Morphological evolution in land plants: new designs with old genes

The colonization and radiation of multicellular plants on land that started over 470 Ma was one of the defining events in the history of this planet. For the first time, large amounts of primary productivity occurred on the continental surface, paving the way for the evolution of complex terrestrial ecosystems and altering global biogeochemical cycles; increased weathering of continental silicates and organic carbon burial resulted in a 90 per cent reduction in atmospheric carbon dioxide levels. The evolution of plants on land was itself characterized by a series of radical transformations of their body plans that included the formation of three-dimensional tissues, de novo evolution of a multicellular diploid sporophyte generation, evolution of multicellular meristems, and the development of specialized tissues and organ systems such as vasculature, roots, leaves, seeds and flowers. In this review, we discuss the evolution of the genes and developmental mechanisms that drove the explosion of plant morphologies on land. Recent studies indicate that many of the gene families which control development in extant plants were already present in the earliest land plants. This suggests that the evolution of novel morphologies was to a large degree driven by the reassembly and reuse of pre-existing genetic mechanisms.     

The Aspergillus fumigatus Protein GliK Protects against Oxidative Stress and Is Essential for Gliotoxin Biosynthesis

The function of a number of genes in the gliotoxin biosynthetic cluster (gli) in Aspergillus fumigatus remains unknown. Here, we demonstrate that gliK deletion from two strains of A. fumigatus completely abolished gliotoxin biosynthesis. Furthermore, exogenous H₂O₂ (1 mM), but not gliotoxin, significantly induced A. fumigatus gliK expression (P = 0.0101). While both mutants exhibited significant sensitivity to both exogenous gliotoxin (P < 0.001) and H₂O₂ (P < 0.01), unexpectedly, exogenous gliotoxin relieved H₂O₂-induced growth inhibition in a dose-dependent manner (0 to 10 μg/ml). Gliotoxin-containing organic extracts derived from A. fumigatus ATCC 26933 significantly inhibited (P < 0.05) the growth of the ΔgliK²⁶⁹³³ deletion mutant. The A. fumigatus ΔgliK²⁶⁹³³ mutant secreted metabolites, devoid of disulfide linkages or free thiols, that were detectable by reverse-phase high-performance liquid chromatography and liquid chromatography-mass spectrometry with m/z 394 to 396. These metabolites (m/z 394 to 396) were present at significantly higher levels in the culture supernatants of the A. fumigatus ΔgliK²⁶⁹³³ mutant than in those of the wild type (P = 0.0024 [fold difference, 24] and P = 0.0003 [fold difference, 9.6], respectively) and were absent from A. fumigatus ΔgliG. Significantly elevated levels of ergothioneine were present in aqueous mycelial extracts of the A. fumigatus ΔgliK²⁶⁹³³ mutant compared to the wild type (P < 0.001). Determination of the gliotoxin uptake rate revealed a significant difference (P = 0.0045) between that of A. fumigatus ATCC 46645 (9.3 pg/mg mycelium/min) and the ΔgliK⁴⁶⁶⁴⁵ mutant (31.4 pg/mg mycelium/min), strongly suggesting that gliK absence and the presence of elevated ergothioneine levels impede exogenously added gliotoxin efflux. Our results confirm a role for gliK in gliotoxin biosynthesis and reveal new insights into gliotoxin functionality in A. fumigatus.     

Southern Ocean Biogeography of Tintinnid Ciliates of the Marine Plankton

Ciliate microzooplankton are important grazers in most pelagic ecosystems and among them, tintinnids, with their largely species‐specific loricas, allow relatively easy assessment of questions of diversity and distributions. Herein, we present the results of a survey of species records of tintinnids from the Southern Ocean (locations below 40°S) reported in 56 publications yielding 2,047 species records (synonyms included) from 402 locations. The 192 species reported can be parsed into two main groups: 32 endemic Southern Ocean species, known only from 40°S and further south, and a second group of 181 widespread species, forms with extensive geographic ranges extending into the Southern Ocean. Widespread species reported from the Southern Ocean can be further divided into a group of 81 species, each recorded multiple times in the Southern Ocean waters and 70 apparent “stray” species which have only been found but once. The endemic and widespread species of the Southern Ocean show both distinct distributional patterns and morphological differences. The assemblage of Southern Ocean endemics is found mostly within the Antarctic zone delimited by the average location of the Polar Front and contains a relatively large portion of wide‐mouthed forms. We give suggestions for future study.     

The Double Burden of Obesity and Malnutrition in a Protracted Emergency Setting: A Cross-Sectional Study of Western Sahara Refugees

Background

Households from vulnerable groups experiencing epidemiological transitions are known to be affected concomitantly by under-nutrition and obesity. Yet, it is unknown to what extent this double burden affects refugee populations dependent on food assistance. We assessed the double burden of malnutrition among Western Sahara refugees living in a protracted emergency.

Methods and Findings

We implemented a stratified nutrition survey in October–November 2010 in the four Western Sahara refugee camps in Algeria. We sampled 2,005 households, collecting anthropometric measurements (weight, height, and waist circumference) in 1,608 children (6–59 mo) and 1,781 women (15–49 y). We estimated the prevalence of global acute malnutrition (GAM), stunting, underweight, and overweight in children; and stunting, underweight, overweight, and central obesity in women. To assess the burden of malnutrition within households, households were first classified according to the presence of each type of malnutrition. Households were then classified as undernourished, overweight, or affected by the double burden if they presented members with under-nutrition, overweight, or both, respectively.The prevalence of GAM in children was 9.1%, 29.1% were stunted, 18.6% were underweight, and 2.4% were overweight; among the women, 14.8% were stunted, 53.7% were overweight or obese, and 71.4% had central obesity. Central obesity (47.2%) and overweight (38.8%) in women affected a higher proportion of households than did GAM (7.0%), stunting (19.5%), or underweight (13.3%) in children. Overall, households classified as overweight (31.5%) were most common, followed by undernourished (25.8%), and then double burden–affected (24.7%).

Conclusions

The double burden of obesity and under-nutrition is highly prevalent in households among Western Sahara refugees. The results highlight the need to focus more attention on non-communicable diseases in this population and balance obesity prevention and management with interventions to tackle under-nutrition. Please see later in the article for the Editors'' Summary     

Dopamine, affordance and active inference

The role of dopamine in behaviour and decision-making is often cast in terms of reinforcement learning and optimal decision theory. Here, we present an alternative view that frames the physiology of dopamine in terms of Bayes-optimal behaviour. In this account, dopamine controls the precision or salience of (external or internal) cues that engender action. In other words, dopamine balances bottom-up sensory information and top-down prior beliefs when making hierarchical inferences (predictions) about cues that have affordance. In this paper, we focus on the consequences of changing tonic levels of dopamine firing using simulations of cued sequential movements. Crucially, the predictions driving movements are based upon a hierarchical generative model that infers the context in which movements are made. This means that we can confuse agents by changing the context (order) in which cues are presented. These simulations provide a (Bayes-optimal) model of contextual uncertainty and set switching that can be quantified in terms of behavioural and electrophysiological responses. Furthermore, one can simulate dopaminergic lesions (by changing the precision of prediction errors) to produce pathological behaviours that are reminiscent of those seen in neurological disorders such as Parkinson's disease. We use these simulations to demonstrate how a single functional role for dopamine at the synaptic level can manifest in different ways at the behavioural level.     

Sanitary Pad Interventions for Girls' Education in Ghana: A Pilot Study

Background

Increased education of girls in developing contexts is associated with a number of important positive health, social, and economic outcomes for a community. The event of menarche tends to coincide with girls'' transitions from primary to secondary education and may constitute a barrier for continued school attendance and performance. Following the MRC Framework for Complex Interventions, a pilot controlled study was conducted in Ghana to assess the role of sanitary pads in girls'' education.

Methods

A sample of 120 schoolgirls between the ages of 12 and 18 from four villages in Ghana participated in a non-randomized trial of sanitary pad provision with education. The trial had three levels of treatment: provision of pads with puberty education; puberty education alone; or control (no pads or education). The primary outcome was school attendance.

Results

After 3 months, providing pads with education significantly improved attendance among participants, (lambda 0.824, F = 3.760, p<.001). After 5 months, puberty education alone improved attendance to a similar level (M = 91.26, SD = 7.82) as sites where pads were provided with puberty education (Rural M = 89.74, SD = 9.34; Periurban M = 90.54, SD = 17.37), all of which were higher than control (M = 84.48, SD = 12.39). The total improvement through pads with education intervention after 5 months was a 9% increase in attendance. After 3 months, providing pads with education significantly improved attendance among participants. The changes in attendance at the end of the trial, after 5 months, were found to be significant by site over time. With puberty education alone resulting in a similar attendance level.

Conclusion

This pilot study demonstrated promising results of a low-cost, rapid-return intervention for girls'' education in a developing context. Given the considerable development needs of poorer countries and the potential of young women there, these results suggest that a large-scale cluster randomized trial is warranted.

Trial Registration

Pan African Clinical Trials Registry PACTR201202000361337     

An upstream regulator and downstream target of phospholipase D1 activity during pheromone response in Saccharomyces cerevisiae

Phospholipase D1 (PLD1), which is the product of the SPO14 gene, has been shown to play a role in the process of polarized cell growth (PCG) during the pheromone response in Saccharomyces cerevisiae. PLD1 hydrolyzes phosphatidylcholine to produce phosphatidic acid (PA) and a free choline headgroup. This study investigated the interactions of PLD1 and PA with two proteins known to be involved in the cellular signaling leading to PCG in yeast, the small GTPase Cdc42p and the PAK family kinase Ste20p. Constitutively activated Cdc42p stimulates PLD1 activity. Protein-lipid binding blots confirmed the specific binding of Ste20p to the PLD1 product, PA. Finally, kinase activity assays provided evidence for the stimulation of Ste20p by PA. These findings highlight the important interactions among PLD1, Cdc42p and Ste20p during PCG in S. cerevisiae.     

CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals

Background

Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4⁺ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk.

Methods and Findings

In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV⁺ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4⁺ cell count thresholds used to guide HAART initiation.

Conclusions

The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management. These findings illustrate how genomic information might be applied to achieve practical benefits of personalized medicine.     

Titrating Theileria parva: single stocks against combination of stocks

Theileria parva is the causative agent of East Coast fever (ECF), an important cattle disease in East and Central Africa. One of the methods for control of ECF is 'infection and treatment', a procedure in which an animal is infected with the live parasite and at the same time treated with a long-acting oxytetracycline formulation, restraining the infection and allowing a protective cellular immune response to develop. Optimal immunizing doses were estimated using models of trichotomous response: dysimmunization (death or severe reaction during immunization), immunization failure (death or severe reaction during lethal challenge) and successful immunization (neither dysimmunization nor immunization failure). In this paper we present methods of interpreting immunization trials and apply these methods to previously unpublished data from two such trials: one with a mixture of three T. parva stocks and one with a single T. parva stock. We explain why titration trials conducted with a cocktail of antigens could predict a suboptimal immunization dose. Indeed it is possible for a combination of three individually efficient stocks to result in a mixture with which optimal immunization response might be difficult to achieve, because of averaging effects. The corresponding interpretation provides insights into why standard immunization trials for T. parva have not yielded the results that might be expected of them. The results of this work may also have implications for the use of antigen cocktails in cancer, HIV and malaria vaccine trials.     

A Human Health Risk Assessment of Pharmaceuticals in the Aquatic Environment

Analyses were conducted on four pharmaceutical compounds, representing different therapeutic classes, to evaluate the presence and potential adverse human health effects of trace levels of these substances in aqueous environmental media. Acetylsalicylic acid, clofibrate, cyclophosphamide, and indomethacin have been detected in aqueous environmental media including sewage treatment plant effluent, surface water, drinking water, and groundwater. An extensive literature search and chemical-specific risk assessments were performed to assess the potential human health significance of each compound's individual presence in environmental media. Safe water quality limits were estimated for each pharmaceutical by following the USEPA Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health and were compared to the concentrations found in the environment. The calculation of the provisional ambient water quality criteria involved estimation of human exposure to contaminated water, including intake via bioaccumulation in fish, and calculation of cancer risk and non-cancer hazard indices. Parameters detailing the toxicological and pharmacological nature, exposure assessment, and environmental fate and transport of each pharmaceutical were also considered. The overall conclusion was that based on available data, no appreciable risk to humans exists, as the detected concentrations of each of these pharmaceutical compounds found in aqueous media were far below the derived safe limits