Where Have All the Utopias Gone? Ritual, Solidarity, and Longevity in a Multifaith Commune in New Mexico

Utopian experiments creating new forms of community have dotted the globe throughout human history. Despite grandiose visions, a majority of communal experiments have faded quickly into oblivion. A wealth of scholarship has focused on reasons why communes typically fail. My research of an ecumenical commune in northern New Mexico examines what has facilitated its perpetuation for over 42 years. I participated in this community for different periods of time for over three years. With the assistance of a resident oral historian, I was able to expand my study into a diachronic view that spanned decades. I conclude that there are multiple and interconnected factors that have given strength to this community. Factors contributing to its persistence throughout its existence have been a strong economic base, strong social structures, overarching ideologies, adaptability, charismatic influence, ritual observances, sacralization of space and material culture, amicable relations with the outside, conflict management mechanisms, and boundary maintenance. In the past two decades other factors have been added or intensified to contribute to its solidarity including a transient population and a widening circle of outside support

INCORPORATING LOW-DOSE EPIDEMIOLOGY DATA IN A CHLORPYRIFOS RISK ASSESSMENT

USEPA assessed whether epidemiology data suggest that fetal or early-life chlorpyrifos exposure causes neurodevelopmental effects and, if so, whether they occur at exposures below those causing the current most sensitive endpoint, 10% inhibition of blood acetylcholinesterase (AChE). We previously conducted a hypothesis-based weight-of-evidence analysis and found that a proposed causal association between chlorpyrifos exposure and neurodevelopmental effects in the absence of AChE inhibition does not have a substantial basis in existing animal or in vitro studies, and there is no plausible basis for invoking such effects in humans at their far lower exposure levels. The epidemiology studies fail to show consistent patterns; the few associations are likely attributable to alternative explanations. Human data are inappropriate for a dose-response assessment because biomarkers were only measured at one time point, may reflect exposure to other pesticides, and many values are at or below limits of quantification. When considered with pharmacokinetic data, however, these biomarkers provide information on exposure levels relative to those in experimental studies and indicate a margin of exposure of at least 1,000. Because animal data take into account the most sensitive lifestages, the use of AChE inhibition as a regulatory endpoint is protective of adverse effects in sensitive populations

The Global Burden of Ozone on Respiratory Mortality: No Clear Evidence for Association

The correspondence section is a public forum and, as such, is not peer-reviewed. EHP is not responsible for the accuracy, currency, or reliability of personal opinion expressed herein; it is the sole responsibility of the authors. EHP neither endorses nor disputes their published commentary

Effects of environment and genetics on western pine shoot borer, Eucosma sonomana, infestation levels in ponderosa pine plantations of central Oregon

Infestations of the western pine shoot borer (Eucosma sonomana Kearfott) in young stands of ponderosa pine (Pinusponderosa Lawson), were surveyed on the Deschutes National Forest. Elevation, slope, aspect, tree height, tree diameter, number of shoots in the terminal whorl, stand density, stand age and plant association for each stand were used in general multiple regression and logistic regression analyses to predict the percentage of infested terminal shoots. Using general multiple regression, taking the arcsin(square root(proportion of infested trees)), the models that were selected as the best predictors included (1) diameter, trees/hectare and elevation (R2= 0.62) and (2) number of shoots in the terminal whorl and stand age (R2= 0.62). Using logistic regression, the best model included number of shoots in the terminal whorl and stand age. Values for these stand characteristics can be used with the appropriate equation to estimate the percentage of terminal whorls damaged by shoot borer in a given stand. A companion study performed in six progeny test sites on the Ochoco National Forest found significant differences in shoot borer infestations among 29 ponderosa pine families (P-value = 0.001, R2=O.62)

Parafoveal degradation during reading reduces preview costs only when it is not perceptually distinct

There is a growing understanding that the parafoveal preview effect during reading may represent a combination of preview benefits and preview costs due to interference from parafoveal masks. It has been suggested that visually degrading the parafoveal masks may reduce their costs, but adult readers were later shown to be highly sensitive to degraded display changes. Four experiments examined how preview benefits and preview costs are influenced by the perception of distinct parafoveal degradation at the target word location. Participants read sentences with four preview types (identity, orthographic, phonological, and letter mask preview) and two levels of visual degradation (0 vs 20%). The distinctiveness of the target word degradation was either eliminated by degrading all words in the sentence (Experiments 1a-2a) or remained present, as in previous research (Experiments 1b-2b). Degrading the letter masks resulted in a reduction in preview costs, but only when all words in the sentence were degraded. When degradation at the target word location was perceptually distinct, it induced costs of its own, even for orthographically and phonologically related previews. These results confirm previous reports that traditional parafoveal masks introduce preview costs that overestimate the size of the true benefit. However, they also show that parafoveal degradation has the unintended consequence of introducing additional costs when participants are aware of distinct degradation on the target word. Parafoveal degradation appears to be easily perceived and may temporarily orient attention away from the reading task, thus delaying word processing

Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus α-synuclein and β-amyloid aggregates

Transcellular propagation of protein aggregate “seeds” has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct interaction with modified heparins to determine the size and sulfation requirements for tau, α-synuclein, and β-amyloid (Aβ) aggregate binding to glycosaminoglycans (GAGs). Varying the GAG length and sulfation patterns, we next conducted competition studies with heparin derivatives in cell-based assays. Tau aggregates required a precise GAG architecture with defined sulfate moieties in the N- and 6-O-positions, whereas the binding of α-synuclein and Aβ aggregates was less stringent. To determine the genes required for aggregate uptake, we used CRISPR/Cas9 to individually knock out the major genes of the HSPG synthesis pathway in HEK293T cells. Knockouts of the extension enzymes exostosin 1 (EXT1), exostosin 2 (EXT2), and exostosin-like 3 (EXTL3), as well as N-sulfotransferase (NDST1) or 6-O-sulfotransferase (HS6ST2) significantly reduced tau uptake, consistent with our biochemical findings, and knockouts of EXT1, EXT2, EXTL3, or NDST1, but not HS6ST2 reduced α-synuclein uptake. In summary, tau aggregates display specific interactions with HSPGs that depend on GAG length and sulfate moiety position, whereas α-synuclein and Aβ aggregates exhibit more flexible interactions with HSPGs. These principles may inform the development of mechanism-based therapies to block transcellular propagation of amyloid protein–based pathologies

Long-term exposure to ambient ozone and mortality : A quantitative systematic review and meta-analysis of evidence from cohort studies

Objectives: While there is good evidence for associations between short-term exposure to ozone and a range of adverse health outcomes, the evidence from narrative reviews for long-term exposure is suggestive of associations with respiratory mortality only. We conducted a systematic, quantitative evaluation of the evidence from cohort studies, reporting associations between long-term exposure to ozone and mortality. Methods: Cohort studies published in peer-reviewed journals indexed in EMBASE and MEDLINE to September 2015 and PubMed to October 2015 and cited in reviews/key publications were identified via search strings using terms relating to study design, pollutant and health outcome. Study details and estimate information were extracted and used to calculate standardised effect estimates expressed as HRs per 10 ppb increment in long-term ozone concentrations. Results: 14 publications from 8 cohorts presented results for ozone and all-cause and cause-specific mortality. We found no evidence of associations between long-term annual O3 concentrations and the risk of death from all causes, cardiovascular or respiratory diseases, or lung cancer. 4 cohorts assessed ozone concentrations measured during the warm season. Summary HRs for cardiovascular and respiratory causes of death derived from 3 cohorts were 1.01 (95% CI 1.00 to 1.02) and 1.03 (95% CI 1.01 to 1.05) per 10 ppb, respectively. Conclusions: Our quantitative review revealed a paucity of independent studies regarding the associations between long-term exposure to ozone and mortality. The potential impact of climate change and increasing anthropogenic emissions of ozone precursors on ozone levels worldwide suggests further studies of the long-term effects of exposure to high ozone levels are warranted

COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

<p>Abstract</p> <p>Background</p> <p>Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation.</p> <p>Methods</p> <p>Tumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival.</p> <p>Results</p> <p>COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196.</p> <p>Conclusions</p> <p>Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.</p