Support for a synaptic chain model of neuronal sequence generation

In songbirds, the remarkable temporal precision of song is generated by a sparse sequence of bursts in the premotor nucleus HVC. To distinguish between two possible classes of models of neural sequence generation, we carried out intracellular recordings of HVC neurons in singing zebra finches (Taeniopygia guttata). We found that the subthreshold membrane potential is characterized by a large, rapid depolarization 5–10 ms before burst onset, consistent with a synaptically connected chain of neurons in HVC. We found no evidence for the slow membrane potential modulation predicted by models in which burst timing is controlled by subthreshold dynamics. Furthermore, bursts ride on an underlying depolarization of ~10-ms duration, probably the result of a regenerative calcium spike within HVC neurons that could facilitate the propagation of activity through a chain network with high temporal precision. Our results provide insight into the fundamental mechanisms by which neural circuits can generate complex sequential behaviours.National Institutes of Health (U.S.) (Grant MH067105)National Institutes of Health (U.S.) (Grant DC009280)National Science Foundation (U.S.) (IOS-0827731)Alfred P. Sloan Foundation (Research Fellowship

A portable prototype magnetometer to differentiate ischemic and non-ischemic heart disease in patients with chest pain

Background: Magnetocardiography (MCG) is a non-invasive technique used to measure and map cardiac magnetic fields. We describe the predictive performance of a portable prototype magnetometer designed for use in acute and routine clinical settings. We assessed the predictive ability of the measurements derived from the magnetometer for the ruling-out of healthy subjects and patients whose chest pain has a non-ischemic origin from those with ischemic heart disease (IHD). Methods: MCG data were analyzed from a technical performance study, a pilot clinical study, and a young healthy reference group. Participants were grouped to enable differentiation of those with IHD versus non-IHD versus controls: Group A (70 IHD patients); Group B (69 controls); Group C (37 young healthy volunteers). Scans were recorded in an unshielded room. Between-group differences were explored using analysis of variance. The ability of 10 candidate MCG predictors to predict normal/abnormal cases was analyzed using logistic regression. Predictive performance was internally validated using repeated five-fold cross-validation. Results: Three MCG predictors showed a significant difference between patients and age-matched controls (P<0.001); eight predictors showed a significant difference between patients and young healthy volunteers (P<0.001). Logistic regression comparing patients with controls yielded a specificity of 35.0%, sensitivity of 95.4%, and negative predictive value for the ruling-out of IHD of 97.8% (area under the curve 0.78). Conclusion: This analysis represents a preliminary indication that the portable magnetometer can help rule-out healthy subjects and patients whose chest pain has a non-ischemic origin from those with IHD

A reafferent and feed-forward model of song syntax generation in the Bengalese finch

Adult Bengalese finches generate a variable song that obeys a distinct and individual syntax. The syntax is gradually lost over a period of days after deafening and is recovered when hearing is restored. We present a spiking neuronal network model of the song syntax generation and its loss, based on the assumption that the syntax is stored in reafferent connections from the auditory to the motor control area. Propagating synfire activity in the HVC codes for individual syllables of the song and priming signals from the auditory network reduce the competition between syllables to allow only those transitions that are permitted by the syntax. Both imprinting of song syntax within HVC and the interaction of the reafferent signal with an efference copy of the motor command are sufficient to explain the gradual loss of syntax in the absence of auditory feedback. The model also reproduces for the first time experimental findings on the influence of altered auditory feedback on the song syntax generation, and predicts song- and species-specific low frequency components in the LFP. This study illustrates how sequential compositionality following a defined syntax can be realized in networks of spiking neurons

Prognostic Significance and Gene Expression Profiles of p53 Mutations in Microsatellite-Stable Stage III Colorectal Adenocarcinomas

Although the prognostic value of p53 abnormalities in Stage III microsatellite stable (MSS) colorectal cancers (CRCs) is known, the gene expression profiles specific to the p53 status in the MSS background are not known. Therefore, the current investigation has focused on identification and validation of the gene expression profiles associated with p53 mutant phenotypes in MSS Stage III CRCs. Genomic DNA extracted from 135 formalin-fixed paraffin-embedded tissues, was analyzed for microsatellite instability (MSI) and p53 mutations. Further, mRNA samples extracted from five p53-mutant and five p53-wild-type MSS-CRC snap-frozen tissues were profiled for differential gene expression by Affymetrix Human Genome U133 Plus 2.0 arrays. Differentially expressed genes were further validated by the high-throughput quantitative nuclease protection assay (qNPA), and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and by immunohistochemistry (IHC). Survival rates were estimated by Kaplan-Meier and Cox regression analyses. A higher incidence of p53 mutations was found in MSS (58%) than in MSI (30%) phenotypes. Both univariate (log-rank, P = 0.025) and multivariate (hazard ratio, 2.52; 95% confidence interval, 1.25–5.08) analyses have demonstrated that patients with MSS-p53 mutant phenotypes had poor CRC-specific survival when compared to MSS-p53 wild-type phenotypes. Gene expression analyses identified 84 differentially expressed genes. Of 49 down-regulated genes, LPAR6, PDLIM3, and PLAT, and, of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8 were confirmed by qNPA, qRT-PCR, and IHC platforms. p53 mutations are associated with poor survival of patients with Stage III MSS CRCs and p53-mutant and wild-type phenotypes have distinct gene expression profiles that might be helpful in identifying aggressive subsets

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Does urbanization explain differences in interactions between an insect herbivore and its natural enemies and mutualists?

Urbanization can alter the composition of arthropod communities. However, little is known about how urbanization affects ecological interactions. Using experimental colonies of the black bean aphid Aphis fabae Scopoli reared on Vicia faba L, we asked if patterns of predator-prey, host-parasitoid and ant-aphid mutualisms varied along an urbanization gradient across a large town in southern England. We recorded the presence of naturally occurring predators, parasitoid wasps and mutualistic ants together with aphid abundance. We examined how biotic (green areas and plant richness) and abiotic features (impervious surfaces and distance to town center) affected (1) aphid colony size, (2) the likelihood of finding predators, mutualistic ants and aphid mummies (indicating the presence of parasitoids), and (3) how the interplay among these factors affected patterns of parasitoid attack, predator abundance, mutualistic interactions and aphid abundance. The best model to predict aphid abundance was the number of mutualistic ants attending the colonies. Aphid predators responded negatively to both the proportion of impervious surfaces and to the number of mutualistic ants farming the colonies, and positively to aphid population size, whereas parasitized aphids were found in colonies with higher numbers of aphids and ants. The number of mutualistic ants attending was positively associated with aphid colony size and negatively with the number of aphid predators. Our findings suggest that for insect-natural enemy interactions, urbanization may affect some groups, while not influencing others, and that local effects (mutualists, host plant presence) will also be key determinants of how urban ecological communities are formed

A Program for At-Risk High School Students Informed by Evolutionary Science

Improving the academic performance of at-risk high school students has proven difficult, often calling for an extended day, extended school year, and other expensive measures. Here we report the results of a program for at-risk 9th and 10th graders in Binghamton, New York, called the Regents Academy that takes place during the normal school day and year. The design of the program is informed by the evolutionary dynamics of cooperation and learning, in general and for our species as a unique product of biocultural evolution. Not only did the Regents Academy students outperform their comparison group in a randomized control design, but they performed on a par with the average high school student in Binghamton on state-mandated exams. All students can benefit from the social environment provided for at-risk students at the Regents Academy, which is within the reach of most public school districts

Interaction between contrasting rice genotypes and soil physical conditions induced by hydraulic stresses typical of alternate wetting and drying irrigation of soil

Background and aims: Alternate wetting and drying (AWD) saves water in paddy rice production but could influence soil physical conditions and root growth. This study investigated the interaction between contrasting rice genotypes, soil structure and mechanical impedance influenced by hydraulic stresses typical of AWD. Methods: Contrasting rice genotypes, IR64 and deeper- rooting Black Gora were grown in various soil conditions for 2 weeks. For the AWD treatments the soil was either maintained in a puddled state, equilibrated to −5 kPa (WET), or dried to −50 kPa and then rewetted at thewater potential of −5 kPa (DRY-WET). There was an additional manipulated macropore structure treatment, i.e. the soil was broken into aggregates, packed into cores and equilibrated to −5 kPa (REPACKED). A flooded treatment (puddled soil remained flooded until harvest) was set as a control (FLOODED). Soil bulk density, penetration resistance and X-ray Computed Tomography (CT) derived macropore structure were measured. Total root length, root surface area, root volume, average diameter, and tip number were determined by WinRhizo. Results: AWD induced formation of macropores and slightly increased soil mechanical impedance. The total root length of the AWD and REPACKED treatments were 1.7–2.2 and 3.5–4.2 times greater than that of the FLOODED treatment. There was no significant difference between WET and DRY-WET treatments. The differences between genotypes were minimal. Conclusions: AWD influenced soil physical properties and some root characteristics of rice seedlings, but drying soil initially to −50 kPa versus −5 kPa had no impact. Macropores formed intentionally from repacking caused a large change in root characteristics

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe