Anatomy and origin of authochthonous late Pleistocene forced regression deposits, east Coromandel inner shelf, New Zealand: implications for the development and definition of the regressive systems tract

High-resolution seismic reflection data from the east Coromandel coast, New Zealand, provide details of the sequence stratigraphy beneath an autochthonous, wave dominated inner shelf margin during the late Quaternary (0-140 ka). Since c. 1 Ma, the shelf has experienced limited subsidence and fluvial sediment input, producing a depositional regime characterised by extensive reworking of coastal and shelf sediments during glacio-eustatic sea-level fluctuations. It appears that only one complete fifth-order (c. 100 000 yr) depositional sequence is preserved beneath the inner shelf, the late Pleistocene Waihi Sequence, suggesting any earlier Quaternary sequences were mainly cannibalised into successively younger sequences. The predominantly Holocene-age Whangamata Sequence is also evident in seismic data and modern coastal deposits, and represents an incomplete depositional sequence in its early stages of formation. A prominent aspect of the sequence stratigraphy off parts of the east Coromandel coast is the presence of forced regressive deposits (FRDs) within the regressive systems tract (RST) of the late Pleistocene Waihi Sequence. The FRDs are interpreted to represent regressive barrier-shoreface sands that were sourced from erosion and onshore reworking of underlying Pleistocene sediments during the period of slow falling sea level from isotope stages 5 to 2 (c. 112-18 ka). The RST is volumetrically the most significant depositional component of the Waihi Sequence; the regressive deposits form a 15-20 m thick, sharp-based, tabular seismic unit that downsteps and progrades continuously across the inner shelf. The sequence boundary for the Waihi Sequence is placed at the most prominent, regionally correlative, and chronostratigraphically significant surface, namely an erosional unconformity characterised in many areas by large incised valleys that was generated above the RST. This unconformity is interpreted as a surface of maximum subaerial erosion generated during the last glacial lowstand (c. 18 ka). Although the base of the RST is associated with a prominent regressive surface of erosion, this is not used as the sequence boundary as it is highly diachronous and difficult to identify and correlate where FRDs are not developed. The previous highstand deposits are limited to subaerial barrier deposits preserved behind several modern Holocene barriers along the coast, while the transgressive systems tract is preserved locally as incised-valley fill deposits beneath the regressive surface of erosion at the base of the RST. Many documented late Pleistocene RSTs have been actively sourced from fluvial systems feeding the shelf and building basinward-thickening, often stacked wedges of FRDs, for which the name allochthonous FRDs is suggested. The Waihi Sequence RST is unusual in that it appears to have been sourced predominantly from reworking of underlying shelf sediments, and thus represents an autochthonous FRD. Autochthonous FRDs are also present on the Forster-Tuncurry shelf in southeast Australia, and may be a common feature in other shelf settings with low subsidence and low sediment supply rates, provided shelf gradients are not too steep, and an underlying source of unconsolidated shelf sediments is available to source FRDs. The preservation potential of such autochthonous FRDs in ancient deposits is probably low given that they are likely to be cannibalised during subsequent sea-level falls

Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells

Dengue virus is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans, affecting over 100 million individuals each year. Currently there is no licensed vaccine or effective antiviral therapy available, and treatment is largely supportive in nature. This study presents a comprehensive analysis of functional T-cell memory against dengue viruses and suggests an HLA-linked protective role for CD8+ T cells. This demonstration of the protective role of T-cell responses points the way forward to identifying robust correlates of protection in natural immunity and vaccination against dengue virus

Human Embryonic Stem Cells Differentiated to Lung Lineage-Specific Cells Ameliorate Pulmonary Fibrosis in a Xenograft Transplant Mouse Model

Our aim was to differentiate human (h) embryonic stem (ES) cells into lung epithelial lineage-specific cells [i.e., alveolar epithelial type I (AEI) and type II (AEII) cells and Clara cells] as the first step in the development of cell-based strategies to repair lung injury in the bleomycin mouse model of idiopathic pulmonary fibrosis (IPF). A heterogeneous population of non-ciliated lung lineage-specific cells was derived by a novel method of embryoid body (EB) differentiation. This differentiated human cell population was used to modulate the profibrotic phenotype in transplanted animals.Omission or inclusion of one or more components in the differentiation medium skewed differentiation of H7 hES cells into varying proportions of AEI, AEII, and Clara cells. ICG-001, a small molecule inhibitor of Wnt/β-catenin/Creb-binding protein (CBP) transcription, changed marker expression of the differentiated ES cells from an AEII-like phenotype to a predominantly AEI-like phenotype. The differentiated cells were used in xenograft transplantation studies in bleomycin-treated Rag2γC(-/-) mice. Human cells were detected in lungs of the transplanted groups receiving differentiated ES cells treated with or without ICG-001. The increased lung collagen content found in bleomycin-treated mice receiving saline was significantly reduced by transplantation with the lung-lineage specific epithelial cells differentiated from ES cells. A significant increase in progenitor number was observed in the airways of bleomycin-treated mice after transplantation of differentiated hES cells.This study indicates that ES cell-based therapy may be a powerful novel approach to ameliorate lung fibrosis

Complement C3d Conjugation to Anthrax Protective Antigen Promotes a Rapid, Sustained, and Protective Antibody Response

B. anthracis is the causative agent of anthrax. Pathogenesis is primarily mediated through the exotoxins lethal factor and edema factor, which bind protective antigen (PA) to gain entry into the host cell. The current anthrax vaccine (AVA, Biothrax™) consists of aluminum-adsorbed cell-free filtrates of unencapsulated B. anthracis, wherein PA is thought to be the principle target of neutralization. In this study, we evaluated the efficacy of the natural adjuvant, C3d, versus alum in eliciting an anti-PA humoral response and found that C3d conjugation to PA and emulsion in incomplete Freund's adjuvant (IFA) imparted superior protection from anthrax challenge relative to PA in IFA or PA adsorbed to alum. Relative to alum-PA, immunization of mice with C3d-PA/IFA augmented both the onset and sustained production of PA-specific antibodies, including neutralizing antibodies to the receptor-binding portion (domain 4) of PA. C3d-PA/IFA was efficacious when administered either i.p. or s.c., and in adolescent mice lacking a fully mature B cell compartment. Induction of PA-specific antibodies by C3d-PA/IFA correlated with increased efficiency of germinal center formation and plasma cell generation. Importantly, C3d-PA immunization effectively protected mice from intranasal challenge with B. anthracis spores, and was approximately 10-fold more effective than alum-PA immunization or PA/IFA based on dose challenge. These data suggest that incorporation of C3d as an adjuvant may overcome shortcomings of the currently licensed aluminum-based vaccine, and may confer protection in the early days following acute anthrax exposure