Lycopene and the lung

The human lung, due to the oxidative and ozone stress to which it is exposed, is particularly vulnerable to oxidative damage. Concentrations of dietary antioxidants in the lung epithelial lining and lining fluids may provide protection against oxidative damage. A randomized clinical trial was conducted to study the effects of supplemental, carotenoid-rich vegetable juice (V-8) on lung function macrophage levels of carotenoids and in moderating ozone-induced lung damage. Healthy young adults (n = 23) were exposed to 0.4 ppm ozone in a chamber for 2 hr after either 2 weeks of antioxidant supplementation (including one can of V-8 juice daily) or placebo. Mean lung concentrations of lycopene increased by 12%, and lung epithelial cell DNA damage as measured by the Comet Assay decreased 20% in supplemented subjects. No change in peripheral blood lymphocyte DNA damage was observed as evidenced by no change in mean comet area or length in supplemented or placebo subjects. We were not able to separate the effects of lycopene from other carotenoids or antioxidants administered in this study; however, lycopene is the predominant carotenoid in V-8 (it represents 88% of total carotenoids). A review of the epidemiologic literature providing evidence for the effect of lycopene (diet or serum) or tomatoes on the risk of lung cancer reveals 27 observational epidemiologic studies (18 case-control and nine cohort studies) reporting relative risk (RR) estimates. RR estimates for cohort studies ranged from 0.63 to 1.24 (mean RR = 0.93, SD = 0.16). Odds ratios (OR) for case-control studies ranged from 0.27 to 0.93 (mean OR = 0.61, SD = 0.16). Both plasma levels (RR = 1.01, OR = 0.37) and estimated intakes of lycopene from dietary sources (mean RR = 0.93, RR range = 0.80-1.05; mean OR = 0.67, OR range = 0.27-0.93) were examined. Seventeen studies, three of which were cohorts, reported their results at the level of tomato consumption rather than, or in addition to, lycopene consumption (mean RR = 0.89, RR range = 0.63-1.24; mean OR = 0.61, OR range = 0.37-0.80). The published epidemiologic literature shows an interaction between study design and the relationship between lycopene and/ or tomatoes and risk of lung cancer. Overall, cohort studies did not show an association, whereas case-control studies showed a decreased risk with greater consumption of lycopene and tomatoes. Although lycopene can be found in the human lung, and there is evidence, albeit weak, for a protective association with lung cancer, its biologic role remains to be elucidated.     

Going the Distance for Protein Function Prediction: A New Distance Metric for Protein Interaction Networks

In protein-protein interaction (PPI) networks, functional similarity is often inferred based on the function of directly interacting proteins, or more generally, some notion of interaction network proximity among proteins in a local neighborhood. Prior methods typically measure proximity as the shortest-path distance in the network, but this has only a limited ability to capture fine-grained neighborhood distinctions, because most proteins are close to each other, and there are many ties in proximity. We introduce diffusion state distance (DSD), a new metric based on a graph diffusion property, designed to capture finer-grained distinctions in proximity for transfer of functional annotation in PPI networks. We present a tool that, when input a PPI network, will output the DSD distances between every pair of proteins. We show that replacing the shortest-path metric by DSD improves the performance of classical function prediction methods across the board.     

In focus: Film,focus groups and working children in Bangladesh

The use of visuals in anthropological research is an established though much debated practice, both as a research tool and as a means of reporting. Pile sorts, mapping, thematic drawing, photographs, visual scales and pictorial triad testing are all visual methods that have been used in participatory and conventional ethnographic research to encourage discussion among study participants and to clarify detail. Our experience in the use of visual tools in a study conducted in 1997–98, among former child garment workers in Bangladesh, reinforces the value of the use of visuals in research. A documentary film was used in focus groups with children, most aged 10–13. The results suggest that film is a powerfully evocative tool and, combined with focus groups, is an excellent qualitative research technique. The research experience in Bangladesh also suggests that children are able to participate meaningfully in the research not in spite of but because of the use of documentary film.     

Habitat fragmentation: A long and tangled tale

In this essay: I provide a brief history of habitat fragmentation research; I describe why its “non‐questions” (‘Is habitat fragmentation a big problem for wildlife species?” and, “Are the effects of habitat fragmentation generally negative or positive?”) are important to conservation; I outline my role in tackling these questions; I discuss reasons why the culture of habitat fragmentation research is largely incapable of accepting the answers; and I speculate on the future of habitat fragmentation research.     

Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase

Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.     

A large-scale forest fragmentation experiment: the Stability of Altered Forest Ecosystems Project

Opportunities to conduct large-scale field experiments are rare, but provide a unique opportunity to reveal the complex processes that operate within natural ecosystems. Here, we review the design of existing, large-scale forest fragmentation experiments. Based on this review, we develop a design for the Stability of Altered Forest Ecosystems (SAFE) Project, a new forest fragmentation experiment to be located in the lowland tropical forests of Borneo (Sabah, Malaysia). The SAFE Project represents an advance on existing experiments in that it: (i) allows discrimination of the effects of landscape-level forest cover from patch-level processes; (ii) is designed to facilitate the unification of a wide range of data types on ecological patterns and processes that operate over a wide range of spatial scales; (iii) has greater replication than existing experiments; (iv) incorporates an experimental manipulation of riparian corridors; and (v) embeds the experimentally fragmented landscape within a wider gradient of land-use intensity than do existing projects. The SAFE Project represents an opportunity for ecologists across disciplines to participate in a large initiative designed to generate a broad understanding of the ecological impacts of tropical forest modification.     

Matt: local flexibility aids protein multiple structure alignment

Even when there is agreement on what measure a protein multiple structure alignment should be optimizing, finding the optimal alignment is computationally prohibitive. One approach used by many previous methods is aligned fragment pair chaining, where short structural fragments from all the proteins are aligned against each other optimally, and the final alignment chains these together in geometrically consistent ways. Ye and Godzik have recently suggested that adding geometric flexibility may help better model protein structures in a variety of contexts. We introduce the program Matt (Multiple Alignment with Translations and Twists), an aligned fragment pair chaining algorithm that, in intermediate steps, allows local flexibility between fragments: small translations and rotations are temporarily allowed to bring sets of aligned fragments closer, even if they are physically impossible under rigid body transformations. After a dynamic programming assembly guided by these “bent” alignments, geometric consistency is restored in the final step before the alignment is output. Matt is tested against other recent multiple protein structure alignment programs on the popular Homstrad and SABmark benchmark datasets. Matt's global performance is competitive with the other programs on Homstrad, but outperforms the other programs on SABmark, a benchmark of multiple structure alignments of proteins with more distant homology. On both datasets, Matt demonstrates an ability to better align the ends of α-helices and β-strands, an important characteristic of any structure alignment program intended to help construct a structural template library for threading approaches to the inverse protein-folding problem. The related question of whether Matt alignments can be used to distinguish distantly homologous structure pairs from pairs of proteins that are not homologous is also considered. For this purpose, a p-value score based on the length of the common core and average root mean squared deviation (RMSD) of Matt alignments is shown to largely separate decoys from homologous protein structures in the SABmark benchmark dataset. We postulate that Matt's strong performance comes from its ability to model proteins in different conformational states and, perhaps even more important, its ability to model backbone distortions in more distantly related proteins.