Members of the low-molecular-mass rhoptry protein complex of Plasmodium falciparum bind to the surface of normal erythrocytes.

The destruction of erythrocytes is one of the most frequently observed causes of severe malarial anemia. Recently, we showed that tagging normal erythrocytes and cells of erythroid precursors with rhoptry-derived proteins can trigger their destruction. In the present study, we used rhoptry-associated protein (RAP)-1 and RAP-3 gene-disruption mutant Plasmodium falciparum parasites and showed that 2 members of a rhoptry protein complex, RAP-1 and RAP-2, bind to the surface of normal erythrocytes. Surface iodination experiments showed that RAP-1 but not RAP-3 mutant parasites lose their capacity to tag erythrocytes. This work opens new doors into the investigation of the molecular mechanism of anemia in patients with malaria.

[Women and sex-specific health research in the German Society for Social Medicine and Prevention]. / Frauen- und geschlechtsspezifische Gesundheitsforschung in der DGSMP.

Since the 1970s women's health research has put gender-specific topics on the agenda of health research and practice. Based on a social science approach, it focuses on social conditions of the maintenance of women's health and of their needs in prevention, health promotion, medical treatment, and rehabilitation. Besides an analysis of woman-specific topics (such as sexual violence or drug abuse) women's health research addresses questions of gender bias in health research. In Germany, guidelines are lacking that ensure appropriate attention to gender issues for health research. The section "Woman-specific and gender-specific health research" of the German Society for Social Medicine and Prevention (DGSMP) intends to intensify the discussion on the gaps in health research and prevention and on the development of guidelines to detect gender bias. The main goal is to implement the concept of gender mainstreaming in public health.

Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum.

Persistent and recurrent infections by Plasmodium falciparum malaria parasites result from the ability of the parasite to undergo antigenic variation and evade host immune attack. P. falciparum parasites generate high levels of variability in gene families that comprise virulence determinants of cytoadherence and antigenic variation, such as the var genes. These genes encode the major variable parasite protein (PfEMP-1), and are expressed in a mutually exclusive manner at the surface of the erythrocyte infected by P. falciparum. Here we identify a mechanism by which var gene sequences undergo recombination at frequencies much higher than those expected from homologous crossover events alone. These recombination events occur between subtelomeric regions of heterologous chromosomes, which associate in clusters near the nuclear periphery in asexual blood-stage parasites or in bouquet-like configurations near one pole of the elongated nuclei in sexual parasite forms. We propose that the alignment of var genes in heterologous chromosomes facilitates gene conversion and promotes the diversity of antigenic and adhesive phenotypes. The association of virulence factors with a specific nuclear subcompartment may also have implications for variation during mitotic recombination in asexual blood stages.

Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection.

Malaria during the first pregnancy causes a high rate of fetal and neonatal death. The decreasing susceptibility during subsequent pregnancies correlates with acquisition of antibodies that block binding of infected red cells to chondroitin sulfate A (CSA), a receptor for parasites in the placenta. Here we identify a domain within a particular Plasmodium falciparum erythrocyte membrane protein 1 that binds CSA. We cloned a var gene expressed in CSA-binding parasitized red blood cells (PRBCs). The gene had eight receptor-like domains, each of which was expressed on the surface of Chinese hamster ovary cells and was tested for CSA binding. CSA linked to biotin used as a probe demonstrated that two Duffy-binding-like (DBL) domains (DBL3 and DBL7) bound CSA. DBL7, but not DBL3, also bound chondroitin sulfate C (CSC) linked to biotin, a negatively charged sugar that does not support PRBC adhesion. Furthermore, CSA, but not CSC, blocked the interaction with DBL3; both CSA and CSC blocked binding to DBL7. Thus, only the DBL3 domain displays the same binding specificity as PRBCs. Because protective antibodies present after pregnancy block binding to CSA of parasites from different parts of the world, DBL-3, although variant, may induce cross-reactive immunity that will protect pregnant women and their fetuses.

[Work capacity, severe disability and needs for disability services in Thüringen with respect to demographic change]. / Erwerbsunfähigkeit, Schwerbehinderung und Schwerpflegebedürftigkeit in Thüringen im demographischen Wandel.

Considerable changes are taking place in germany in respect of age groups (fewer youngsters, more old people), and this is bound to be reflected by the demography of the working population (15 to 64 years) during the next 50 years. It is shown in this contribution how the expected changes in age distribution in Thuringia will probably be reflected by the number of pensioners who are incapable of gainful employment or of exercising their original job for which they were trained. The proportion of younger persons who had to be pensioned because of inability to work or major disablement or severe need of nursing care, will decrease until 2040 A.D., these persons being in most cases about 10 years younger than the usual pensioning age. This entails a great need for medical, social and job rehabilitation in tremendous measure: a major challenge both in sociomedical and labour market policy respects.