Population genetic analysis of large sequence polymorphisms in Plasmodium falciparum blood-stage antigens

Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed as potential vaccine candidates. Members of the multi-gene PfRh family are surface antigens that have been shown to play a central role in directing merozoites to alternative erythrocyte receptors for invasion. Recently, we identified a large structural polymorphism, a 0.58 Kb deletion, in the C-terminal region of the PfRh2b gene, present at a high frequency in parasite populations from Senegal. We hypothesize that this region is a target of humoral immunity. Here, by analyzing 371 P. falciparum isolates we show that this major allele is present at varying frequencies in different populations within Senegal, Africa, and throughout the world. For allelic dimorphisms in the asexual stage antigens, Msp-2 and EBA-175, we find minimal geographic differentiation among parasite populations from Senegal and other African localities, suggesting extensive gene flow among these populations and/or immune-mediated frequency-dependent balancing selection. In contrast, we observe a higher level of inter-population divergence (as measured by F(st)) for the PfRh2b deletion, similar to that observed for SNPs from the sexual stage Pfs45/48 loci, which is postulated to be under directional selection. We confirm that the region containing the PfRh2b polymorphism is a target of humoral immune responses by demonstrating antibody reactivity of endemic sera. Our analysis of inter-population divergence suggests that in contrast to the large allelic dimorphisms in EBA-175 and Msp-2, the presence or absence of the large PfRh2b deletion may not elicit frequency-dependent immune selection, but may be under positive immune selection, having important implications for the development of these proteins as vaccine candidates. (C) 2009 Elsevier B.V. All rights reserved.

Evolutionary dynamics of the immunodominant repeats of the Plasmodium vivax malaria-vaccine candidate circumsporozoite protein (CSP)

The circumsporozoite protein (CSP) of Plasmodium vivax, a major target for malaria vaccine development, has immunodominant B-cell epitopes mapped to central nonapeptide repeat arrays. To determine whether rearrangements of repeat motifs during mitotic DNA replication of parasites create significant CSP diversity under conditions of low effective meiotic recombination rates, we examined csp alleles from sympatric P. vivax isolates systematically sampled from an area of low malaria endemicity in Brazil over a period of 14 months. Nine unique csp types, comprising six different nona peptide repeats, were observed in 45 isolates analyzed. Identical or nearly identical repeats predominated in most arrays, consistent with their recent expansion. We found strong linkage disequilibrium at sites across the chromosome 8 segment flanking the csp locus, consistent with rare meiotic recombination in this region. We conclude that CSP repeat diversity may not be severely constrained by rare meiotic recombination in areas of low malaria endemicity. New repeat variants may be readily created by nonhomologous recombination even when meiotic recombination is rare, with potential implications for CSP-based vaccine development. (C) 2010 Elsevier B.V. All rights reserved.

Comparative phylogeography of Trypanosoma cruzi TCIIc: New hosts, association with terrestrial ecotopes, and spatial clustering

We characterized 28 new isolates of Trypanosoma cruzi IIc (TCIIc) of mammals and triatomines from Northern to Southern Brazil, confirming the widespread distribution of this lineage. Phylogenetic analyses using cytochrome b and SSU rDNA sequences clearly separated TCIIc from TCIIa according to terrestrial and arboreal ecotopes of their preferential mammalian hosts and vectors. TCIIc was more closely related to TCIId/e, followed by TCIIa, and separated by large distances from TCIIb and TCI. Despite being indistinguishable by traditional genotyping and generally being assigned to Z3, we provide evidence that TCIIa from South America and TCIIa from North America correspond to independent lineages that circulate in distinct hosts and ecological niches. Armadillos, terrestrial didelphids and rodents, and domestic dogs were found infected by TCIIc in Brazil. We believe that, in Brazil, this is the first description of TCIIc from rodents and domestic dogs. Terrestrial triatomines of genera Panstrongylus and Triatoma were confirmed as vectors of TCIIc. Together, habitat, mammalian host and vector association corroborated the link between TCIIc and terrestrial transmission cycles/ecological niches. Analysis of ITS1 rDNA sequences disclosed clusters of TCIIc isolates in accordance with their geographic origin, independent of their host species. (C) 2009 Elsevier B.V. All rights reserved.

Limited global diversity of the Plasmodium vivax merozoite surface protein 4 gene

Merozoite surface proteins (MSPs) of the malaria parasites are major candidates for vaccine development targeting asexual blood stages. However, the diverse antigenic repertoire of these antigens that induce strain-specific protective immunity in human is a major challenge for vaccine design and often determines the efficacy of a vaccine. Here we further assessed the genetic diversity of Plasmodium vivax MSP4 (PvMSP4) protein using 195 parasite samples collected mostly from Thailand, Indonesia and Brazil. Overall, PvMSP4 is highly conserved with only eight amino acid substitutions. The majority of the haplotype diversity was restricted to the two short tetrapeptide repeat arrays in exon 1 and 2, respectively. Selection and neutrality tests indicated that exon 1 and the entire coding region of PvMSP4 were under purifying selection. Despite the limited nucleotide polymorphism of PvMSP4, significant genetic differentiation among the three major parasite populations was detected. Moreover, microgeographical heterogeneity was also evident in the parasite populations from different endemic areas of Thailand. (C) 2009 Elsevier B.V. All rights reserved.

Phylogenetic, morphological and behavioural analyses support host switching of Trypanosoma (Herpetosoma) lewisi from domestic rats to primates

We characterized four Brazilian trypanosomes isolated from domestic rats and three from captive nonhuman primates that were morphologically similar to T. lewisi, a considered non-pathogenic species restricted to rodents and transmitted by fleas, despite its potential pathogenicity for infants. These isolates were identified as T. lewisi by barcoding using V7V8 SSU rDNA sequences. In inferred phylogenetic trees, all isolates clustered tightly with reference T. lewisi and T. lewisi-like trypanosomes from Europe, Asia and Africa and despite their high sequence conservation formed a homogeneous clade separate from other species of the subgenus T. (Herpetosoma). With the aim of clearly resolving the relationships between the Brazilian isolates from domestic rats and primates, we compared sequences from more polymorphic ITS rDNA. Results corroborated that isolates from Brazilian rats and monkeys were indeed of the same species and quite close to T. lewisi isolates of humans and rats from different geographical regions. Morphology of the monkey isolates and their behaviour in culture and in experimentally infected rats were also compatible with T. lewisi. However, infection with T. lewisi is rare among monkeys. We have examined more than 200 free-ranging and 160 captive monkeys and found only three infected individuals among the monkeys held in captivity. The findings of this work suggest that proximity of monkeys and infected rats and their exposure to infected fleas may be responsible for the host switching of T. Iewisi from their natural rodent species to primates. This and previous studies reporting T. lewisi in humans suggest that this trypanosome can cause sporadic and opportunistic fleaborne infection in primates. (C) 2010 Elsevier B.V. All rights reserved.

Network genealogy of 195-bp satellite DNA supports the superimposed hybridization hypothesis of Trypanosoma cruzi evolutionary pattern

Trypanosoma cruzi is highly diverse genetically and has been partitioned into six discrete typing units (DTUs), recently re-named T. cruzi I-VI. Although T. cruzi reproduces predominantly by binary division, accumulating evidence indicates that particular DTUs are the result of hybridization events. Two major scenarios for the origin of the hybrid lineages have been proposed. It is accepted widely that the most heterozygous TcV and TcVI DTUs are the result of genetic exchange between TcII and TcIII strains. On the other hand, the participation of a TcI parental in the current genome structure of these hybrid strains is a matter of debate. Here, sequences of the T. cruzi-specific 195-bp satellite DNA of TcI, TcII, Tat, TcV, and TcVI strains have been used for inferring network genealogies. The resulting genealogy showed a high degree of reticulation, which is consistent with more than one event of hybridization between the Tc DTUs. The data also strongly suggest that Tat is a hybrid with two distinct sets of satellite sequences, and that genetic exchange between TcI and TcII parentals occurred within the pedigree of the TcV and TcVI DTUs. Although satellite DNAs belong to the fast-evolving portion of eukaryotic genomes, in >100 satellite units of nine T. cruzi strains we found regions that display 100% identity. No DTU-specific consensus motifs were identified, inferring species-wide conservation. (C) 2010 Elsevier B.V. All rights reserved.

Implants of polyanionic collagen matrix in bone defects of ovariectomized rats

In recent years, there has been a great interest in the development of biomaterials that could be used in the repair of bone defects. Collagen matrix (CM) has the advantage that it can be modified chemically to improve its mechanical properties. The aim of the present study was to evaluate the effect of three-dimensional membranes of native or anionic (submitted to alkaline treatment for 48 or 96 h) collagen matrix on the consolidation of osteoporosis bone fractures resulting from the gonadal hormone alterations caused by ovariectomy in rats subjected to hormone replacement therapy. The animals received the implants 4 months after ovariectomy and were sacrificed 8 weeks after implantation of the membranes into 4-mm wide bone defects created in the distal third of the femur with a surgical bur. Macroscopic analysis revealed the absence of pathological alterations in the implanted areas, suggesting that the material was biocompatible. Microscopic analysis showed a lower amount of bone ingrowth in the areas receiving the native membrane compared to the bone defects filled with the anionic membranes. In ovariectomized animals receiving anionic membranes, a delay in bone regeneration was observed mainly in animals not subjected to hormone replacement therapy. We conclude that anionic membranes treated with alkaline solution for 48 and 96 h presented better results in terms of bone ingrowth.

Approaches to study of three Chinese national groups.

Although numerous studies have examined the learning approaches of Chinese students, very few comparative studies have been carried out with Chinese students from different nations. The present research was designed to identify differences in study approach between Chinese university students drawn from Malaysia, Singapore, and Hong Kong.

Use of an auditory looming task to test infants' sensitivity to sound pressure level as an auditory distance cue

This study describes how an auditory looming technique was used to investigate 4-to 6-month-old infants' sensitivity to sound pressure level (SPL) as an auditory distance cue. Thirty-two infants were tested in complete darkness and presented with auditory stimuli that underwent unidirectional variations in SPL (40–70dB). The rate at which SPL was varied during the course of trials (past vs. slow) was manipulated by varying trial length (5s vs. 10s).

Tolling for the luckless, the abandoned and forsaked : therapeutic jurisprudence and international human rights law as applied to prisoners and detainees by forensic psychologists

Objectives. There has been an explosion of interest in therapeutic jurisprudence as both a filter and lens for viewing the extent to which the legal system serves therapeutic or anti-therapeutic consequences. However, little attention has been paid to the impact of therapeutic jurisprudence on questions of international human rights law and the role of forensic psychologists. The paper aims to provide an intersection between human rights, therapeutic jurisprudence, and forensic psychology.

Method. Human rights are based on legal, social, and moral rules. Human rights literature generally considers legal rights but such policy statements do not provide principles to guide forensic psychologists in addressing moral or social rights. Therefore, a framework to guide forensic psychologists is required.

Conclusion. As duty-bearers, forensic psychologists need to address the core values of freedom and well-being in rights holders (in this instance, prisoners and detainees with a mental illness). The paper proposes that human rights principles can add to the normative base of a therapeutic jurisprudence framework, and in-turn, therapeutic jurisprudence can assist forensic psychologists to actively address human rights.

Absolute versus relative difference measures of priming: Which is appropriate when baseline scores change with age?

It is often of theoretical interest to know if implicit memory (repetition priming) develops across childhood under a given circumstance. Methodologically, however, it is difficult to determine whether development is present when baseline performance for unstudied items improves with age. Calculation of priming in absolute (priming=studied - unstudied) or relative-to-baseline terms can lead to different conclusions. In first noting this problem, Parkin (1993) suggested using the Snodgrass (1989a) calculation of relative priming [priming=(studied - unstudied)/(maximum - unstudied)], and most developmental studies have since adopted this procedure. Here, we question the Snodgrass method because the Snodgrass method's results are not replicated in the picture identification task when baselines are equated experimentally across age groups. Instead, results support an absolute measure of priming. Theoretically, we argue against its core assumption; namely, that children and adults always lie on the same learning curve, with an equal maximum performance level and equal rate of learning.

Gregory Palamas on the relationship between philosophy and theology

The relationship between philosophy and theology has rarely been a harmonious and fruitful one. The two disciplines are often segmented into mutually exclusive compartments. On the one hand, philosophers, particularly contemporary philosophers working within the Anglo-American analytic tradition, widely agree that the claims made by theologians – such as the claim that there is a God and that God is a trinity of persons – are meaningless, or false, or irrational, or unsupported by evidence, or in some other way epistemically below par. On the other hand, it is not unusual to find theologians following in the footsteps of writers such as Tertullian, Kierkegaard and Barth in arguing that, when it comes to theology, faith suffices and reason merely perverts.

The philosophy-theology dispute was no stranger to fourteenth-century Byzantium, particularly in the writings of the most prominent spiritual and intellectual figure of this period, viz., Gregory Palamas (c.1296-1359). In his debates with Barlaam of Calabria (c.1290-1348), Gregory Akindynos (c.1300-1348) and Nikephoros Gregoras (c.1290-c.1358), the issue of the appropriateness of employing philosophical terms and modes of reasoning in theology occupied a central place.[1] But before looking at how Palamas tackled this issue, it will be helpful, firstly, to briefly outline how the Christian world (especially in the East) prior to Palamas tended to see the relationship between secular learning (including philosophy) and theology; and secondly, to ascertain what exactly was Palamas’ conception of philosophy.

The relationship between job status, interviewing experience, gender, and police officers' adherence to open-ended questions

Purpose : The current study examined whether several factors related to the job and demographic profile of police officers are associated with adherence to best-practice guidelines when interviewing children.

Method : One hundred and seventy-eight police officers completed a standardized (simulated) interview regarding an allegation of abuse by a 5-year-old child. Immediately prior to this interview, details were obtained from the officers' regarding their job status, gender, interview experience, the timing and nature of prior training/supervision, and experience outside the policing profession with young children.

Results : The results showed that timing of training was the only factor that related to interview performance. The proportion of open-ended questions among participants who completed their interviewer training course less than 1 month prior to the simulated interview was better than those who completed the training earlier. Interestingly, the performance of the latter group was identical to that of a group of participants who had not yet received any formal interview training. The implications of the findings are discussed, along with directions for future research.

Perceptions of athletic competence and fear of negative evaluation during physical education

Background. Physical education (PE) aims to enhance self-esteem, develop sporting interests and to encourage a physically active life-style. However, little is known about how a fear of negative evaluation (FNE), the socially evaluative aspect of social anxiety, affects children's attitudes to PE.

Aim. The aim of the study was to investigate the relationships between perceived athletic competence and FNE within PE lessons, specifically looking at differences between boys and girls and primary and secondary schools.

Sample. The participants were 192 children in three primary schools (N=85, mean age=9.5±1.1 years) and two secondary schools (N=107, mean age=14.5±0.8 years) from rural areas of North Wales and the Midlands region of England.

Methods. The participants completed the Brief-FNE Scale and the Self-Perception Profile for Children immediately post-lesson on one occasion.

Results. Girls had higher FNE but lower perceptions of athletic competence than did boys. Older girls had higher FNE and lower perceived competence than the remaining three groups. Additionally, a significant and reverse but weak correlation was observed between girls' perceived athletic competence and FNE.

Conclusions. The findings suggest that girls with a high FNE report lower perceptions of their athletic competence. Individuals who are high in FNE behave in ways to avoid the prospect of being evaluated negatively. However, they may seek feedback from significant others as a signal that unfavourable evaluations have been avoided. Therefore, positive, encouraging feedback used in child-centred learning strategies may foster feelings of competence in boys and girls and could reduce the girls' social anxiety.