Aging is characterized by compromised organ and tissue function. A decrease in stem cell number and/or activity could lead to the aging-related decline in tissue homeostasis. We have analyzed how the process of aging affects germ line stem cell (GSC) behavior in the Drosophila testis and report that significant changes within the stem cell microenvironment, or niche, occur that contribute to a decline in stem cell number over time. Specifically, somatic niche cells in testes from older males display reduced expression of the cell adhesion molecule DE-cadherin and a key self-renewal signal unpaired (upd). Loss of upd correlates with an overall decrease in stem cells residing within the niche. Conversely, forced expression of upd within niche cells maintains GSCs in older males. Therefore, our data indicate that age-related changes within stem cell niches may be a significant contributing factor to reduced tissue homeostasis and regeneration in older individuals.
The Drosophila Myb-Muv B (MMB)/dREAM complex regulates gene expression and DNA replication site-specifically, but its activities in vivo have not been thoroughly explored. In ovarian amplification-stage follicle cell nuclei, the largest subunit, Mip130, is a negative regulator of replication, whereas another subunit, Myb, is a positive regulator. Here, we identified a mutation in mip40 and generated a mutation in mip120, two additional MMB subunits. Both mutants were viable, but mip120 mutants had many complex phenotypes including shortened longevity and severe eye defects. mip40 mutant females had severely reduced fertility, whereas mip120 mutant females were sterile, substantiating ovarian regulatory role(s) for MMB. Myb accumulation and binding to polytene chromosomes was dependent on the core factors of the MMB complex. In contrast to the documented mip130 mutant phenotypes, both mip40 and mip120 mutant males were sterile. We purified Mip40-containing complexes from testis nuclear extracts and identified tMAC, a new testis-specific meiotic arrest complex that contained Mip40, Caf1/p55, the Mip130 family member, Always early (Aly), and a Mip120 family member, Tombola (Tomb). Together, these data demonstrate that MMB serves diverse roles in different developmental pathways, and members of MMB can be found in alternative, noninteracting complexes in different cell types.[Keywords: Drosophila; Myb-Muv B; replication; spermatid differentiation; chorion amplification] Supplemental material is available at http://www.genesdev.org.
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 rhoptryassociated 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.Plasmodium falciparum malaria is still one of the most predominant public health problems worldwide. A better comprehension of the physiopathology of malaria is essential to the proposition of new therapeutic approaches. Anemia is a major cause of morbidity and mortality in developing countries. It is the main manifestation of severe malaria in young children and primigravid women in regions where malaria is holoendemic [1,2]. The physiopathology of malaria-associated anemia is thought to be a combination of peripheral and central factors such as the accelerated elimination of infected erythrocytes (IEs) and normal erythrocytes (NEs), the destruction of parasitized red blood cells during schizont bursting, and diserythropoiesis. The removal of NEs is considered to be a key factor.In a previous work, we described 2 ring stage-infected erythrocyte (RIE) surface molecules: ring surface protein (RSP)-1 and -2 [3]. Using specific monoclonal antibodies (MAbs) directed against the RIE surface, we identified RSP-2 as a rhoptry protein that binds to the surface of NEs and erythroid lineage during a process termed "abortive merozoite invasion" [4]. Given the natural immune response against RSP-2 during infection in the human host, antibodies against these molecules can lead to the destruction of RSP-2-tagged host cells in vitro [5]. The aim of the present study was to characterize a rhoptry protein complex that is transferred during abortive merozoite invasion to the surface of erythrocytes. Furthermore, we show that mouse MAbs raised against the rhoptry complex at the surface of erythrocytes are directed against the N-terminal region of rhoptry-associated protein (RAP)-2.Materials and methods. P. falciparum asexual erythrocyticstage parasites were cultivated under standard culture conditions [6] with some minor modifications: for the liquid immunofluorescence assay (L-IFA), we replaced 10% human serum with 0.25% (wt/vol) Albumax I (Life Technology). We used FCR3CSA , D10 (MRA-201 from the Malaria Research and Reference Reagent Resource Center [MR4]), D10DRAP1 [7], W2 (MRA-157 from the MR4), and W2mefDRAP3 [8] laboratory strains. In D10DRAP1 and W2mefDRAP3, gene-targeting technology was used to disrupt the rap-1 and rap-3 genes, respectively. Transfected parasites were grown on selective pressure with 1 m...
This research concerns a practical on-line analytic processing (OLAP) project given to 2nd year information systems major students. They were required to analyse two sets of sales data with two different OLAP software tools, and report both on their findings and on their experiences of working with the two products. Students then completed a validated instrument with questions about each OLAP tool, and data was analysed to assess whether proposed relationships in an adapted technology acceptance model (TAM) were supported. For each OLAP product the cognitive instrumental factors of result demonstrability, output quality, job relevance and perceived ease of use were found to be positively related to perceived usefulness. This supported local and international studies of business users. Facilitating conditions affected perceived ease of use, but anxiety played no significant role. Qualitative student experiences and perceptions are briefly commented on, and suggestions made about future OLAP projects.
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