Phylogenetic perspectives on reef fish functional traits

Functional traits have been fundamental to the evolution and diversification of entire fish lineages on coral reefs. Yet their relationship with the processes promoting speciation, extinction and the filtering of local species pools remains unclear. We review the current literature exploring the evolution of diet, body size, water column use and geographic range size in reef-associated fishes. Using published and new data, we mapped functional traits on to published phylogenetic trees to uncover evolutionary patterns that have led to the current functional diversity of fishes on coral reefs. When examining reconstructed patterns for diet and feeding mode, we found examples of independent transitions to planktivory across different reef fish families. Such transitions and associated morphological alterations may represent cases in which ecological opportunity for the exploitation of different resources drives speciation and adaptation. In terms of body size, reconstructions showed that both large and small sizes appear multiple times within clades of mid-sized fishes and that extreme body sizes have arisen mostly in the last 10 million years (Myr). The reconstruction of range size revealed many cases of disparate range sizes among sister species. Such range size disparity highlights potential vicariant processes through isolation in peripheral locations. When accounting for peripheral speciation processes in sister pairs, we found a significant relationship between labrid range size and lineage age. The diversity and evolution of traits within lineages is influenced by trait–environment interactions as well as by species and trait–trait interactions, where the presence of a given trait may trigger the development of related traits or behaviours. Our effort to assess the evolution of functional diversity across reef fish clades adds to the burgeoning research focusing on the evolutionary and ecological roles of functional traits. We argue that the combination of a phylogenetic and a functional approach will improve the understanding of the mechanisms of species assembly in extraordinarily rich coral reef communities

Factors associated with cholera in Kenya, 2008-2013

Introduction: Kenya experienced widespread cholera outbreaks in 1997-1999 and 2007-2010. The re-emergence of cholera in Kenya in 2015 indicates that cholera remains a public health threat. Understanding past outbreaks is important for preventing future outbreaks. This study investigated the relationship between cholera occurrence in Kenya and various environmental and demographic factors related to water, sanitation, socio-economic status, education, urbanization and availability of health facilities during the time period 2008-2013. Methods: the primary outcome analyzed was the number of cholera cases at the district level, obtained from the Kenya Ministry of Health's national cholera surveillance records. Values of independent variables were obtained from the 2009 Kenya Population and Housing Census and other national surveys. The data were analyzed using a zero-inflated negative binomial regression model. Results: multivariate analysis indicated that the risk of cholera was associated with open defecation, use of unimproved water sources, poverty headcount ratio and the number of health facilities per 100,000 population (p < 0.05). No statistically significant association was found between cholera occurrence and education, percentage of population living in urban areas or population density. Conclusion: the Sustainable Development Goals and Kenya's blueprint for development, Kenya Vision 2030, call for access to sanitation facilities and clean water for all by 2030. Kenya has made important economic strides in recent years but continues to be affected by diseases like cholera that are associated with low socio-economic status. Further expansion of access to sanitation facilities and clean water is necessary for preventing cholera in Kenya

Invasion by P. falciparum Merozoites Suggests a Hierarchy of Molecular Interactions

Central to the pathology of malaria disease are the repeated cycles of parasite invasion and destruction of human erythrocytes. In Plasmodium falciparum, the most virulent species causing malaria, erythrocyte invasion involves several specific receptor–ligand interactions that direct the pathway used to invade the host cell, with parasites varying in their dependency on these different pathways. Gene disruption of a key invasion ligand in the 3D7 parasite strain, the P. falciparum reticulocyte binding-like homolog 2b (PfRh2b), resulted in the parasite invading via a novel pathway. Here, we show results that suggest the molecular basis for this novel pathway is not due to a molecular switch but is instead mediated by the redeployment of machinery already present in the parent parasite but masked by the dominant role of PfRh2b. This would suggest that interactions directing invasion are organized hierarchically, where silencing of dominant invasion ligands reveal underlying alternative pathways. This provides wild parasites with the ability to adapt to immune-mediated selection or polymorphism in erythrocyte receptors and has implications for the use of invasion-related molecules in candidate vaccines

Promising Functional Readouts of Immunity in a Blood-Stage Malaria Vaccine Trial

The authors discuss results from an early trial of a vaccine based on Plasmodium MSP-3 protein reported by Pierre Druilhe and colleagues

Analysis of Structure and Function of the Giant Protein Pf332 in Plasmodium falciparum

Virulence of Plasmodium falciparum, the most lethal parasitic disease in humans, results in part from adhesiveness and increased rigidity of infected erythrocytes. Pf332 is trafficked to the parasite-infected erythrocyte via Maurer's clefts, structures for protein sorting and export in the host erythrocyte. This protein has a domain similar to the Duffy-binding-like (DBL) domain, which functions by binding to receptors for adherence and invasion. To address structure of the Pf332 DBL domain, we expressed this region, and validated its fold on the basis of the disulphide bond pattern, which conformed to the generic pattern for DBL domains. The modelled structure for Pf332 DBL had differences compared with the erythrocyte-binding region of the αDBL domain of Plasmodium knowlesi Duffy-binding protein (Pkα-DBL). We addressed the function of Pf332 by constructing parasites that either lack expression of the protein or express an altered form. We found no evidence that Pf332 is involved in cytoadhesion or merozoite invasion. Truncation of Pf332 had a significant effect on deformability of the P. falciparum-infected erythrocyte, while loss of the full protein deletion did not. Our data suggest that Pf332 may contribute to the overall deformability of the P. falciparum-infected erythrocyte by anchoring and scaffolding

Plasmodium falciparum Heterochromatin Protein 1 Marks Genomic Loci Linked to Phenotypic Variation of Exported Virulence Factors

Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3 marks at silenced loci. Here, we show that P. falciparum heterochromatin protein 1 (PfHP1) binds specifically to H3K9me3 but not to other repressive histone methyl marks. Based on nuclear fractionation and detailed immuno-localization assays, PfHP1 constitutes a major component of heterochromatin in perinuclear chromosome end clusters. High-resolution genome-wide chromatin immuno-precipitation demonstrates the striking association of PfHP1 with virulence gene arrays in subtelomeric and chromosome-internal islands and a high correlation with previously mapped H3K9me3 marks. These include not only var genes, but also the majority of P. falciparum lineage-specific gene families coding for exported proteins involved in host–parasite interactions. In addition, we identified a number of PfHP1-bound genes that were not enriched in H3K9me3, many of which code for proteins expressed during invasion or at different life cycle stages. Interestingly, PfHP1 is absent from centromeric regions, implying important differences in centromere biology between P. falciparum and its human host. Over-expression of PfHP1 results in an enhancement of variegated expression and highlights the presence of well-defined heterochromatic boundaries. In summary, we identify PfHP1 as a major effector of virulence gene silencing and phenotypic variation. Our results are instrumental for our understanding of this widely used survival strategy in unicellular pathogens

Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding

Acknowledgements We thank the Red Cross blood bank in Melbourne for human erythrocytes. We thank Svenja Gunther for expression of GBP130 66–196 proteins; Michelle Gazdik and Chris Burns for help in preparing lipids; Lachlan Whitehead (Centre for Dynamic Imaging, Walter and Eliza Hall Institute) for assistance with quantification of export; and David Bocher for help with generation of STEVOR constructs. This work was supported by the National Health and Medical Research Council of Australia (grants 637406, 1010326, 1049811 and 1057960), a Ramaciotti Foundation Establishment Grant (3197/2010), a Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS, and the Canadian Institutes for Health Research (MOP#130359). J.A.B is an Australian Research Council QEII Fellow, SF was supported by the Research Training Group GRK1459 of the German Research Foundation, and AFC is a Howard Hughes International Scholar.Peer reviewedPublisher PD

Cognitive remediation and social recovery in early psychosis (CReSt-R): protocol for a pilot randomised controlled study

Background Psychosis, even in its early stages, is associated with significant disability, causing it to be ranked ahead of paraplegia and blindness in those aged 18–35 in terms of years lived with disability. Current pharmacological and psychological interventions intervention have focused primarily on the reduction of positive symptoms (hallucinations and delusions), with little benefit to domains of psychosis such as cognitive difficulties and social and occupational functioning. Methods/design The CReSt-R intervention trial is a single center, pilot randomised controlled study based at the National University of Ireland (NUI), Galway. The trial will recruit participants from four clinical sites with assessment and intervention completed by the primary NUI Galway team. The trial will explore the feasibility, acceptability, and effectiveness of a novel psychosocial intervention for early psychosis based on a combined cognitive remediation training and cognitive behavioural therapy approach focused on social recovery. Participants, aged 16–35 within the first 5 years of a diagnosed psychotic disorder, will be recruited from the Children and Adolescent Mental Health Service and the Adult Mental Health Services in the region. Discussion Cognitive remediation training (for improving cognition) and social recovery focused cognitive behavioural therapy, have both separately demonstrated effectiveness. This trial will evaluate the feasibility, acceptability, and explore the efficacy of a treatment approach that combines both approaches as part of an integrated, multicomponent intervention