<Emphasis Type="Italic">ScreenMill</Emphasis>: A freely available software suite for growth measurement,analysis and visualization of high-throughput screen data

Background  

Many high-throughput genomic experiments, such as Synthetic Genetic Array and yeast two-hybrid, use colony growth on solid media as a screen metric. These experiments routinely generate over 100,000 data points, making data analysis a time consuming and painstaking process. Here we describe ScreenMill, a new software suite that automates image analysis and simplifies data review and analysis for high-throughput biological experiments.     

Age-Specific Mortality During the 1918 Influenza Pandemic: Unravelling the Mystery of High Young Adult Mortality

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

“The war is over – and I must go” Egon Schiele, 1890–1918.

     

Seed caching by woylies Bettongia penicillata can increase sandalwood Santalum spicatum regeneration in Western Australia

Abstract The role a small marsupial, the woylie Bettongia penicillata, might play in the recruitment and regeneration of Western Australian sandalwood Santalum spicatum through its seed caching behaviour was investigated in this study. To determine the fate of the seeds, cotton thread was attached to the seeds and the trail followed. A total of 25 seed caches were located. All of the seeds were found in separate caches, which was consistent with scatter‐hoarding behaviour. The average distance from the source of the seeds to the cache was 43.1 m ± 5.8 m at Dryandra woodland and 29.1 m ± 3.8 m at Karakamia sanctuary. The mean cache depth was 4.3 cm ± 0.2 cm at Dryandra woodland compared with 4.6 cm ± 0.3 cm at Karakamia sanctuary. Significantly more seedlings and saplings grew away from sandalwood trees at sites where woylies were present than at sites with no woylies. In contrast, significantly more seedlings and saplings grew under adult sandalwood trees at the site without woylies than where they were present, although there were significantly lower rates of recruitment and sandalwood regeneration at these sites. In addition, significantly more whole, undisturbed sandalwood seeds were found under the parent trees at the woylie‐free site than at the site with woylies. These findings strongly suggest that little seed dispersal or regeneration of sandalwood occurs in the absence of woylies. Through scatter‐hoarding, woylies have the potential to disperse and cache sandalwood seeds away from the source and significantly alter the subsequent regeneration of sandalwood. Furthermore, by caching seeds large distances away from a source, woylies could modify the distribution of sandalwood in an area.     

Phytoplankton pigments and community composition in Lake Tanganyika

1. A 2‐year (2002–2003) survey of chlorophyll and carotenoid pigments is reported for two off‐shore stations of Lake Tanganyika, Kigoma (Tanzania) and Mpulungu (Zambia), and from three cruises between those sites. Chlorophyll a concentrations were low (0.3–3.4 mg m^?3) and average chlorophyll a integrated through the 100 m water column were similar for both stations and years (36.4–41.3 mg m^?2). Most pigments were located in the 0–60 m layer and decreased sharply downward. Chlorophyll a degradation products (phaeophytins and phaeophorbides) were detected at 100 m depth, whereas carotenoids became undetectable. Temporal and seasonal variation of the vertical distribution of pigments was high. 2. The biomass of phytoplankton groups was calculated from marker pigment concentrations over the 0–100 m water column using the CHEMTAX software. On average for the study period, chlorophytes dominated in the northern station, followed by cyanobacteria T1 (type 1, or Synechococcus pigment type), whereas cyanobacteria T1 dominated in the south. Cyanobacteria T2 (type 2, containing echinenone), presumably corresponding to filamentous taxa, were detected in the rainy season. Diatoms (and chrysophytes) developed better in the dry season conditions, with a deep mixed layer and increased nutrient availability. Very large variation in the vertical distribution of algal groups was observed. 3. Our observations on phytoplankton composition are broadly consistent with those from previous studies. Our pigment data provide evidence for the lake‐wide importance of picocyanobacteria and high interannual variation and spatial heterogeneity of phytoplankton in Lake Tanganyika, which may render difficult assessment of long‐term changes in phytoplankton driven by climate change.     

The phylogeny of stiletto flies (Diptera: Therevidae)

The therevoid clade represents a group of four families (Apsilocephalidae, Evocoidae, Scenopinidae and Therevidae) of lower brachyceran Diptera in the superfamily Asiloidea. The largest of these families is that of the stiletto flies (Therevidae). A large‐scale (i.e. supermatrix) phylogeny of Therevidae is presented based on DNA sequence data from seven genetic loci (16S, 18S and 28S ribosomal DNA and four protein‐encoding genes: elongation factor 1‐alpha, triose phosphate isomerase, short‐wavelength rhodopsin and the CPSase region of carbamoyl‐phosphate synthase‐aspartate transcarbamoylase‐dihydroorotase). Results are presented from Bayesian phylogenetic analyses of approximately 8.7 kb of sequence data for 204 taxa representing all subfamilies and genus groups of Therevidae. Our results strongly support the sister‐group relationship between Therevidae and Scenopinidae, with Apsilocephalidae as sister to Evocoidae. Previous estimates of stiletto fly phylogeny based on morphology or DNA sequence data, or supertree analysis, have failed to find significant support for relationships among subfamilies. We report for the first time strong support for the placement of the subfamily Phycinae as sister to the remaining Therevidae, originating during the Mid Cretaceous. As in previous studies, the sister‐group relationship between the species‐rich subfamilies Agapophytinae and Therevinae is strongly supported. Agapophytinae are recovered as monophyletic, inclusive of the Taenogera group. Therevinae comprise the bulk of the species richness in the family and appear to be a relatively recent and rapid radiation originating in the southern hemisphere (Australia + Antarctica + South America) during the Late Cretaceous. Genus groups are defined for all subfamilies based on these results.     

European society of intensive care medicine study of therapeutic hypothermia (32-35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial)

Background

Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2) has recently been shown to function as a key regulator. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO) gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates.

Methods/Design

This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy), among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae.

Discussion

Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa.

Trial Registration

ClinicalTrials.gov Identifier: NCT01255215     

The distribution and evolutionary history of the PRP8 intein

Background  

We recently described a mini-intein in the PRP8 gene of a strain of the basidiomycete Cryptococcus neoformans, an important fungal pathogen of humans. This was the second described intein in the nuclear genome of any eukaryote; the first nuclear encoded intein was found in the VMA gene of several saccharomycete yeasts. The evolution of eukaryote inteins is not well understood. In this report we describe additional PRP8 inteins (bringing the total of these to over 20). We compare and contrast the phylogenetic distribution and evolutionary history of the PRP8 intein and the saccharomycete VMA intein, in order to derive a broader understanding of eukaryote intein evolution. It has been suggested that eukaryote inteins undergo horizontal transfer and the present analysis explores this proposal.