reproduction).
3.We found that the risk of death and state each independently influenced the extent of reproductive investment. Specifically, we found a state-dependent decline in reproductive investment as females grew older that could be attributed to both adaptive reproductive restraint and senescence. A perceived increase in the risk of death, induced by activation of the immune system, caused females to switch from a strategy of reproductive restraint to terminal investment. Nevertheless, absolute reproductive investment was lower in older females, indicating constraints of senescence.
4.Our results show that a decline in reproductive investment with age does not necessarily constitute evidence of reproductive senescence but can also result from adaptive reproductive restraint.
5.Our results further suggest that the extent of reproductive investment is dependent on several different intrinsic cues and that the particular blend of cues available at any given age can yield very different patterns of investment. Perhaps this explains why age-related reproductive investment patterns seen in nature are so diverse.

Association of LETM1 and MRPL36 Contributes to the Regulation of Mitochondrial ATP Production and Necrotic Cell Death

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is a mitochondrial inner membrane protein that was first identified in Wolf-Hirschhorn syndrome, and was deleted in nearly all patients with the syndrome. LETM1 encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. Here, we describe LETM1-mediated regulation of mitochondrial ATP production and biogenesis. We show that LETM1 overexpression can induce necrotic cell death in HeLa cells, in which LETM1 reduces mitochondria) biogenesis and ATP production. LETM1 acts as an anchor protein and associates with mitochondrial ribosome protein L36. Adenovirus-mediated overexpression of LETM1 reduced mitochondrial mass and expression of many mitochondrial proteins. LETM1-mediated inhibition of mitochondrial biogenesis enhanced glycolytic ATP supply and activated protein kinase B activity and cell survival signaling. The expression levels of LETM1 were significantly increased in multiple human cancer tissues compared with normals. These data suggest that LETM1 serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis. The increased expression of LETM1 in human cancer suggests that deregulation of LETM1 is a key feature of tumorigenesis. [Cancer Res 2009;69(8):3397-404]

Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha

Phosphoinositide 3-kinases produce 3'-phosphorylated phosphoinositides that act as second messengers to recruit other signalling proteins to the membrane(1). Pi3ks are activated by many extracellular stimuli and have been implicated in a variety of cellular responses(1). The Pi3k gene family is complex and the physiological roles of different classes and isoforms are not clear. The gene Pik3r1 encodes three proteins (p85 alpha, p55 alpha and p50 alpha) that serve as regulatory subunits of class I-A Pi3ks (ref. 2). Mice lacking only the p85a isoform are viable but display hypoglycaemia and increased insulin sensitivity correlating with upregulation of the p55 alpha and p50 alpha variants(3). Here we report that loss of all protein products of Pik3r1 results in perinatal lethality. We observed, among other abnormalities, extensive hepatocyte necrosis and chylous ascites, We also noted enlarged skeletal muscle fibres, brown fat necrosis and calcification of cardiac tissue. In liver and muscle, loss of the major regulatory isoform caused a great decrease in expression and activity of class I-A Pi3k catalytic subunits: nevertheless, homozygous mice still displayed hypoglycaemia, lower insulin levels and increased glucose tolerance. Our findings reveal that p55 alpha and/or p50 alpha are required for survival, but not for development of hypoglycaemia, in mice lacking p85 alpha.

Living through the death of a child: A qualitative study of bereaved parents’ experiences

Design: Cross-sectional qualitative study.

Data sources: Interviews with purposeful sample of 25 recently bereaved parents.

Methods: Semi-structured in-depth interviews.

Results: Four analytically distinct processes were identified in the responses of parents to the death of a child. These are referred to as ‘piloting’, ‘providing’, ‘protecting’ and ‘preserving’. Regardless of individual circumstances, these processes were integral to all parents’ coping, enabling an active ‘doing’ for their child and family throughout the trajectory of their child's illness and into bereavement.

Conclusions: Facilitating the capacity of parents to ‘do’ is central to coping with the stress and uncertainty of living through the death of a child. The provision of informational, instrumental and emotional support by health care professionals in the context of ‘doing’ is core to quality palliative care.

Keywords: Bereaved parents; Cancer; Dying child; End-of-life; Palliative care; Non-malignant

The Geography of Conflict and Death in Belfast, Northern Ireland

The conflict known as the oTroubleso in Northern Ireland began during the late 1960s and is defined by political and ethno-sectarian violence between state, pro-state, and anti-state forces. Reasons for the conflict are contested and complicated by social, religious, political, and cultural disputes, with much of the debate concerning the victims of violence hardened by competing propaganda-conditioning perspectives. This article introduces a database holding information on the location of individual fatalities connected with the contemporary Irish conflict. For each victim, it includes a demographic profile, home address, manner of death, and the organization responsible. Employing geographic information system (GIS) techniques, the database is used to measure, map, and analyze the spatial distribution of conflict-related deaths between 1966 and 2007 across Belfast, the capital city of Northern Ireland, with respect to levels of segregation, social and economic deprivation, and interfacing. The GIS analysis includes a kernel density estimator designed to generate smooth intensity surfaces of the conflict-related deaths by both incident and home locations. Neighborhoods with high-intensity surfaces of deaths were those with the highest levels of segregation ( 90 percent Catholic or Protestant) and deprivation, and they were located near physical barriers, the so-called peacelines, between predominantly Catholic and predominantly Protestant communities. Finally, despite the onset of peace and the formation of a power-sharing and devolved administration (the Northern Ireland Assembly), disagreements remain over the responsibility and ocommemorationo of victims, sentiments that still uphold division and atavistic attitudes between spatially divided Catholic and Protestant populations.

Decreased respiratory system compliance on the sixth day of mechanical ventilation is a predictor of death in patients with established acute lung injury

Background: Multiple studies have identified single variables or composite scores that help risk stratify patients at the time of acute lung injury (ALI) diagnosis. However, few studies have addressed the important question of how changes in pulmonary physiologic variables might predict mortality in patients during the subacute or chronic phases of ALI. We studied pulmonary physiologic variables, including respiratory system compliance, P/F ratio and oxygenation index, in a cohort of patients with ALI who survived more than 6 days of mechanical ventilation to see if changes in these variables were predictive of death and whether they are informative about the pathophysiology of subacute ALI.