A Folding Pathway-Dependent Score to Recognize Membrane Proteins

While various approaches exist to study protein localization, it is still a challenge to predict where proteins localize. Here, we consider a mechanistic viewpoint for membrane localization. Taking into account the steps for the folding pathway of α-helical membrane proteins and relating biophysical parameters to each of these steps, we create a score capable of predicting the propensity for membrane localization and call it FP3mem. This score is driven from the principal component analysis (PCA) of the biophysical parameters related to membrane localization. FP3mem allows us to rationalize the colocalization of a number of channel proteins with the Cav1.2 channel by their fewer propensities for membrane localization

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

The tip of the iceberg: evidence of seasonality in institutional maternal mortality and implications for health resources management in Burkina Faso.

AIMS: The aims of this study were to investigate seasonal patterns of institutional maternal deaths and complications, and to test for an association with malaria seasons, rainfall, and household income. METHODS: A systematic case review of hospital records in the Boucle du Mouhoun health region (Burkina Faso) was conducted over a 2-year period. A statistical smoothing procedure (T4253H) and Freedman's test were used to investigate seasonality and association with malaria, rainfall or household income variations. RESULTS: The data consistently showed the greatest rates of maternal deaths, eclampsia and haemorrhage cases during the dry season, which is the low malaria transmission season, and the period of the year when households have most money available and the lowest opportunity cost of travelling to seek medical attention, suggesting that financial and geographical barriers may be major underlying factors. CONCLUSIONS: The management both of health resources in hospital and of referral systems should accommodate cyclical variations in the presentation of maternal complications. Effective mechanisms are needed to help reduce the significant barriers to uptake faced by women and their families at particular times of the year

RESPONSE OF GROWTH AND CARBON ALLOCATION TO ELEVATED CO2 IN YOUNG CHERRY (PRUNUS-AVIUM L) SAPLINGS IN RELATION TO ROOT ENVIRONMENT

The hypothesis that inadequate rooting volume may reduce the growth stimulation by elevated CO2 in potted tree seedlings and saplings was tested experimentally and by surveying the literature. One-year-old cherry saplings were grown for one season in naturally lit growth chambers in eight combinations of CO2 concentration (ambient; ambient + 250 ppm) and root environment (four types). The latter included (1) moderately restrictive pot volume (4 l) in combination with two levels of fertilizer addition (1a, 1b); (2) 10 l pots with total fertilizer content per pot as in treatment 1a, and (3) 20 l pots with five plants sharing five times the space and nutrient resources of treatment 1a. Plants were harvested in April, May, June, August and September. The overall mean effect of high CO2 plant dry mass by the end of the season was +24%. Interactive effects of root environments and CO2 concentrations on dry mass were not significant at the 5% level, but repeated measurements of basal stem diameter of individual plants indicated a significant impact of root environment on the response to CO2. Overall growth enhancement by elevated CO2 did not differ significantly between harvests, but it tended to increase during the season in those root environments which restricted growth in ambient CO2 most strongly (1a and 3). The hypothesis was rejected for this experiment. Leaf area and stem height were not affected by any treatment. The variation of carbon allocation to roots and shoots with plant size was very similar in all treatments. Plants grew faster in elevated CO2 very early in the season, and this resulted in small but significant differences between seasonal patterns of biomass partitioning in ambient and elevated CO2. A survey of 33 studies on growth responses of 47 tree species to elevated CO2 (600-800 ppm) showed that the relative change in biomass was not related to the ratio of plant biomass and pot volume found in either ambient or elevated CO2. We conclude that there is no evidence that inadequate pot volume had a negative impact on the stimulation of growth of tree species in elevated CO2

The effect of elevated CO2 and grazing by Gastrophysa viridula on the physiology and regrowth of Rumex obtusifolius.

Plants of Rumex obtusifolius L. were grown in Solardomes under ambient and elevated (+ 250 μmol mol−1) mole fractions of CO2 and were exposed to two levels of herbivory by Gastrophysa viridula Degeer larvae. The herbivory treatment lasted 1 month, thereafter half of the plants were harvested and over the following month during a period of regrowth physiological measurements were made on the remaining plants. At the termination of the herbivory treatment uninfested plants showed no damage, whereas the low and high herbivore treatments caused 20–40% and 50–70% loss of leaf area as a proportion of total leaf area, respectively. The CO2 treatment did not affect the degree of defoliation. Total leaf area was not significantly affected by either CO2 or herbivory. Uninfested plants grown in elevated concentrations of CO2 showed increased growth, root-to-shoot ratios (RS), rates of photosynthesis and reduced stomatal conductance compared with uninfested plants grown in ambient CO2. A/C1 analysis revealed that plants grown in elevated CO2 showed reductions in Vcmax. For plants grown in ambient CO2 the high herbivory treatment led to increased rates of photosynthesis and decreased rates of dark respiration per unit leaf area, and caused increases in stomatal conductance and RS. For plants grown in elevated CO2 the high herbivory treatment increased plant biomass and RS. The increases in RS in response to elevated CO2 and herbivory appeared to be additive. Defoliation did not reduce the degree of photosynthetic down-regulation caused by growth in elevated concentrations of CO2, but appeared to reduce the rate of ontogenic decline in photosynthesis in ambient CO2