Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen especially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, spontaneously appeared on the face, neck, ears and dorsal skin of inbred NC/Nga mice when they were raised in non-sterile (conventional) circumstances, but not under specific pathogen-free conditions. Plasma levels of total IgE in conventional NC/Nga mice were markedly elevated from 8 weeks of age, correlating with clinical skin severity of dermatitis. Immunohistochemical examination of the skin lesion showed increased numbers of mast cells and CD4+ T cells containing IL-4 necessary for IgE synthesis. Thus, NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction, which may be triggered by some environmental factor(s).

Sr isotope stratigraphy provides a new age model for the fi rst complete section drilled through a deep-water coral mound. The 155-m-long section from Challenger Mound in the Porcupine Seabight, southwest of Ireland, is on Miocene siliciclastics and consists entirely of sediments bearing well-preserved cold-water coral Lophelia pertusa. The 87 Sr/ 86 Sr values of 28 coral specimens from the mound show an upward-increasing trend, correspond to ages from 2.6 to 0.5 Ma, and identify a signifi cant hiatus from ca. 1.7 to 1.0 Ma at 23.6 m below seafl oor. The age of the basal mound sediments coincides with the intensifi cation of Northern Hemisphere glaciations that set up the modern stratifi cation of the northeast Atlantic and enabled coral growth. Mound growth persisted throughout glacial-interglacial fl uctuations, reached a maximum rate (24 cm/k.y.) ca. 2.0 Ma, and ceased at 1.7 Ma. Unlike other buried mounds in Porcupine Seabight, Challenger Mound was only partly covered during its growth interruption, and growth restarted ca. 1.0 Ma.

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SummaryPeptide immunotherapy using dominant T-cell epitopes is safer and more effective than conventional immunotherapy for the treatment of immunoglobulin E (IgE)-mediated allergic diseases. When allergenic T-cell epitope peptides are expressed in the edible part of transgenic plants, successful mucosal immune tolerance to these allergens may be attainable by the consumption of these plants. In this study, we generated transgenic rice seed that accumulated high concentrations (about 60 µ g per grain) of polypeptide consisting of seven dominant human T-cell epitopes derived from the Japanese cedar pollen allergens, Cry j 1 and Cry j 2, in the endosperm. Oral administration of these transgenic rice seeds to B10.S mice before or after they were immunized with Cry j 1 holoprotein reduced not only their T-cell proliferative response to Cry j 1, but also their serum IgE levels, proving the efficacy of oral immunotherapy for the treatment of pollinosis.

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Warming of high northern latitudes in the Pliocene (5.33–2.58 Myr ago) has been linked to the closure of the Central American Seaway and intensification of North Atlantic Deep Water. Subsequent cooling in the late Pliocene may be related to the effects of freshwater input from the Arctic Ocean via the Bering Strait, disrupting North Atlantic Deep Water formation and enhancing sea ice formation. However, the timing of Arctic freshening has not been defined. Here we present neodymium and lead isotope records of detrital sediment from the Bering Sea for the past 4.3 million years. Isotopic data suggest the presence of Alaskan glaciers as far back as 4.2 Myr ago, while diatom and C37:4 alkenone records show a long-term trend towards colder and fresher water in the Bering Sea beginning with the M2 glaciation (3.3 Myr ago). We argue that the introduction of low-salinity Bering Sea water to the Arctic Ocean by 3.3 Myr ago preconditioned the climate system for global cooling.

Numerous studies along the northern Mediterranean borderland have documented the use of shellfish by Neanderthals but none of these finds are prior to Marine Isotopic Stage 3 (MIS 3). In this paper we present evidence that gathering and consumption of mollusks can now be traced back to the lowest level of the archaeological sequence at Bajondillo Cave (Málaga, Spain), dated during the MIS 6. The paper describes the taxonomical and taphonomical features of the mollusk assemblages from this level Bj19 and briefly touches upon those retrieved in levels Bj18 (MIS 5) and Bj17 (MIS 4), evidencing a continuity of the shellfishing activity that reaches to MIS 3. This evidence is substantiated on 29 datings through radiocarbon, thermoluminescence and U series methods. Obtained dates and paleoenvironmental records from the cave include isotopic, pollen, lithostratigraphic and sedimentological analyses and they are fully coherent with paleoclimate conditions expected for the different stages. We conclude that described use of shellfish resources by Neanderthals (H. neanderthalensis) in Southern Spain started ∼150 ka and were almost contemporaneous to Pinnacle Point (South Africa), when shellfishing is first documented in archaic modern humans.

Human telomeres can form DNA G-quadruplex (G4), an attractive target for anticancer drugs. Human telomeric G4s bear inherent structure polymorphism, challenging for understanding specific recognition by ligands or proteins. Protoberberines are medicinal natural-products known to stabilize telomeric G4s and inhibit telomerase. Here we report epiberberine (EPI) specifically recognizes the hybrid-2 telomeric G4 predominant in physiologically relevant K solution and converts other telomeric G4 forms to hybrid-2, the first such example reported. Our NMR structure in K solution shows EPI binding induces extensive rearrangement of the previously disordered 5'-flanking and loop segments to form an unprecedented four-layer binding pocket specific to the hybrid-2 telomeric G4; EPI recruits the (-1) adenine to form a "quasi-triad" intercalated between the external tetrad and a T:T:A triad, capped by a T:T base pair. Our study provides structural basis for small-molecule drug design targeting the human telomeric G4.