Systems biology and its potential role in radiobiology

About a century ago, Conrad Röentgen discovered X-rays, and Henri Becquerel discovered a new phenomenon, which Marie and Pierre Curie later coined as radio-activity. Since their seminal work, we have learned much about the physical properties of radiation and its effects on living matter. Alas, the more we discover, the more we appreciate the complexity of the biological processes that are triggered by radiation exposure and eventually lead (or do not lead) to disease. Equipped with modern biological methods of high-throughput experimentation, imaging, and vastly increased computational prowess, we are now entering an era where we can piece some of the multifold aspects of radiation exposure and its sequelae together, and develop a more systemic understanding of radiogenic effects such as radio-carcinogenesis than has been possible in the past. It is evident from the complexity of even the known processes that such an understanding can only be gained if it is supported by mathematical models. At this point, the construction of comprehensive models is hampered both by technical inadequacies and a paucity of appropriate data. Nonetheless, some initial steps have been taken already and the generally increased interest in systems biology may be expected to speed up future progress. In this context, we discuss in this article examples of relatively small, yet very useful models that elucidate selected aspects of the effects of exposure to ionizing radiation and may shine a light on the path before us.     

Preparation of pure populations of covalently stabilized amyloid β-protein oligomers of specific sizes

Evidence suggests that amyloid β-protein (Aβ) oligomers may be seminal pathogenic agents in Alzheimer's disease (AD). If so, developing oligomer-targeted therapeutics requires an understanding of oligomer structure. This has been difficult due to the instability of these non-covalently associated Aβ assemblies. We previously used rapid, zero-length, in situ chemical cross-linking to stabilize oligomers of Aβ40. These enabled us to isolate pure, stable populations of dimers, trimers, and tetramers and to determine their structure-activity relationships. However, equivalent methods applied to Aβ42 did not produce stable oligomers. We report here that the use of an Aβ42 homologue, [F10, Y42]Aβ42, coupled with sequential denaturation/dissociation and gel electrophoresis procedures, provides the means to produce highly pure, stable populations of oligomers of sizes ranging from dimer through dodecamer that are suitable for structure-activity relationship determination.     

Species pairs of north temperate freshwater fishes: Evolution,taxonomy, and conservation

Many fish species contain morphologically, ecologically and geneticallydistinct populations that are sympatric during at least some portion oftheir life cycle. Such reproductively isolated populations act asdistinct biological species, but are identified by a common Latinbinomial. These species pairs are particularly common in freshwaterfish families such as Salmonidae, Gasterosteidae and Osmeridae and aretypically associated with postglacial lakes in north temperateenvironments. The nature of the divergences between sympatric species,factors contributing to reproductive isolation, and modes of evolutionare reviewed with particular emphasis on benthic and limnetic pairs ofthreespine sticklebacks, Gasterosteus aculeatus, and anadromous(sockeye salmon) and nonanadromous (kokanee) pairs of Oncorhynchusnerka. Phylogenetic analyses typically indicate that divergencesbetween members of replicate pairs have occurred independently and,hence, particular phenotypes are not monophyletic. Consequently,taxonomic resolution of such species complexes is a vexing problem foradherents to our traditional Linnaean classification system. Sympatricspecies pairs represent a significant component of the biodiversity oftemperate freshwater ecosystems which may be underestimated because oursystem of formal taxonomy tends to obscure diversity encompassed byspecies pairs. Conservation of such systems should be recognized as apriority without formal taxonomic designation of members of speciespairs because taxonomic resolution will likely continue to proveextremely difficult when employing traditional hierarchies andprocedures.     

Barred owl occupancy surveys within the range of the northern spotted owl

The range expansion by barred owls (Strix varia) into western North America has raised considerable concern regarding their potential effects on declining northern spotted owl (Strix occidentalis caurina) populations, yet most information on the occurrence of barred owls in the region is limited to incidental detections during surveys for spotted owls. To address this shortcoming we investigated response behavior, detection probabilities, and landscape occupancy patterns of barred owls in western Oregon, USA, during conspecific versus spotted owl call-broadcast surveys. Subtle differences in barred owl response behavior to conspecific versus spotted owl vocalizations combined with minor procedural differences between species-specific survey protocols led to a sizeable difference in estimated detection probabilities during conspecific (0.66, 95% CI = 0.61–0.71) versus spotted owl (0.48, 95% CI = 0.39–0.56) surveys. We identified 61 territorial pairs of barred owls during repeated surveys of a multi-ownership study area with the probability of occupancy being highest in the structurally diverse mixture of mature and old forests that occurred almost entirely on public lands. Our findings suggest that research and management strategies to address potential competitive interactions between spotted owls and barred owls will require carefully designed, species-specific survey methods that account for erratic response behaviors and imperfect detection of both species. Our sampling methods can be used by forest managers to determine the occurrence and distribution of barred owls with high confidence. © 2011 The Wildlife Society.     

Decline in American marten occupancy rates at Sagehen Experimental Forest,California

We compared the distribution and frequency of American marten (Martes americana) detections during historic surveys and a recent survey on the Sagehen Experimental Forest (SEF) in the Sierra Nevada Mountains, California. This area has been the location of 9 previous marten surveys during 1980–1993, each involving a systematic detection/non-detection survey on the same grid. These data are a time series of information on the occupancy of martens that can be related to habitat change in the study area. Our objectives were to 1) resurvey martens in SEF using methodology similar to previous studies to assess current marten occupancy; 2) evaluate changes in marten occupancy during the period 1980–2008; and 3) examine associations between marten occurence and changes in habitat and landscape metrics. Current marten occupancy was estimated using surveys conducted in summer 2007, winter 2007–2008, and summer 2008. From 1978 to 2007 there was a decrease in predicted habitat patch size, core area, and total amount of marten habitat in the study area, as well as an increase in distance between patches. Marten detections in 2007–2008 were approximately 60% lower than in surveys in the 1980s. We detected no martens in the summers of 2007 and 2008, and 10 detections in winter 2007–2008 were limited to higher elevations in the southwestern portion of SEF. No martens were detected in the lower elevations where most of the recent forest management activity occurred. We suggest that the marten population at SEF has been negatively affected by the loss and fragmentation of habitat. We recommend that future management of forests in the Sagehen basin focus on restoring and connecting residual marten habitat to improve habitat quality for martens. © 2011 The Wildlife Society.