Comparative genomics of the neglected human malaria parasite Plasmodium vivax

The human malaria parasite Plasmodium vivax is responsible for 25 - 40% of the similar to 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non- human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

Quantitative analysis of indexed publications on seventeen model organisms in nine countries, from 1974 to 2006

Developed countries have an even distribution of published papers on the seventeen model organisms. Developing countries have biased preferences for a few model organisms which are associated with endemic human diseases. A variant of the Hirsch-index, that we call the mean (mo)h-index (""model organism h-index""), shows an exponential relationship with the amount of papers published in each country on the selected model organisms. Developing countries cluster together with low mean (mo)h-indexes, even those with high number of publications. The growth curves of publications on the recent model Caenorhabditis elegans in developed countries shows different formats. We also analyzed the growth curves of indexed publications originating from developing countries. Brazil and South Korea were selected for this comparison. The most prevalent model organisms in those countries show different growth curves when compared to a global analysis, reflecting the size and composition of their research communities.

A quasispecies approach to the evolution of sexual replication in unicellular organisms

This study develops a simplified model describing the evolutionary dynamics of a population composed of obligate sexually and asexually reproducing, unicellular organisms. The model assumes that the organisms have diploid genomes consisting of two chromosomes, and that the sexual organisms replicate by first dividing into haploid intermediates, which then combine with other haploids, followed by the normal mitotic division of the resulting diploid into two new daughter cells. We assume that the fitness landscape of the diploids is analogous to the single-fitness-peak approach often used in single-chromosome studies. That is, we assume a master chromosome that becomes defective with just one point mutation. The diploid fitness then depends on whether the genome has zero, one, or two copies of the master chromosome. We also assume that only pairs of haploids with a master chromosome are capable of combining so as to produce sexual diploid cells, and that this process is described by second-order kinetics. We find that, in a range of intermediate values of the replication fidelity, sexually reproducing cells can outcompete asexual ones, provided the initial abundance of sexual cells is above some threshold value. The range of values where sexual reproduction outcompetes asexual reproduction increases with decreasing replication rate and increasing population density. We critically evaluate a common approach, based on a group selection perspective, used to study the competition between populations and show its flaws in addressing the evolution of sex problem.

Genome-wide association mapping in a wild avian population identifies a link between genetic and phenotypic variation in a life-history trait

Understanding the genetic basis of traits involved in adaptation is a major challenge in evolutionary biology but remains poorly understood. Here, we use genome-wide association mapping using a custom 50 k single nucleotide polymorphism (SNP) array in a natural population of collared flycatchers to examine the genetic basis of clutch size, an important life-history trait in many animal species. We found evidence for an association on chromosome 18 where one SNP significant at the genome-wide level explained 3.9% of the phenotypic variance. We also detected two suggestive quantitative trait loci (QTLs) on chromosomes 9 and 26. Fitness differences among genotypes were generally weak and not significant, although there was some indication of a sex-by-genotype interaction for lifetime reproductive success at the suggestive QTL on chromosome 26. This implies that sexual antagonism may play a role in maintaining genetic variation at this QTL. Our findings provide candidate regions for a classic avian life-history trait that will be useful for future studies examining the molecular and cellular function of, as well as evolutionary mechanisms operating at, these loci.

Trapping of a spiral-like intermediate of the bacterial cytokinetic protein FtsZ

The earliest stage in bacterial cell division is the formation of a ring, composed of the tubulin-like protein FtsZ, at the division site. Tight spatial and temporal regulation of Z-ring formation is required to ensure that division occurs precisely at midcell between two replicated chromosomes. However, the mechanism of Z-ring formation and its regulation in vivo remain unresolved. Here we identify the defect of an interesting temperature-sensitive ftsZ mutant (ts1) of Bacillus subtilis. At the nonpermissive temperature, the mutant protein, FtsZ(Ts1), assembles into spiral-like structures between chromosomes. When shifted back down to the permissive temperature, functional Z rings form and division resumes. Our observations support a model in which Z-ring formation at the division site arises from reorganization of a long cytoskeletal spiral form of FtsZ and suggest that the FtsZ(Ts1) protein is captured as a shorter spiral-forming intermediate that is unable to complete this reorganization step. The ts1 mutant is likely to be very valuable in revealing how FtsZ assembles into a ring and how this occurs precisely at the division site.

Functional analysis of yeast snoRNA and snRNA 3' end formation mediated by uncoupling of cleavage and polyadenylation

Many nuclear and nucleolar small RNAs are accumulated as nonpolyadenylated species and require 3′-end processing for maturation. Here, we show that several genes coding for box C/D and H/ACA snoRNAs and for the U5 and U2 snRNAs contain sequences in their 3′ portions which direct cleavage of primary transcripts without being polyadenylated. Genetic analysis of yeasts with mutations in different components of the pre-mRNA cleavage and polyadenylation machinery suggests that this mechanism of 3"-end formation requires cleavage factor IA (CF IA) but not cleavage and polyadenylation factor activity. However, in vitro results indicate that other factors participate in the reaction besides CF IA. Sequence analysis of snoRNA genes indicated that they contain conserved motifs in their 3" noncoding regions, and mutational studies demonstrated their essential role in 3"-end formation. We propose a model in which CF IA functions in cleavage and polyadenylation of pre-mRNAs and, in combination with a different set of factors, in 3"-end formation of nonpolyadenylated polymerase II transcripts.

Fuzzy ARTMAP and a hybrid chaos genetic algorithm for medical pattern classification

In this paper, an Evolutionary Artificial Neural Network (EANN), which combines the Fuzzy ARTMAP (FAM) neural network and a hybrid Chaos Genetic Algorithm (CGA), is proposed for undertaking pattern classification tasks. The hybrid CGA is a modified version of the hybrid real-coded genetic algorithms that includes a Chaotic Mapping Operator (CMO) in its search and adaptation process. It is used to evolve the connection weights in FAM, and the resulting EANN is known as FAM-hybrid CGA. The CMO in the hybrid CGA is used to generate a group of chromosomes that incorporates the characteristics of chaos. The chromosomes are then adapted with an arbitrary small amount of variation in every generation. As the evolution procedure proceeds, chromosomes with considerable differences are produced. Such chromosomes, which are located at different regions of interest in the solution space, are able to provide good solutions to undertake search and adaption problems. The effectiveness of the proposed FAM-hybrid CGA model is first evaluated using benchmark medical data sets from the UCI machine learning repository. Its applicability to medical decision support is then demonstrated using a real database of patient records with suspected Acute Coronary Syndrome. The results indicate that FAM-hybrid CGA is able to outperform its neural network counterpart (i.e., FAM), and it can be employed as a useful pattern classification tool for tackling medical decision support tasks.

The COMPASS subunit Spp1 links histone methylation to initiation of meiotic recombination

During meiosis, combinatorial associations of genetic traits arise from homologous recombination between parental chromosomes. Histone H3 lysine 4 trimethylation marks meiotic recombination hotspots in yeast and mammals, but how this ubiquitous chromatin modification relates to the initiation of double-strand breaks (DSBs) dependent on Spo11 remains unknown. Here, we show that the tethering of a PHD-containing protein, Spp1 (a component of the COMPASS complex), to recombinationally cold regions is sufficient to induce DSB formation. Furthermore, we found that Spp1 physically interacts with Mer2, a key protein of the differentiated chromosomal axis required for DSB formation. Thus, by interacting with H3K4me3 and Mer2, Spp1 promotes recruitment of potential meiotic DSB sites to the chromosomal axis, allowing Spo11 cleavage at nearby nucleosome-depleted regions.

Genetic architecture of sexually selected traits - lessons from guppies

I discuss a number of experiments designed to explore the genetic basis of sexual ornamentation and associated life history traits in guppies. This system is unusual because of the large Y-linked contribution to ornamentation and male fitness, and because the Y-chromosome is implicated in inbreeding depression. I discuss the implications of intralocus sexual conflict for the evolution of sex-linkage in guppies and the potential for such a process to drive the evolutionary erosion of Y-chromosomes.

Sex and death: CHD1Z associated with high mortality in moorhens

Sex ratios in clutches of moorhens (Gallinula chloropus) in Britain were measured on 83 chicks using the sex-linked CHD1 gene (Chromo-helicase/ATPase-DNA binding protein 1). Among birds, the female is the hetero-gametic sex (Z and W chromosomes), and the male is homogametic (two copies of the Z chromosome). We report variation among the PCR-amplified fragments of the CHD1Z, and the death of nearly all heterozygous male chicks (92%). In contrast, survivorship among females and homozygote males was 54–60%. Mortality in male heterozygotes was significantly higher than that of male homozygotes (P < 0.001). Chick and egg biometrics were not significantly different between these males. The CHD1Z was unlikely to be directly responsible but may have been hitchhiked by the causal gene(s). The observations appear to follow a classic underdominance (heterozygote inferiority) pattern, but raise the paradoxical question of why one form of the Z chromosome has not been fixed, as is expected from evolutionary theory. We discuss possible explanations and include a survey of British populations based on skin specimens.

Mentorship in the health disciplines

AbstractLearning outcomes:On completion of this continuing professional development (CPD) activity, participants will be able to:• identify strategies to support undergraduate students and new staff working in a supernumerary role;• define the roles and responsibilities of the mentor and mentee;• identify key attributes of successful mentors;• discuss the stages of the mentor–mentee relationship and the key elements of each;• describe a suitable strategy for engaging mentees and developing a mutually beneficial mentor–mentee partnership;• enable staff to reflect on their current approaches to providing feedback to mentees and identify areas that mayrequire change; and• identify barriers to a successful mentor–mentee relationship;

Graduate Nurse Program Coordinators' perspectives on graduate nurse programs in Victoria, Australia: A descriptive qualitative approach

Aims: The purpose of this study was to describe the formal preparation nursing graduates are given throughout their first year of nursing in terms of educational structure and content of work-based year-long graduate nurse programs, from the perspectives of Graduate Nurse Program Coordinators. Background: In Australia, graduate nurse programs aim to provide a supportive learning environment, assisting nursing graduates in applying their theory to practice and supporting them in becoming safe, competent and responsible professionals. Internationally, research has demonstrated an increase in the job satisfaction and more importantly retention rates of newly qualified nurses who are supported in their first year of employment in some type of transition program. Method: Using a descriptive qualitative approach, individual semi-structured interviews were used. These interviews were audio recorded, transcribed verbatim and thematically analysed to reveal themes and sub-themes. Results: The interviews provided an insight into the various aspects of preparation that nursing graduates are given in their first year of practice with the main theme to emerge from analysis, nature of transition programs. The three subthemes associated with nature of transition programs consisted of composition of rotations and study days and supernumerary strategies. Findings indicate variation in pedagogical models underpinning graduate nurse programs across Victoria. Clinical rotations varied between three to twelve months, the number of study days offered were between four and thirteen days and there was variation in supernumerary time and strategies within the programs investigated.

Multi-Objective Pipe Smoothing Genetic Algorithm For Water Distribution Network Design

This paper describes the formulation of a Multi-objective Pipe Smoothing Genetic Algorithm (MOPSGA) and its application to the least cost water distribution network design problem. Evolutionary Algorithms have been widely utilised for the optimisation of both theoretical and real-world non-linear optimisation problems, including water system design and maintenance problems. In this work we present a pipe smoothing based approach to the creation and mutation of chromosomes which utilises engineering expertise with the view to increasing the performance of the algorithm whilst promoting engineering feasibility within the population of solutions. MOPSGA is based upon the standard Non-dominated Sorting Genetic Algorithm-II (NSGA-II) and incorporates a modified population initialiser and mutation operator which directly targets elements of a network with the aim to increase network smoothness (in terms of progression from one diameter to the next) using network element awareness and an elementary heuristic. The pipe smoothing heuristic used in this algorithm is based upon a fundamental principle employed by water system engineers when designing water distribution pipe networks where the diameter of any pipe is never greater than the sum of the diameters of the pipes directly upstream resulting in the transition from large to small diameters from source to the extremities of the network. MOPSGA is assessed on a number of water distribution network benchmarks from the literature including some real-world based, large scale systems. The performance of MOPSGA is directly compared to that of NSGA-II with regard to solution quality, engineering feasibility (network smoothness) and computational efficiency. MOPSGA is shown to promote both engineering and hydraulic feasibility whilst attaining good infrastructure costs compared to NSGA-II.

The bacterial chromosome segregation protein Spo0J spreads along DNA from parS nucleation sites

Regulation of chromosome inheritance is essential to ensure proper transmission of genetic information. To accomplish accurate genome segregation, cells organize their chromosomes and actively separate them prior to cytokinesis. In Bacillus subtilis the Spo0J protein is required for accurate chromosome segregation and it regulates the developmental switch from vegetative growth to sporulation. Spo0J is a DNA-binding protein that recognizes at least eight identified parS sites located near the origin of replication. As judged by fluorescence microscopy, Spo0J forms discrete foci associated with the oriC region of the chromosome throughout the cell cycle. In an attempt to determine the mechanisms utilized by Spo0J to facilitate productive chromosome segregation, we have investigated the DNA binding activity of Spo0J. In vivo we find Spo0J associates with several kilobases of DNA flanking its specific binding sites (parS) through a parS-dependent nucleation event that promotes lateral spreading of Spo0J along the chromosome. Using purified components we find that Spo0J has the ability to coat non-specific DNA substrates. These 'Spo0J domains' provide large structures near oriC that could potentially demark, organize or localize the origin region of the chromosome.

Cytogenetic analysis of the neotropical spider Nephilengys cruentata (Araneomorphae, tetragnathidae): standard staining, NORs, C-bands and base-specific fluorochromes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)