Neural Correlates of Threat Perception: Neural Equivalence of Conspecific and Heterospecific Mobbing Calls Is Learned

Songbird auditory areas (i.e., CMM and NCM) are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise [1]–[2]. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators [3]. Mobbing calls produced in response to smaller, higher-threat predators contain more “D” notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators [4]. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG) expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned

Dose escalation of a curcuminoid formulation

BACKGROUND: Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. METHODS: A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C(3 )Complex™, Sabinsa Corporation). Healthy volunteers were administered escalating doses from 500 to 12,000 mg. RESULTS: Seven of twenty-four subjects (30%) experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. CONCLUSION: The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent

Reduced occupancy of hedgehogs (Erinaceus europaeus) in rural England and Wales: the influence of habitat and an asymmetric intra-guild predator

Agricultural landscapes have become increasingly intensively managed resulting in population declines across a broad range of taxa, including insectivores such as the hedgehog (Erinaceus europaeus). Hedgehog declines have also been attributed to an increase in the abundance of badgers (Meles meles), an intra-guild predator. The status of hedgehogs across the rural landscape at large spatial scales is, however, unknown. In this study, we used footprint tracking tunnels to conduct the first national survey of rural hedgehog populations in England and Wales. Single and two-species occupancy modelling was used to quantify hedgehog occupancy in relation to habitat and predator covariates. Hedgehog occupancy was low (22% nationally), and significantly negatively related to badger sett density and positively related to the built environment. Hedgehogs were also absent from 71% of sites that had no badger setts, indicating that large areas of the rural landscape are not occupied by hedgehogs. Our results provide the first field based national survey of hedgehogs, providing a robust baseline for future monitoring. Furthermore, the combined effects of increasing badger abundance and intensive agriculture may have provided a perfect storm for hedgehogs in rural Britain, leading to worryingly low levels of occupancy over large spatial scales

Neonatal Colonisation Expands a Specific Intestinal Antigen-Presenting Cell Subset Prior to CD4 T-Cell Expansion, without Altering T-Cell Repertoire

Interactions between the early-life colonising intestinal microbiota and the developing immune system are critical in determining the nature of immune responses in later life. Studies in neonatal animals in which this interaction can be examined are central to understanding the mechanisms by which the microbiota impacts on immune development and to developing therapies based on manipulation of the microbiome. The inbred piglet model represents a system that is comparable to human neonates and allows for control of the impact of maternal factors. Here we show that colonisation with a defined microbiota produces expansion of mucosal plasma cells and of T-lymphocytes without altering the repertoire of alpha beta T-cells in the intestine. Importantly, this is preceded by microbially-induced expansion of a signal regulatory protein α-positive (SIRPα+) antigen-presenting cell subset, whilst SIRPα−CD11R1+ antigen-presenting cells (APCs) are unaffected by colonisation. The central role of intestinal APCs in the induction and maintenance of mucosal immunity implicates SIRPα+ antigen-presenting cells as orchestrators of early-life mucosal immune development

The living microarray: a high-throughput platform for measuring transcription dynamics in single cells

<p>Abstract</p> <p>Background</p> <p>Current methods of measuring transcription in high-throughput have led to significant improvements in our knowledge of transcriptional regulation and Systems Biology. However, endpoint measurements obtained from methods that pool populations of cells are not amenable to studying time-dependent processes that show cell heterogeneity.</p> <p>Results</p> <p>Here we describe a high-throughput platform for measuring transcriptional changes in real time in single mammalian cells. By using reverse transfection microarrays we are able to transfect fluorescent reporter plasmids into 600 independent clusters of cells plated on a single microscope slide and image these clusters every 20 minutes. We use a fast-maturing, destabilized and nuclear-localized reporter that is suitable for automated segmentation to accurately measure promoter activity in single cells. We tested this platform with synthetic drug-inducible promoters that showed robust induction over 24 hours. Automated segmentation and tracking of over 11 million cell images during this period revealed that cells display substantial heterogeneity in their responses to the applied treatment, including a large proportion of transfected cells that do not respond at all.</p> <p>Conclusions</p> <p>The results from our single-cell analysis suggest that methods that measure average cellular responses, such as DNA microarrays, RT-PCR and chromatin immunoprecipitation, characterize a response skewed by a subset of cells in the population. Our method is scalable and readily adaptable to studying complex systems, including cell proliferation, differentiation and apoptosis.</p

When is working memory important for arithmetic?: the impact of strategy and age

Our ability to perform arithmetic relies heavily on working memory, the manipulation and maintenance of information in mind. Previous research has found that in adults, procedural strategies, particularly counting, rely on working memory to a greater extent than retrieval strategies. During childhood there are changes in the types of strategies employed, as well as an increase in the accuracy and efficiency of strategy execution. As such it seems likely that the role of working memory in arithmetic may also change, however children and adults have never been directly compared. This study used traditional dual-task methodology, with the addition of a control load condition, to investigate the extent to which working memory requirements for different arithmetic strategies change with age between 9-11 years, 12-14 years and young adulthood. We showed that both children and adults employ working memory when solving arithmetic problems, no matter what strategy they choose. This study highlights the importance of considering working memory in understanding the difficulties that some children and adults have with mathematics, as well as the need to include working memory in theoretical models of mathematical cognition

Motor activity improves temporal expectancy

Certain brain areas involved in interval timing are also important in motor activity. This raises the possibility that motor activity might influence interval timing. To test this hypothesis, we assessed interval timing in healthy adults following different types of training. The pre- and post-training tasks consisted of a button press in response to the presentation of a rhythmic visual stimulus. Alterations in temporal expectancy were evaluated by measuring response times. Training consisted of responding to the visual presentation of regularly appearing stimuli by either: (1) pointing with a whole-body movement, (2) pointing only with the arm, (3) imagining pointing with a whole-body movement, (4) simply watching the stimulus presentation, (5) pointing with a whole-body movement in response to a target that appeared at irregular intervals (6) reading a newspaper. Participants performing a motor activity in response to the regular target showed significant improvements in judgment times compared to individuals with no associated motor activity. Individuals who only imagined pointing with a whole-body movement also showed significant improvements. No improvements were observed in the group that trained with a motor response to an irregular stimulus, hence eliminating the explanation that the improved temporal expectations of the other motor training groups was purely due to an improved motor capacity to press the response button. All groups performed a secondary task equally well, hence indicating that our results could not simply be attributed to differences in attention between the groups. Our results show that motor activity, even when it does not play a causal or corrective role, can lead to improved interval timing judgments

A Morphometric Assessment of the Intended Function of Cached Clovis Points

A number of functions have been proposed for cached Clovis points. The least complicated hypothesis is that they were intended to arm hunting weapons. It has also been argued that they were produced for use in rituals or in connection with costly signaling displays. Lastly, it has been suggested that some cached Clovis points may have been used as saws. Here we report a study in which we morphometrically compared Clovis points from caches with Clovis points recovered from kill and camp sites to test two predictions of the hypothesis that cached Clovis points were intended to arm hunting weapons: 1) cached points should be the same shape as, but generally larger than, points from kill/camp sites, and 2) cached points and points from kill/camp sites should follow the same allometric trajectory. The results of the analyses are consistent with both predictions and therefore support the hypothesis. A follow-up review of the fit between the results of the analyses and the predictions of the other hypotheses indicates that the analyses support only the hunting equipment hypothesis. We conclude from this that cached Clovis points were likely produced with the intention of using them to arm hunting weapons

An Assessment of the Impact of Hafting on Paleoindian Point Variability

It has long been argued that the form of North American Paleoindian points was affected by hafting. According to this hypothesis, hafting constrained point bases such that they are less variable than point blades. The results of several studies have been claimed to be consistent with this hypothesis. However, there are reasons to be skeptical of these results. None of the studies employed statistical tests, and all of them focused on points recovered from kill and camp sites, which makes it difficult to be certain that the differences in variability are the result of hafting rather than a consequence of resharpening. Here, we report a study in which we tested the predictions of the hafting hypothesis by statistically comparing the variability of different parts of Clovis points. We controlled for the potentially confounding effects of resharpening by analyzing largely unused points from caches as well as points from kill and camp sites. The results of our analyses were not consistent with the predictions of the hypothesis. We found that several blade characters and point thickness were no more variable than the base characters. Our results indicate that the hafting hypothesis does not hold for Clovis points and indicate that there is a need to test its applicability in relation to post-Clovis Paleoindian points