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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Abnormal AVE migration and cellular geometry in mutants with disrupted PCP signalling.

<p>(A) Rosette density (number of rosettes divided by total VE cell number) at different wild-type stages (“pre-AVE”: before AVE induction, <i>n</i> = 9; “distal”: AVE at distal tip before migration, <i>n</i> = 5; “migrating”: AVE migrating, <i>n</i> = 5; and “anterior”: AVE finished proximal migration and moving laterally, <i>n</i> = 4) and in <i>ROSA26^Lyn-Celsr1</i> mutants (<i>n</i> = 7) with disrupted PCP signalling. There is a significant reduction in rosette density in <i>ROSA26^Lyn-Celsr1</i> mutants compared with “migrating” and “anterior” embryos. (A′) The same data as in (A), but depicted as mean number of rosettes per embryo (blue line), and mean number of VE cells per embryo (green bars) at the various stages. <i>ROSA26^Lyn-Celsr1</i> mutants have a comparable number of VE cells to stage matched “anterior” embryos, but show significantly fewer rosettes, leading to the reduced rosette density. (B, B′) En face and profile view of a representative “anterior” embryo, illustrating stereotypical ordered migration of AVE cells. The AVE is marked with a dotted line in (B′) and shows a single group of cells that does not extend more than half-way around the side of the embryo. (C, C′) En face and profile views of an equivalent stage <i>ROSA26^Lyn-Celsr1</i> mutant, showing abnormal AVE migration. AVE cells appear to have broken into several groups (outlined with dotted lines in (C′)) and spread much more broadly within the Epi-VE and even into the ExE-VE. Cell outlines in the embryos in (B) and (C) were visualised by staining for ZO-1 (magenta), and AVE cells by the expression of Hex-GFP (green). Nuclei are visualised with DAPI (dim grey). (D) Comparison of mean polygon number in the Epi-VE and ExE-VE of “anterior” embryos (<i>n</i> = 480 Epi-VE and 409 ExE-VE cells from three embryos) and equivalent stage <i>ROSA26^Lyn-Celsr1</i> mutants (<i>n</i> = 563 Epi-VE and 546 ExE-VE cells from four embryos). As in wild-type “anterior” embryos, the mean polygon number in the Epi-VE of <i>ROSA26^Lyn-Celsr1</i> mutants is significantly lower than that in the ExE-VE. (D′) The same polygon number data grouped according to the VE region. Though the mean polygon number in the ExE-VE is comparable for “anterior” and <i>ROSA26^Lyn-Celsr1</i> embryos, in the Epi-VE it is significantly lower in <i>ROSA26^Lyn-Celsr1</i> embryos, suggestive of increased disequilibrium in cell packing. The scale bar represents 50 µm. <i>p</i> values shown on the graphs were determined using Student's <i>t</i> test.</p

Modelling AVE migration.

<p>(A) Two-dimensional representation of force directions in the vertex model. At each vertex, tension forces act along the edges connecting neighbouring vertices, with unit direction vectors Tc (clockwise) and Ta (anti-clockwise). Pressure forces act normally at the vertex, bisecting the internal angle Φ, with unit direction vector P. (B) On the ellipsoid surface, forces act tangentially. To calculate the forces on a given vertex, its neighbours are projected onto the tangential plane. Unit direction vectors are then determined on this plane. (C) Each cell in the vertex model is 3-D, with associated height and volume. Forces act on the apical surface and depend on quantities such as surface area, edge lengths, height, and perimeter. (D) An initial cell configuration on the ellipsoid surface. Cells highlighted in green are the AVE. The polygon mesh represents the apical surfaces of cells of the VE. See <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001256#pbio.1001256.s005" target="_blank">Text S1</a> for further details. (E) Comparison of mean polygon number in the ExE-VE and Epi-VE early and late in simulation (roughly equivalent to “distal” and “anterior” embryos). As in wild-type embryos, there is a significant reduction in mean polygon number in the Epi-VE late in simulation as compared to early in simulation (Students <i>t</i> test, <i>p</i><0.001). (F) Frequencies of polygon numbers early and late in simulations. Late in simulations, there is a significant difference in the distribution in the Epi-VE as compared to the ExE-VE, with an increase in four-sided cells and a decrease in six-sided cells (Kolmogorov-Smirnov test, <i>p</i><0.001). There is no significant difference between the distribution in the ExE-VE and Epi-VE early in simulations. Early in simulations: <i>n</i> = 458 Epi-VE and 507 ExE-VE cells from five simulations. Late in simulations: <i>n</i> = 656 Epi-VE and 744 ExE-VE cells from five simulations.</p

Quantitative characterisation of rosettes.

<p>(A) Rosette density (number of rosettes divided by total VE cell number) at different wild-type stages (“pre-AVE”: before AVE induction, <i>n</i> = 9; “distal”: AVE at distal tip before migration, <i>n</i> = 5; “migrating”: AVE migrating, <i>n</i> = 5; and “anterior”: AVE finished proximal migration and moving laterally, <i>n</i> = 4) and in the AVE arrest mutants <i>Nodal^Δ600/lacZ</i> (<i>n</i> = 5) and <i>Cripto</i>^−/− (<i>n</i> = 9). There is a significant increase in rosettes' density in “migrating” embryos as compared to “distal” embryos. The AVE arrest mutants <i>Nodal^Δ600/lacZ</i> and <i>Cripto</i>^−/− show significantly reduced rosette density compared to “migrating” and “anterior” embryos, suggestive of a direct link between rosettes and AVE migration. (A′) The same data as in (A), but depicted as mean number of rosettes per embryo (blue line), and mean number of VE cells per embryo (green bars) at the various stages. “Migrating” embryos have a comparable number of VE cells to “distal” embryos, but have significantly more rosettes, leading to an increase in rosette density. AVE arrest mutants have similar average VE cell numbers to stage matched “anterior” embryos, but show significantly fewer rosettes, leading to the reduced rosette density. (B) Polar plot showing distribution of rosettes in the VE of embryos. Migrating AVE cells were used to determine the anterior of embryos. Rosettes are localised predominantly to the Epi-VE. Within the Epi-VE, rosettes appear to be uniformly distributed with respect to the anterior-posterior axis (<i>n</i> = 39 rosettes from 7 embryos). <i>p</i> values shown on the graphs were determined using Student's <i>t</i> test.</p

The VE contains multi-cellular rosettes.

<p>(A) A ZO-1 stained embryo in which cells are coloured in to illustrate the presence of junctions where three, four, or five cells meet at a point. (B) Rosettes are formed by five or more cells meeting at a point. A variety of rosettes are shown, including two that share some cells (last panel).</p

Education in Twins and Their Parents Across Birth Cohorts Over 100 years : An Individual-Level Pooled Analysis of 42-Twin Cohorts

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.Peer reviewe