Size-selective fishing drives species composition in the Celtic Sea

Fishing alters community size structure by selectively removing larger individual fish and by changing the relative abundance of different-sized species. To assess the relative importance of individual-and species-level effects, two indices of fish community structure were compared, the relative abundance of large fish individuals (large fish indicator, LFI) and the relative abundance of large fish species (large species indicator, LSI). The two indices were strongly correlated for empirical data from the Celtic Sea and for data from simulated model communities, suggesting that much of the variability in the LFI is caused by shifts in the relative abundance of species (LSI). This correlation is explained by the observation that most of the biomass of a given species is spread over few length classes, a range spanning the factor 2 of individual length, such that most species contributed predominantly to either the small or the large component of the LFI. The results suggest that the effects of size-selective fishing in the Celtic Sea are mediated mainly through changes in community composition.

Functional analysis of predicted coiled-coil regions in the Escherichia coli K-12 O-antigen polysaccharide chain length determinant Wzz

Wzz is a membrane protein that determines the chain length distribution of the O-antigen lipopolysaccharide by an unknown mechanism. Wzz proteins consist of two transmembrane helices separated by a large periplasmic loop. The periplasmic loop of Escherichia coli K-12 Wzz (244 amino acids from K65 to A308) was purified and found to be a monomer with an extended conformation, as determined by gel filtration chromatography and analytical ultracentrifugation. Circular dichroism showed that the loop has a 60% helical content. The Wzz periplasmic loop also contains three regions with predicted coiled coils. To probe the function of the predicted coiled coils, we constructed amino acid replacement mutants of the E. coli K-12 Wzz protein, which were designed so that the coiled coils could be separate without compromising the helicity of the individual molecules. Mutations in one of the regions, spanning amino acids 108 to 130 (region I), were associated with a partial defect in O-antigen chain length distribution, while mutants with mutations in the region spanning amino acids 209 to 223 (region III) did not have an apparent functional defect. In contrast, mutations in the region spanning amino acids 153 to 173 (region II) eliminated the Wzz function. This phenotype was associated with protein instability, most likely due to conformational changes caused by the amino acid replacements, which was confirmed by limited trypsin proteolysis. Additional mutagenesis based on a three-dimensional model of region I demonstrated that the amino acids implicated in function are all located at the same face of a predicted alpha-helix, suggesting that a coiled coil actually does not exist in this region. Together, our results suggest that the regions predicted to be coiled coils are important for Wzz function because they maintain the native conformation of the protein, although the existence of coiled coils could not be demonstrated experimentally.

A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma

Oxidative stress appears to be important in the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Single-nucleotide polymorphisms (SNPs) of antioxidant enzyme genes may play a part in determining individual susceptibility to these diseases. The Factors Influencing the Barrett's Adenocarcinoma Relationship (FINBAR) study is a population-based, case-control study of BE and EAC in Ireland. DNA from EAC (n = 207), BE (> or =3 cm BE at endoscopy with specialized intestinal metaplasia on biopsy, n = 189) and normal population controls (n = 223) were analyzed. Several SNPs spanning the genes for glutathione S-transferase P1 (GSTP1), manganese superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPX2) were genotyped using multiplex polymerase chain reaction and SNaPshottrade mark. The chi(2) test was used to compare genotype and allele frequencies between case and control subjects. Linkage disequilibrium between SNPs was quantified using Lewontin's D' value and haplotype frequency estimates obtained using Haploview. Eleven SNPs were genotyped (six for GSTP1, three for MnSOD and two for GPX2); all were in Hardy-Weinberg equilibrium. None was significantly associated with EAC or BE even before Bonferroni correction. Odds ratios for EAC for individual SNPs ranged from 0.68 [95% confidence interval (CI) 0.43-1.08] to 1.25 (95% CI 0.73-2.16), and for BE from 0.84 (95% CI 0.52-1.30) to 1.30 (95% CI 0.85-1.97). SNPs in all three genes were in strong linkage disequilibrium (D' > 0.887) but haplotype analysis did not show any significant association with EAC or BE. SNPs involving the GSTP1, MnSOD and GPX2 genes were not associated with BE or EAC. Further studies aimed at identifying susceptibility genes should focus on different antioxidant genes or different pathways.

Predictive markers for colorectal cancer:current status and future prospects

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Although there is clear evidence of the benefit of chemotherapy in adjuvant and metastatic settings, its use continues to be suboptimal because of intrinsic or acquired drug resistance. 5-Fluorouracil continues to be the mainstay of CRC therapy, and combinations with newer chemotherapeutic agents such as irinotecan and oxaliplatin have resulted in improved response rates and survival. The role of other agents including cyclooxygenase-2 inhibitors, epidermal growth factor receptor, and farnsyl transferase inhibitors remains to be elucidated. Despite these improvements, many patients undergo chemotherapy without benefit. Increased understanding of the biology of CRC has led to the identification of prognostic markers that may help identify patients who will benefit from chemotherapy. Furthermore, studies have also begun to identify markers that predict whether a tumor will respond to a particular chemotherapy. The ultimate goal of this research is to prospectively identify patients who should receive chemotherapy and, thus, to tailor treatment to the molecular profile of the tumor and patient. Such an approach has the potential to dramatically improve response rates. This review highlights potentially important prognostic and predictive factors in CRC and discusses the potential for their use in the treatment of this disease.

A calcium-dependent interaction between calmodulin and the calponin homology domain of human IQGAP1

IQGAPs are cytoskeletal scaffolding proteins which collect information from a variety of signalling pathways and pass it on to the microfilaments and microtubules. There is a well-characterised interaction between IQGAP and calmodulin through a series of IQ-motifs towards the middle of the primary sequence. However, it has been shown previously that the calponin homology domain (CHD), located at the N-terminus of the protein, can also interact weakly with calmodulin. Using a recombinant fragment of human IQGAP1 which encompasses the CHD, we have demonstrated that the CHD undergoes a calcium ion-dependent interaction with calmodulin. The CHD can also displace the hydrophobic fluorescent probe 1-anilinonaphthalene-8-sulphonate from calcium-calmodulin, suggesting that the interaction involves non-polar residues on the surface of calmodulin. Molecular modelling identified a possible site on the CHD for calmodulin interaction. The physiological significance of this interaction remains to be discovered.

The role of p63 in epidermal morphogenesis and neoplasia

The p53 family of transcription factors is made up of p53, p63 and p73, which share significant structural homology. In particular, transcriptional complexity and the expression of multiple protein isoforms are an emergent trait of all family members. p63 is the evolutionarily eldest member of the p53 family and the various isoforms have critical roles in the development of stratifying epithelia. Recent results have uncovered additional splice variants, adding to the complexity of the transcriptional architecture of p63. These observations and the emerging extensive interplay between p63 and p53 in development, proliferation and differentiation underline the importance of considering all isoforms and family members in studies of the function of p53 family members.

Failure of thick-skinned stiffener runout sections loaded in uniaxial compression

Recent efforts towards the development of the next generation of large civil and military transport aircraft within the European community have provided new impetus for investigating the potential use of composite material in the primary structure. One concern in this development is the vulnerability of co-cured stiffened structures to through-thickness stresses at the skin-stiffener interfaces particularly in stiffener runout regions. These regions are an inevitable consequence of the requirement to terminate stiffeners at cutouts, rib intersections or other structural features which interrupt the stiffener load path. In this respect, thickerskinned components are more vulnerable than thin-skinned ones. This work presents an experimental and numerical study of the failure of thick-sectioned stiffener runout specimens loaded in uniaxial compression. The experiments revealed that failure was initiated at the edge of the runout and propagated across the skin-stiffener interface. High frictional forces at the edge of the runout were also deduced from a fractographic analysis and it is postulated that these forces may enhance the fracture toughness of the specimens. Finite element analysis using an efficient thick-shell element and the Virtual Crack Closure Technique was able to qualitatively predict the crack growth characteristics for each specimen

Community convergence and recruitment of keystone species as performance indicators of artificial reefs

An experimental artificial reefwas constructed in Strangford Lough, Northern Ireland as part of trials to regenerate damaged biogenic reefs formed by the horse mussel Modiolus modiolus. Experimental reef plots were constructed using Pecten maximus shell as cultch. Clumps of live adult M. modiolus were translocated from nearby natural reefs into cultchwith a high profile (elevated cultch), cultch with a lowprofile (flattened cultch), as well as directly into the seafloor. The aim of the study was to test the hypothesis that translocated mussel clumps would increase habitat complexity thus accelerating community succession and enhancing natural recruitment of M. modiolus spat. These effects were predicted to be greater on elevated cultch due to greater protection from
predators and increased accessibility to food resources. Within the artificial reef array the translocated clumps had a significant positive effect on recruitment compared to cultch without mussels with average densities of spat settled on the translocated M. modiolus clumps ranging from 100 to 200 individuals m-2 compared to 4 to 52 spat m-2 on cultch without mussels. Recruitment of M. modiolus spat was also significantly higher on translocated horse mussels when compared to natural reefs where densities of 8–36 spat m-2 were recorded.
Reef elevation appeared to provide some degree of protection from predators but differences in translocated M. modiolus survival on the different elevation treatments were not significant. In total, 223 taxa were recorded 12 months after reef construction. The presence of translocated clumps ofM. modiolus was the main driver of the increases in faunal diversity and species abundance. Application of objective criteria to assess the performance of artificial reefs suggested that translocation of M. modiolus clumps alone achieved most of the restoration objectives. Consequently this pilot study demonstrates a straightforward and realistic intervention technique that could be used to kick start the regeneration and expansion of impacted mussel and similar biogenic reefs elsewhere.