Lifetime mobility of an Arctic woolly mammoth.

Little is known about woolly mammoth (Mammuthus primigenius) mobility and range. Here we use high temporal resolution sequential analyses of strontium isotope ratios along an entire 1.7-meter-long tusk to reconstruct the movements of an Arctic woolly mammoth that lived 17,100 years ago, during the last ice age. We use an isotope-guided random walk approach to compare the tusk's strontium and oxygen isotope profiles to isotopic maps. Our modeling reveals patterns of movement across a geographically extensive range during the animal's ~28-year life span that varied with life stages. Maintenance of this level of mobility by megafaunal species such as mammoth would have been increasingly difficult as the ice age ended and the environment changed at high latitudes.

NMDA receptors promote hippocampal sharp-wave ripples and the associated coactivity of CA1 pyramidal cells.

Hippocampal sharp-wave ripples (SWRs) support the reactivation of memory representations, relaying information to neocortex during "offline" and sleep-dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is known to affect both learning and subsequent consolidation, the specific contributions of NMDAR activation to SWR-associated activity remain unclear. Here, we combine biophysical modeling with in vivo local field potential (LFP) and unit recording to quantify changes in SWR dynamics following inactivation of NMDAR. In a biophysical model of CA3-CA1 SWR activity, we find that NMDAR removal leads to reduced SWR density, but spares SWR properties such as duration, cell recruitment and ripple frequency. These predictions are confirmed by experiments in which NMDAR-mediated transmission in rats was inhibited using three different NMDAR antagonists, while recording dorsal CA1 LFP. In the model, loss of NMDAR-mediated conductances also induced a reduction in the proportion of cell pairs that co-activate significantly above chance across multiple events. Again, this prediction is corroborated by dorsal CA1 single-unit recordings, where the NMDAR blocker ketamine disrupted correlated spiking during SWR. Our results are consistent with a framework in which NMDA receptors both promote activation of SWR events and organize SWR-associated spiking content. This suggests that, while SWR are short-lived events emerging in fast excitatory-inhibitory networks, slower network components including NMDAR-mediated currents contribute to ripple density and promote consistency in the spiking content across ripples, underpinning mechanisms for fine-tuning of memory consolidation processes.

Exploring the roles of spectral detail and intonation contour in speech intelligibility: an FMRI study.

The melodic contour of speech forms an important perceptual aspect of tonal and nontonal languages and an important limiting factor on the intelligibility of speech heard through a cochlear implant. Previous work exploring the neural correlates of speech comprehension identified a left-dominant pathway in the temporal lobes supporting the extraction of an intelligible linguistic message, whereas the right anterior temporal lobe showed an overall preference for signals clearly conveying dynamic pitch information [Johnsrude, I. S., Penhune, V. B., & Zatorre, R. J. Functional specificity in the right human auditory cortex for perceiving pitch direction. Brain, 123, 155-163, 2000; Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000]. The current study combined modulations of overall intelligibility (through vocoding and spectral inversion) with a manipulation of pitch contour (normal vs. falling) to investigate the processing of spoken sentences in functional MRI. Our overall findings replicate and extend those of Scott et al. [Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000], where greater sentence intelligibility was predominately associated with increased activity in the left STS, and the greatest response to normal sentence melody was found in right superior temporal gyrus. These data suggest a spatial distinction between brain areas associated with intelligibility and those involved in the processing of dynamic pitch information in speech. By including a set of complexity-matched unintelligible conditions created by spectral inversion, this is additionally the first study reporting a fully factorial exploration of spectrotemporal complexity and spectral inversion as they relate to the neural processing of speech intelligibility. Perhaps surprisingly, there was little evidence for an interaction between the two factors-we discuss the implications for the processing of sound and speech in the dorsolateral temporal lobes.

Computational tools and resources for prediction and analysis of gene regulatory regions in the chick genome.

The discovery of cis-regulatory elements is a challenging problem in bioinformatics, owing to distal locations and context-specific roles of these elements in controlling gene regulation. Here we review the current bioinformatics methodologies and resources available for systematic discovery of cis-acting regulatory elements and conserved transcription factor binding sites in the chick genome. In addition, we propose and make available, a novel workflow using computational tools that integrate CTCF analysis to predict putative insulator elements, enhancer prediction, and TFBS analysis. To demonstrate the usefulness of this computational workflow, we then use it to analyze the locus of the gene Sox2 whose developmental expression is known to be controlled by a complex array of cis-acting regulatory elements. The workflow accurately predicts most of the experimentally verified elements along with some that have not yet been discovered. A web version of the CTCF tool, together with instructions for using the workflow can be accessed from http://toolshed.g2.bx.psu.edu/view/mkhan1980/ctcf_analysis. For local installation of the tool, relevant Perl scripts and instructions are provided in the directory named "code" in the supplementary materials.

Tracing geographic and temporal trafficking patterns for marijuana in Alaska using stable isotopes (C, N, O and H).

A large proportion of Alaska Bureau of Alcohol and Drug Enforcement's time is spent controlling the production and distribution of marijuana. Marijuana in Alaska can originate from within (e.g., Fairbanks and the Matanuska-Susitna Valley) or from outside Alaska (e.g., Latin America, Canada and other locations in the United States of America). However it is difficult to track the supply proportions from various potential geographic areas in remote areas of the globe, such as Alaska. This is due to an insufficient ability to trace the source regions from which confiscated marijuana was originally grown. We analyzed multiple stable isotopes (C, N, O and H) in marijuana confiscated in Alaska, to identify the likely geographic source from which the marijuana originated. Fifty-six of the marijuana samples were from known grow locations in Alaska. These samples exhibited stable oxygen and hydrogen isotope ratios (δ(18)O and δD) of 10.4‰ to 37.0‰ and -203.1‰ to -136.7‰, respectively. Stable carbon and nitrogen isotope ratios (δ(13)C and δ(15)N) of the same samples ranged from -53.8‰ to -26.4‰ and -12.5‰ to 12.1‰, respectively. We use these data to compare with stable isotope analyses of marijuana confiscated in Alaska, but from unknown grow locations, which were found to have δ(18)O and δD ranging from 10.0‰ to 34.5‰ and -214.6‰ to -107.5‰, respectively. The large range of data suggests that the samples originated from multiple sources ranging from low to high latitudes. A large range in δ(15)N values from the samples was also evident (-5.0‰ to 14.7‰). Most intriguing of all was the unexpected large range in the stable carbon isotope compositions of the samples (-61.8‰ to -24.6‰). Twelve of the samples were found to have an exceedingly low δ(13)C values (-36.1‰ to -61.8‰) compared to typical δ(13)C values of other plants using C3 photosynthesis. Interior growing conditions (e.g., hydroponic and green house) and a variety of CO(2) sources (e.g., CO(2) from tanks and fermentation CO(2) generators) supplied to growing marijuana (in addition to atmospheric CO(2)) that are sometimes used to improve marijuana yields likely account for these exceptionally low δ(13)C values. Our project has implications for monitoring broad scale trafficking patterns over time in relatively remote regions such as Alaska, where the resources allocated for law enforcement must be utilized over a wide geographic area.

Sources of polycyclic aromatic hydrocarbons and hexachlorobenzene in spruce needles of eastern Alaska.

The concentrations of phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, and hexachlorobenzene (HCB) were measured in spruce needles at 36 sites in eastern Alaska during early spring. Concentrations of each polycyclic aromatic hydrocarbon (PAH) varied by an order of magnitude. Samples taken from near the city of Fairbanks had higher concentrations than samples taken from more rural areas. Anthropogenic activities near Fairbanks are most likely a source of PAHs. Variation in the concentration ratios of isomeric PAHs indicates the relative importance of combustion and petrogenic sources. The relative combustion contribution is largest in coastal samples and smallest near Fairbanks. In contrast, the concentration of HCB varied by only a factor of 2. Lipid content of needles and distance from the coast were the major factors correlated with the concentration of HCB.