Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures.

Although there have been major advances in elucidating the functional biology of the human brain, relatively little is known of its cellular and molecular organization. Here we report a large-scale characterization of the expression of ∼1,000 genes important for neural functions by in situ hybridization at a cellular resolution in visual and temporal cortices of adult human brains. These data reveal diverse gene expression patterns and remarkable conservation of each individual gene's expression among individuals (95%), cortical areas (84%), and between human and mouse (79%). A small but substantial number of genes (21%) exhibited species-differential expression. Distinct molecular signatures, comprised of genes both common between species and unique to each, were identified for each major cortical cell type. The data suggest that gene expression profile changes may contribute to differential cortical function across species, and in particular, a shift from corticosubcortical to more predominant corticocortical communications in the human brain.

Immortalized sheep microglial cells are permissive to a diverse range of ruminant viruses.

BACKGROUND: Ruminants, including sheep and goats (small ruminants), are key agricultural animals in many parts of the world. Infectious diseases, including many viral diseases, are significant problems to efficient production of ruminants. Unfortunately, reagents tailored to viruses of ruminants, and especially small ruminants, are lacking compared to other animals more typically used for biomedical research. OBJECTIVE: The purpose of this study was to determine the permissibility of a stably immortalized, sheep microglial cell line to viruses that are reported to infect ruminants: bovine viral diarrhea virus (BVDV), bovine herpesvirus 1 (BoHV-1), small ruminant lentiviruses (SRLV), and bovine respiratory syncytial virus (BRSV). METHODS: Sublines A and H of previously isolated, immortalized, and characterized (CD14-positive) ovine microglial cells were used. Bovine turbinate cells and goat synovial membrane cells were used for comparison. Cytopathic changes were used to confirm infection of individual wells, which were then counted and used to calculate the 50% tissue culture infectious dose. Uninoculated cells served as negative controls and confirmed that the cells were not previously infected with these viruses using polymerase chain reaction (PCR). RESULTS: Inoculation of the two microglial cell sublines with laboratory and field isolates of BVDV, BoHV-1, and BRSV resulted in viral infection in a manner similar to bovine turbinate cells. Immortalized microglia cells are also permissive to SRLV, similar to goat synovial membrane cells. CONCLUSION AND CLINICAL RELEVANCE: These immortalized sheep microglial cells provide a new tool for the study of ruminant viruses in ruminant microglial cell line.

Circadian timing of REM sleep is coupled to an oscillator within the dorsomedial suprachiasmatic nucleus.

Sleep is consistently concentrated to a specific time of the day. Its timing and consolidation depend on the interplay between a homeostatic and a circadian process of sleep regulation [1-3]. Sleep propensity rises as a homeostatic response to increasing wake time, whereas a circadian clock determines the specific time when sleep will probably occur. This two-process regulation of sleep also determines which specific sleep stage will be manifested, and the circadian process governs tightly the manifestation of rapid eye movement sleep (REMS) [1, 4]. The role of the hypothalamic suprachiasmatic nucleus (SCN) in the circadian gating of sleep and wakefulness has been unequivocally established by lesion studies [5], but its role in the timing of specific sleep stages has remained unknown. Using a forced desynchrony paradigm that induces the stable dissociation of the ventrolateral (vl) and dorsomedial (dm) SCN, and a jetlag paradigm that induces desynchronization between these SCN subregions, we show that the SCN can time the occurrence of specific sleep stages. Specifically, the circadian regulation of REMS is associated with clock gene expression within the dmSCN. We provide the first neurophysiological model for the disruption of sleep architecture that may result from temporal challenges such as rotational-shift work and jetlag.