Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy

A growing body of work suggests epigenetic dysregulation contributes to endometriosis pathophysiology and female infertility. The chromatin remodeling complex subunit AT-rich interaction domain 1A (ARID1A) must be properly expressed to maintain normal uterine function. Endometrial epithelial ARID1A is indispensable for pregnancy establishment in mice through regulation of endometrial gland function; however, ARID1A expression is decreased in infertile women with endometriosis. We hypothesized that ARID1A performs critical operations in the endometrial epithelium necessary for fertility besides maintaining gland function. To identify alterations in uterine gene expression resulting from loss of epithelial ARID1A, we performed RNA-sequencing analysis on pre-implantation uteri from Ltf^iCre/+Arid1a^f/f and control mice. Differential expression analysis identified 4181 differentially expressed genes enriched for immune-related ingenuity canonical pathways including agranulocyte adhesion and diapedesis and natural killer cell signaling. RT-qPCR confirmed an increase in pro-inflammatory cytokine and macrophage-related gene expression but a decrease in natural killer cell signaling. Immunostaining confirmed a uterus-specific increase in macrophage infiltration. Flow cytometry delineated an increase in inflammatory macrophages and a decrease in uterine dendritic cells in Ltf^iCre/+Arid1a^f/f uteri. These findings demonstrate a role for endometrial epithelial ARID1A in suppressing inflammation and maintaining uterine immune homeostasis, which are required for successful pregnancy and gynecological health.     

Nurr1 Is Not an Essential Regulator of BDNF in Mouse Cortical Neurons

Nurr1 and brain-derived neurotrophic factor (BDNF) play major roles in cognition. Nurr1 regulates BDNF in midbrain dopaminergic neurons and cerebellar granule cells. Nurr1 and BDNF are also highly expressed in the cerebral cortex, a brain area important in cognition. Due to Nurr1 and BDNF tissue specificity, the regulatory effect of Nurr1 on BDNF in different brain areas cannot be generalized. The relationship between Nurr1 and BDNF in the cortex has not been investigated previously. Therefore, we examined Nurr1-mediated BDNF regulation in cortical neurons in activity-dependent and activity-independent states. Mouse primary cortical neurons were treated with the Nurr1 agonist, amodiaquine (AQ). Membrane depolarization was induced by KCl or veratridine and reversed by nimodipine. AQ and membrane depolarization significantly increased Nurr1 (p < 0.001) and BDNF (p_AQ < 0.001, p_KCl < 0.01) as assessed by real-time qRT-PCR. However, Nurr1 knockdown did not affect BDNF gene expression in resting or depolarized neurons. Accordingly, the positive correlation between Nurr1 and BDNF expression in AQ and membrane depolarization experiments does not imply co-regulation because Nurr1 knockdown did not affect BDNF gene expression in resting or depolarized cortical neurons. Therefore, in contrast to midbrain dopaminergic neurons and cerebellar granule cells, Nurr1 does not regulate BDNF in cortical neurons.     

Prospective predictors of posttraumatic stress disorder symptoms: Direct and mediated relations.

This study assessed the relations between pretrauma risk (neuroticism, negative affect, prior distress) and protective (self-esteem, optimism) factors and posttraumatic stress disorder (PTSD) symptoms and potential mediators (subjective event-related distress, unsupportive social interactions, perceived control) of those relations. Students (N = 1,528) at four U.S. universities completed online surveys assessing pretrauma risk and protective factors at Time 1 (T1); 84% (N = 1,281) completed a survey 2 months later (T2). PTSD symptoms and the three potential mediators were assessed among those who experienced potentially traumatic events between T1 and T2 (n = 264). PTSD symptoms related to prior traumas were controlled in all analyses. In structural equation modeling (SEM) analyses, the relation between risk factors and PTSD symptoms was mediated by unsupportive social interactions. Protective factors did not independently predict PTSD symptoms when risk factors also were included in the SEM models. Implications for research and practice are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Norman Garmezy (1918–2009).

Norman Garmezy, a pioneer in research on risk and resilience, died in Nashville, Tennessee, on November 21, 2009, at the age of 91. He was a legendary mentor as well as an eminent scientist in clinical psychology. Norm was born on June 18, 1918, in New York City and grew up in the Bronx in a Jewish neighborhood where educational attainment was highly valued. The scientific study of resilience as conceived by Norman Garmezy, his peers, and students has transformed the science and practice of multiple disciplines, from the molecular level to the global ecosystem, infusing a strength-based and recovery-oriented approach into psychology, education, social work, and psychiatry. Current research on resilience ranges from studies of plasticity in brain development to effective planning for resilience in the context of disaster. Norm’s influential ideas and research earned him international acclaim and many honors for lifetime achievements in science. Throughout his career, Norm held many leadership roles. Throughout his life, Norm spoke with great love about his wife of 63 years, Edie Garmezy (who died just months before him in 2009), and their children. In addition to his work and his family, Norm had three abiding passions—theater, movies, and politics. During the last two decades of his life, Norm and those who loved him endured his long decline from Alzheimer’s, which slowly stole his brilliant mind and hilarious sense of humor. Nonetheless, the incredible spirit and humanity of this giant scholar continued to shine through this terrible disease. To the end of his life, Norm’s face would light up with a smile as he greeted the people he loved, and he would often exclaim, “Wonderful!” Norman Garmezy was a remarkable person and scholar who left an extraordinary legacy of love and work to inspire future generations in their efforts to understand and promote the human capacity for competence and resilience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Still no phonological typicality effect on word reading time (and no good explanation of one, either): A rejoinder to Farmer, Monaghan, Misyak, and Christiansen.

In this brief rejoinder, we respond to Farmer, Monaghan, Misyak, and Christiansen (2011). We argue that the data still do not support the claim that reading time is affected by the phonological typicality of a word for its part of speech. We also question Farmer et al.'s claim that interleaving syntactic structures in an experiment modifies grammatically based syntactic expectations. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Efficient stockpiling and shipping policies for humanitarian relief: UNHCR��s inventory challenge

The United Nations High Commissioner for Refugees (UNHCR) establishes and maintains refugee camps to meet the needs of 34.5 million people affected by disaster or war worldwide. Like other international humanitarian organizations, UNHCR maintains central stockpiles which supply these refugee operations. Management at UNHCR seeks to improve the timeliness and quality of its disaster response subject to its budget constraints. We develop an inventory model to analyze the interaction between a stockpile and a downstream refugee camp or relief operation. We consider two inventory decisions: first, how to partition a fixed budget between stockpiling and shipping costs in order to best meet the needs of beneficiaries; and second, given the shipping budget determined by the budget partition, how to ship relief items from the stockpile to a downstream relief operation in an efficient manner. We solve for the shipment policy using dynamic programming, then determine the optimal stockpile size given knowledge of the optimal shipment policy. The optimization balances a key tradeoff: a larger stockpile is costly to procure and maintain, but enhances a humanitarian organization’s ability to respond to relief operation demands. We provide insights into shipment strategies and stockpile size. We also develop a spreadsheet model to help humanitarian organizations in their operational decision-making, leading to improved response to beneficiaries. Humanitarian organizations must use their financial resources wisely to carry out their mandates, and models of this type can help them make the best use of their limited response resources.     

Male Rat Offspring Are More Impacted by Maternal Obesity Induced by Cafeteria Diet than Females—Additive Effect of Postweaning Diet

Maternal obesity increases the risk of health complications in offspring, but whether these effects are exacerbated by offspring exposure to unhealthy diets warrants further investigation. Female Sprague-Dawley rats were fed either standard chow (n = 15) or ‘cafeteria’ (Caf, n = 21) diets across pre-pregnancy, gestation, and lactation. Male and female offspring were weaned onto chow or Caf diet (2–3/sex/litter), forming four groups; behavioural and metabolic parameters were assessed. At weaning, offspring from Caf dams were smaller and lighter, but had more retroperitoneal (RP) fat, with a larger effect in males. Maternal Caf diet significantly increased relative expression of ACACA and Fasn in male and female weanling liver, but not CPT-1, SREBP and PGC1; PPARα was increased in males from Caf dams. Maternal obesity enhanced the impact of postweaning Caf exposure on adult body weight, RP fat, liver mass, and plasma leptin in males but not females. Offspring from Caf dams appeared to exhibit reduced anxiety-like behaviour on the elevated plus maze. Hepatic CPT-1 expression was reduced only in adult males from Caf fed dams. Post weaning Caf diet consumption did not alter liver gene expression in the adult offspring. Maternal obesity exacerbated the obesogenic phenotype produced by postweaning Caf diet in male, but not female offspring. Thus, the impact of maternal obesity on adiposity and liver gene expression appeared more marked in males. Our data underline the sex-specific detrimental effects of maternal obesity on offspring.     

Effects of buffer gas composition on low temperature ignition of iso-octane and n-heptane

Experimental and numerical studies have been performed on the thermal and chemical effects of buffer gas composition on low temperature ignition of iso-octane and n-heptane. Experiments were conducted using a recently developed rapid compression machine in the temperature range of 600–850 K. Three buffer gases were studied including nitrogen (N₂), argon (Ar), and a mixture of Ar and carbon dioxide (CO₂) at a mole ratio of 65.1%/34.9%. Iso-octane was studied at 20 bar, ? = 1, and a dilution level of buffer gas to O₂ of 3.76:1 (mole ratio). n-Heptane was studied at 9 bar, ? = 1, and a dilution level of buffer gas to O₂ of 5.63:1 (mole ratio). For experiments where two-stage ignition was observed, the buffer gas composition had no impact on the first-stage ignition time but, as expected, it caused differences in the total heat release, pressure and temperature rise after the first-stage ignition. As a consequence, significant differences were observed for the total ignition delay time as a function of the buffer gas composition, with up to 40% and 42.5% faster total ignition time for iso-octane and n-heptane, respectively, by using Ar instead of N₂. The chemical effects of the buffer gas composition were studied experimentally by comparing the results of the N₂ and Ar/CO₂ (65.1%/34.9%) mixtures, recognizing that while the Ar/CO₂ mixture has the same heat capacity as N₂, its predicted combined third-body collision efficiency is about 76% higher than N₂. The experimental results showed negligible chemical effects on the first-stage and total ignition delay times. Numerical simulations were carried out over a wider range of temperatures for pure N₂, Ar, and CO₂ as buffer gases. Results showed that thermal effects are very pronounced and dominated at the negative temperature coefficient and two-stage ignition conditions, which is consistent with the experimental results and previous studies in the literature. However, the simulation results also showed at temperatures higher than 850 K, the chemical effects of CO₂ became more important than the thermal effects.