Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CD8+ CTL responses in vivo

Dendritic cells (DCs) require a maturation signal to acquire efficient CTL-priming capacity. In vitro FcgammaR-mediated internalization of Ag-Ab immune complexes (ICs) can induce maturation of DCs. In this study, we show that IC-induced DC maturation in vitro enables DCs to prime peptide-specific CD8+ CTLs in vivo, independently of CD4+ Th cells. Importantly, OVA/anti-OVA IC-treated DCs not only primed CD8+ CTLs to an exogenously loaded peptide nonrelated to OVA, but also efficiently primed CTLs against the dominant CTL epitope derived from the OVA Ag present in the ICs. Our studies show that ICs fulfill a dual role in priming of CD8+ CTL responses to exogenous Ags: enhancement of Ag uptake by DCs and activation of DCs, resulting in "license to kill." These findings indicate that the presence of specific Abs can crucially affect the induction of cytotoxic cellular responses.     

CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions

Better understanding of tolerance and autoimmunity toward melanocyte-specific Ags is needed to develop effective treatment for vitiligo and malignant melanoma; yet, a systematic assessment of these mechanisms has been hampered by the difficulty in tracking autoreactive T cells. To address this issue, we have generated transgenic mice that express hen egg lysozyme as a melanocyte-specific neoantigen. By crossing these animals to a hen egg lysozyme-specific CD4 TCR transgenic line we have been able to track autoreactive CD4+ T cells from their development in the thymus to their involvement in spontaneous autoimmune disease with striking similarity to human vitiligo vulgaris and Vogt-Koyanagi-Harada syndrome. Our findings show that CD4-dependent destruction of melanocytes is partially inhibited by blocking Fas-Fas ligand interactions and also highlights the importance of local control of autoimmunity, as vitiligo remains patchy and never proceeds to confluence even when Ag and autoreactive CD4+ T cells are abundant. Immune therapy to enhance or suppress melanocyte-specific T cells can be directed at a series of semiredundant pathways involving tolerance and cell death.     

Revision of the genus <Emphasis Type="Italic">Placostromella</Emphasis> and inclusion of <Emphasis Type="Italic">Palawaniella castanopsis</Emphasis> as a third species

The current status of Placostromella (Ascomycota, Dothideomycetes inc. sed.) is discussed, and a third species is added to the genus based on Palawaniella castanopsis J.N. Kapoor. Both species occur on living leaves of Castanopsis (Fagaceae) in South and East Asia. Placostromella castanopsis and the type P. macrospora are fully redescribed and illustrated.     

Fire as a selective force in a Bornean tropical everwet forest

Tree species rarely exposed to burning, like in everwet tropical forests, are unlikely to be fire adapted. Therefore, one could hypothesize that these species are affected equally by burning and that tree abundance changes are linked solely to fire behavior. Alternatively, if species do react differentially to burning, abundance changes should be linked to tree habitat preference and morphology. Using tree inventories from old-growth and adjacent burned Bornean forest in combination with a database on tree morphology and habitat preference, we test these alternative hypotheses by (1) determining whether species specific abundance changes after fire differ significantly from equal change, and (2) whether observed abundance changes are linked to species morphology and habitat preference. We found that of 196 species tested, 125 species showed an abundance change significantly different from that expected under our null model of equal change. These abundance changes were significantly linked to both tree morphology and habitat preference. Abundance declines were associated with slope or ridge preference, thin barks, and limited seed dormancy. Abundance increases were associated with high light preference, small adult stature, light wood, large leaves, small seeds and long seed dormancy. While species habitat preference and morphology explained observed abundance increases well, abundance declines were only weakly associated with them (R ² ~ 0.09). This suggests that most tree mortality was random and everwet tropical tree species are poorly fire adapted. As fire frequencies are increasing in the everwet tropics, this might eventually result in permanently altered species compositions and even species extinctions.     

Seed Dispersal in Páramo Plants: Epizoochorous and Hydrochorous Taxa

Abstract: On the basis of a recent checklist of plant diversity in páramos, diaspores collected from herbaria were studied for adaptations to dispersal on animals and by water. This study shows that the páramo flora has a relatively high percentage of genera with morphological adaptations to epizoochorous and to hydrochorous diaspore dispersal. Genera with hooked and straight appendages are present throughout the páramo belt, while their number decreases in the higher páramo zones. About half of the hydrochorous genera and one-third of the epizoochorous ones can be found throughout all páramo zones. The contribution of holarctic epizoochorous genera to the páramo flora seems to be greater than that of austral-antarctic genera, whereas in hydrochorous genera it is the reverse.     

Crystal structure of phosphotransacetylase from the methanogenic archaeon Methanosarcina thermophila

Phosphotransacetylase (Pta) [EC 2.3.1.8] is ubiquitous in the carbon assimilation and energy-yielding pathways in anaerobic prokaryotes where it catalyzes the reversible transfer of the acetyl group from acetyl phosphate to CoA forming acetyl CoA and inorganic phosphate. The crystal structure of Pta from the methane-producing archaeon Methanosarcina thermophila, representing the first crystal structure of any Pta, was determined by multiwavelength anomalous diffraction at 2.7 A resolution. In solution and in the crystal, the enzyme forms a homodimer. Each monomer consists of two alpha/beta domains with a cleft along the domain boundary, which presumably contains the substrate binding sites. Comparison of the four monomers present in the asymmetric unit indicates substantial variations in the relative orientation of the two domains and the structure of the putative active site cleft. A search for structural homologs revealed the NADP(+)-dependent isocitrate and isopropylmalate dehydrogenases as the only homologs with a similar two-domain architecture.     

Design,Synthesis and In Vitro Evaluation of Novel Benzo[b]thiophene Derivatives as Serotonin N-acetyltransferase (AANAT) Inhibitors

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is the penultimate enzyme in melatonin (5-methoxy-N-acetyltryptamine) biosynthesis. It is the key-enzyme responsible of the nocturnal rhythm of melatonin production in the pineal gland. Specific AANAT inhibitors could be useful for treatment of different physiopathological disorders encountered in diseases such as seasonal affective disorders or obesity. On the basis of previous works and 3D-QSAR studies carried out in our laboratory, we have synthesized and evaluated four novel benzo[b]thiophene derivatives designed as AANAT inhibitors. Compound 13 exhibited high inhibitory activity (IC₅₀=1.4?μM) and low affinities for both MT1 (1100?nM) and MT2 (1400?nM) receptors.