Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells

NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors.

Residential segregation, dividing walls and mental health: A population-based record linkage study

Background
Neighbourhood segregation has been described as a fundamental determinant of physical health, but literature on its effect on mental health is less clear. Whilst most previous research has relied on conceptualized measures of segregation, Northern Ireland is unique as it contains physical manifestations of segregation in the form of segregation barriers (or “peacelines”) which can be used to accurately identify residential segregation.
Methods
We used population-wide health record data on over 1.3 million individuals, to analyse the effect of residential segregation, measured by both the formal Dissimilarity Index and by proximity to a segregation barrier, on the likelihood of poor mental health.
Results
Using multi-level logistic regression models we found residential segregation measured by the Dissimilarity Index poses no additional risk to the likelihood of poor mental health after adjustment for area-level deprivation. However, residence in an area segregated by a “peaceline” increases the likelihood of antidepressant medication by 19% (OR=1.19, 95% CI: 1.14, 1.23) and anxiolytic medication by 39% (OR=1.39, 95% CI: 1.32, 1.48), even after adjustment for gender, age, conurbation, deprivation and crime.
Conclusions
Living in an area segregated by a ‘peaceline’ is detrimental to mental health suggesting segregated areas characterised by a heightened sense of ‘other’ pose a greater risk to mental health. The difference in results based on segregation measure highlights the importance of choice of measure when studying segregation.

A novel TRNSYS type for short-term borehole heat exchanger simulation: B2G model

Models of ground source heat pump (GSHP) systems are used as an aid for the correct design and optimization of the system. For this purpose, it is necessary to develop models which correctly reproduce the dynamic thermal behavior of each component in a short-term basis. Since the borehole heat exchanger (BHE) is one of the main components, special attention should be paid to ensuring a good accuracy on the prediction of the short-term response of the boreholes. The BHE models found in literature which are suitable for short-term simulations usually present high computational costs. In this work, a novel TRNSYS type implementing a borehole-to-ground (B2G) model, developed for modeling the short-term dynamic performance of a BHE with low computational cost, is presented. The model has been validated against experimental data from a GSHP system located at Universitat Politècnica de València, Spain. Validation results show the ability of the model to reproduce the short-term behavior of the borehole, both for a step-test and under normal operating conditions.

Parametric scans of HB and LS-RPA regimes employing Petawatt laser

By contrast to the Target Normal Sheath acceleration (TNSA) mechanism [1], Radiation Pressure Acceleration (RPA) is currently attracting a substantial amount of experimental [2,3] and theoretical [4-6] attention worldwide due to its superior scaling in terms of ion energy and laser-ion conversion efficiency. Employing Vulcan Petawatt lasers of the Rutherford Appleton Laboratory, UK, both the Hole-boring (HB) and the Light-Sail (LS) regimes of the RPA have been extensively explored. When the target thickness is of the order of hole-boring velocity times the laser pulse duration, highly collimated plasma jets of near solid density are ejected from the foil, lasting up to ns after the laser interaction. By changing the linear polarisation of the laser to circular, improved homogeneity in the jet's spatial density profile is achieved which suggests more uniform and sustained radiation pressure drive on target ions. By decreasing the target areal density or increasing irradiance on the target, the LS regime of the RPA is accessed where relatively high flux (~ 1012 particles/MeV/Sr) of ions are accelerated to ~ 10 MeV/nucleon energies in a narrow energy bandwidth. The ion energy scaling obtained from the parametric scans agrees well with theoretical estimation based on RPA mechanism and the narrow bandwidth feature in the ion spectra is studied by 2D particle-in-simulations.

Is Longer-Distance Migration Slowing? An Analysis of the Annual Record for England and Wales since the 1970s

This paper is prompted by the widespread acceptance that the rates of inter-county and inter-state migration have been falling in the USA and sets itself the task of examining whether this decline in migration intensities is also the case in the UK. It uses annual inter-area migration matrices available for England and Wales since the 1970s by broad age group. The main methodological challenge, arising from changes in the geography of health areas for which the inter-area flows are given, is addressed by adopting the lowest common denominator of 80 areas. Care is also taken to allow for the effect of economic cycles in producing short-term fluctuations on migration rates and to isolate the effect of a sharp rise in rates for 16-24 year olds in the 1990s, which is presumed to be related to the expansion of higher education. The findings suggest that, unlike for the USA, there has not been a substantial decline in the intensity of internal migration between the first two decades of the study period and the second two. If there has been any major decline in the intensity of address changing in England and Wales, it can only be for the within-area moves that this time series does not cover. This latter possibility is examined in a companion paper using a very different data set (Champion and Shuttleworth, 2016).

Lake Kumphawapi revisited – The complex climatic and environmental record of a tropical wetland in NE Thailand

Kumphawapi, which is Thailand’s largest natural freshwater lake, contains a >10,000-year-long climatic and environmental archive. New data sets (stratigraphy, chronology, hydrogen isotopes, plant macrofossil and charcoal records) for two sedimentary sequences are here combined with earlier multi-proxy studies to provide a comprehensive reconstruction of past climatic and environmental changes for Northeast Thailand. Gradually higher moisture availability due to a strengthening of the summer monsoon led to the formation of a large shallow lake in the Kumphawapi basin between >10,700 and c. 7000 cal. BP. The marked increase in moisture availability and lower evaporation between c. 7000 and 6400 cal. BP favoured the growth and expansion of vegetation in and around the shallow lake. The increase in biomass led to gradual overgrowing and infilling, to an apparent lake level lowering and to the development of a wetland. Multiple hiatuses are apparent in all investigated sequences between c. 6500 and 1400 cal. BP and are explained by periodic desiccation events of the wetland and erosion due to the subsequent lake level rise. The rise in lake level, which started c. 2000 cal. BP and reached shallower parts c. 1400 cal. BP, is attributed to an increase in effective moisture availability. The timing of hydroclimatic conditions during the past 2000 years cannot be resolved because of chronological limitations.