Treatment of autoimmune disease with extracorporeal photochemotherapy: pemphigus vulgaris--preliminary report

Extracorporeal photochemotherapy is a new form of immunotherapy which involves the extracorporeal photoinactivation of peripheral blood cells by 8-methoxypsoralen in the presence of ultraviolet A irradiation, followed by readministration of the cells. To explore the efficacy of this therapy in the treatment of autoimmune disease, four patients with a lengthy history of corticosteroid and immunosuppressive drug-resistant pemphigus vulgaris were initiated on extracorporeal photochemotherapy. Three patients experienced a complete remission in cutaneous disease expression, permitting discontinuation of medications in two and a substantial decrease in the third. Significant reductions in serum antiepidermal cell antibody titers occurred in all four patients. The treatments were well tolerated without the occurrence of adverse events. These results in a small number of patients suggest that extracorporeal photochemotherapy may prove to be a useful tool in the treatment of aggressive autoimmune disease.     

Palaeoenvironments of the Buia Homo site: High-resolution facies analysis and non-marine sequence stratigraphy in the Alat formation (Pleistocene Dandiero Basin, Danakil depression, Eritrea)

The Early to Middle Pleistocene Dandiero rift basin is located near the Buia village, 110 km south of Massawa (Eritrea), and is filled by about 1000 m of continental deposits bearing 1 My erectus-like human remains. The basin fill consists of six formations (from bottom up): Bukra sand and gravels (fluvial), Alat formation (fluvio-lacustrine), Wara sand and gravel (fluvial), Goreya formation (lacustrine), Aro sand (fluvio-deltaic) and Addai fanglomerate (alluvial fan). This paper is focused on the Homo-bearing deposits of the Alat formation. The Alat formation records several episodes of changing accommodation space, with repeated shifts from fluvial to lacustrine conditions. The first episode points to rapid lake formation followed by a progressive shallowing. The second episode records fluvial aggradation above a sequence boundary, followed by the development and progressive infill of a second lake. The third episode points to a rapid lake formation followed by deposition of deltaic and fluvial sediments. The last episode is characterised by fluvial deposition under low-accommodation conditions. The development of the lacustrine environments was probably controlled by tectonics, in accordance with its formation during regionally dry climatic conditions, although minor shifts toward wetter conditions cannot be excluded. Human remains occur in the upper Alat formation, where the transition from a deltaic to alluvial setting is characterised by high frequency, potentially millennial-scale, lake-level oscillations. The palaeoanthropological record in the Buia area seems to be correlated with water availability (lacustrine coastal plains and floodplains) in a relatively open and grassy environment (grassland- and savannah-dominated). The increase in fluvial discharge that occurred at the top of the Alat formation led to erosion and winnowing of the underlying fossil-bearing, fluvio-deltaic deposits. A large number of bones and artefacts were consequently accumulated at the base of channel fills, which represent a preferential horizon for fossil searching.     

Genetic Screening Identifies Cyanogenesis-Deficient Mutants of Lotus japonicus and Reveals Enzymatic Specificity in Hydroxynitrile Glucoside Metabolism

Cyanogenesis, the release of hydrogen cyanide from damaged plant tissues, involves the enzymatic degradation of amino acid–derived cyanogenic glucosides (α-hydroxynitrile glucosides) by specific β-glucosidases. Release of cyanide functions as a defense mechanism against generalist herbivores. We developed a high-throughput screening method and used it to identify cyanogenesis deficient (cyd) mutants in the model legume Lotus japonicus. Mutants in both biosynthesis and catabolism of cyanogenic glucosides were isolated and classified following metabolic profiling of cyanogenic glucoside content. L. japonicus produces two cyanogenic glucosides: linamarin (derived from Val) and lotaustralin (derived from Ile). Their biosynthesis may involve the same set of enzymes for both amino acid precursors. However, in one class of mutants, accumulation of lotaustralin and linamarin was uncoupled. Catabolic mutants could be placed in two complementation groups, one of which, cyd2, encoded the β-glucosidase BGD2. Despite the identification of nine independent cyd2 alleles, no mutants involving the gene encoding a closely related β-glucosidase, BGD4, were identified. This indicated that BGD4 plays no role in cyanogenesis in L. japonicus in vivo. Biochemical analysis confirmed that BGD4 cannot hydrolyze linamarin or lotaustralin and in L. japonicus is specific for breakdown of related hydroxynitrile glucosides, such as rhodiocyanoside A. By contrast, BGD2 can hydrolyze both cyanogenic glucosides and rhodiocyanosides. Our genetic analysis demonstrated specificity in the catabolic pathways for hydroxynitrile glucosides and implied specificity in their biosynthetic pathways as well. In addition, it has provided important tools for elucidating and potentially modifying cyanogenesis pathways in plants.