Oligodeoxynucleotide 5mers containing a 5'-CpG induce apoptosis through a mitochondrial mechanism in T lymphocytic leukaemia cells

A chimeric methylphosphonodiester/phosphodiester 15mer oligodeoxynucleotide of randomly selected sequence was observed to rapidly induce apoptosis in MOLT-4 and Jurkat E6 T lymphocytic leukaemia cells following intracytoplasmic delivery. A series of further methylphosphonate substitutions and mutations and truncations of the oligodeoxynucleotide served to establish that the phosphodiester-linked sequence CGGTA present in the 15mer was responsible for this biological activity. End-protected CpG oligodeoxynucleotide 5mers of sequence type CGNNN exhibited a range of apoptosis-inducing potencies, with CGTTA being the most active. The latter was shown to significantly reduce the rate of RNA synthesis in MOLT-4 cells within 1 h; DNA laddering and redistribution of phosphatidylserine to the outer surface of the plasma membrane were marked by 160 min and mitochondrial transmembrane potential collapsed over roughly the same time scale. Pro-caspase 8 was reduced within 130 min and the proteolytically activated caspase 8 substrate Bid was also down by this time, implicating release of cytochrome c from mitochondria by the active 15 kDa fragment of Bid. Substantial proteolytic activation of pro-caspase 3 was relatively delayed. These findings support a mitochondrial amplification mechanism for apoptosis triggered by CpG 5mers.     

Defining the role of laminin-332 in carcinoma

The deadly feature of cancer, metastasis, requires invasion of cells through basement membranes (BM), which normally act as barriers between tissue compartments. In the case of many epithelially-derived cancers (carcinomas), laminin-332 (Ln-332) is a key component of the BM barrier. This review provides a historical examination of Ln-332 from its discovery through identification of its functions in BM and possible role in carcinomas. Current understanding points to distinct roles for the three Ln-332 subunits (α3, β3, γ2) in cell adhesion, extracellular matrix stability, and cell signaling processes in cancer. Given the large number of studies linking Ln-332 γ2 subunit with cancer prognosis, particular attention is given to the crucial role of this subunit in cancer invasion and to the unanswered questions in this area.     

Fishing for Space: Fine-Scale Multi-Sector Maritime Activities Influence Fisher Location Choice

The European Union and other states are moving towards Ecosystem Based Fisheries Management to balance food production and security with wider ecosystem concerns. Fishing is only one of several sectors operating within the ocean environment, competing for renewable and non-renewable resources that overlap in a limited space. Other sectors include marine mining, energy generation, recreation, transport and conservation. Trade-offs of these competing sectors are already part of the process but attempts to detail how the seas are being utilised have been primarily based on compilations of data on human activity at large spatial scales. Advances including satellite and shipping automatic tracking enable investigation of factors influencing fishers’ choice of fishing grounds at spatial scales relevant to decision-making, including the presence or avoidance of activities by other sectors. We analyse the determinants of English and Welsh scallop-dredging fleet behaviour, including competing sectors, operating in the eastern English Channel. Results indicate aggregate mining activity, maritime traffic, increased fishing costs, and the English inshore 6 and French 12 nautical mile limits negatively impact fishers’ likelihood of fishing in otherwise suitable areas. Past success, net-benefits and fishing within the 12 NM predispose fishers to use areas. Systematic conservation planning has yet to be widely applied in marine systems, and the dynamics of spatial overlap of fishing with other activities have not been studied at scales relevant to fisher decision-making. This study demonstrates fisher decision-making is indeed affected by the real-time presence of other sectors in an area, and therefore trade-offs which need to be accounted for in marine planning. As marine resource extraction demands intensify, governments will need to take a more proactive approach to resolving these trade-offs, and studies such as this will be required as the evidential foundation for future seascape planning.     

Helicobacter anseris sp. nov. and Helicobacter brantae sp. nov., isolated from feces of resident Canada geese in the greater Boston area

Numbers of nonmigratory Canada geese have increased substantially in the past decade, and they have become a nuisance in some urban areas. Because of their close contact with humans in parks and areas adjacent to surface waterways, contact with their feces poses a zoonotic risk. A total of 97 geese from 10 separate geographic locales in the greater Boston area had their feces sampled for detection of Helicobacter spp. Identification of Helicobacter spp. based on 16S rRNA genus-specific helicobacter primers was noted in 39 of 97 (40.2%) DNA fecal extracts. Twenty-seven (27.8%) of these geese had helicobacters isolated from their feces. A urease-positive novel species, Helicobacter anseris, based on phenotypic, biochemical, and 16S rRNA analyses, was isolated from 20 geese from seven different flocks. A second, novel, urease-negative Helicobacter sp., H. brantae, was identified in seven geese. Four geese had both novel Helicobacter spp. cultured from their feces. Whether these two novel helicobacters pose a zoonotic risk, similar to other enteric helicobacters (e.g., H. canadensis, previously isolated from diarrheic and bacteremic humans and from geese in Europe), will require further studies.     

Initial results for urban metal distributions in house dusts of syracuse,New York,USA

A program of house dust sample collection and analysis has begun in Syracuse, New York, USA, in order to determine the feasibility of a geography-based exposure assessment for urban metals. The sampling program, and the protocols it employs, is described for two different types of wipe media, Ghost Wipes and Whatman Filters. Preliminary results show that strong spatial patterns of floor dust loading (mg dust per square foot) can be observed for data aggregated at a spatial scale of about 1600 m (～2.5 km²). Floor dust metal concentrations were similar to those found in other urban environments, with some regional variation. The median floor dust Pb concentration was ～108 mg · kg^?1 for this initial data set of ～264 sampled residential locations, and varied from 50 to 1100 mg Pb · kg^?1.     

Phenology and North Sea cod Gadus morhua L.: has climate change affected otolith annulus formation and growth?

Timing and rate of seasonal zone formation in southern North Sea cod Gadus morhua otoliths was studied. Samples were taken from two time periods, representing low and high temperature regimes. Opaque zones were laid down between January and June, in contrast with the pattern described in other published studies. Translucent zone formation started earlier in the warmer period, corresponding to peak annual sea surface temperatures, and a period of slow body growth and low metabolic activity. Translucent zone formation, however, continued once temperatures decreased and growth rate increased. It is hypothesized that translucent zone formation is triggered at a threshold of metabolic stress, and that the combined energetic requirements of reproduction, growth and migration may maintain translucent zone formation even if feeding conditions improve. Higher temperatures had a significant negative effect on the rate of translucent zone deposition, but caused a slight increase in opaque zone formation rate. The findings of this study indicate that historical otolith collections could provide key inputs into future phenological studies to improve the understanding of climate change impacts and the dynamics of otolith structure.     

Identification of a good c-myc antisense oligodeoxynucleotide target site and the inactivity at this site of novel NCH triplet--targeting ribozymes.

A region of c-myc mRNA was identified which permitted very efficient antisense effects to be achieved in living cells using chimeric methylphosphonate--phosphodiester antisense effectors. Novel inosine--containing ribozymes (which cleave after NCH triplets) were directed to an ACA triplet within this region and delivered into living cells. No ribozyme intracellular activity could be identified. Very low ribozyme function was also observed in in vitro assays using a 1700nt substrate RNA.