flowCore: a Bioconductor package for high throughput flow cytometry

Background  

Recent advances in automation technologies have enabled the use of flow cytometry for high throughput screening, generating large complex data sets often in clinical trials or drug discovery settings. However, data management and data analysis methods have not advanced sufficiently far from the initial small-scale studies to support modeling in the presence of multiple covariates.     

How to preserve a butterfly species within an urbanising settlement and its surroundings: a study of the scarce copper (<Emphasis Type="Italic">Lycaena virgaureae</Emphasis> L.) in southern Sweden

Urbanisation is a rapidly ongoing process worldwide with profound consequences for wildlife in urban and peri-urban areas. Species are affected by habitat loss, habitat alternation and degradation, fragmentation and increased human population and activity. Habitat loss can occur due to construction of housing and infrastructure in peri-urban areas and within urban areas due to compaction. Undeveloped areas can also be changed from ruderal land, wilderness areas or leftover green space to more formal and more intensively used urban green space. This study investigated a butterfly species, the scarce copper (Lycaena virgaureae L.), in an urbanising and expanding settlement in a rural location in southern Sweden. The scarce copper is still relatively common in Sweden, but has experienced severe decline in certain areas and in other parts of Europe. Patch occupancy and abundance of the species were investigated in 44 patches ranging from urban and peri-urban to rural locations. Habitats investigated were parks, urban grasslands managed for biodiversity by the local authority, unmanaged abandoned arable sites, road verges, meadows and pastures. In total, 624 sightings of scarce coppers were recorded. The highest abundances were observed in larger unmanaged patches and in meadows in peri-urban areas, while pastures had low abundances. In urban parks, no coppers were found. The smaller sites managed for biodiversity by the local authority within the settlement were often occupied by the scarce copper, although abundances were low (mean number of individuals 3?±?1.2). In patches which were cut, copper numbers dropped in almost all cases to zero after cutting. Patch occupancy was affected by habitat characteristics such vegetation height, tree succession, abundance of Rumex acetosella (sheep’s sorrel), as well as landscape features such as length of forest edge. Factors identified as influencing abundance were the same, but additionally also flower abundance. The current high abundances of the scarce copper in the area will not be ensured in the longer term when all building plans are implemented and no other measures are taken. Recommendations are made on management and planning to preserve the species in the study area.     

Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype

The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.     

Mathematical and computational modeling in biology at multiple scales

A variety of topics are reviewed in the area of mathematical and computational modeling in biology, covering the range of scales from populations of organisms to electrons in atoms. The use of maximum entropy as an inference tool in the fields of biology and drug discovery is discussed. Mathematical and computational methods and models in the areas of epidemiology, cell physiology and cancer are surveyed. The technique of molecular dynamics is covered, with special attention to force fields for protein simulations and methods for the calculation of solvation free energies. The utility of quantum mechanical methods in biophysical and biochemical modeling is explored. The field of computational enzymology is examined.     

Variation in the ribosomal internal transcribed spacers and 5.8S rDNA among five species of Acropora (Cnidaria; Scleractinia): patterns of variation consistent with reticulate evolution

The ITS sequences of Acropora spp. are the shortest so far identified in any metazoan and are among the shortest seen in eukaryotes; ITS1 was 70-80 bases, and ITS2 was 100-112 bases. The ITS sequences were also highly variable, but base composition and secondary structure prediction indicate that divergent sequence variants are unlikely to be pseudogenes. The pattern of variation was unusual in several other respects: (1) two distinct ITS2 types were detected in both A. hyacinthus and A. cytherea, species known to hybridize in vitro with high success rates, and a putative intermediate ITS2 form was also detected in A. cytherea; (2) A. valida was found to contain highly (29%) diverged ITS1 variants; and (3) A. longicyathus contained two distinct 5.8S rDNA types. These data are consistent with a reticulate evolutionary history for the genus Acropora.      

Comparative tests of ectoparasite species richness in seabirds

Background  

The diversity of parasites attacking a host varies substantially among different host species. Understanding the factors that explain these patterns of parasite diversity is critical to identifying the ecological principles underlying biodiversity. Seabirds (Charadriiformes, Pelecaniformes and Procellariiformes) and their ectoparasitic lice (Insecta: Phthiraptera) are ideal model groups in which to study correlates of parasite species richness. We evaluated the relative importance of morphological (body size, body weight, wingspan, bill length), life-history (longevity, clutch size), ecological (population size, geographical range) and behavioural (diving versus non-diving) variables as predictors of louse diversity on 413 seabird hosts species. Diversity was measured at the level of louse suborder, genus, and species, and uneven sampling of hosts was controlled for using literature citations as a proxy for sampling effort.     

An atlas of human kinase regulation

The coordinated regulation of protein kinases is a rapid mechanism that integrates diverse cues and swiftly determines appropriate cellular responses. However, our understanding of cellular decision‐making has been limited by the small number of simultaneously monitored phospho‐regulatory events. Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. This atlas identifies commonly regulated kinases as those that are central in the signaling network and defines the logic relationships between kinase pairs. Co‐regulation along the conditions predicts kinase–complex and kinase–substrate associations. Additionally, the kinase regulation profile acts as a molecular fingerprint to identify related and opposing signaling states. Using this atlas, we identified essential mediators of stem cell differentiation, modulators of Salmonella infection, and new targets of AKT1. This provides a global view of human phosphorylation‐based signaling and the necessary context to better understand kinase‐driven decision‐making.     

Antimicrobial peptide interactions with silica bead supported bilayers and E. coli: buforin II,magainin II,and arenicin

Using the unique quantitative capabilities of hyperspectral confocal microscopy combined with multivariate curve resolution, a comparative approach was employed to gain a deeper understanding of the different types of interactions of antimicrobial peptides (AMPs) with biological membranes and cellular compartments. This approach allowed direct comparison of the dynamics and local effects of buforin II, magainin II, and arenicin with nanoporous silica bead supported bilayers and living E. coli. Correlating between experiments and comparing these responses have yielded several important discoveries for pursuing the underlying biophysics of bacteriocidal specificity and the connection between structure and function in various cellular environments. First, a novel fluorescence method for direct comparison of a model and living system is demonstrated by utilizing the membrane partitioning and environmental sensitivity of propidium iodide. Second, measurements are presented comparing the temporal dynamics and local equilibrium concentrations of the different antimicrobial agents in the membrane and internal matrix of the described systems. Finally, we discuss how the data lead to a deeper understanding of the roles of membrane penetration and permeabilization in the action of these AMPs. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Dissolved organic carbon concentrations in runoff from shallow heathland catchments: effects of frequent excessive leaching in summer and autumn

Transport and turnover of dissolved organic carbon (DOC) is important in the C cycle of organic soils. The concentration of DOC in soil water is buffered by adsorption to the soil matrix, and has been hypothesized to depend on the pool size of adsorbed DOC. We have studied the effect of frequent artificial excessive leaching events on concentration and flux of DOC in shallow, organic rich mountain soils. Assuming a constant Kd value for DOC adsorption to the soil matrix, we used these data to assess the change in the pool of adsorbed (or potential) DOC in the soil. The study involved manipulation of precipitation amount and frequency in summer and autumn in small, heathland catchments at Storgama, southern Norway. The shallow soils (16–34 cm deep on average) limit the possibility for changes in water flow paths during events. The mini-catchments range in size from 75 to 98 m². Our data show that after leaching of about 1.2 g DOC m⁻² the DOC concentration in runoff declines by approximately 50%. From this we conclude that the pool size of adsorbed potential DOC in the shallow soils at any time is of the order 2–3 g m⁻². Frequent episodes suggest that the replenishment rate, which depends on the decomposition rate of soil organic matter, is fast and the potential DOC pool could be fully restored probably within days during summer, but with some more time required in autumn, due to lower temperatures. Both pool size of potential DOC and replenishment rate are seasonally dependent. The pool of potential DOC, and thus the DOC concentration in discharge, is at their maximum in the growing season. However, under non-leaching conditions, the concentration of DOC in soil water and thus the pool size of potential DOC seems to level off, possibly due to conversion of DOC to less reversibly bound forms, or to further decomposition to CO₂.