Commissural axon guidance in the developing spinal cord: from Cajal to the present day.

During neuronal development, the formation of neural circuits requires developing axons to traverse a diverse cellular and molecular environment to establish synaptic contacts with the appropriate postsynaptic partners. Essential to this process is the ability of developing axons to navigate guidance molecules presented by specialized populations of cells. These cells partition the distance traveled by growing axons into shorter intervals by serving as intermediate targets, orchestrating the arrival and departure of axons by providing attractive and repulsive guidance cues. The floor plate in the central nervous system (CNS) is a critical intermediate target during neuronal development, required for the extension of commissural axons across the ventral midline. In this review, we begin by giving a historical overview of the ventral commissure and the evolutionary purpose of decussation. We then review the axon guidance studies that have revealed a diverse assortment of midline guidance cues, as well as genetic and molecular regulatory mechanisms required for coordinating the commissural axon response to these cues. Finally, we examine the contribution of dysfunctional axon guidance to neurological diseases

Molecular Genetics of T Cell Development

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment

Assessing Significance in High-Throughput Experiments by Sequential Goodness of Fit and q-Value Estimation

We developed a new multiple hypothesis testing adjustment called SGoF+ implemented as a sequential goodness of fit metatest which is a modification of a previous algorithm, SGoF, taking advantage of the information of the distribution of p-values in order to fix the rejection region. The new method uses a discriminant rule based on the maximum distance between the uniform distribution of p-values and the observed one, to set the null for a binomial test. This new approach shows a better power/pFDR ratio than SGoF. In fact SGoF+ automatically sets the threshold leading to the maximum power and the minimum false non-discovery rate inside the SGoF' family of algorithms. Additionally, we suggest combining the information provided by SGoF+ with the estimate of the FDR that has been committed when rejecting a given set of nulls. We study different positive false discovery rate, pFDR, estimation methods to combine q-value estimates jointly with the information provided by the SGoF+ method. Simulations suggest that the combination of SGoF+ metatest with the q-value information is an interesting strategy to deal with multiple testing issues. These techniques are provided in the latest version of the SGoF+ software freely available at http://webs.uvigo.es/acraaj/SGoF.htm

Experimental realisation of Shor's quantum factoring algorithm using qubit recycling

Quantum computational algorithms exploit quantum mechanics to solve problems exponentially faster than the best classical algorithms. Shor's quantum algorithm for fast number factoring is a key example and the prime motivator in the international effort to realise a quantum computer. However, due to the substantial resource requirement, to date, there have been only four small-scale demonstrations. Here we address this resource demand and demonstrate a scalable version of Shor's algorithm in which the n qubit control register is replaced by a single qubit that is recycled n times: the total number of qubits is one third of that required in the standard protocol. Encoding the work register in higher-dimensional states, we implement a two-photon compiled algorithm to factor N=21. The algorithmic output is distinguishable from noise, in contrast to previous demonstrations. These results point to larger-scale implementations of Shor's algorithm by harnessing scalable resource reductions applicable to all physical architectures.Comment: 7 pages, 3 figure

Hydrodynamics of a 5D Einstein-dilaton black hole solution and the corresponding BPS state

We apply the potential reconstruction approach to generate a series of asymptotically AdS (aAdS) black hole solutions, with a self-interacting bulk scalar field. Based on the method, we reproduce the pure AdS solution as a consistency check and we also generate a simple analytic 5D black hole solution. We then study various aspects of this solution, such as temperature, entropy density and conserved charges. Furthermore, we study the hydrodynamics of this black hole solution in the framework of fluid/gravity duality, e.g. the ratio of the shear viscosity to the entropy density. In a degenerate case of the 5D black hole solution, we find that the c function decreases monotonically from UV to IR as expected. Finally, we investigate the stability of the degenerate solution by studying the bosonic functional energy of the gravity and the Witten-Nester energy $E_{WN}$. We confirm that the degenerate solution is a BPS domain wall solution. The corresponding superpotential and the solution of the killing spinor equation are found explicitly.Comment: V2: 23 pages, no figure, minor changes, typos corrected, new references and comments added, version accepted by JHE

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

Characterization of mercury bioremediation by transgenic bacteria expressing metallothionein and polyphosphate kinase

<p>Abstract</p> <p>Background</p> <p>The use of transgenic bacteria has been proposed as a suitable alternative for mercury remediation. Ideally, mercury would be sequestered by metal-scavenging agents inside transgenic bacteria for subsequent retrieval. So far, this approach has produced limited protection and accumulation. We report here the development of a transgenic system that effectively expresses metallothionein (<it>mt-1</it>) and polyphosphate kinase (<it>ppk</it>) genes in bacteria in order to provide high mercury resistance and accumulation.</p> <p>Results</p> <p>In this study, bacterial transformation with transcriptional and translational enhanced vectors designed for the expression of metallothionein and polyphosphate kinase provided high transgene transcript levels independent of the gene being expressed. Expression of polyphosphate kinase and metallothionein in transgenic bacteria provided high resistance to mercury, up to 80 μM and 120 μM, respectively. Here we show for the first time that metallothionein can be efficiently expressed in bacteria without being fused to a carrier protein to enhance mercury bioremediation. Cold vapor atomic absorption spectrometry analyzes revealed that the <it>mt-1 </it>transgenic bacteria accumulated up to 100.2 ± 17.6 μM of mercury from media containing 120 μM Hg. The extent of mercury remediation was such that the contaminated media remediated by the <it>mt-1 </it>transgenic bacteria supported the growth of untransformed bacteria. Cell aggregation, precipitation and color changes were visually observed in <it>mt-1 </it>and <it>ppk </it>transgenic bacteria when these cells were grown in high mercury concentrations.</p> <p>Conclusion</p> <p>The transgenic bacterial system described in this study presents a viable technology for mercury bioremediation from liquid matrices because it provides high mercury resistance and accumulation while inhibiting elemental mercury volatilization. This is the first report that shows that metallothionein expression provides mercury resistance and accumulation in recombinant bacteria. The high accumulation of mercury in the transgenic cells could present the possibility of retrieving the accumulated mercury for further industrial applications.</p

Environmental and Parental Influences on Offspring Health and Growth in Great Tits (Parus major)

PMCID: PMC3728352This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Direct Integration and Non-Perturbative Effects in Matrix Models

We show how direct integration can be used to solve the closed amplitudes of multi-cut matrix models with polynomial potentials. In the case of the cubic matrix model, we give explicit expressions for the ring of non-holomorphic modular objects that are needed to express all closed matrix model amplitudes. This allows us to integrate the holomorphic anomaly equation up to holomorphic modular terms that we fix by the gap condition up to genus four. There is an one-dimensional submanifold of the moduli space in which the spectral curve becomes the Seiberg--Witten curve and the ring reduces to the non-holomorphic modular ring of the group $\Gamma(2)$. On that submanifold, the gap conditions completely fix the holomorphic ambiguity and the model can be solved explicitly to very high genus. We use these results to make precision tests of the connection between the large order behavior of the 1/N expansion and non-perturbative effects due to instantons. Finally, we argue that a full understanding of the large genus asymptotics in the multi-cut case requires a new class of non-perturbative sectors in the matrix model.Comment: 51 pages, 8 figure

The a-theorem and conformal symmetry breaking in holographic RG flows

We study holographic models describing an RG flow between two fixed points driven by a relevant scalar operator. We show how to introduce a spurion field to restore Weyl invariance and compute the anomalous contribution to the generating functional in even dimensional theories. We find that the coefficient of the anomalous term is proportional to the difference of the conformal anomalies of the UV and IR fixed points, as expected from anomaly matching arguments in field theory. For any even dimensions the coefficient is positive as implied by the holographic a-theorem. For flows corresponding to spontaneous breaking of conformal invariance, we also compute the two-point functions of the energy-momentum tensor and the scalar operator and identify the dilaton mode. Surprisingly we find that in the simplest models with just one scalar field there is no dilaton pole in the two-point function of the scalar operator but a stronger singularity. We discuss the possible implications.Comment: 50 pages. v2: minor changes, added references, extended discussion. v3: we have clarified some of the calculations and assumptions, results unchanged. v4: published version in JHE