The skin of primates. XXIX. The skin of the pigmy bushbaby (Galago demidovii)

The skin of the pigmy bushbaby (Galago demidovii), the smallest existing prosimian, is largely similar to that of the other African Lorisidae, although this animal has certain peculiar features. The very thin epidermis contains alkaline phosphatase-reactive dendritic cells which resemble those in the other bushbabies and the potto. The hair follicles of this animal are similar to those of the lesser bushbaby, while the sebaceous glands are different from those of the other bushbabies in being reactive for alkaline phosphatase. The histological and histochemical properties of the sweat glands are similar to those of the other bushbabies.     

The elixir phase of chain molecules

A phase of matter is a familiar notion for inanimate physical matter. The nature of a phase of matter transcends the microscopic material properties. For example, materials in the liquid phase have certain common properties independent of the chemistry of the constituents: liquids take the shape of the container; they flow; and they can be poured—alcohol, oil, and water as well as a Lennard-Jones computer model exhibit similar behavior when poised in the liquid phase. Here, we identify a hitherto unstudied “phase” of matter, the elixir phase, in a simple model of a polymeric chain whose backbone has the correct local cylindrical symmetry induced by the tangent to the chain. The elixir phase appears on breaking the cylindrical symmetry by adding side spheres along the negative normal direction, as in proteins. This phase, nestled between other phases, has multiple ground states made up of building blocks of helices and almost planar sheets akin to protein native folds. We discuss the similarities of this “phase” of a finite size system to the liquid crystal and spin glass phases. Our findings are relevant for understanding proteins; the creation of novel bioinspired nanomachines; and also may have implications for life elsewhere in the cosmos.     

Ethics committees in western and central Africa: concrete foundations

The involvement of developing countries in international clinical trials is necessary for the development of appropriate medicines for local populations. However, the absence of appropriate structures for ethical review represents a barrier for certain countries. Currently there is very little information available on existing structures dedicated to ethics in western and central Africa. This article briefly describes historical milestones in the development of networks dedicated to capacity building in ethical review in these regions and outlines the major conclusions of two workshops on this issue, which were held in September and October 2002 in Libreville, Gabon, and Paris, France. The workshops were the culmination of collaboration between the African Malaria Network Trust (AMANET) and the Pan African Bioethics Initiative (PABIN). They produced an update on ethics organizations with regard to mission, function, activities, members, and contact people, in eight countries within the regions discussed. As a result of the commitment of mandated delegates, a further prominent outcome followed these workshops: the creation of national structures, where none existed before, dedicated to the ethical review of clinical trials.     

Deciphering the Role of CD1e Protein in Mycobacterial Phosphatidyl-myo-inositol Mannosides (PIM) Processing for Presentation by CD1b to T Lymphocytes

Lipids are important antigens that induce T cell-mediated specific immune responses. They are presented to T lymphocytes by a specific class of MHC-I like proteins, termed CD1. The majority of the described CD1-presented mycobacterial antigens are presented by the CD1b isoform. We previously demonstrated that the stimulation of CD1b-restricted T cells by the hexamannosylated phosphatidyl-myo-inositol (PIM(6)), a family of mycobacterial antigens, requires a prior partial digestion of the antigen oligomannoside moiety by α-mannosidase and that CD1e is an accessory protein absolutely required for the generation of the lipid immunogenic form. Here, we show that CD1e behaves as a lipid transfer protein influencing lipid immunoediting and membrane transfer of PIM lipids. CD1e selectively assists the α-mannosidase-dependent digestion of PIM(6) species according to their degree of acylation. Moreover, CD1e transfers only diacylated PIM from donor to acceptor liposomes and also from membranes to CD1b. This study provides new insight into the molecular mechanisms by which CD1e contributes to lipid immunoediting and CD1-restricted presentation to T cells.     

Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation

Glucocorticoid-induced TNFR-related gene (GITR) participates in the immune/inflammatory response. Because GITR expression has been described in cells other than T lymphocytes, we investigated whether it also modulates acute inflammatory response. Using GITR-deficient (GITR(-/-)) mice, we analyzed the role of GITR in the development of carrageenan-induced lung inflammation (pleurisy) by studying several proinflammatory markers 2-8 h after carrageenan injection. When compared with GITR(+/+), GITR(-/-) mice exhibited decreased production of turbid exudate containing a lower number of leukocytes. This was correlated with the reduction of inflammatory markers (including TNF-alpha, IL-1beta, myeloperoxidase, inducible NO synthase, and cyclooxygenase 2) in the pleural exudate and/or in the lung. Moreover, endothelial cells expressed lower levels of adhesion molecules. In lungs of GITR(+/+) mice, GITR ligand expression was not modulated during pleurisy, while that of GITR increased, as a consequence of increased infiltration by GITR-expressing cells and of GITR up-regulation in macrophages and endothelial cells. Finally, cotreatment of GITR(+/+) mice with carrageenan and Fc-GITR fusion protein decreased the number of inflammatory cells (pleural macrophages and lung neutrophils) as compared with carrageenan treatment alone, confirming that GITR plays a role in the modulation of pleurisy.     

TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn's disease

The CD40/CD40 ligand (CD40L) pathway is involved in Crohn's disease (CD) pathogenesis. In the patients' circulation, soluble CD40L (sCD40L) levels are elevated and surface CD40L is increased in platelets and T cells, whereas in the intestine CD40 is overexpressed in the microvasculature and CD40L in platelets and T cells. The therapeutic effects of infliximab in CD are attributed to its systemic anti-TNF-alpha action, but because TNF-alpha modulates both CD40 and CD40L, we investigated whether infliximab affects the CD40/CD40L pathway in the intestine. Eighteen CD patients were evaluated before and after infliximab therapy. Plasma sCD40L was measured by ELISA and platelet and peripheral blood T cell (PBT) CD40L expression by flow cytometry. Microvascular CD40 and VCAM-1 expression were assessed in mucosal biopsies by immunohistochemistry and by flow cytometry in human intestinal microvascular endothelial cells (HIMEC). Cell cultures were performed in the presence and absence of infliximab. Infliximab treatment significantly reduced plasma sCD40L levels and eliminated CD40 and VCAM-1 from mucosal microvessels. In vitro infliximab prevented TNF-alpha-induced CD40 and VCAM-1 expression by HIMEC, and reduced PBT, but not platelet, surface CD40L expression and sCD40L release. In addition, infliximab decreased T cell-induced VCAM-1 expression in HIMEC by down-regulating CD40L in T cells and promoting T cells apoptosis. These findings point to a novel mechanism of action of infliximab, i.e., the disruption of CD40/CD40L-dependent cognate interactions between intestinal microvessels and T cells. Thus, in addition to neutralizing TNF-alpha and inducing T cell death, the therapeutic effects of infliximab in CD appear to be also mediated by inhibition of vascular inflammation in the gut.     

Effects of the antimicrobial peptide BMAP-27 in a mouse model of obstructive jaundice stimulated by lipopolysaccharide

An experimental study was designed to investigate the efficacy of BMAP-27, a compound of the cathelicidin family, in neutralizing Escherichia coli 0111:B4 lipopolysaccharide (LPS) in bile duct-ligated mice. Main outcome measures were: endotoxin and TNF-alpha concentrations in plasma, evidence of bacterial translocation in blood and peritoneum, and lethality. Adult male BALB/c mice were injected intraperitoneally with 2 mg/kg E. coli 0111:B4 LPS 1 week after sham operation or bile duct ligation (BDL). Six groups were studied: sham with placebo, sham with 120 mg/kg tazobactam-piperacillin (TZP), sham with 1 mg/kg BMAP-27, BDL with placebo, BDL with 120 mg/kg TZP, and BDL with 1mg/kg BMAP-27. After LPS, TNF-alpha plasma levels were significantly higher in BDL mice compared to sham-operated animals. BMAP-27 achieved a significant reduction of plasma endotoxin and TNF-alpha concentration when compared with placebo- and TZP-treated groups. On the other hand, both TZP and BMAP-27 significantly reduced the bacterial growth compared with saline treatment. Finally, LPS induced 60% and 55% lethality in BDL placebo- and TZP-treated treated mice and no lethality in sham-operated mice, while only BMAP-27 significantly reduced the lethality to 10%. In light of its dual antimicrobial and anti-endotoxin properties, BMAP-27 could be an interesting compound to inhibit bacterial translocation and endotoxin release in obstructive jaundice.     

Phylogeny and evolution of Malagasy plated lizards

The endemic plated lizards (Gerrhosauridae) of Madagascar are one of the most diverse groups of lizards on the island (19 species) and are found in all ecoregions. On an island that presents so many interesting biological questions, plated lizards are an ideal group for examining patterns of diversification due to their high (but tractable) diversity and wide distribution. To resolve the taxonomy and evolutionary relationships of Malagasy plated lizards, and to explore their biogeographic history, we have generated a molecular phylogeny based on >2kb of both mitochondrial (cob, 1142 bp) and nuclear (NT-3, 419 bp; c-mos, 542 bp) DNA sequences. Phylogenetic relationships and divergence-time estimates indicate Zonosaurinae are monophyletic, arising from a single colonization event, likely from Africa to Madagascar in the Paleogene (Paleocene/early Eocene), with subsequent radiation. Furthermore, our results reveal widespread mischaracterization of species delimitation and assignment based on phenotypic characteristics. Paraphyly of a number of zonosaurine species was strongly supported by our dataset, revealing not only instances of likely cryptic species (phenotypic conservatism) but also phenotypic/genotypic discordance in the delimitation of species (phenotypic variability). These results clearly demonstrate the complex history of biotic diversification on Madagascar and provide novel insight into biogeographic patterns on the island.     

Checkpoint mechanisms at the intersection between DNA damage and repair

In response to genomic insults cells trigger a signal transduction pathway, known as DNA damage checkpoint, whose role is to help the cell to cope with the damage by coordinating cell cycle progression, DNA replication and DNA repair mechanisms. Accumulating evidence suggests that activation of the first checkpoint kinase in the cascade is not due to the lesion itself, but it requires recognition and initial processing of the lesion by a specific repair mechanism. Repair enzymes likely convert a variety of physically and chemically different lesions to a unique common structure, a ssDNA region, which is the checkpoint triggering signal. Checkpoint kinases can modify the activity of repair mechanisms, allowing for efficient repair, on one side, and modulating the generation of the ssDNA signal, on the other. This strategy may be important to allow the most effective repair and a prompt recovery from the damage condition. Interestingly, at least in some cases, if the damage level is low enough the cell can deal with the lesions and it does not need to activate the checkpoint response. On the other hand if damage level is high or if the lesions are not rapidly repairable, checkpoint mechanisms become important for cell survival and preservation of genome integrity.     

Women’s Traditional Knowledge,Use Value,and the Contribution of Tamarind (<Emphasis Type="Italic">Tamarindus indica</Emphasis> L.) to Rural Households’ Cash Income in Benin

Women’s Traditional Knowledge, Use Value, and the Contribution of Tamarind ( Tamarindus indica L.) to Rural Households’ Cash Income in Benin. This study examined differences in knowledge, use values, and contribution of tamarind (Tamarindus indica) to women’s cash income during the dry season, focusing on seven tribal groups in Benin. Data were gathered using semistructured individual interviews and monitoring, and were analyzed using quantitative ethnobotanical methods. Principal component analysis was applied to describe the use value and use forms of tamarind according to different tribes. Tamarind was found to play an important role in local communities’ livelihoods. Overall, 26 different uses were mentioned for tamarind products. Most commonly, the fruit (pulp) was used to make beverages, as a laxative and purgative, and it seems to be the only plant part sold commercially. Bark was frequently used as a medicine to treat wounds, and leaves were used to make porridge and as an antibiotic. Medicinal, cultural, and material use categories were correlated best with the Fulani, whereas commerce was most correlated with Gourma tribes (PCA analysis). There were significant differences for tamarind utilization among the tribal groups, with overall ethnobotanical use values (EUV_T) ranging from 10 to 14, and contribution to cash income ranging from 8.8% to 56.4%. In view of its domestication potential, it is crucial that traditional tribal knowledge of tamarind be preserved and integrated into management policies. Further development and research needs for utilization and conservation are improvement of commercialization, organization of market channels, and extent of genetic diversity within and among populations.