Action des différentes formes actives de la vitamine A sur le mécanisme immunitaire chez le rat

Summary In this work, we have studied the role of different active forms of vitamin A considered as adjuvant of the immune mechanism in the rat. We also pointed out the adjuvant effect of retinol and retinal in comparison with the other active components of that vitamin with the bovine -globulin which is not an immunogenic antigen in itself in the control rat. Despite the fact that vitamin A has no antigenecity, it still possess an extrinsic adjuvanticity in presence of bovine -globulin. The degree of the immune response is increased.

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Action des différentes formes actives de la vitamine A sur le mécanisme immunitaire chez le rat

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Supporté par le C.N.R.S., Liban.     

Aligning Academic Activities: Implications for Teaching and Research in a New Zealand Institute of Technology

A problem situation that is at the heart of a New Zealand higher education institute applying for university status is meeting the requirement for sufficient academic staff with postgraduate qualifications. For this particular New Zealand higher education institute that was originally a teaching institution offering only sub-degree qualifications, the move to firstly offering degrees and secondly seeking university status has meant that employment conditions have shifted for many academics. In order to explore the multiple world views on the impact to the whole system of a significant number of staff upgrading qualifications whilst engaged in full-time teaching at the same time, views were sought from senior executives, heads of schools, human resource personnel and staff engaged in their own postgraduate study. Multiple conceptual models have been utilised to gain an understanding of this problem situation: Soft Systems Methodology (Checkland and Scholes, 1990, 1999) in both its original and its current form; complexity theory (McKenna, 1999; Merry, 1995; Stacey, 1996) and context-dependent cluster model (CDCM) (Fielden and London, 2001). These multiple conceptual models have all contributed to providing a basis upon which to compare multiple-perceived worlds with appropriate conceptual models upon which to base a future action plan.Outcomes discussed are both positive and negative factors including: recognition, time, stress, employment contracts, senior staff expectations, family, collegial and institutional support and the integration of own study with teaching practice and content. Implications for alignment across institutional organisational levels and also for higher education outside of the university sector are also discussed.     

Global hotspots of species richness are not congruent with endemism or threat

Biodiversity hotspots have a prominent role in conservation biology, but it remains controversial to what extent different types of hotspot are congruent. Previous studies were unable to provide a general answer because they used a single biodiversity index, were geographically restricted, compared areas of unequal size or did not quantitatively compare hotspot types. Here we use a new global database on the breeding distribution of all known extant bird species to test for congruence across three types of hotspot. We demonstrate that hotspots of species richness, threat and endemism do not show the same geographical distribution. Only 2.5% of hotspot areas are common to all three aspects of diversity, with over 80% of hotspots being idiosyncratic. More generally, there is a surprisingly low overall congruence of biodiversity indices, with any one index explaining less than 24% of variation in the other indices. These results suggest that, even within a single taxonomic class, different mechanisms are responsible for the origin and maintenance of different aspects of diversity. Consequently, the different types of hotspots also vary greatly in their utility as conservation tools.     

Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner

Multiple ovulations are uncommon in humans, cattle and many breeds of sheep. Pituitary gonadotrophins and as yet unidentified ovarian factors precisely regulate follicular development so that, normally, only one follicle is selected to ovulate. The Inverdale (FecXI) sheep, however, carries a naturally occurring X-linked mutation that causes increased ovulation rate and twin and triplet births in heterozygotes (FecXI/FecX+; ref. 1), but primary ovarian failure in homozygotes (FecXI/FecXI; ref. 2). Germ-cell development, formation of the follicle and the earliest stages of follicular growth are normal in FecXI/FecXI sheep, but follicular development beyond the primary stage is impaired. A second family unrelated to the Inverdale sheep also has the same X-linked phenotype (Hanna, FecXH). Crossing FecXI with FecXH animals produces FecXI/FecXH infertile females phenotypically indistinguishable from FecXI/FecXI females. We report here that the FecXI locus maps to an orthologous chromosomal region syntenic to human Xp11.2-11.4, which contains BMP15, encoding bone morphogenetic protein 15 (also known as growth differentiation factor 9B (GDF9B)). Whereas BMP15 is a member of the transforming growth factor beta (TGFbeta) superfamily and is specifically expressed in oocytes, its function is unknown. We show that independent germline point mutations exist in FecXI and FecXH carriers. These findings establish that BMP15 is essential for female fertility and that natural mutations in an ovary-derived factor can cause both increased ovulation rate and infertility phenotypes in a dosage-sensitive manner.     

Widespread aneuploidy revealed by DNA microarray expression profiling

Expression profiling using DNA microarrays holds great promise for a variety of research applications, including the systematic characterization of genes discovered by sequencing projects. To demonstrate the general usefulness of this approach, we recently obtained expression profiles for nearly 300 Saccharomyces cerevisiae deletion mutants. Approximately 8% of the mutants profiled exhibited chromosome-wide expression biases, leading to spurious correlations among profiles. Competitive hybridization of genomic DNA from the mutant strains and their isogenic parental wild-type strains showed they were aneuploid for whole chromosomes or chromosomal segments. Expression profile data published by several other laboratories also suggest the use of aneuploid strains. In five separate cases, the extra chromosome harboured a close homologue of the deleted gene; in two cases, a clear growth advantage for cells acquiring the extra chromosome was demonstrated. Our results have implications for interpreting whole-genome expression data, particularly from cells known to suffer genomic instability, such as malignant or immortalized cells.     

Regulation of phyllotaxis by polar auxin transport

The regular arrangement of leaves around a plant's stem, called phyllotaxis, has for centuries attracted the attention of philosophers, mathematicians and natural scientists; however, to date, studies of phyllotaxis have been largely theoretical. Leaves and flowers are formed from the shoot apical meristem, triggered by the plant hormone auxin. Auxin is transported through plant tissues by specific cellular influx and efflux carrier proteins. Here we show that proteins involved in auxin transport regulate phyllotaxis. Our data indicate that auxin is transported upwards into the meristem through the epidermis and the outermost meristem cell layer. Existing leaf primordia act as sinks, redistributing auxin and creating its heterogeneous distribution in the meristem. Auxin accumulation occurs only at certain minimal distances from existing primordia, defining the position of future primordia. This model for phyllotaxis accounts for its reiterative nature, as well as its regularity and stability.     

MDC1 is a mediator of the mammalian DNA damage checkpoint

To counteract the continuous exposure of cells to agents that damage DNA, cells have evolved complex regulatory networks called checkpoints to sense DNA damage and coordinate DNA replication, cell-cycle arrest and DNA repair. It has recently been shown that the histone H2A variant H2AX specifically controls the recruitment of DNA repair proteins to the sites of DNA damage. Here we identify a novel BRCA1 carboxy-terminal (BRCT) and forkhead-associated (FHA) domain-containing protein, MDC1 (mediator of DNA damage checkpoint protein 1), which works with H2AX to promote recruitment of repair proteins to the sites of DNA breaks and which, in addition, controls damage-induced cell-cycle arrest checkpoints. MDC1 forms foci that co-localize extensively with gamma-H2AX foci within minutes after exposure to ionizing radiation. H2AX is required for MDC1 foci formation, and MDC1 forms complexes with phosphorylated H2AX. Furthermore, this interaction is phosphorylation dependent as peptides containing the phosphorylated site on H2AX bind MDC1 in a phosphorylation-dependent manner. We have shown by using small interfering RNA (siRNA) that cells lacking MDC1 are sensitive to ionizing radiation, and that MDC1 controls the formation of damage-induced 53BP1, BRCA1 and MRN foci, in part by promoting efficient H2AX phosphorylation. In addition, cells lacking MDC1 also fail to activate the intra-S phase and G2/M phase cell-cycle checkpoints properly after exposure to ionizing radiation, which was associated with an inability to regulate Chk1 properly. These results highlight a crucial role for MDC1 in mediating transduction of the DNA damage signal.     

A proteomic view of the Plasmodium falciparum life cycle

The completion of the Plasmodium falciparum clone 3D7 genome provides a basis on which to conduct comparative proteomics studies of this human pathogen. Here, we applied a high-throughput proteomics approach to identify new potential drug and vaccine targets and to better understand the biology of this complex protozoan parasite. We characterized four stages of the parasite life cycle (sporozoites, merozoites, trophozoites and gametocytes) by multidimensional protein identification technology. Functional profiling of over 2,400 proteins agreed with the physiology of each stage. Unexpectedly, the antigenically variant proteins of var and rif genes, defined as molecules on the surface of infected erythrocytes, were also largely expressed in sporozoites. The detection of chromosomal clusters encoding co-expressed proteins suggested a potential mechanism for controlling gene expression.     

Genome sequence of the human malaria parasite Plasmodium falciparum

The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.     

Mechanism of force generation by myosin heads in skeletal muscle

Muscles generate force and shortening in a cyclical interaction between the myosin head domains projecting from the myosin filaments and the adjacent actin filaments. Although many features of the dynamic performance of muscle are determined by the rates of attachment and detachment of myosin and actin, the primary event in force generation is thought to be a conformational change or 'working stroke' in the actin-bound myosin head. According to this hypothesis, the working stroke is much faster than attachment or detachment, but can be observed directly in the rapid force transients that follow step displacement of the filaments. Although many studies of the mechanism of muscle contraction have been based on this hypothesis, the alternative view-that the fast force transients are caused by fast components of attachment and detachment--has not been excluded definitively. Here we show that measurements of the axial motions of the myosin heads at ?ngstr?m resolution by a new X-ray interference technique rule out the rapid attachment/detachment hypothesis, and provide compelling support for the working stroke model of force generation.