Vertebrate host specificity of wild-caught blackflies revealed by mitochondrial DNA in blood

Blood-feeding blackflies (Diptera: Simuliidae) transmit pathogens, harass vertebrate hosts and may cause lethal injuries in attacked victims, but with traditional methods it has proved difficult to identify their hosts. By matching mitochondrial DNA (mtDNA) sequences in blood collected from engorged blackflies with stored sequences in the GenBank database, relationships between 17 blackfly species and 25 species of vertebrate hosts were revealed. Our results demonstrate a predominance of large hosts and marked discrimination between blackflies using either avian or mammalian hosts. Such information is of vital interest in studies of disease transmission, coevolutionary relationships, population ecology and wildlife management.     

Detection of crosslinks within and between proteins by LC-MALDI-TOFTOF and the software FINDX to reduce the MSMS-data to acquire for validation

Lysine-specific chemical crosslinking in combination with mass spectrometry is emerging as a tool for the structural characterization of protein complexes and protein-protein interactions. After tryptic digestion of crosslinked proteins there are thousands of peptides amenable to MSMS, of which only very few are crosslinked peptides of interest. Here we describe how the advantage offered by off-line LC-MALDI-TOF/TOF mass spectrometry is exploited in a two-step workflow to focus the MSMS-acquisition on crosslinks mainly. In a first step, MS-data are acquired and all the peak list files from the LC-separated fractions are merged by the FINDX software and screened for presence of crosslinks which are recognized as isotope-labeled doublet peaks. Information on the isotope doublet peak mass and intensity can be used as search constraints to reduce the number of false positives that match randomly to the observed peak masses. Based on the MS-data a precursor ion inclusion list is generated and used in a second step, where a restricted number of MSMS-spectra are acquired for crosslink validation. The decoupling of MS and MSMS and the peptide sorting with FINDX based on MS-data has the advantage that MSMS can be restricted to and focused on crosslinks of Type 2, which are of highest biological interest but often lowest in abundance. The LC-MALDI TOF/TOF workflow here described is applicable to protein multisubunit complexes and using (14)N/(15)N mixed isotope strategy for the detection of inter-protein crosslinks within protein oligomers.     

First clinical experience with the magnetic resonance imaging contrast agent and superoxide dismutase mimetic mangafodipir as an adjunct in cancer chemotherapy-a translational study

Preclinical research suggests that the clinically approved magnetic resonance imaging contrast agent mangafodipir may protect against adverse events (AEs) caused by chemotherapy, without interfering negatively with the anticancer efficacy. The present translational study tested if pretreatment with mangafodipir lowers AEs during curative (adjuvant) FOLFOX6 chemotherapy in stage III colon cancer (Dukes' C). The study was originally scheduled to include 20 patients, but because of the unforeseen withdrawal of mangafodipir from the market, the study had to be closed after 14 patients had been included. The withdrawal of mangafodipir was purely based on commercial considerations from the producer and not on any safety concerns. The patients were treated throughout the first 3 of 12 scheduled cycles. Patients were randomized to a 5-minute infusion of either mangafodipir or placebo (7 in each group). AEs were evaluated according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events and the Sanofi-NCI criteria. The primary end points were neutropenia and neurosensory toxicity. There were four AEs of grade 3 (severe) and one AE of grade 4 (life threatening) in four patients in the placebo group, whereas there were none in the mangafodipir group (P < .05). Of the grade 3 and 4 events, two were neutropenia and one was neurosensory toxicity. Furthermore, white blood cell count was statistically, significantly higher in the mangafodipir group than in the placebo group (P < .01) after treatment with FOLFOX. This small feasibility study seems to confirm what has been demonstrated preclinically, namely, that pretreatment with mangafodipir lowers AEs during adjuvant 5-fluorouracil plus oxaliplatin-based chemotherapy in colon cancer patients.     

Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: evidence from the International Consortium for Prostate Cancer Genetics (ICPCG)

Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65?years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.     

Assessing the influence of prey–predator ratio,prey age structure and packs size on wolf kill rates

Traditional predation theory assumes that prey density is the primary determinant of kill rate. More recently, the ratio of prey‐to‐predator has been shown to be a better predictor of kill rate. However, the selective behavior of many predators also suggests that age structure of the prey population should be an important predictor of kill rate. We compared wolf–moose predation dynamics in two sites, south‐central Scandinavia (SCA) and Isle Royale, Lake Superior, North America (IR), where prey density was similar, but where prey age structure and prey‐to‐predator ratio differed. Per capita kill rates of wolves preying on moose in SCA are three times greater than on IR. Because SCA and IR have similar prey densities differences in kill rate cannot be explained by prey density. Instead, differences in kill rate are explained by differences in the ratio of prey‐to‐predator, pack size and age structure of the prey populations. Although ratio‐dependent functional responses was an important variable for explaining differences in kill rates between SCA and IR, kill rates tended to be higher when calves comprised a greater portion of wolves’ diet (p =0.05). Our study is the first to suggest how age structure of the prey population can affect kill rate for a mammalian predator. Differences in age structure of the SCA and IR prey populations are, in large part, the result of moose and forests being exploited in SCA, but not in IR. While predator conservation is largely motivated by restoring trophic cascades and other top–down influences, our results show how human enterprises can also alter predation through bottom–up processes.     

Contrasting effects of habitat area and connectivity on evenness of pollinator communities

Losses of both habitat area and connectivity have been identified as important drivers of species richness declines, but little theoretical and empirical work exists that addresses the effect of fragmentation on relative commonness of highly mobile species such as pollinating insects. With a large dataset of wild bee and butterfly abundances collected across Europe, we first tested the effect of habitat area and connectivity on evenness in pollinator communities using a large array of indexes that give different weight to dominance and rarity. Second, we tested if traits related to mobility and diet breadth could explain the observed evenness patterns. We found a clear negative effect of area and a weaker, but positive effect of connectivity on evenness. Communities in small habitat fragments were mainly composed of mobile and generalist species. The higher evenness in small fragments could thereby be generated by highly mobile species that maintain local populations with frequent inter‐fragment movements. Trait analysis suggested an increasing importance of dispersal over local recruitment, as we move from large to small fragments and from less to more connected fragments. Species richness and evenness were negatively correlated indicating that the two variables responded differently to habitat area and connectivity, although the mechanisms underlying the observed patterns are difficult to isolate. Even though habitat area and connectivity often decrease simultaneously due to habitat fragmentation, an interesting practical implication of the contrasting effect of the two variables is that the resulting community composition will depend on the relative strength of these two processes.     

Accounting for overfishing in life cycle assessment: new impact categories for biotic resource use

Purpose

Overfishing is a relevant issue to include in all life cycle assessments (LCAs) involving wild caught fish, as overfishing of fish stocks clearly targets the LCA safeguard objects of natural resources and natural ecosystems. Yet no robust method for assessing overfishing has been available. We propose lost potential yield (LPY) as a midpoint impact category to quantify overfishing, comparing the outcome of current with target fisheries management. This category primarily reflects the impact on biotic resource availability, but also serves as a proxy for ecosystem impacts within each stock.

Methods

LPY represents average lost catches owing to ongoing overfishing, assessed by simplified biomass projections covering different fishing mortality scenarios. It is based on the maximum sustainable yield concept and complemented by two alternative methods, overfishing though fishing mortality (OF) and overfishedness of biomass (OB), that are less data-demanding.

Results and discussion

Characterization factors are provided for 31 European commercial fish stocks in 2010, representing 74 % of European and 7 % of global landings. However, large spatial and temporal variations were observed, requiring novel approaches for the LCA practitioner. The methodology is considered compliant with the International Reference Life Cycle Data System (ILCD) standard in most relevant aspects, although harmonization through normalization and endpoint characterization is only briefly discussed.

Conclusions

Seafood LCAs including any of the three approaches can be a powerful communicative tool for the food industry, seafood certification programmes, and for fisheries management.