Microglia are resident immune cells of the CNS that are activated by infection, neuronal injury and inflammation. Here we utilize flow cytometry and deep RNA sequencing of acutely isolated spinal cord microglia to define their activation in vivo. Analysis of resting microglia identified 29 genes that distinguish microglia from other CNS cells and peripheral macrophages/monocytes. We then analyzed molecular changes in microglia during neurodegenerative disease activation using the SOD1G93A mouse model of ALS. We find that SOD1G93A microglia are not derived from infiltrating monocytes, and that both potentially neuroprotective and toxic factors are concurrently up-regulated, including Alzheimer’s disease genes. Mutant microglia differed from SOD1WT, LPS activated microglia, and M1/M2 macrophages, that define an ALS-specific phenotype. Concurrent mRNA/FACS analysis revealed post-transcriptional regulation of microglia surface receptors, and T cell-associated changes in the transcriptome. These results provide insights into microglia biology and establish a resource for future studies of neuroinflammation.

The deleterious consequences of fatty acid (FA) and neutral lipid accumulation in nonadipose tissues, such as the heart, contribute to the pathogenesis of type 2 diabetes. To elucidate mechanisms of FA-induced cell death, or lipotoxicity, we generated Chinese hamster ovary (CHO) cell mutants resistant to palmitate-induced death and isolated a clone with disruption of eukaryotic elongation factor (eEF) 1A-1. eEF1A-1 involvement in lipotoxicity was confirmed in H9c2 cardiomyoblasts, in which small interfering RNA-mediated knockdown also conferred palmitate resistance. In wild-type CHO and H9c2 cells, palmitate increased reactive oxygen species and induced endoplasmic reticulum (ER) stress, changes accompanied by increased eEF1A-1 expression. Disruption of eEF1A-1 expression rendered these cells resistant to hydrogen peroxide-and ER stress-induced death, indicating that eEF1A-1 plays a critical role in the cell death response to these stressors downstream of lipid overload. Disruption of eEF1A-1 also resulted in actin cytoskeleton defects under basal conditions and in response to palmitate, suggesting that eEF1A-1 mediates lipotoxic cell death, secondary to oxidative and ER stress, by regulating cytoskeletal changes critical for this process. Furthermore, our observations of oxidative stress, ER stress, and induction of eEF1A-1 expression in a mouse model of lipotoxic cardiomyopathy implicate this cellular response in the pathophysiology of metabolic disease. INTRODUCTIONThe increased prevalence of obesity worldwide has contributed to the emergence of a disease cluster, the metabolic syndrome, that includes insulin resistance, type 2 diabetes, and cardiovascular disease. Elevated serum triglyceride and fatty acid (FA) levels associated with this syndrome contribute to lipid accumulation in many nonadipose tissues, including the heart. This inappropriate accumulation of excess lipid can lead to cellular dysfunction and cell death-a process called lipotoxicity (Unger, 2003).Lipotoxic cardiomyocyte death has been proposed to play a central role in heart failure associated with diabetes and obesity in animal models and in humans. Although FAs are the principal source of energy for cardiomyocytes, high serum triglyceride and FA levels result in FA uptake by the heart that exceeds the anabolic and catabolic needs of the tissue. Triglyceride accumulation in cardiomyocytes of leptin-or leptin receptor-deficient obese diabetic animal models is associated with cardiomyocyte apoptosis (Zhou et al., 2000) and contractile dysfunction (Zhou et al., 2000;Aasum et al., 2002;Christoffersen et al., 2003), suggesting that lipotoxic cell death in the heart may be important in the genesis of diabetic cardiomyopathy. Recently, similar observations were reported in patients with metabolic syndrome and nonischemic heart failure (Sharma et al., 2004). Consistent with this apparent cardiac lipotoxicity, cardiomyocyte-specific increases in FA uptake in mice with cardiac-restricted overexpression of long-chain acyl-CoA synthetase 1 (ACS1), li...

Autoimmune pancreatitis showed high signal intensity on DWI, which improved after steroid treatment. ADCs reflected disease activity. Thus, diffusion-weighted MRI might be useful for diagnosing AIP, determining the affected area, and evaluating the effect of treatment.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Drosophila dot chromosomes

Sequencing and analysis of fosmid hybridization to the dot chromosomes of Drosophila virilis and D. melanogaster suggest that repetitive elements and density are important in determining higher-order chromatin packaging.

Little is known about the relationship between Becker Muscular Dystrophy (BMD) and mental disorders. This study aimed to clarify whether BMD is a risk factor for psychiatric diseases. We asked genetically or immunohistochemically confirmed BMD patients to participate in the study interview. Participants who consented to psychiatric tests underwent further assessments of intellectual, psychological, and neurodevelopmental disorders. In total, 76 (73%) of 105 BMD patients (median age, 37 years) completed the interview. Of these, 6 had developmental disorders (mental retardation, pervasive developmental disorder), 33/76 (43%) experienced bullying in school, 11 exhibited problematic behaviors such as cutting class and violent incidents, and 16 had psychiatric disorders (schizophrenia spectrum, 5; depressive spectrum, 4; stress-related disorders, 3; obsessive-compulsive and related disorders, 2; somatic symptom and related disorders, 2; bipolar and related disorders, 1). Mean IQ was normal, whereas 13/40 (32.5%) of participants were in a depressive state. High trait anxiety was found in 20/40 (50%) of patients, while 15/40 (38.5%) were in an anxious state. Review of MRI data from 14 participants revealed brain atrophy caused solely by BMD and unrelated to any other complication. Our findings suggest that BMD patients are at risk of developing psychiatric disorders. Physical handicap or bullying may influence their mental state, as many of them have high trait anxiety. Parents, teachers, and supporters should be mindful of the daily environment of BMD patients and provide support to help them cope with stress.