Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

The Paradox of Engagement: Land Stewardship and Invasive Weeds in Amenity Landscapes

In New South Wales, Australia, rural landscapes are undergoing profound change as a result of exurbanization. Newcomers-amenity migrants-are drawn to the scenic beaches, forests, and open landscape character of this part of Australia near Sydney and they join existing communities of long-term residents, notably ranchers involved in dairy, beef, and other types of primary agricultural production. The rural to exurban transition is stimulating both intended and unintended socio-ecological changes, especially the proliferation of invasive weeds, which are considered to be a top national priority as they threaten Australia\u27s agricultural economy. Drawing on interview and survey research from three case studies in New South Wales, locations where an influx of exurbanites has led to mixed landscapes of production and consumption, we explore landowners\u27 diverse environmental ideologies, the degree to which they collaborate with one another, and their specific land-use practices. Results show that an overwhelming majority of both exurbanites and ranchers express concerns about weeds, but there is a marked lack of coordinated engagement on invasive species between the two types of groups. This chapter is an example of social disengagement over land-use and land-cover change, rather than competition or cooperation, and contributes to a political ecological understanding of the co-construction of social relations and land management regimes

Identification and Replication of a Novel Obesity Locus on Chromosome 1q24 in Isolated Populations of Cilento.

Objective: Obesity is a complex trait with a variety of genetic susceptibility variants. Several loci linked to obesity and/or obesity-related traits have been identified so far and relatively few regions have been replicated. Isolated populations can be a useful approach to identify rare variants, that will not be detected with whole genome association studies in large populations. Research Design and Methods: Random individuals are sampled from Campora, an isolated village of the Cilento area in South Italy, phenotyped for body mass index (BMI) and genotyped a dense microsatellite marker map. An efficient pedigree-breaking strategy is applied to perform genome-wide linkage analyses of both BMI and obesity. Significance is assessed with ad hoc simulations for the two traits and with an original lFDR approach to quantitative trait linkage analysis for BMI. A genealogy-corrected association test is performed for a SNP located in one of the linkage regions. A replication study is conducted in the neighboring village of Gioi. Results: A new locus on chr1q24 significantly linked to BMI is identified in Campora. Linkage at the same locus is suggested with obesity. Three additional loci linked to BMI are also detected. Among them, the locus including the INSIG2 gene region. No evidence of association between the rs7566605 variant and BMI or obesity is found. In Gioi, the linkage on chr1q24 is replicated with both BMI and obesity. Conclusions: Overall our results confirm that successful linkage studies can be accomplished in these populations both to replicate known linkages and to identify novel QTLs

Grey Nurse Shark (Carcharias taurus) Diving Tourism: Tourist Compliance and Shark Behaviour at Fish Rock, Australia

Humans can dive with critically endangered grey nurse sharks (Carcharias taurus) along the east coast of Australia. This study investigated both compliance of tourist divers to a code of conduct and legislation and the behaviour of grey nurse sharks in the presence of divers. A total of 25 data collection dives were conducted from December 2008 to January 2009. Grey nurse shark and diver behaviour were documented using 2-min scan samples and continuous observation. The proportion of time spent observing human–shark interactions was 9.4% of total field time and mean human–shark interaction time was 15.0 min. Results were used to gauge the effectiveness of current management practices for the grey nurse shark dive industry at Fish Rock in New South Wales, Australia. Grey nurse shark dive tourists were compliant to stipulations in the code of conduct and legislation (compliance ranged from 88 to 100%). The research detailed factors that may promote compliance in wildlife tourism operations such as the clarity of the stipulations, locality of the target species and diver perceptions of sharks. Results indicated that grey nurse sharks spent the majority of their time milling (85%) followed by active swimming (15%). Milling behaviour significantly decreased in the presence of more than six divers. Distance between sharks and divers, interaction time and number of sharks were not significantly correlated with grey nurse shark school behaviour. Jaw gaping, rapid withdrawal and stiff or jerky movement were the specific behaviours of grey nurse sharks that occurred most frequently and were associated with distance between divers and sharks and the presence of six or more divers. Revision of the number of divers allowed per interaction with a school of grey nurse sharks and further research on the potential impacts that shark-diving tourism may pose to grey nurse sharks is recommended

Cardiolipin and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis

We previously reported that during death receptor-mediated apoptosis, cardiolipin (CL) relocates to the cell surface, where it reacts with autoantibodies from antiphospholipid syndrome sera. Here, we analysed the intracellular distribution of CL and its metabolites during the early phase of cell death signalling triggered by Fas stimulation in U937 cells and mouse liver. We found a redistribution of mitochondrial CL to the cell surface by using confocal microscopy and flow cytometry. Mass spectrometry revealed that CL and its metabolites relocated from mitochondria to other intracellular organelles during apoptosis, with a conversion into non-mitochondrial lipids. Concomitantly, cytosolic Bid relocated to the light membranes comprised in fraction P100, including the plasma membrane and associated vesicular systems. A direct Bid-CL interaction was demonstrated by the observation that CL and monolysoCL coimmunoprecipitated with Bid especially after Fas stimulation, suggesting a dynamic interaction of the protein with CL and its metabolites. © 2004 Nature Publishing Group All rights reserved