Discovery of sediment indicating rapid lake-level fall in the late Pleistocene Gokarna Formation, Kathmandu Valley, Nepal: implication for terrace formation

Sediment indicating a rapid fall in lake level has been discovered in the late Pleistocene Gokarna Formation, Kathmandu Valley, Nepal. The indicator is observed along a widely traceable erosional surface in this formation, and is characterized by (1) gently inclined (ca. 10°) tabular cross-stratified sand beds of delta front origin consisting of coarser material and showing gradual decrease in elevation of its top to the progradation direction, (2) an antidune cross-laminated sand bed that interfingers with the delta front deposit, and (3) an approximately 5 m-deep erosional depression filled with convolute laminated sand beds and recognized at a location distal to that where deposits (1) and (2) were found. The early phase of rapid lake level fall caused minor erosion of the delta plain deposits by fluvial processes, introducing a higher rate of progradation of the delta front and resulting in the accumulation of deposit (1). The delta emerged as dry land due to further lowering of the lake level. The antidune cross-laminated sand bed shows evidence of having accumulated from a high-velocity stream that may have formed as the lake water drained from the delta front during the lowering of lake level. When the lake level fell below the level of the topographic high created by delta accumulation, incised valleys may have formed and part of them may have been filled with sediment at that time. The rapid fall in lake level is interpreted to have been the result of lake-wall failure, which would have occurred at the gorge outlet as the only discharge path for the basin. The initial rise of lake level causing accumulation of terrace sediments may have been due to the formation of a plug at this outlet, attributable to mass movement along the gorge

Discovery of sediment indicating rapid lake-level fall in the late Pleistocene Gokarna Formation, Kathmandu Valley, Nepal: implication for terrace formation

Sediment indicating a rapid fall in lake level has been discovered in the late Pleistocene Gokarna Formation, Kathmandu Valley, Nepal. The indicator is observed along a widely traceable erosional surface in this formation, and is characterized by (1) gently inclined (ca. 10°) tabular cross-stratified sand beds of delta front origin consisting of coarser material and showing gradual decrease in elevation of its top to the progradation direction, (2) an antidune cross-laminated sand bed that interfingers with the delta front deposit, and (3) an approximately 5 m-deep erosional depression filled with convolute laminated sand beds and recognized at a location distal to that where deposits (1) and (2) were found. The early phase of rapid lake level fall caused minor erosion of the delta plain deposits by fluvial processes, introducing a higher rate of progradation of the delta front and resulting in the accumulation of deposit (1). The delta emerged as dry land due to further lowering of the lake level. The antidune cross-laminated sand bed shows evidence of having accumulated from a high-velocity stream that may have formed as the lake water drained from the delta front during the lowering of lake level. When the lake level fell below the level of the topographic high created by delta accumulation, incised valleys may have formed and part of them may have been filled with sediment at that time. The rapid fall in lake level is interpreted to have been the result of lake-wall failure, which would have occurred at the gorge outlet as the only discharge path for the basin. The initial rise of lake level causing accumulation of terrace sediments may have been due to the formation of a plug at this outlet, attributable to mass movement along the gorge

Gamma Interferon Produced by Antigen-Specific CD4+ T Cells Regulates the Mucosal Immune Responses to Citrobacter rodentium Infection▿

Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the surface of intestinal epithelial cells and causes mucosal inflammation. This bacterium is an ideal model for investigating pathogen-host immune interactions in the gut. It is well known that gene transcripts for Th1 cytokines are highly induced in colonic tissue from mice infected with C. rodentium. However, it remains to be seen whether the Th1 or Th2 cytokines produced by antigen-specific CD4+ T cells provide effective regulation of the host immune defense against C. rodentium infection. To investigate the antigen-specific immune responses, C. rodentium expressing ovalbumin (OVA-C. rodentium), a model antigen, was generated and used to define antigen-specific responses under gamma interferon (IFN-γ)-deficient or interleukin-4 (IL-4)-deficient conditions in vivo. The activation of antigen-specific CD4+ T cells and macrophage phagocytosis were evaluated in the presence of IFN-γ or IL-4 in vitro. IFN-γ-deficient mice exhibited a loss of body weight and a higher bacterial concentration in feces during OVA-C. rodentium infection than C57BL/6 (wild type) or IL-4-deficient mice. This occurred through the decreased efficiency of macrophage phagocytosis and the activation of antigen-specific CD4+ T cells. Furthermore, a deficiency in antigen-specific CD4+ T-cell-expressed IFN-γ led to a higher susceptibility to mucosal and gut-derived systemic OVA-C. rodentium infection. These results show that the IFN-γ produced by antigen-specific CD4+ T cells plays an important role in the defense against C. rodentium

NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases

Background/Aims: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD).Methods: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing.Results: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined.Conclusions: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD