Neuronal Shot Noise and Brownian 1/f2 Behavior in the Local Field Potential

We demonstrate that human electrophysiological recordings of the local field potential (LFP) from intracranial electrodes, acquired from a variety of cerebral regions, show a ubiquitous 1/f² scaling within the power spectrum. We develop a quantitative model that treats the generation of these fields in an analogous way to that of electronic shot noise, and use this model to specifically address the cause of this 1/f² Brownian noise. The model gives way to two analytically tractable solutions, both displaying Brownian noise: 1) uncorrelated cells that display sharp initial activity, whose extracellular fields slowly decay in time and 2) rapidly firing, temporally correlated cells that generate UP-DOWN states.     

Severity of Mitral Valve Degeneration Is Associated with Chromosome 15 Loci in Whippet Dogs

Mitral valve degeneration (MVD) is the most common form of heart disease in dogs, frequently leading to left-sided congestive heart failure and cardiac mortality. Although breed-specific disease characteristics and overrepresentation point towards a genetic origin for MVD, a causative mutation and complete molecular pathogenesis are unknown. Whippet dogs are overrepresented in incidence of MVD, suggesting an inherited component in this breed. Expressivity of this condition is variable with some dogs showing evidence of more severe disease at earlier ages than other dogs. This phenomenon makes a traditional case versus control genetic study prone to phenotyping error. This study sought to avoid these common pitfalls by identifying genetic loci associated with severity of MVD in Whippets through a genome-wide association study (GWAS). 138 Whippet dogs were characterized for MVD by echocardiographic examination and a novel disease severity score was developed and adjusted for age in each subject. Single nucleotide polymorphism (SNP) genotype data (170k Illumina CanineHD SnpChip) was obtained for DNA isolated from blood of each study subject. Continuous variable genome wide association was performed after correction for population stratification by efficient mixed model association expedited (EMMAX) in 130 dogs. A genome wide significant association was identified on chromosome 15 (peak locus 57,770,326; P_adj = 0.049) and secondary loci of suggestive association were identified on chromosome 2 (peak locus 37,628,875; P_adj = 0.079). Positional candidate genes were identified within the primary and secondary loci including follistatin-related protein 5 precursor (FSTL5) and Rho GTPase-activating protein 26 (ARHGAP26). These results support the hypothesis that severity of MVD in whippets has a genetic basis and warrants further study by either candidate gene sequencing or next-generation techniques.     

Consequences of defaunation for a tropical tree community

Hunting affects a considerably greater area of the tropical forest biome than deforestation and logging combined. Often even large remote protected areas are depleted of a substantial proportion of their vertebrate fauna. However, understanding of the long‐term ecological consequences of defaunation in tropical forests remains poor. Using tree census data from a large‐scale plot monitored over a 15‐year period since the approximate onset of intense hunting, we provide a comprehensive assessment of the immediate consequences of defaunation for a tropical tree community. Our data strongly suggest that over‐hunting has engendered pervasive changes in tree population spatial structure and dynamics, leading to a consistent decline in local tree diversity over time. However, we do not find any support for suggestions that over‐hunting reduces above‐ground biomass or biomass accumulation rate in this forest. To maintain critical ecosystem processes in tropical forests increased efforts are required to protect and restore wildlife populations.     

Unsupervised statistical clustering of environmental shotgun sequences

Background  

The development of effective environmental shotgun sequence binning methods remains an ongoing challenge in algorithmic analysis of metagenomic data. While previous methods have focused primarily on supervised learning involving extrinsic data, a first-principles statistical model combined with a self-training fitting method has not yet been developed.     

Individual Variations in Serum Melatonin Levels through Time: Implications for Epidemiologic Studies

Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p = 0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.     

Seasonal geochemistry of an arctic tundra drainage basin

The snow melt food at Imnavait Creek takes place sometime between 12 May and 2 June and constitutes the single most important hydrological and geochemical event. Three years of study indicate this event spans 7 to 10 days and that peak discharge can be expected to be between 0.6 and 0.9 cu. mes. Ion concentrations peak during the first 15% of the event while pH is at a minimum. In all cases, ion concentrations in the spring runoff are 4 to 9 times those of the snow pack, Precipitaion, including dryfall, contributes significant amounts of Ca, Mg, K, Na, Cl and SO₄. Postassium is present in surface waters only during melt-off and for a short time after. Calcium. Mg. suspended solids and electrical conductivity all reach broad, poorly defined peaks in mid-summer. Only pH shows a significant relationship to discharge. On a seasonal basis a substantial charge imbalance favoring cations occurs. It seems probable that the, as yet, unmeasured negative charge is associated with organic anions. No seasonal trends were recorded for Mg, K or Mn in subsurface flow in the surrounding slopes. Calcium. Fe and Al showed a late season peak, and the concentration of Na and Si decreased as the melt season progressed.     

Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression

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Fhit Deficiency-Induced Global Genome Instability Promotes Mutation and Clonal Expansion

Loss of Fhit expression, encoded at chromosome fragile site FRA3B, leads to increased replication stress, genome instability and accumulation of genetic alterations. We have proposed that Fhit is a genome ‘caretaker’ whose loss initiates genome instability in preneoplastic lesions. We have characterized allele copy number alterations and expression changes observed in Fhit-deficient cells in conjunction with alterations in cellular proliferation and exome mutations, using cells from mouse embryo fibroblasts (MEFs), mouse kidney, early and late after establishment in culture, and in response to carcinogen treatment. Fhit ^-/- MEFs escape senescence to become immortal more rapidly than Fhit ^+/+ MEFs; -/- MEFs and kidney cultures show allele losses and gains, while +/+ derived cells show few genomic alterations. Striking alterations in expression of p53, p21, Mcl1 and active caspase 3 occurred in mouse kidney -/- cells during progressive tissue culture passage. To define genomic changes associated with preneoplastic changes in vivo, exome DNAs were sequenced for +/+ and -/- liver tissue after treatment of mice with the carcinogen, 7,12-dimethylbenz[a]anthracene, and for +/+ and -/- kidney cells treated in vitro with this carcinogen. The -/- exome DNAs, in comparison with +/+ DNA, showed small insertions, deletions and point mutations in more genes, some likely related to preneoplastic changes. Thus, Fhit loss provides a ‘mutator’ phenotype, a cellular environment in which mild genome instability permits clonal expansion, through proliferative advantage and escape from apoptosis, in response to pressures to survive.     

Biosynthesis and incorporation into protein of norleucine by Escherichia coli

The methionine analog norleucine was produced during the synthesis of bovine somatotropin by Escherichia coli strain W3110G containing the recombinant plasmid pBGH1. Norleucine was generated by the leucine biosynthetic pathway from pyruvate or alpha-ketobutyrate in place of alpha-ketoisovalerate as the initial substrate. The intracellular level of norleucine was high enough to permit the analog to compete successfully with methionine for incorporation into protein. Two ways were found to prevent either the formation of norleucine or its incorporation into protein. The endogenous synthesis of norleucine was eliminated by deleting the leucine operon. The addition of sufficient methionine or 2-hydroxy-4-methylthiobutanoic acid, a precursor of methionine, to the culture medium prevented any norleucine from being incorporated into protein.