State Intervention to (Un)manage Growth

The classic dream of moving to a spacious, single-family home in the suburbs has led urban sprawl to become the standard pattern of American growth. Unfortunately, this type of growth—in the aggregate—has created a vast array of unintended consequences. From increased commuting times and traffic congestion to the degradation of ecosystems to the demise of the classic, American “Main Street,” sprawl has left its footprint on many facets of the environment and human life. Sprawl’s harms are often periodic and delayed, thus it is unlikely that the underlying issues causing and exacerbating the harms will ever be addressed. Further, as local governments predominantly regulate land use decisions, municipalities rarely, if at all, consider the statewide and regional harms their regulations may create in the aggregate

Anxiété, dépression, syndrome de stress post-traumatique et vécu parental après une mort in utéro: impact de l'accompagnement et des modalités de rencontre entre le couple et son enfant mort-né : travail de Bachelor

Objectif : Évaluer les impacts de l’accompagnement et des modalités de rencontre entre le couple et son enfant mort-né sur l’anxiété, la dépression, le syndrome de stress post-traumatique (SSPT) et le vécu parental. Méthode : Revue de la littérature basée sur l’analyse descriptive et critique de quatre articles quantitatifs et d’un article qualitatif. Résultats : Voir, porter et passer suffisamment de temps avec son enfant semblent avoir un effet bénéfique sur la santé psychique maternelle. Cependant, lors d’une grossesse ultérieure ainsi qu’à une année post-partum de la grossesse suivante, les effets positifs d’avoir vu et/ou porté son enfant peuvent s’inverser et amener à de moins bons résultats sur la santé psychique des mères. De plus, le vécu de la rencontre peut être influencé par l’aspect physique de l’enfant. En effet, des malformations et des dommages corporels peuvent rendre plus difficile le vécu de la mère lors de la rencontre avec l’enfant. Certaines variables semblent être également corrélées à plus de problèmes de santé psychique tels qu’un antécédent d’interruption de grossesse, la multiparité ainsi qu’un intervalle de temps important avant une nouvelle grossesse. De manière générale, la complexité de la mortinaissance rend l’impact de variables isolées difficile à évaluer. Ces résultats sont donc à considérer avec précaution. Conclusion : Un modèle unique d’accompagnement des couples n’existe pas. En tant que soignants, il est important de soutenir les parents dans un choix éclairé et de les accompagner selon leurs besoins et leurs demandes

Far-Infrared Emission From E and E/S0 Galaxies

Studies of cold material through IRAS 60um and 100um observations indicated that half of ordinary E and E/S0 galaxies were detected above the 3 sigma level, indicating that cold gas is common, although no correlation was found between the optical and far- infrared fluxes. Most detections were near the instrumental threshold, and given an improved understanding of detection confidence, we reconsider the 60um and 100um detection rate. After excluding active galactic nuclei, peculiar systems, and background contamination, only 15 non-peculiar E and E/S0 galaxies from the RSA catalog are detected above the 98% confidence level, about 12% of the sample. An unusually high percentage of these 15 galaxies possess cold gas (HI, CO) and optical emission lines (Halpha), supporting the presence of gas cooler than 10E4 K. The 60um to 100um flux ratios imply a median dust temperature for the sample of 30 K, with a range of 23-38 K. These detections define the upper envelope of the optical to far-infrared relationship, F_fir propto F_B^0.24+/-0.08, showing that optically bright objects are also brighter in the infrared, although with considerable dispersion. A luminosity correlation is present with L_fir propto L_B^1.65+/-0.28, but the dust temperature is uncorrelated with luminosity. Models that contain large dust grains composed of amorphous carbon plus silicates come close to reproducing the typical 60um to 100um flux ratios, the far-infrared luminosity, and the L_fir - L_B relationship.Comment: 10 postscript pages, 2 tables, and 2 figure

Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander Disease severity

Alexander Disease (AxD) is a fatal neurodegenerative disorder caused by mutations in glial fibrillary acidic protein (GFAP), which supports the structural integrity of astrocytes. Over 70 GFAP missense mutations cause AxD, but the mechanism linking different mutations to disease-relevant phenotypes remains unknown. We used AxD patient brain tissue and induced pluripotent stem cell (iPSC)-derived astrocytes to investigate the hypothesis that AxD-causing mutations perturb key post-translational modifications (PTMs) on GFAP. Our findings reveal selective phosphorylation of GFAP-Ser13 in patients who died young, independently of the mutation they carried. AxD iPSC-astrocytes accumulated pSer13-GFAP in cytoplasmic aggregates within deep nuclear invaginations, resembling the hallmark Rosenthal fibers observed in vivo. Ser13 phosphorylation facilitated GFAP aggregation and was associated with increased GFAP proteolysis by caspase-6. Furthermore, caspase-6 was selectively expressed in young AxD patients, and correlated with the presence of cleaved GFAP. We reveal a novel PTM signature linking different GFAP mutations in infantile AxD

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

TGF-beta triggers rapid fibrillogenesis via a Novel T beta RII-Dependent Fibronectin-Trafficking Mechanism

Fibronectin (FN) is a critical regulator of extracellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, and fibrillogenesis is a multistep, integrin-dependent process essential for cell migration, proliferation, and tissue function. Transforming growth factor β (TGF-β) is an established regulator of ECM remodeling via transcriptional control of ECM proteins. Here we show that TGF-β, through increased FN trafficking in a transcription- and SMAD-independent manner, is a direct and rapid inducer of the fibrillogenesis required for TGF-β–induced cell migration. Whereas TGF-β signaling is dispensable for rapid fibrillogenesis, stable interactions between the cytoplasmic domain of the type II TGF-β receptor (TβRII) and the FN receptor (α5β1 integrin) are required. We find that, in response to TGF-β, cell surface–internalized FN is not degraded by the lysosome but instead undergoes recycling and incorporation into fibrils, a process dependent on TβRII. These findings are the first to show direct use of trafficked and recycled FN for fibrillogenesis, with a striking role for TGF-β in this process. Given the significant physiological consequences associated with FN availability and polymerization, our findings provide new insights into the regulation of fibrillogenesis for cellular homeostasis

Select Atrophied Regions in Alzheimer disease (SARA): An improved volumetric model for identifying Alzheimer disease dementia

INTRODUCTION: Volumetric biomarkers for Alzheimer disease (AD) are attractive due to their wide availability and ease of administration, but have traditionally shown lower diagnostic accuracy than measures of neuropathological contributors to AD. Our purpose was to optimize the diagnostic specificity of structural MRIs for AD using quantitative, data-driven techniques. METHODS: This retrospective study assembled several non-overlapping cohorts (total n = 1287) with publicly available data and clinical patients from Barnes-Jewish Hospital (data gathered 1990-2018). The Normal Aging Cohort (n = 383) contained amyloid biomarker negative, cognitively normal (CN) participants, and provided a basis for determining age-related atrophy in other cohorts. The Training (n = 216) and Test (n = 109) Cohorts contained participants with symptomatic AD and CN controls. Classification models were developed in the Training Cohort and compared in the Test Cohort using the receiver operating characteristics areas under curve (AUCs). Additional model comparisons were done in the Clinical Cohort (n = 579), which contained patients who were diagnosed with dementia due to various etiologies in a tertiary care outpatient memory clinic. RESULTS: While the Normal Aging Cohort showed regional age-related atrophy, classification models were not improved by including age as a predictor or by using volumetrics adjusted for age-related atrophy. The optimal model used multiple regions (hippocampal volume, inferior lateral ventricle volume, amygdala volume, entorhinal thickness, and inferior parietal thickness) and was able to separate AD and CN controls in the Test Cohort with an AUC of 0.961. In the Clinical Cohort, this model separated AD from non-AD diagnoses with an AUC 0.820, an incrementally greater separation of the cohort than by hippocampal volume alone (AUC of 0.801, p = 0.06). Greatest separation was seen for AD vs. frontotemporal dementia and for AD vs. non-neurodegenerative diagnoses. CONCLUSIONS: Volumetric biomarkers distinguished individuals with symptomatic AD from CN controls and other dementia types but were not improved by controlling for normal aging

The Potential of N-Rich Plasma-Polymerized Ethylene (PPE:N) Films for Regulating the Phenotype of the Nucleus Pulposus

We recently developed a nitrogen-rich plasma-polymerized biomaterial, designated “PPE:N” (N-doped plasma-polymerized ethylene) that is capable of suppressing cellular hypertrophy while promoting type I collagen and aggrecan expression in mesenchymal stem cells from osteoarthritis patients. We then hypothesized that these surfaces would form an ideal substrate on which the nucleus pulposus (NP) phenotype would be maintained. Recent evidence using microarrays showed that in young rats, the relative mRNA levels of glypican-3 (GPC3) and pleiotrophin binding factor (PTN) were significantly higher in nucleus pulposus (NP) compared to annulus fibrosus (AF) and articular cartilage. Furthermore, vimentin (VIM) mRNA levels were higher in NP versus articular cartilage. In contrast, the levels of expression of cartilage oligomeric matrix protein (COMP) and matrix gla protein precursor (MGP) were lower in NP compared to articular cartilage. The objective of this study was to compare the expression profiles of these genes in NP cells from fetal bovine lumbar discs when cultured on either commercial polystyrene (PS) tissue culture dishes or on PPE:N with time. We found that the expression of these genes varies with the concentration of N ([N]). More specifically, the expression of several genes of NP was sensitive to [N], with a decrease of GPC3, VIM, PTN, and MGP in function of decreasing [N]. The expression of aggrecan, collagen type I, and collagen type II was also studied: no significant differences were observed in the cells on different surfaces with different culture time. The results support the concept that PPE:N may be a suitable scaffold for the culture of NP cells. Further studies are however necessary to better understand their effects on cellular phenotypes

Expanding mental health services in low- and middle-income countries: A task-shifting framework for delivery of comprehensive, collaborative, and community-based care

This paper proposes a framework for comprehensive, collaborative, and community-based care (C4) for accessible mental health services in low-resource settings. Because mental health conditions have many causes, this framework includes social, public health, wellness and clinical services. It accommodates integration of stand-alone mental health programs with health and non-health community-based services. It addresses gaps in previous models including lack of community-based psychotherapeutic and social services, difficulty in addressing comorbidity of mental and physical conditions, and how workers interact with respect to referral and coordination of care. The framework is based on task-shifting of services to non-specialized workers. While the framework draws on the World Health Organization’s Mental Health Gap Action Program and other global mental health models, there are important differences. The C4 Framework delineates types of workers based on their skills. Separate workers focus on: basic psychoeducation and information sharing; community-level, evidence-based psychotherapeutic counseling; and primary medical care and more advanced, specialized mental health services for more severe or complex cases. This paper is intended for individuals, organizations and governments interested in implementing mental health services. The primary aim is to provide a framework for the provision of widely accessible mental health care and services