Astrocytes and Aging

By 2050, the aging population is predicted to expand by over 100%. Considering this rapid growth, and the additional strain it will place on healthcare resources because of age-related impairments, it is vital that researchers gain a deeper understanding of the cellular interactions that occur with normal aging. A variety of mammalian cell types have been shown to become compromised with age, each with a unique potential to contribute to disease formation in the aging body. Astrocytes represent the largest group of glial cells and are responsible for a variety of essential functions in the healthy central nervous system (CNS). Like other cell types, aging can cause a loss of normal function in astrocytes which reduces their ability to properly maintain a healthy CNS environment, negatively alters their interactions with neighboring cells, and contribute to the heightened inflammatory state characteristic of aging. The goal of this review article is to consolidate the knowledge and research to date regarding the role of astrocytes in aging. In specific, this review article will focus on the morphology and molecular profile of aged astrocytes, the consequence of astrocyte dysfunction on homeostatic functions during aging, and the role of astrocytes in age-related neurodegenerative diseases

Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function.

Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27-60 years) and elderly donors (70-89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike CDKN1A, CDKN2A (using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased CDKN2A expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of CDKN2A was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed: n = 12-14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon

The Study on Stress, Spirituality, and Health (SSSH): Psychometric Evaluation and Initial Validation of the SSSH Baseline Spirituality Survey

This paper describes the development and initial psychometric testing of the baseline Spirituality Survey (SS-1) from the Study on Stress, Spirituality, and Health (SSSH) which contained a mixture of items selected from validated existing scales and new items generated to measure important constructs not captured by existing instruments. The purpose was to establish the validity of new and existing measures in our racially/ethnically diverse sample. Psychometric properties of the SS-1 were evaluated using standard psychometric analyses in 4,634 SSSH participants. Predictive validity of SS-1 scales was assessed in relation to the physical and mental health component scores from the Short-Form 12 Health Survey (SF-12). Scales exhibited adequate to strong psychometric properties and demonstrated construct and predictive validity. Overall, the correlational findings provide solid evidence that the SS-1 scales are associated with a wide range of relevant R/S attitudes, mental health, and to a lesser degree physical health

Diagnostic accuracy of 1p/19q codeletion tests in oligodendroglioma:a comprehensive meta-analysis based on a Cochrane Systematic Review

Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for oligodendroglioma, IDH mutant and 1p/19q codeleted. 1p/19q codeletion is a diagnostic marker and allows prognostication and prediction of the best drug response within IDH‐mutant tumours. We performed a Cochrane review and simple economic analysis to establish the most sensitive, specific and cost‐effective techniques for determining 1p/19q codeletion status. Fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)‐based loss of heterozygosity (LOH) test methods were considered as reference standard. Most techniques (FISH, chromogenic in situ hybridisation [CISH], PCR, real‐time PCR, multiplex ligation‐dependent probe amplification [MLPA], single nucleotide polymorphism [SNP] array, comparative genomic hybridisation [CGH], array CGH, next‐generation sequencing [NGS], mass spectrometry and NanoString) showed good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma, irrespective of whether FISH or PCR‐based LOH was used as the reference standard. Both NGS and SNP array had a high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. Our findings suggest that G banding is not a suitable test for 1p/19q analysis. Within these limits, considering cost per diagnosis and using FISH as a reference, MLPA was marginally more cost‐effective than other tests, although these economic analyses were limited by the range of available parameters, time horizon and data from multiple healthcare organisations

Improving and Assessing Planet Sensitivity of the GPI Exoplanet Survey with a Forward Model Matched Filter

We present a new matched filter algorithm for direct detection of point sources in the immediate vicinity of bright stars. The stellar Point Spread Function (PSF) is first subtracted using a Karhunen-Lo\'eve Image Processing (KLIP) algorithm with Angular and Spectral Differential Imaging (ADI and SDI). The KLIP-induced distortion of the astrophysical signal is included in the matched filter template by computing a forward model of the PSF at every position in the image. To optimize the performance of the algorithm, we conduct extensive planet injection and recovery tests and tune the exoplanet spectra template and KLIP reduction aggressiveness to maximize the Signal-to-Noise Ratio (SNR) of the recovered planets. We show that only two spectral templates are necessary to recover any young Jovian exoplanets with minimal SNR loss. We also developed a complete pipeline for the automated detection of point source candidates, the calculation of Receiver Operating Characteristics (ROC), false positives based contrast curves, and completeness contours. We process in a uniform manner more than 330 datasets from the Gemini Planet Imager Exoplanet Survey (GPIES) and assess GPI typical sensitivity as a function of the star and the hypothetical companion spectral type. This work allows for the first time a comparison of different detection algorithms at a survey scale accounting for both planet completeness and false positive rate. We show that the new forward model matched filter allows the detection of $50\%$ fainter objects than a conventional cross-correlation technique with a Gaussian PSF template for the same false positive rate.Comment: ApJ accepte

Performance of the Gemini Planet Imager Non-Redundant Mask and spectroscopy of two close-separation binaries HR 2690 and HD 142527

The Gemini Planet Imager (GPI) contains a 10-hole non-redundant mask (NRM), enabling interferometric resolution in complement to its coronagraphic capabilities. The NRM operates both in spectroscopic (integral field spectrograph, henceforth IFS) and polarimetric configurations. NRM observations were taken between 2013 and 2016 to characterize its performance. Most observations were taken in spectroscopic mode with the goal of obtaining precise astrometry and spectroscopy of faint companions to bright stars. We find a clear correlation between residual wavefront error measured by the AO system and the contrast sensitivity by comparing phase errors in observations of the same source, taken on different dates. We find a typical 5-$\sigma$ contrast sensitivity of $2-3~\times~10^{-3}$ at $\sim\lambda/D$. We explore the accuracy of spectral extraction of secondary components of binary systems by recovering the signal from a simulated source injected into several datasets. We outline data reduction procedures unique to GPI's IFS and describe a newly public data pipeline used for the presented analyses. We demonstrate recovery of astrometry and spectroscopy of two known companions to HR 2690 and HD 142527. NRM+polarimetry observations achieve differential visibility precision of $\sigma\sim0.4\%$ in the best case. We discuss its limitations on Gemini-S/GPI for resolving inner regions of protoplanetary disks and prospects for future upgrades. We summarize lessons learned in observing with NRM in spectroscopic and polarimetric modes.Comment: Accepted to AJ, 22 pages, 14 figure

Dynamical Mass Measurement of the Young Spectroscopic Binary V343 Normae AaAb Resolved With the Gemini Planet Imager

We present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the beta Pictoris moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10" M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components of M_Aa = 1.10 +/- 0.10 M_sun and M_Ab = 0.290 +/- 0.018 M_sun. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the beta Pic moving group. We derive a model-dependent age for the beta Pic moving group of 26 +/- 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.Comment: 12 pages, 7 figures. Accepted to A

GPI spectra of HR 8799 c, d, and e from 1.5 to 2.4μ\mum with KLIP Forward Modeling

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in H & K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same dataset. We also present a K band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H & K spectra, but do not find any conclusive differences between d and e or c and e, likely due to large error bars in the recovered spectrum of e. Compared to M, L, and T-type field brown dwarfs, all three planets are most consistent with mid and late L spectral types. All objects are consistent with low gravity but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets' near-IR flux and discuss how differences between the properties of these planets can be further explored.Comment: Accepted to AJ, 25 pages, 16 Figure

The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics From 10-100 AU

We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semi-major axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M $>$ 1.5 $M_\odot$ more likely to host planets with masses between 2-13 M$_{\rm Jup}$ and semi-major axes of 3-100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semi-major axis (a) for planet populations around high-mass stars (M $>$ 1.5M$_\odot$) of the form $\frac{d^2 N}{dm da} \propto m^\alpha a^\beta$, finding $\alpha$ = -2.4 $\pm$ 0.8 and $\beta$ = -2.0 $\pm$ 0.5, and an integrated occurrence rate of $9^{+5}_{-4}$% between 5-13 M$_{\rm Jup}$ and 10-100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with 0.8$^{+0.8}_{-0.5}$% of stars hosting a brown dwarf companion between 13-80 M$_{\rm Jup}$ and 10-100 au. Brown dwarfs also appear to be distributed differently in mass and semi-major axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the RV method, our results are consistent with a peak in occurrence of giant planets between ~1-10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability.Comment: 52 pages, 18 figures. AJ in pres