Empirically-based spatial projections of U.S. population age structure consistent with the shared socioeconomic pathways

Spatially-explicit population projections by age are increasingly needed for understanding bilateral human-environment interactions. Conventional demographic methods for projecting age structure experience substantial challenges at small spatial scales. In search of a potentially better performing alternative, we develop an empirically-based spatial model of population age structure and test its application in projecting U.S. population age structure over the 21st century under various socioeconomic scenarios (SSPs). The model draws on 40 years of historical data explaining changes in spatial age distribution at the county level. It demonstrates that a very good model fit is achievable even with parsimonious data input, and distinguishes itself from existing methods as a promising approach to spatial age structure modelling at the global level where data availability is often limited. Results suggest that wide variations in the spatial pattern of county-level age structure are plausible, with the possibility of substantial aging clustered in particular parts of the country. Aging is experienced most drastically by thinly-populated counties in the Midwest and the Rocky Mountains, while cities and surrounding counties, particularly in California, as well as the southern parts of New England and the Mid-Atlantic region, maintain a younger population age structure with a lower proportion in the most vulnerable 70+ age group. The urban concentration of younger people, as well as the absolute number of vulnerable elderly people can vary strongly by SSP

Mechanisms Responsible for omega-Pore Currents in Ca-v Calcium Channel Voltage-Sensing Domains

Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in CaV1.1 and CaV1.3 Ca2+ channels bearing several S4 charge mutations. Our modeling predicts that mutations of CaV1.1-R1 (R528H/G, R897S) or CaV1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of CaV1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation. The mechanism responsible for the ω-current and its amplitude depend on the number of charges in S4, the position of the mutated S4 charge and countercharges, and the nature of the replacing amino acid. Functional characterization validates the modeling prediction showing that CaV1.3-R990H channels conduct ω-currents at hyperpolarizing potentials, but not upon membrane depolarization compared with wild-type channels

A Harmonized Dataset on Global Educational Attainment between 1970 and 2060 – An Analytical Window into Recent Trends and Future Prospects in Human Capital Development

We hereby present a dataset produced at the Wittgenstein Centre (WIC) containing comprehensive time series on educational attainment and mean years of schooling (MYS). The dataset is split by 5-year age groups and sex for 171 countries and covers the period between 1970 and 2010. It also contains projections of educational attainment to 2060 based on several scenarios of demographic and educational development. The dataset is constructed around collected and harmonized empirical census and survey data sets for the projection base year. The paper presents the principles and methodology associated with the reconstruction and the projection, and how it differs from several previous exercises. It also proposes a closer look at the diffusion of education in world regions and how the existing gaps in terms of generation, gender, and geography have been evolving in the last 40 years

Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca(2+) channel activators.

Cav1.2 and Cav1.3 are the main L-type Ca(2+) channel subtypes in the brain. Cav1.3 channels have recently been implicated in the pathogenesis of Parkinson’s disease. Therefore, Cav1.3-selective blockers are developed as promising neuroprotective drugs. We studied the pharmacological properties of a pyrimidine-2,4,6-trione derivative (1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione, Cp8) recently reported as the first highly selective Cav1.3 blocker. Here we show, in contrast to this previous study, that Cp8 reproducibly increases inward Ca(2+) currents of Cav1.3 and Cav1.2 channels expressed in tsA-201 cells by slowing activation, inactivation and enhancement of tail currents. Similar effects are also observed for native Cav1.3 and Cav1.2 channels in mouse chromaffin cells, while non-L-type currents are unaffected. Evidence for a weak and non-selective inhibition of Cav1.3 and Cav1.2 currents is only observed in a minority of cells using Ba(2+) as charge carrier. Therefore, our data identify pyrimidine-2,4,6-triones as Ca(2+) channel activators