Environmental Toxins Linked to Neurodegeneration and Autism Activate the Brain’s Immune System

Microglia are the primary immune cells of the central nervous system and become activated in response to noxious stimuli, leading to a cycle of inflammation and cell death that has been implicated in the development of Parkinson’s disease and autism. This study examines the effects of environmental toxins, at levels commonly found in humans, on microglial cell survival and activation. The toxins used in this study include polybrominated diphenyl ether (PBDE) flame retardants, the food additive propionic acid (PPA), and the organochlorine pesticide dieldrin. These chemicals have been linked to neuronal damage, although their effects on microglial cells have not been fully studied. Our results indicate that microglial cell survival could be decreased by as much as 50% due to exposure to these toxins, without the production of certain cytokines produced by lipopolysaccharide (LPS)-induced activation. These effects are significant as further understanding of the role of microglia in neuronal damage could provide a pharmacologic target for future drug development as well as elucidate the pathology of neurodegenerative diseases

High-throughput gene discovery in the rat

The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3′ ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ∼50,000 rat UniGene clusters. We have identified, arrayed, and derived 5′ ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI

Environmental Toxins Linked to Neurodegeneration and Autism Activate the Brain’s Immune System

Microglia are the primary immune cells of the central nervous system and become activated in response to noxious stimuli, leading to a cycle of inflammation and cell death that has been implicated in the development of Parkinson’s disease and autism. This study examines the effects of environmental toxins, at levels commonly found in humans, on microglial cell survival and activation. The toxins used in this study include polybrominated diphenyl ether (PBDE) flame retardants, the food additive propionic acid (PPA), and the organochlorine pesticide dieldrin. These chemicals have been linked to neuronal damage, although their effects on microglial cells have not been fully studied. Our results indicate that microglial cell survival could be decreased by as much as 50% due to exposure to these toxins, without the production of certain cytokines produced by lipopolysaccharide (LPS)-induced activation. These effects are significant as further understanding of the role of microglia in neuronal damage could provide a pharmacologic target for future drug development as well as elucidate the pathology of neurodegenerative diseases

A Single-Chip, 1.6-Billion, 16-b MAC/s Multiprocessor DSP

An MIMD multiprocessor digital signal- processing (DSP) chip containing four 64-b processing elements (PE's) interconnected by a 128-b pipelined split transaction bus (STBus) is presented. Each PE contains a 32-b RISC core with DSP enhancements and a 64-b single-instruction, multiple-data vector coprocessor with four 16-b MAC/s and a vector reduction unit. PE's are connected to the STBus through reconfigurable dual-ported snooping L1 cache memories that support shared memory multiprocessing using a modified-MESI data coherency protocol. High-bandwidth data transfers between system memory and on-chip caches are managed in a pipelined memory controller that supports multiple outstanding transactions. An embedded RTOS dynamically schedules multiple tasks onto the PE's. Process synchronization is achieved using cached semaphores. The 200-mm 2 , 0.25- m CMOS chip operates at 100 MHz and dissipates 4 W from a 3.3-V supply