The Clouds: A Portrait of One Family in Wartime Cambridge

The following is a portion of a work in progress, a biography of Mark DeWolfe and Helen Howe, two Bostonians born soon after the turn of the century. The book describes the adult years of this sister and brother, each of whom participated in American life at many levels important to the social and intellectual currents of the country. This section of the biography describes Cambridge in the World War II years

The Pulse of War: Writing a Response

Introduction and a series of articles and poetry concerning the war on terror being imposed by the U.S., and more. Writes Kevin Bowen: One year into the war in Iraq, the ugliness of the undertaking has become more and more inescapable. If anything, the experience has reaffirmed a few simple facts that deserve reiteration. There is no such thing as an easily winnable war. There is no such thing as a humane war. In every war, long after the fighting ends, peace will remain elusive, and memories of suffering will endure through generations. Of course we knew all this before. Writers have been trying to tell us such things for centuries. The writings that follow illustrate ways contemporary writers confront these truths. From Tony Aiello\u27s memories of the First Gulf War, a war that Colin Powell told us was conducted more humanely than any war in history through Almira El-Zein\u27s incredible evocation of mortality in Is this Desolation for Me Alone ; through Carolyn Forche\u27s testimony to the role of writers; Chris Agee\u27s meditation on conflicts in Bosnia and Rwanda to present-day Iraq; Fred Marchant\u27s essay on war poetry and Fanny Howe\u27s beautiful understated testiment we are reminded of the ways good writers take the complicated pulse of war and why now, more than ever, we need their voices

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

Race of the Radical

150 p. ; 21 cm

Early-life socioeconomic circumstances and the comorbidity of depression and overweight in adolescence and young adulthood: a prospective study

Depression and overweight both often emerge early in life and have been found to be associated, but few studies examine depression-overweight comorbidity and its social patterning early in the life course. Drawing on data from 4,948 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort from the UK (2,798 female, 2,150 male), we investigated how different aspects of early-life socioeconomic circumstances are associated with depression-overweight comorbidity from adolescence to young adulthood exploring any differences by age and sex. We estimated how parental education, social class and financial difficulties reported in pregnancy were associated with depression and overweight, and their comorbidity at approximately the ages 17 and 24 in males and females. The results from multinomial logistic regression models showed that all three socioeconomic markers were associated with depression-overweight comorbidity and results were similar across age. Lower parental education (relative risk ratio (RRR) and 95% confidence interval (CI) of low education v high education: 3.61 (2.30-5.67) in females and 1.54 (1.14-2.07) in males) and social class (class IV/V v class I: 5.67 (2.48-12.94) in females and 3.11 (0.70-13.91) in males) had strong associations with comorbidity at age 17 relative to having neither depression or overweight. Financial difficulties were also a risk factor in females, with less clear results in males. These findings highlight how early socioeconomic circumstances are linked with the accumulation of mental and physical health problems already in adolescence, which has implications for life-long health inequalities

qPCR in human eosinophils after glucocorticoid exposure

<p>Eosinophils were isolated from the peripheral blood of each of five human subjects. Purified eosinophils were then incubated for 4 hours, followed by exposure to dexamethasone (0.5 mcM) or vehicle (culture medium) for an additional 30, 60, or 120 minutes. RNA was purified from each sample and reverse-transcription quantitative real-time PCR (qPCR) was performed on the QuantStudio6 Flex System with the TaqMan Fast Universal PCR Master Mix and FAM-labeled TaqMan gene expression assay sets for human <i>CXCR4</i>, <i>CCR1</i>, <i>XIAP</i>, <i>CCR3</i>, <i>NOTCH1</i>, <i>ZBTB16</i>, <i>PAK1</i>, <i>CASP9</i>, <i>TNFAIP3</i>, <i>BCL2L11</i> and <i>TSC22D3</i>. The gene encoding 18S rRNA was used as an endogenous control. The mean Ct values for each subject, under each condition (dexamethasone or medium), at each time point, were calculated as the mean of two technical replicates, and are presented in the Excel file, with one tab for each gene.</p

An Unbiased Approach To Identify Endogenous Substrates of “Histone” Deacetylase 8

Despite being extensively characterized structurally and biochemically, the functional role of histone deacetylase 8 (HDAC8) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics methods to identify novel non-histone nuclear substrates of HDAC8, including the tumor suppressor ARID1A. These newly discovered substrates of HDAC8 are involved in diverse biological processes including mitosis, transcription, chromatin remodeling, and RNA splicing and may help guide therapeutic strategies that target the function of HDAC8