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Claudin-15 (CLDN15) molecules form channels that directly regulate cation and water transport. In the gastrointestinal tract, this transport indirectly impacts nutrient absorption. However, the mechanisms governing ion transport through these channels remain poorly understood. We addressed this question by building on our previous cell culture studies and all atom molecular dynamic simulation model of CLDN15. By mutating D55 to a bulkier glutamic acid (E) or neutral amino acid asparagine (N), our in vitro measurements showed that the D55E mutation decreased charge selectivity and favored small ion permeability, while the D55N mutation led to reduced charge selectivity without markedly altering size selectivity. By establishing a simplified (reduced) CLDN15 molecular dynamics model that excludes non-essential transmembrane regions, we were able to probe how D55 modified cation dehydration, charge interaction, and permeability. These results provide novel insight into organization of the CLDN15 selectivity filter and suggests that D55 plays a dual role in shaping both electrostatic and steric properties of the pore, but its electrostatic role is more prominent in determining CLDN15 cation permeability. This knowledge can be used toward the development of effective strategies to modulate CLDN15 function. The experimental approach established can be further extended to study the function of other claudin channels. Together, these advancements will help us to modulate tight junctions to promote human health. 

The Valanginian period is marked by significant events, including the earliest perturbations of the global carbon cycle and the initial emplacement of large igneous provinces on land. Recent years have seen the ratification of the global boundary stratotype sections and points (GSSPs) for the Valanginian and Hauterivian stages, reflecting increased stratigraphic and palaeoenvironmental research on the Valanginian. However, paleoceanographic information remains limited for the Early Cretaceous Panthalassa, which was the largest ocean during early Cretaceous. In Northeast Japan, Lower Cretaceous marine sequences, formed in the northwest region of Panthalassa along the northeastern margin of Eurasia, are exposed intermittently. These sequences have been challenging to date accurately due to the limited availability of age-diagnostic fossils. We establish new global stratigraphic correlations using U–Pb zircon ages from tuffs and carbon isotope stratigraphy for the Lower Cretaceous formations of the Karakuwa and Oshima Groups in Northeast Japan. We identify the Berriasian/Valanginian boundary and the Weissert Event within these strata. In addition, we recognize a potential stratigraphic level for the Valanginian/Hauterivian boundary. Notably, the Weissert Event interval within these sequences does not exhibit the significant lithological changes, such as the intercalation of black shales or a decrease in bioturbation observed elsewhere . By contrast, observed lithological changes are indicative of regional tectonics, including large-scale sinistral strike-slip movement and subsequent ridge subduction along the active continental margin of Eurasia. 

The Pleistocene Epoch was characterized by extensive glacier systems in numerous mountain ranges around the world. Mapping glacial landforms and deposits over many decades of prior work has afforded reconstructions of mountain glaciers, chiefly during the last Pleistocene glaciation and subsequent deglaciation. The availability of high-resolution satellite imagery, digital terrain models, and numerical chronologies of glacial deposits and landforms provides opportunities for mapping paleoglacier outlines and reconstructing ice thickness and volume during specific periods across glaciated regions at different spatial scales. Most paleoglacier reconstructions require outlines corresponding to a specific valley and terminus. However, various formats of digital paleoglacier outlines exist in the literature, some of which encompass entire glacier complexes or ice caps without differentiating between individual valleys and outlet glaciers. Also, unlike inventories of present-day glaciers such as the Randolph Glacier Inventory, digitized paleoglacier outlines lack standardized attributes. In this study, we developed an ArcGIS toolbox to subdivide paleoglacier outlines into individual polygons constrained within watershed boundaries (drainage basins) and to derive a consistent set of attributes related to the geometry, topography, and ice thickness of paleoglaciers. We demonstrate the applications of this toolbox in glaciated mountain areas in Costa Rica, the western U.S., and the central Tibetan Plateau. Although some manual adjustments are still necessary, this toolbox provides an efficient means to standardize the format and derive attributes for paleoglacier outlines. Our proposed framework and newly developed ArcGIS toolbox for standardizing paleoglacier outline formats and attributes improve the value, accuracy, and utility of paleoglacier mapping and paleoclimate reconstruction, and facilitate consistency and comparability among model simulations of glacier and climate changes from the past to present and into the future.