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Abstract The Upper Indus Basin (UIB) heavily depends on its frozen water resources, and an accelerated melt due to the projected climate change may significantly alter future water availability. The future hydro-climatic regime and water availability of the Hunza basin (a sub-basin of UIB) were analysed using the newly released Coupled Model Intercomparison Project Phase 6 (CMIP6) climate projections. A data and parameter parsimonious precipitation-runoff model, the Distance Distribution Dynamics (DDD) model, was used with energy balance-based subroutines for snowmelt, glacier melt and evapotranspiration. The DDD model was set up for baseline (1991–2010), mid-century (2041–2060) and end-century (2081–2100) climates projections from two global circulation models (GCM), namely EC-Earth3 and MPI-ESM. The projections indicate a substantial increase in temperature (1.1–8.6 °C) and precipitation (12–32%) throughout the twenty-first century. The simulations show the future flow increase between 23–126% and the future glacier melt increase between 30–265%, depending on the scenarios and GCMs used. Moreover, the simulations suggest an increasing glacier melt contribution from all elevations with a significant increase from the higher elevations. The findings provide a basis for planning and modifying reservoir operation strategies with respect to hydropower generation, irrigation withdrawals, flood control, and drought management.

In the high altitude Hindukush Karakoram Himalaya (HKH) mountains, the complex weather system, inaccessible terrain and sparse measurements make the elevation-distributed precipitation and temperature among the most significant unknowns. The elevation-distributed snow and glacier dynamics in the HKH region are also little known, leading to serious concerns about the current and future water availability and management. The Hunza Basin in the HKH region is a scarcely monitored, and snow- and glacier-dominated part of the Upper Indus Basin (UIB). The current study investigates the elevation-distributed hydrological regime in the Hunza Basin. The Distance Distribution Dynamics (DDD) model, with a degree day and an energy balance approach for simulating glacial melt, is forced with precipitation derived from two global datasets (ERA5-Land and JRA-55). The mean annual precipitation for 1997–2010 is estimated as 947 and 1,322 mm by ERA5-Land and JRA-55, respectively. The elevation-distributed precipitation estimates showed that the basin receives more precipitation at lower elevations. The daily river flow is well simulated, with KGE ranging between 0.84 and 0.88 and NSE between 0.80 and 0.82. The flow regime in the basin is dominated by glacier melt (45%–48%), followed by snowmelt (30%–34%) and rainfall (21%–23%). The simulated snow cover area (SCA) is in good agreement with the MODIS satellite-derived SCA. The elevation-distributed glacier melt simulation suggested that the glacial melt is highest at the lower elevations, with a maximum in the elevation 3,218–3,755 masl (14%–21% of total melt). The findings improve the understanding of the local hydrology by providing helpful information about the elevation-distributed meltwater contributions, water balance and hydro-climatic regimes. The simulation showed that the DDD model reproduces the hydrological processes satisfactorily for such a data-scarce basin.

Partially unfolded alpha-lactalbumin forms an oleic acid complex with antitumorigenic properties. Here, the authors define a structurally flexible, peptide-based oleate complex and report a phase I/II clinical trial where this complex is used to treat patients with bladder cancer.

The α-pore-forming toxins (α-PFTs) from pathogenic bacteria damage host cell membranes by pore formation. We demonstrate a remarkable, hitherto unknown mechanism by an α-PFT protein from Vibrio cholerae. As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other α-PFTs. In contrast, MakA in isolation induces tube-like structures in acidic endosomal compartments of epithelial cells in vitro. The present study unravels the dynamics of tubular growth, which occurs in a pH-, lipid-, and concentration-dependent manner. Within acidified organelle lumens or when incubated with cells in acidic media, MakA forms oligomers and remodels membranes into high-curvature tubes leading to loss of membrane integrity. A 3.7 Å cryo-electron microscopy structure of MakA filaments reveals a unique protein-lipid superstructure. MakA forms a pinecone-like spiral with a central cavity and a thin annular lipid bilayer embedded between the MakA transmembrane helices in its active α-PFT conformation. Our study provides insights into a novel tubulation mechanism of an α-PFT protein and a new mode of action by a secreted bacterial toxin.

Reversible switching between opaque and translucent colony formation is a novel feature of Acinetobacter baumannii that has been associated with variations in the cell morphology, surface motility, biofilm formation, antibiotic resistance and virulence. Here, we assessed a number of phenotypic alterations related to colony switching in A. baumannii clinical isolates belonging to different multi-locus sequence types. Our findings demonstrated that these phenotypic alterations were mostly strain-specific. In general, the translucent subpopulations of A. baumannii produced more dense biofilms, were more piliated, and released larger amounts of outer membrane vesicles (OMVs). In addition, the translucent subpopulations caused reduced fertility of Caenorhabditis elegans. When assessed for effects on the immune response in RAW 264.7 macrophages, the OMVs isolated from opaque subpopulations of A. baumannii appeared to be more immunogenic than the OMVs from the translucent form. However, also the OMVs from the translucent subpopulations had the potential to evoke an immune response. Therefore, we suggest that OMVs may be considered for development of new immunotherapeutic treatments against A. baumannii infections.