Spatio-Temporal Patterning in Primary Motor Cortex at Movement Onset

Voluntary movement initiation involves the engagement of large populations of motor cortical neurons around movement onset. Despite knowledge of the temporal dynamics that lead to movement, the spatial structure of these dynamics across the cortical surface remains unknown. In data from 4 rhesus macaques, we show that the timing of attenuation of beta frequency local field potential oscillations, a correlate of locally activated cortex, forms a spatial gradient across primary motor cortex (MI). We show that these spatio-temporal dynamics are recapitulated in the engagement order of ensembles of MI neurons. We demonstrate that these patterns are unique to movement onset and suggest that movement initiation requires a precise spatio-temporal sequential activation of neurons in MI

Large-scale Spatiotemporal Spike Patterning Consistent with Wave Propagation in Motor Cortex

Aggregate signals in cortex are known to be spatiotemporally organized as propagating waves across the cortical surface, but it remains unclear whether the same is true for spiking activity in individual neurons. Furthermore, the functional interactions between cortical neurons are well documented but their spatial arrangement on the cortical surface has been largely ignored. Here we use a functional network analysis to demonstrate that a subset of motor cortical neurons in non-human primates spatially coordinate their spiking activity in a manner that closely matches wave propagation measured in the beta oscillatory band of the local field potential. We also demonstrate that sequential spiking of pairs of neuron contains task-relevant information that peaks when the neurons are spatially oriented along the wave axis. We hypothesize that the spatial anisotropy of spike patterning may reflect the underlying organization of motor cortex and may be a general property shared by other cortical areas

Identification and Analysis of Bacterial Genomic Metabolic Signatures

With continued rapid growth in the number and quality of fully sequenced and accurately annotated bacterial genomes, we have unprecedented opportunities to understand metabolic diversity. We selected 101 diverse and representative completely sequenced bacteria and implemented a manual curation effort to identify 846 unique metabolic variants present in these bacteria. The presence or absence of these variants act as a metabolic signature for each of the bacteria, which can then be used to understand similarities and differences between and across bacterial groups. We propose a novel and robust method of summarizing metabolic diversity using metabolic signatures and use this method to generate a metabolic tree, clustering metabolically similar organisms. Resulting analysis of the metabolic tree confirms strong associations with well-established biological results along with direct insight into particular metabolic variants which are most predictive of metabolic diversity. The positive results of this manual cu ration effort and novel method development suggest that future work is needed to further expand the set of bacteria to which this approach is applied and use the resulting tree to test broad questions about metabolic diversity and complexity across the bacterial tree of life

Evolution of eukaryotic transcription : insights from the genome of Giardia lamblia

Author Posting. © Cold Spring Harbor Laboratory Press, 2004. This article is posted here by permission of Cold Spring Harbor Laboratory Press for personal use, not for redistribution. The definitive version was published in Genome Research 14 (2004): 1537-1547, doi:10.1101/gr.2256604.The Giardia lamblia genome sequencing project affords us a unique opportunity to conduct comparative analyses of core cellular systems between early and late-diverging eukaryotes on a genome-wide scale. We report a survey to identify canonical transcription components in Giardia, focusing on RNA polymerase (RNAP) subunits and transcription-initiation factors. Our survey revealed that Giardia contains homologs to 21 of the 28 polypeptides comprising eukaryal RNAPI, RNAPII, and RNAPIII; six of the seven RNAP subunits without giardial homologs are polymerase specific. Components of only four of the 12 general transcription initiation factors have giardial homologs. Surprisingly, giardial TATA-binding protein (TBP) is highly divergent with respect to archaeal and higher eukaryotic TBPs, and a giardial homolog of transcription factor IIB was not identified. We conclude that Giardia represents a transition during the evolution of eukaryal transcription systems, exhibiting a relatively complete set of RNAP subunits and a rudimentary basal initiation apparatus for each transcription system. Most class-specific RNAP subunits and basal initiation factors appear to have evolved after the divergence of Giardia from the main eukaryotic line of descent. Consequently, Giardia is predicted to be unique in many aspects of transcription initiation with respect to paradigms derived from studies in crown eukaryotes.This work was supported in part by NIH grant AI43273 to M.L.S., by NIH grant AI51089 to A.G.M, and DOE grant DE-FG02-01ER63201 to G.J.O. Additional support was provided by the G. Unger Vetlesen Foundation and LI-COR Biotechnology

Gene set analyses for interpreting microarray experiments on prokaryotic organisms

Background Despite the widespread usage of DNA microarrays, questions remain about how best to interpret the wealth of gene-by-gene transcriptional levels that they measure. Recently, methods have been proposed which use biologically defined sets of genes in interpretation, instead of examining results gene-by-gene. Despite a serious limitation, a method based on Fisher\u27s exact test remains one of the few plausible options for gene set analysis when an experiment has few replicates, as is typically the case for prokaryotes. Results We extend five methods of gene set analysis from use on experiments with multiple replicates, for use on experiments with few replicates. We then use simulated and real data to compare these methods with each other and with the Fisher\u27s exact test (FET) method. As a result of the simulation we find that a method named MAXMEAN-NR, maintains the nominal rate of false positive findings (type I error rate) while offering good statistical power and robustness to a variety of gene set distributions for set sizes of at least 10. Other methods (ABSSUM-NR or SUM-NR) are shown to be powerful for set sizes less than 10. Analysis of three sets of experimental data shows similar results. Furthermore, the MAXMEAN-NR method is shown to be able to detect biologically relevant sets as significant, when other methods (including FET) cannot. We also find that the popular GSEA-NR method performs poorly when compared to MAXMEAN-NR. Conclusion MAXMEAN-NR is a method of gene set analysis for experiments with few replicates, as is common for prokaryotes. Results of simulation and real data analysis suggest that the MAXMEAN-NR method offers increased robustness and biological relevance of findings as compared to FET and other methods, while maintaining the nominal type I error rate

Evaluating the Efficacy of Point-of-Use Water Filtration Units in Fiji

Background: To develop and evaluate a strategy for reducing the prevalence and impact of waterborne disease, a water quality intervention was developed for Fiji by Give Clean Water, Inc. in partnership with the Fiji Ministry of Health. Residents were provided and trained on how to use a Sawyer® PointONE™ filter, while also being taught proper handwashing techniques. At the time of the filter installation, all households were surveyed inquiring about the prior 2- to 4-week period. Households were measured a second time between 19 and 225 days later (mean = 66 days). Results: To date, five economic and health outcomes have been tracked on 503 households to evaluate the efficacy of the intervention. When comparing baseline to follow-up among the 503 households, the 2-week diarrhea prevalence decreased in households from 17.5% at baseline to 1.8% at follow-up. Also, the 2-week prevalence of severe diarrhea decreased per household from 9.7% at baseline to 0.6% at follow-up. Finally, monthly diarrhea-related medical costs reduced by an average of Fijian (FJ) $3.54 per person, and monthly water expenses reduced by FJ$0.63 per person. All estimated values are obtained from general linear and logistic mixed-effect models, which adjusted for location, season, time to follow-up, household size, water source, and respondent changing. Changes in economic and health outcomes from installation to follow-up were statistically significant (p \u3c 0.05) in all cases, in both unadjusted and adjusted models. Conclusions: The installation of water filters shows promise for the reduction of diarrhea prevalence in Fiji, as well as the reduction of diarrhea-related medical costs and water expenses. Future work entails evaluation in other countries and contexts, long-term health monitoring, and comparison to alternative water quality interventions

Comparative Genomics And Functional Analysis Of Rhamnose Catabolic Pathways And Regulons In Bacteria

L-rhamnose (Rha) is a deoxy-hexose sugar commonly found in nature. L-Rha catabolic pathways were previously characterized in various bacteria including Escherichia coli. Nevertheless, homology searches failed to recognize all the genes for the complete L Rha utilization pathways in diverse microbial species involved in biomass decomposition. Moreover, the regulatory mechanisms of L-Rha catabolism have remained unclear in most species. A comparative genomics approach was used to reconstruct the L-Rha catabolic pathways and transcriptional regulons in the phyla Actinobacteria, Bacteroidetes, Chloroflexi, Firmicutes, Proteobacteria, and Thermotogae. The reconstructed pathways include multiple novel enzymes and transporters involved in the utilization of L-Rha and L-Rha-containing polymers. Large-scale regulon inference using bioinformatics revealed remarkable variations in transcriptional regulators for L-Rha utilization genes among bacteria. A novel bifunctional enzyme, L-rhamnulose-phosphate aldolase (RhaE) fused to L-lactaldehyde dehydrogenase (RhaW), which is not homologous to previously characterized L-Rha catabolic enzymes, was identified in diverse bacteria including Chloroflexi, Bacilli, and Alphaproteobacteria. By using in vitro biochemical assays we validated both enzymatic activities of the purified recombinant RhaEW proteins from Chloroflexus aurantiacus and Bacillus subtilis. Another novel enzyme of the L-Rha catabolism, L-lactaldehyde reductase (RhaZ), was identified in Gammaproteobacteria and experimentally validated by in vitro enzymatic assays using the recombinant protein from Salmonella typhimurium. C. aurantiacus induced transcription of the predicted L-Rha utilization genes when L-Rha was present in the growth medium and consumed L-Rha from the medium. This study provided comprehensive insights to L-Rha catabolism and its regulation in diverse Bacteria

Developing young people's sense of self and place through sport

Previous research has recognized positive health implications, both physical and mental, as an outcome of participation in leisure pursuits. They provide opportunities for self-expression and stress reduction, as well as an environment in which people can socialize. Leisure activities, specifically sport activities, can play a significant role in young people's identity development. This paper explores the leisure activities in which young people in Adelaide, Australia participate. It examines the role of leisure activities in terms of young people's identity and feelings towards their hometown. This study consisted of semi-structured focus groups conducted with 24 senior high school students, followed by a survey resulting in 226 useable responses. Respondents were aged between 16 and 18 years of age. From the range of activities identified and explored, the results revealed sports activities to have the greatest impact on young people's lives. The results demonstrated that frequency of participation has a significant effect on young people's involvement levels and how they identify with the activity

How large should whales be?

The evolution and distribution of species body sizes for terrestrial mammals is well-explained by a macroevolutionary tradeoff between short-term selective advantages and long-term extinction risks from increased species body size, unfolding above the 2g minimum size induced by thermoregulation in air. Here, we consider whether this same tradeoff, formalized as a constrained convection-reaction-diffusion system, can also explain the sizes of fully aquatic mammals, which have not previously been considered. By replacing the terrestrial minimum with a pelagic one, at roughly 7000g, the terrestrial mammal tradeoff model accurately predicts, with no tunable parameters, the observed body masses of all extant cetacean species, including the 175,000,000g Blue Whale. This strong agreement between theory and data suggests that a universal macroevolutionary tradeoff governs body size evolution for all mammals, regardless of their habitat. The dramatic sizes of cetaceans can thus be attributed mainly to the increased convective heat loss is water, which shifts the species size distribution upward and pushes its right tail into ranges inaccessible to terrestrial mammals. Under this macroevolutionary tradeoff, the largest expected species occurs where the rate at which smaller-bodied species move up into large-bodied niches approximately equals the rate at which extinction removes them.Comment: 7 pages, 3 figures, 2 data table

Cluster J Mycobacteriophages: Intron Splicing in Capsid and Tail Genes

Bacteriophages isolated on Mycobacterium smegmatis mc2155 represent many distinct genomes sharing little or no DNA sequence similarity. The genomes are architecturally mosaic and are replete with genes of unknown function. A new group of genomes sharing substantial nucleotide sequences constitute Cluster J. The six mycobacteriophages forming Cluster J are morphologically members of the Siphoviridae, but have unusually long genomes ranging from 106.3 to 117 kbp. Reconstruction of the capsid by cryo-electron microscopy of mycobacteriophage BAKA reveals an icosahedral structure with a triangulation number of 13. All six phages are temperate and homoimmune, and prophage establishment involves integration into a tRNA-Leu gene not previously identified as a mycobacterial attB site for phage integration. The Cluster J genomes provide two examples of intron splicing within the virion structural genes, one in a major capsid subunit gene, and one in a tail gene. These genomes also contain numerous freestanding HNH homing endonuclease, and comparative analysis reveals how these could contribute to genome mosaicism. The unusual Cluster J genomes provide new insights into phage genome architecture, gene function, capsid structure, gene mobility, intron splicing, and evolution