Annotating Synapses in Large EM Datasets

Reconstructing neuronal circuits at the level of synapses is a central problem in neuroscience and becoming a focus of the emerging field of connectomics. To date, electron microscopy (EM) is the most proven technique for identifying and quantifying synaptic connections. As advances in EM make acquiring larger datasets possible, subsequent manual synapse identification ({\em i.e.}, proofreading) for deciphering a connectome becomes a major time bottleneck. Here we introduce a large-scale, high-throughput, and semi-automated methodology to efficiently identify synapses. We successfully applied our methodology to the Drosophila medulla optic lobe, annotating many more synapses than previous connectome efforts. Our approaches are extensible and will make the often complicated process of synapse identification accessible to a wider-community of potential proofreaders

Differential Gene Expression in Liver, Gill, and Olfactory Rosettes of Coho Salmon (Oncorhynchus kisutch) After Acclimation to Salinity.

Most Pacific salmonids undergo smoltification and transition from freshwater to saltwater, making various adjustments in metabolism, catabolism, osmotic, and ion regulation. The molecular mechanisms underlying this transition are largely unknown. In the present study, we acclimated coho salmon (Oncorhynchus kisutch) to four different salinities and assessed gene expression through microarray analysis of gills, liver, and olfactory rosettes. Gills are involved in osmotic regulation, liver plays a role in energetics, and olfactory rosettes are involved in behavior. Between all salinity treatments, liver had the highest number of differentially expressed genes at 1616, gills had 1074, and olfactory rosettes had 924, using a 1.5-fold cutoff and a false discovery rate of 0.5. Higher responsiveness of liver to metabolic changes after salinity acclimation to provide energy for other osmoregulatory tissues such as the gills may explain the differences in number of differentially expressed genes. Differentially expressed genes were tissue- and salinity-dependent. There were no known genes differentially expressed that were common to all salinity treatments and all tissues. Gene ontology term analysis revealed biological processes, molecular functions, and cellular components that were significantly affected by salinity, a majority of which were tissue-dependent. For liver, oxygen binding and transport terms were highlighted. For gills, muscle, and cytoskeleton-related terms predominated and for olfactory rosettes, immune response-related genes were accentuated. Interaction networks were examined in combination with GO terms and determined similarities between tissues for potential osmosensors, signal transduction cascades, and transcription factors

The pseudorabies virus protein, pUL56, enhances virus dissemination and virulence but is dispensable for axonal transport

Neurotropic herpesviruses exit the peripheral nervous system and return to exposed body surfaces following reactivation from latency. The pUS9 protein is a critical viral effector of the anterograde axonal transport that underlies this process. We recently reported that while pUS9 increases the frequency of sorting of newly assembled pseudorabies virus particles to axons from the neural soma during egress, subsequent axonal transport of individual virus particles occurs with wild-type kinetics in the absence of the protein. Here, we examine the role of a related pseudorabies virus protein, pUL56, during neuronal infection. The findings indicate that pUL56 is a virulence factor that supports virus dissemination in vivo, yet along with pUS9, is dispensable for axonal transport

Enkephalin Therapy Improves Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is accompanied by decreases in serum endogenous enkephalin/endorphins and alterations in inflammatory cytokines. This retrospective analysis of serum levels was conducted in 53 patients with established relapsing-remitting MS treated with the disease-modifying therapies (DMT) glatiramer acetate, dimethyl fumarate or with the biotherapeutic low dose naltrexone (LDN) to elevate enkephalins, an off-label alternative. Opioid growth factor (OGF), an inhibitory endogenous opioid involved in modulating cellular replication, was measured and correlated to serum β-endorphin, IL-17A and TNFα. Results revealed that MS leads to a significant reduction in OGF levels in subjects on DMTs, but patients on LDN had OGF levels comparable to non-MS controls. Individuals on DMTs had significantly elevated TNFα levels, while IL-17A levels were significantly elevated only in patients taking dimethyl fumarate. A direct correlation was established between OGF and IL17A indicating a potential interaction between the OGF-OGFr axis and pro-inflammatory T-helper cells providing insight into the disease etiology

Use of Ecological Sites in Managing Wildlife and Livestock: An Example with Prairie Dogs

On the Ground•The perception of prairie dogs among Native Americans living on the Standing Rock Sioux Reservation is mixed. Some Native Americans focus on the loss of forage productivity, whereas others are interested in the cultural and ecological aspects of prairie dogs.•The use of ecological sites may provide a mechanism for developing a management framework that would consider both livestock and prairie dogs.•The three ecological sites we surveyed had large differences in off-colony standing crop, but in 2 of the 3 years we surveyed, there were no differences between standing crop on-colony.•This suggests that management of prairie dogs on rangelands should focus on limiting prairie dogs on more productive ecological sites with less productive sites receiving less emphasis

Use of Ecological Sites in Managing Wildlife and Livestock: An Example with Prairie Dogs

On the Ground The perception of prairie dogs among Native Americans living on the Standing Rock Sioux Reservation is mixed. Some Native Americans focus on the loss of forage productivity, whereas others are interested in the cultural and ecological aspects of prairie dogs. The use of ecological sites may provide a mechanism for developing a management framework that would consider both livestock and prairie dogs. The three ecological sites we surveyed had large differences in off-colony standing crop, but in 2 of the 3 years we surveyed, there were no differences between standing crop on-colony. This suggests that management of prairie dogs on rangelands should focus on limiting prairie dogs on more productive ecological sites with less productive sites receiving less emphasis

The Apollo Lunar Sample Image Collection: Digital Archiving and Online Access

The primary goal of the Apollo Program was to land human beings on the Moon and bring them safely back to Earth. This goal was achieved during six missions - Apollo 11, 12, 14, 15, 16, and 17 - that took place between 1969 and 1972. Among the many noteworthy engineering and scientific accomplishments of these missions, perhaps the most important in terms of scientific impact was the return of 382 kg (842 lb.) of lunar rocks, core samples, pebbles, sand, and dust from the lunar surface to Earth. Returned samples were curated at JSC (then known as the Manned Spacecraft Center) and, as part of the original processing, high-quality photographs were taken of each sample. The top, bottom, and sides of each rock sample were photographed, along with 16 stereo image pairs taken at 45-degree intervals. Photographs were also taken whenever a sample was subdivided and when thin sections were made. This collection of lunar sample images consists of roughly 36,000 photographs; all six Apollo missions are represented

Novel Algorithms Reveal Streptococcal Transcriptomes and Clues about Undefined Genes

Bacteria–host interactions are dynamic processes, and understanding transcriptional responses that directly or indirectly regulate the expression of genes involved in initial infection stages would illuminate the molecular events that result in host colonization. We used oligonucleotide microarrays to monitor (in vitro) differential gene expression in group A streptococci during pharyngeal cell adherence, the first overt infection stage. We present neighbor clustering, a new computational method for further analyzing bacterial microarray data that combines two informative characteristics of bacterial genes that share common function or regulation: (1) similar gene expression profiles (i.e., co-expression); and (2) physical proximity of genes on the chromosome. This method identifies statistically significant clusters of co-expressed gene neighbors that potentially share common function or regulation by coupling statistically analyzed gene expression profiles with the chromosomal position of genes. We applied this method to our own data and to those of others, and we show that it identified a greater number of differentially expressed genes, facilitating the reconstruction of more multimeric proteins and complete metabolic pathways than would have been possible without its application. We assessed the biological significance of two identified genes by assaying deletion mutants for adherence in vitro and show that neighbor clustering indeed provides biologically relevant data. Neighbor clustering provides a more comprehensive view of the molecular responses of streptococci during pharyngeal cell adherence