Cytochrome P450-dependent metabolism of PCB52 in the nematode Caenorhabditis elegans

There are 75 full length cytochrome P450 (CYP) genes known in the genome of the nematode Caenorhabditis elegans. The individual biological functions of the vast majority are mostly as yet unknown. Here the impact of cytochrome P450 isoforms on the metabolism of PCB52, an ortho-substituted, non-coplanar 2,2′,5,5′-tetrachlorbiphenyl, as a model PCB of these worldwide distributed pollutants is investigated. Organic extracts, isolated from treated worms and analyzed by GC/MS, contained two obvious PCB52-derived products which have been identified as C3-, C4- and/or C6-hydroxy-PCB52. Moreover, these hydroxylase reactions strictly required the functional expression of the NADPH-dependent cytochrome P450 reductase (CPR) encoding emb-8 gene, which was recently shown to be essential also for several other cytochrome P450-dependent enzymatic reactions. Multiple and subsequent single RNAi-gene silencing experiments, as well as the use of cyp-mutant strains, identified members of the CYP-14A subfamily and CYP-34A6 as the major isoforms contributing to PCB52 metabolism in C. elegans. In the gene-silenced worms and mutants, the reduction in formation of hydroxylated products ranged from 55% to 78%. These results demonstrate for the first time that C. elegans shares with mammals the capacity to produce CYP-dependent PCB metabolites and may thus facilitate future studies on biotransformation.     

Temporal and dietary niche is context-dependent in tropical ants

1. Niche traits (those that describe a species' niche) are not constant within a species, and the importance of intraspecific variation is increasingly appreciated. However, little is known about the extent of niche variability across species. This study investigated variation in dietary and temporal niches of ant species in two tropical rainforests. 2. Ants were collected from baits reflecting seven different natural resources and from pitfalls at 128 grid points. Sampling was done separately for day and night. Co-occurrence analyses were used to estimate the monopolisation capacity of each species. 3. It was expected that species would show similar dietary and temporal preferences across sites. Therefore, species with high or low niche variability between grid points (within a site) should show similar tendencies when comparing sites. It was predicted that between sites, intraspecific variability should be lower than interspecific variability, and that numerically dominant species should have higher monopolisation rates and lower intraspecific niche variability than less common ones. 4. These results showed that niche traits such as temporal activity and realised food niche shifted drastically between conspecifics of different sites. Even the most common species showed different food or temporal preferences between sites. In general, species with the highest monopolisation rates displayed lower niche variability. 5. This study also demonstrates that niche characterisation via combined continuous rather than categorical values permits a quantification of a species' niche variability. Categorising niche traits without considering context dependency may be misleading if one tries to assess niche width and a species' ability to cope with environmental change.     

Does flower phenology mirror the slowdown of global warming?

Although recent global warming trends in air temperature are not as pronounced as those observed only one decade ago, global mean temperature is still at a very high level. Does plant phenology – which is believed to be a suitable indicator of climate change – respond in a similar way, that is, does it still mirror recent temperature variations? We explored in detail long-term flowering onset dates of snowdrop, cherry, and lime tree and relevant spring temperatures at three sites in Germany (1901–2012) using the Bayesian multiple change-point approach. We investigated whether mean spring temperature changes were amplified or slowed down in the past decade and how plant phenology responded to the most recent temperature changes. Incorporating records with different end points (i.e., 2002 and 2012), we compared differences in trends and inferred possible differences caused by extrapolating phenological and meteorological data. The new multiple-change point approach is characterized by an enhanced structure and greater flexibility compared to the one change point model. However, the highest model probabilities for phenological (meteorological) records were still obtained for the one change point (linear) model. Marked warming trends in the recent decade were only revealed for mean temperatures of March to May, here better described with one or two change point models. In the majority of cases analyzed, changes in temperatures were well mirrored by phenological changes. However, temperatures in March to May were linked to less strongly advancing onset dates for lime tree flowering during the period 1901-2012, pointing to the likely influence of photoperiodic constraints or unfulfilled chilling requirements. Due to the slowdown of temperature increase, analyses conducted on records ending in 2002 demonstrated distinct differences when compared with records ending in 2012. Extrapolation of trends could therefore (along with the choice of the statistical method) lead to distinctly different results and most recent data should be integrated in order not to over- or underestimate future phenological changes.     

Worker Personality and Its Association with Spatially Structured Division of Labor

Division of labor is a defining characteristic of social insects and fundamental to their ecological success. Many of the numerous tasks essential for the survival of the colony must be performed at a specific location. Consequently, spatial organization is an integral aspect of division of labor. The mechanisms organizing the spatial distribution of workers, separating inside and outside workers without central control, is an essential, but so far neglected aspect of division of labor. In this study, we investigate the behavioral mechanisms governing the spatial distribution of individual workers and its physiological underpinning in the ant Myrmica rubra. By investigating worker personalities we uncover position-associated behavioral syndromes. This context-independent and temporally stable set of correlated behaviors (positive association between movements and attraction towards light) could promote the basic separation between inside (brood tenders) and outside workers (foragers). These position-associated behavior syndromes are coupled with a high probability to perform tasks, located at the defined position, and a characteristic cuticular hydrocarbon profile. We discuss the potentially physiological causes for the observed behavioral syndromes and highlight how the study of animal personalities can provide new insights for the study of division of labor and self-organized processes in general.     

SNP-Array genotyping and spectral karyotyping reveal uniparental disomy as early mutational event in MSS- and MSI-colorectal cancer cell lines

In this study nine colorectal cancer cell lines were analysed by 10K SNP-arrays and spectral karyotyping (SKY). Complex chromosomal alterations and breakpoints of deleted or translocated fragments found by SKY could further be characterized by SNP-array analysis. Interestingly many monoallelic regions identified by SNP-array analysis display no copy number alterations, representing uniparental disomy (UPD). It was demonstrated that UPD seems to be involved in activation of early-acting tumor suppressor genes in MSS- (APC, CDKN2A) and MSI- (MLH1, MSH2, APC, CDKN2A) colorectal cancer cell lines. Genes involved later on in the adenoma-carcinoma sequence (i.e. TP53/SMAD4) were not found to be inactivated by UPD. Furthermore, identified amplified monoallelic regions may include oncogenes activated by allele-specific-amplification (i.e. Cyclin D1). However, at present, the majority of the monoallelic regions located in the present study have not yet been associated with known tumor suppressor genes and oncogenes. Further studies are warranted to identify relevant genes in the respective regions and to further verify the results presented here.     

Biohumanities: rethinking the relationship between biosciences, philosophy and history of science, and society

We argue that philosophical and historical research can constitute a "Biohumanities" that deepens our understanding of biology itself engages in constructive "science criticism," helps formulate new "visions of biology," and facilitates "critical science communication." We illustrate these ideas with two recent "experimental philosophy" studies of the concept of the gene and of the concept of innateness conducted by ourselves and collaborators. We conclude that the complex and often troubled relations between science and society are critical to both parties, and argue that the philosophy and history of science can help to make this relationship work.     

Guidance by odors in honeybee navigation

Animal navigation is guided by multiple sensory cues. Here, we ask whether and how olfactory stimuli emanating from places other than the trained feeding site redirect the flight paths of honeybees. The flight trajectories of individual bees were registered using harmonic radar tracking. Sensory cues (compass direction, distance, visual cues en route and close to the feeding site) associated with the trained flight route dominated wayfinding, but a learned odorant carried by air flow induced excursions into the wind. These redirections were largely restricted to rather small deviations from the trained route (<60°, <200 m) and occurred only if the animal did not receive the trained odorant stimulus at the trained feeding site. Under certain conditions, larger excursions were observed. These findings are discussed in the context of odor guidance of honeybees over longer distances (>300 m from the hive).     

Profiling of alopecia areata autoantigens based on protein microarray technology

Protein biochips have a great potential in future parallel processing of complex samples as a research tool and in diagnostics. For the generation of protein biochips, highly automated technologies have been developed for cDNA expression library production, high throughput protein expression, large scale analysis of proteins, and protein microarray generation. Using this technology, we present here a strategy to identify potential autoantigens involved in the pathogenesis of alopecia areata, an often chronic disease leading to the rapid loss of scalp hair. Only little is known about the putative autoantigen(s) involved in this process. By combining protein microarray technology with the use of large cDNA expression libraries, we profiled the autoantibody repertoire of sera from alopecia areata patients against a human protein array consisting of 37,200 redundant, recombinant human proteins. The data sets obtained from incubations with patient sera were compared with control sera from clinically healthy persons and to background incubations with anti-human IgG antibodies. From these results, a smaller protein subset was generated and subjected to qualitative and quantitative validation on highly sensitive protein microarrays to identify novel alopecia areata-associated autoantigens. Eight autoantigens were identified by protein chip technology and were successfully confirmed by Western blot analysis. These autoantigens were arrayed on protein microarrays to generate a disease-associated protein chip. To confirm the specificity of the results obtained, sera from patients with psoriasis or hand and foot eczema as well as skin allergy were additionally examined on the disease-associated protein chip. By using alopecia areata as a model for an autoimmune disease, our investigations show that the protein microarray technology has potential for the identification and evaluation of autoantigens as well as in diagnosis such as to differentiate alopecia areata from other skin diseases.     

A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores > or =1.18 (P< or =.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest.     

Fine Structural Analysis of Brefeldin A-Induced Compartment Formation After High-Pressure Freeze Fixation of Maize Root Epidermis: Compound Exocytosis Resembling Cell Plate Formation during Cytokinesis

Formation of large perinuclear brefeldin A (BFA)-induced compartments is a characteristic feature of root apex cells, but it does not occur in shoot apex cells. BFA-induced compartments have been studied mostly using low resolution fluorescence microscopy techniques. Here, we have employed a high-resolution ultrastructural method based on ultra rapid freeze fixation of samples in order to study the formation of BFA-induced compartments in intact maize root epidermis cells in detail. This approach reveals five novel findings. Firstly, plant TGN/PGN elements are not tubular networks, as generally assumed, but rather vesicular compartments. Secondly, TGN/PGN vesicles interact with one another extensively via stalk-like connections and even fuse together via bridge-like structures. Thirdly, BFA-induced compartments are formed via extensive homotypic fusions of the TGN/PGN vesicles. Fourthly, multivesicular bodies (MVBs) are present within the BFA-induced compartments. Fifthly, mitochondria and small vacuoles accummulate abundantly around the large perinuclear BFA-induced compartments.Key Words: brefeldin A, BFA-induced compartments, golgi, endosomes, root apex