The non-magical realism of Jacques Roumain's Gouverneurs de la Rosée

Gouverneurs de la rosée has received more critical attention than any other Haitian novel, and much of that attention has been focused on the "realist" credentials of that novel. That realism has been variously defined—from those who have read the novel as a thinly disguised Marxist treatise to those who see in it a kind of fictionalized ethnography, allowing the reader a glimpse of the "real" daily life of the peasants of the mornes.1 Not all such judgements have been favorable, and it is remarkable how many readings of the novel excoriate it for its failure to live up to the aims that they, in fact, ascribe to it. Thus, the novel has been criticized for purporting to address the real problems of the peasants while ignoring the documented historical travails of analogous peasant communities in the Plaine du Cul-de-Sac in the 1930s; Roumain has been accused of eluding the contradictions inherent in applying a Marxist revolutionary theory to an undeveloped agrarian society by transforming his hero, Manuel, from militant into messiah; ethnologists have drawn attention to Roumain's supposed ignorance of the informal laws of land tenure and succession observed in Haitian rural communities and of the way that Vodou was actually practiced by the peasants.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection

Phase II metabolic enzymes are a battery of critical proteins that detoxify xenobiotics by increasing their hydrophilicity and enhancing their disposal. These enzymes have long been studied for their preventative and protective effects against mutagens and carcinogens and for their regulation via the Keap1 (Kelch-like ECH associated protein 1)/Nrf2 (Nuclear factor erythroid 2 related factor 2)/ARE (antioxidant response elements) pathway. Recently, a series of studies have reported the altered expression of phase II genes in postmortem tissue of patients with various neurological diseases. These observations hint at a role for phase II enzymes in the evolution of such conditions. Furthermore, promising findings reveal that overexpression of phase II genes, either by genetic or chemical approaches, confers neuroprotection in vitro and in vivo. Therefore, there is a need to summarize the current literature on phase II genes in the central nervous system (CNS). This should help guide future studies on phase II genes as therapeutic targets in neurological diseases. In this review, we first briefly introduce the concept of phase I, II and III enzymes, with a special focus on phase II enzymes. We then discuss their expression regulation, their inducers and executors. Following this background, we expand our discussion to the neuroprotective effects of phase II enzymes and the potential application of Nrf2 inducers to the treatment of neurological diseases. © 2012 Elsevier Ltd

Demyelination as a rational therapeutic target for ischemic or traumatic brain injury

Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination. In the current review, we will provide an overview of the major causes of demyelination and oligodendrocyte cell death following acute brain injuries, and discuss the crosstalk between myelin, axons, microglia, and astrocytes during the process of demyelination. Recent discoveries of molecules that regulate the processes of remyelination may provide novel therapeutic targets to restore white matter integrity and improve long-term neurological recovery in stroke or TBI patients

Neurobiology of microglial action in CNS injuries: Receptor-mediated signaling mechanisms and functional roles

Microglia are the first line of immune defense against central nervous system (CNS) injuries and disorders. These highly plastic cells play dualistic roles in neuronal injury and recovery and are known for their ability to assume diverse phenotypes. A broad range of surface receptors are expressed on microglia and mediate microglial \u27On\u27 or \u27Off\u27 responses to signals from other host cells as well as invading microorganisms. The integrated actions of these receptors result in tightly regulated biological functions, including cell mobility, phagocytosis, the induction of acquired immunity, and trophic factor/inflammatory mediator release. Over the last few years, significant advances have been made toward deciphering the signaling mechanisms related to these receptors and their specific cellular functions. In this review, we describe the current state of knowledge of the surface receptors involved in microglial activation, with an emphasis on their engagement of distinct functional programs and their roles in CNS injuries. It will become evident from this review that microglial homeostasis is carefully maintained by multiple counterbalanced strategies, including, but not limited to, \u27On\u27 and \u27Off\u27 receptor signaling. Specific regulation of theses microglial receptors may be a promising therapeutic strategy against CNS injuries. © 2014 Elsevier Ltd

Molecular dialogs between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke