Epidermal necrolysis: mechanisms of keratinocyte apoptosis

Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute and severe adverse reaction to drugs, characterized by the widespread destruction of the epithelium of the skin and mucous membranes. This destruction by massive apoptosis leads to a clinical pattern of epidermal necrolysis resembling second degree burns, with sheets of necrotic epidermis detached from the underlying dermis. The mechanisms of acute and extensive destruction of the skin are not yet fully understood. At the onset of the reaction blisters develop from the fluid that accumulates between the dead epidermis and the dermis. High concentrations of mononuclear cells are present in this blister fluid, principally CD8 T-lymphocytes that may exhibit a drug specific MHC class I restricted cytotoxicity against autologous cells. The intervention of soluble mediators such as TNFalpha, perforin/granzyme, or Fas-Ligand may be necessary for amplifying the apoptosis of keratinocytes. A strong association between epidermal necrolysis to certain drugs and rare HLA-B genotypes suggests that direct interaction between these drugs and HLA-B molecules may initiate a reaction resembling the acute rejection of allogeneic epidermis.     

The expression pattern of the Picea glauca Defensin 1 promoter is maintained in Arabidopsis thaliana, indicating the conservation of signalling pathways between angiosperms and gymnosperms

A 1149 bp genomic fragment corresponding to the 5' non-coding region of the PgD1 (Picea glauca Defensin 1) gene was cloned, characterized, and compared with all Arabidopsis thaliana defensin promoters. The cloned fragment was found to contain several motifs specific to defence or hormonal response, including a motif involved in the methyl jasmonate reponse, a fungal elicitor responsive element, and TC-rich repeat cis-acting element involved in defence and stress responsiveness. A functional analysis of the PgD1 promoter was performed using the uidA (GUS) reporter system in stably transformed Arabidopsis and white spruce plants. The PgD1 promoter was responsive to jasmonic acid (JA), to infection by fungus and to wounding. In transgenic spruce embryos, GUS staining was clearly restricted to the shoot apical meristem. In Arabidopsis, faint GUS coloration was observed in leaves and flowers and a strong blue colour was observed in guard cells and trichomes. Transgenic Arabidopsis plants expressing the PgD1::GUS construct were also infiltrated with the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000. It caused a suppression of defensin expression probably resulting from the antagonistic relationship between the pathogen-stimulated salicylic acid pathway and the jasmonic acid pathway. It is therefore concluded that the PgD1 promoter fragment cloned appears to contain most if not all the elements for proper PgD1 expression and that these elements are also recognized in Arabidopsis despite the phylogenetic and evolutionary differences that separates them.     

The first report of <Emphasis Type="Italic">Spondias</Emphasis> native to Madagascar: <Emphasis Type="Italic">Spondias tefyi</Emphasis>, sp. nov. (Anacardiaceae)

Spondias represents a genus new to Madagascar’s native flora. Like Campnosperma, it is now known from both American and Asian tropics and Madagascar but not from continental Africa. The new species Spondias tefyi is easily distinguished from all of its Asian congeners by having the stamens shorter than the pistil and fruits brown and lenticellate at maturity (vs. greenish, yellow, orange or red, and relatively smooth). The new species is one of several Anacardiaceae whose fruits are eaten by lemurs in the Analavelona Forest, highlighting the importance of conserving this threatened subhumid forest remnant in southern Madagascar.     

Life on high: the diversity of small mammals at high altitude in South Africa

The Great Escarpment is the major mountain system in South Africa, yet very few biological surveys have been conducted outside of the well-known Drakensberg section. This is surprising given the important role that mountains play in local and global biodiversity patterns. In this study, small mammal diversity and community composition were estimated at three high altitude (>1,700?m) sites within the Sneeuberg Mountain Complex (SMC) of the Great Escarpment, South Africa from June 2009 to May 2010. The influences of selected environmental variables on diversity were also tested. Of 423 live-captures, a total of 292 unique individuals of 12 small mammal species (one shrew, one elephant shrew and 10 rodents) were identified during 5,280 trap nights. No single environmental variable could account for the variation observed in diversity measurements but vegetation height appeared to be the most important factor to influence the number of individuals captured. It is hypothesised that the high species richness and diversity of small mammals observed in the SMC compared to other parts of the Great Escarpment is due to the SMC being located in a transition zone of the Grassland and Nama-Karoo biomes. Our results suggest that the SMC could be important in conserving small mammal species from western and eastern assemblages across South Africa.     

An all-purpose antimalarial drug target

The recent re-emphasis on malaria eradication has made developing drugs that block transmission and terminate latent disease critical. Most drugs do not affect the liver stages-an ability that is crucial to the latter goal. Addressing this problem, Hoepfner et?al. (2012) uncover the parasite's lysyl-tRNA synthetase as?a druggable target.     

Mesenchymal stromal cells: new directions

Research into mesenchymal stromal/stem cells (MSCs) has been particularly exciting in the past five years. Our understanding of mechanisms of MSC-mediated tissue regeneration has undergone considerable evolution. Recent investigation of the primary in situ counterpart of cultured MSCs has led to fresh insights into MSC physiology and its role in the immune system. At the same time, the clinical application of MSCs continues to increase markedly. Taken together, a reappraisal of the definition of MSCs, a review of current research directions, and a reassessment of the approach to clinical investigation are timely and prudent.     

TWEAK affects keratinocyte G2/M growth arrest and induces apoptosis through the translocation of the AIF protein to the nucleus

The soluble TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) binds to the fibroblast growth factor-inducible 14 receptor (FN14, TNFRSF12A) on the cell membrane and induces multiple biological responses, such as proliferation, migration, differentiation, angiogenesis and apoptosis. Previous reports show that TWEAK, which does not contain a death domain in its cytoplasmic tail, induces the apoptosis of tumor cell lines through the induction of TNFα secretion. TWEAK induces apoptosis in human keratinocytes. Our experiments clearly demonstrate that TWEAK does not induce the secretion of TNFα or TRAIL proteins. The use of specific inhibitors and the absence of procaspase-3 cleavage suggest that the apoptosis of keratinocytes follows a caspase- and cathepsin B-independent pathway. Further investigation showed that TWEAK induces a decrease in the mitochondrial membrane potential of keratinocytes. Confocal microscopy showed that TWEAK induces the cleavage and the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus, thus initiating caspase-independent apoptosis. Moreover, TWEAK induces FOXO3 and GADD45 expression, cdc2 phosphorylation and cdc2 and cyclinB1 degradation, resulting in the arrest of cell growth at the G2/M phase. Finally, we report that TWEAK and FN14 are normally expressed in the basal layer of the physiological epidermis and are greatly enhanced in benign (psoriasis) and malignant (squamous cell carcinoma) skin pathologies that are characterized by an inflammatory component. TWEAK might play an essential role in skin homeostasis and pathology.     

Reef Fishes Have Higher Parasite Richness at Unfished Palmyra Atoll Compared to Fished Kiritimati Island

We compared parasite communities at two coral atolls in the Line Islands chain of the central Pacific (Kiritimati Island and Palmyra Atoll). Palmyra Atoll is relatively pristine while Kiritimati Island is heavily fished. At each island, we sampled five fish species for helminth and arthropod endoparasites: Chromis margaritifer, Plectroglyphidodon dickii, Paracirrhites arcatus, Acanthurus nigricans, and Lutjanus bohar. The surveys found monogeneans, digeneans, cestodes, nematodes, acanthocephalans, and copepods. Parasite richness was higher at Palmyra compared to Kiritimati for all five fish species. Fishes from Palmyra also tended to have more parasites species per host, higher parasite prevalence, and higher parasite abundance than did fishes from Kiritimati. The lower parasitism at Kiritimati may result from a simplified food web due to over fishing. Low biodiversity could impair parasite transmission by reducing the availability of hosts required by parasites with complex life cycles. Most notably, the lower abundances of larval shark tapeworms at Kiritimati presumably reflect the fact that fishing has greatly depleted sharks there in comparison to Palmyra.