An efficient platform for astrocyte differentiation from human induced pluripotent stem cells

Summary: Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. : Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis. Keywords: human induced pluripotent stem cell, iPSC, astrocyt

Long-term pattern and magnitude of soil carbon feedback to the climate system in a warming world

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Science 358 (2017): 101-105, doi:10.1126/science.aan2874.In a 26-year soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon cycling to investigate the potential consequences for the climate system. We found that soil warming results in a four-phase pattern of soil organic matter decay and carbon dioxide fluxes to the atmosphere, with phases of substantial soil carbon loss alternating with phases of no detectable loss. Several factors combine to affect the timing, magnitude, and thermal acclimation of soil carbon loss. These include depletion of microbially accessible carbon pools, reductions in microbial biomass, a shift in microbial carbon use efficiency, and changes in microbial community composition. Our results support projections of a long-term, self-reinforcing carbon feedback from mid-latitude forests to the climate system as the world warms.This research has been supported by grants from the Department of Energy - DE-SC0010740; DOE DE-SC0016590: and the National Science Foundation - DEB 1237491 (LTER) ; DEB 1456528 (LTREB)

Does Smoking Status Influence Health-Related Quality of Life Outcome Measures in Patients Undergoing ACDF?

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: Whereas smoking has been shown to affect the fusion rates for patients undergoing an anterior cervical discectomy and fusion (ACDF), the relationship between smoking and health-related quality of life outcome measurements after an ACDF is less clear. The purpose of this study was to evaluate whether smoking negatively affects patient outcomes after an ACDF for cervical degenerative pathology. METHODS: Patients with tumor, trauma, infection, and previous cervical spine surgery and those with less than a year of follow-up were excluded. Smoking status was assessed by self-reported smoking history. Patient outcomes, including Neck Disability Index, Short Form 12 Mental Component Score, Short Form 12 Physical Component Score (PCS-12), Visual Analogue Scale (VAS) arm pain, VAS neck pain, and pseudarthrosis rates were evaluated. Outcomes were compared between smoking groups using multiple linear and logistic regression, controlling for age, sex, and body mass index (BMI), among other factors. A P value \u3c.05 was considered significant. RESULTS: A total of 264 patients were included, with a mean follow-up of 19.8 months, age of 53.1 years, and BMI of 29.6 kg/m2. There were 43 current, 69 former, and 152 nonsmokers in the cohort. At baseline, nonsmokers had higher PCS-12 scores than current smokers (P = .010), lower VAS neck pain than current (P = .035) and former (P = .014) smokers, as well as lower VAS arm pain than former smokers (P = .006). Postoperatively, nonsmokers had higher PCS-12 scores than both current (P = .030) and former smokers (P = .035). Smoking status was not a significant predictor of change in patient outcome in multivariate analysis. CONCLUSIONS: Whereas nonsmokers had higher function and lower pain than former or current smokers preoperatively, smoking status overall was not found to be an independent predictor of outcome scores after ACDF. This supports the notion that smoking status alone should not deter patients from undergoing ACDF for cervical degenerative pathology

Clinical Evaluation of Rod Photoreceptor Function: Measuring Fractional Sensitivity in Normal and Diseased Retinas

The electroretinogram (ERG) can assess photoreceptor and postreceptoral retinal function. Robson and Frishman have suggested that the prevailing model of photoreceptor contributions to the a-wave, based only on outer segment contributions, is inadequate, as it does not account for the a-wave nose, a recovery of voltage towards baseline prior to rise of the b-wave, which reflects On-bipolar cell activity. Instead, they proposed a model in which the nose is shaped by capacitive currents in the outer nuclear layer (ONL) during rod hyperpolarization. The purpose of this dissertation was to assess clinical application of the new model, focusing on a parameter of the model, fractional sensitivity (FS). Experiment 1: Dark-adapted (DA) ERG responses to brief achromatic flashes doubling in energy from 7.5 to 933 scot cd.s/m2 were recorded in healthy subjects, ages 20-29 years (n=20). The cohort’s average FS was 0.86% per R*/rod ± 0.14 and followed model template curves from 29 to 212 scot cd.s/m2. A decline in FS with increasing age for these flash energies was found for subjects, ages 11 to 72 years (-0.0055 log unit/year, n=80); Vmax did not change. FS test-retest values had a bias close to zero (-4.9% ± 15.3, n=20) and repeatability coefficient of ± 30%. Experiment 2: Rod-isolated a-waves were obtained using a paired flash paradigm in healthy subjects (n=8). Rod-isolated FS was greater than FS for mixed rod/cone responses, but mean factor of increase was just 13.2% (range=1%-29%, p=0.011). Mean rod-isolated a-wave implicit time (IT) was 3% earlier than mixed IT. Rod-isolated amplitude was 22% lower than mixed a-wave amplitude. Experiment 3: ISCEV Standard ERGs and responses to a higher energy “DA30” stimulus of 64 scot cd.s/m2, about 30 phot cd.s/m2, were elicited in subjects with 1-2 ABCA4 mutations (n=16). Subjects had at least one ISCEV light-adapted parameter outside normal limits. DA30 a-wave IT was impaired more (n=7) than DA3.0 a-wave IT (n=3) or amplitude (n=5). FS was impaired more than DA30 IT; 9 vs. 7. Conclusions: FS obtained with an achromatic flash, decreased with age and was found to be an indicator of rod dysfunction in subjects with known cone dysfunction. FS could provide a useful clinical measure.Optometry, College o

Agroecology for the Shrinking City

Many cities are experiencing long-term declines in population and economic activity. As a result, frameworks for urban sustainability need to address the unique challenges and opportunities of such shrinking cities. Shrinking, particularly in the U.S., has led to extensive vacant land. The abundance of vacant land reflects a loss of traditional urban amenities, economic opportunity, neighbors, businesses, and even basic city services and often occurs in neighborhoods with socially and economically vulnerable or underserved populations. However, vacant land also provides opportunities, including the space to invest in green infrastructure that can provide ecosystem services and support urban sustainability. Achieving desirable amenities that provide ecosystem services from vacant land is the central tenet of a recent urban sustainability framework termed ecology for the shrinking city. An agroecological approach could operationalize ecology for the shrinking city to both manage vacancy and address ecosystem service goals. Developing an agroecology in shrinking cities not only secures provisioning services that use an active and participatory approach of vacant land management but also transforms and enhances regulating and supporting services. The human and cultural dimensions of agroecology create the potential for social-ecological innovations that can support sustainable transformations in shrinking cities. Overall, the strength of agroecological principles guiding a green infrastructure strategy stems from its explicit focus on how individuals and communities can shape their environment at multiple scales to produce outcomes that reflect their social and cultural context. Specifically, the shaping of the environment provides a pathway for communities to build agency and manage for resilience in urban social-ecological systems. Agroecology for the shrinking city can support desirable transformations, but to be meaningful, we recognize that it must be part of a greater strategy that addresses larger systemic issues facing shrinking cities and their residents

Association Between Enacted Stigma and HIV-Related Risk Behavior Among MSM, National HIV Behavioral Surveillance System, 2011.

MSM bear a disproportionate burden of the HIV epidemic. Enacted stigma (overt negative actions) against sexual minorities may play an important role in increasing HIV risk among this population. Using data from the 2011 National HIV Behavioral Surveillance system, MSM cycle, we examined the independent associations between three measures of enacted stigma (verbal harassment, discrimination, physical assault) and engagement in each of four HIV-related risk behaviors as outcomes: condomless anal intercourse (CAI) at last sex with a male partner of HIV discordant or unknown status and, in the past 12 months, CAI with a male partner, ≥4 male sex partners, and exchange sex. Of 9819 MSM, 32% experienced verbal harassment in the past 12 months, 23% experienced discrimination, and 8% experienced physical assault. Discordant CAI at last sex with a male partner was associated with previous discrimination and physical assault. Past 12 month CAI with a male partner, ≥4 male sex partners, and exchange sex were each associated with verbal harassment, discrimination, and physical assault. These findings indicate that a sizable proportion of MSM report occurrences of past 12 month enacted stigma and suggest that these experiences may be associated with HIV-related risk behavior. Addressing stigma towards sexual minorities must involve an integrated, multi-faceted approach, including interventions at the individual, community, and societal level