Scientific reports
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The intensification of precipitation extremes in a warming world has been reported on a global scale and is traditionally explained with the Clausius-Clapeyron (C-C) relation. The relationship is observed to be valid in mid-latitudes; however, the debate persists in tropical monsoon regions, with the extremes of the Indian Summer Monsoon Rainfall (ISMR) being a prime example. Here, we present a comprehensive study on the dependence of ISMR extremes on both the 2 m surface air temperature over India and on the sea surface temperature over the tropical Indian Ocean. ⋯ We find that the theoretical C-C relation overestimates the positive changes in precipitation extremes, which is also reflected in the Coupled Model Intercomparison Project 5 (CMIP5) simulations. We emphasize that the changing patterns of extremes over the Indian subcontinent need a scientific re-evaluation, which is possible due to availability of the unique long-term in-situ data. This can aid bias correction of model projections of extremes whose value for climate adaptation can hardly be overemphasized, especially for the developing tropical countries.
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The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer's disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients' brain. We have previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (Aβ42) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis. ⋯ Structural and thermodynamic analyses showed that apoE4-165 has a compact structure, in contrast to other carboxyl-terminal truncated apoE4 forms that are instead destabilized. Compared however to other allelic backgrounds, apoE4-165 is structurally distinct and less thermodynamically stable suggesting that the combination of a well-folded structure with structural plasticity is a unique characteristic of this fragment. Overall, our findings suggest that the ability of apoE fragments to promote Aβ42 intraneuronal accumulation is specific for both the apoE4 isoform and the particular structural and thermodynamic properties of the fragment.
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The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. ⋯ Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson's disease.