Substance P regulates puberty onset and fertility in the female mouse

Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1-/- mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice. Copyright © 2015 by the Endocrine Society

Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems

Recent Progress on Anomalous X-ray Pulsars

I review recent observational progress on Anomalous X-ray Pulsars, with an emphasis on timing, variability, and spectra. Highlighted results include the recent timing and flux stabilization of the notoriously unstable AXP 1E 1048.1-5937, the remarkable glitches seen in two AXPs, the newly recognized variety of AXP variability types, including outbursts, bursts, flares, and pulse profile changes, as well as recent discoveries regarding AXP spectra, including their surprising hard X-ray and far-infrared emission, as well as the pulsed radio emission seen in one source. Much has been learned about these enigmatic objects over the past few years, with the pace of discoveries remaining steady. However additional work on both observational and theoretical fronts is needed before we have a comprehensive understanding of AXPs and their place in the zoo of manifestations of young neutron stars.Comment: 10 pages, 6 figures; to appear in proceedings of the conference "Isolated Neutron Stars: From the Interior to the Surface" eds. S. Zane, R. Turolla, D. Page; Astrophysics & Space Science in pres

QED can explain the non-thermal emission from SGRs and AXPs : Variability

Owing to effects arising from quantum electrodynamics (QED), magnetohydrodynamical fast modes of sufficient strength will break down to form electron-positron pairs while traversing the magnetospheres of strongly magnetised neutron stars. The bulk of the energy of the fast mode fuels the development of an electron-positron fireball. However, a small, but potentially observable, fraction of the energy ($\sim 10^{33}$ ergs) can generate a non-thermal distribution of electrons and positrons far from the star. This paper examines the cooling and radiative output of these particles. Small-scale waves may produce only the non-thermal emission. The properties of this non-thermal emission in the absence of a fireball match those of the quiescent, non-thermal radiation recently observed non-thermal emission from several anomalous X-ray pulsars and soft-gamma repeaters. Initial estimates of the emission as a function of angle indicate that the non-thermal emission should be beamed and therefore one would expect this emission to be pulsed as well. According to this model the pulsation of the non-thermal emission should be between 90 and 180 degrees out of phase from the thermal emission from the stellar surface.Comment: 7 pages, 5 figures, to appear in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 2006, London), eds. D. Page, R. Turolla, & S. Zane, Astrophysics & Space Scienc

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis [version 1; referees: 2 approved]

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions.  Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome. Stage 1 report: http://dx.doi.org/10.12688/wellcomeopenres.13828.

Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions. Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome

The Anatomy of a Magnetar: XMM Monitoring of the Transient Anomalous X-ray Pulsar XTE J1810-197

We present the latest results from a multi-epoch timing and spectral study of the Transient Anomalous X-ray Pulsar XTE J1810-197. We have acquired seven observations of this pulsar with the Newton X-ray Multi-mirror Mission (XMM-Newton) over the course of two and a half years, to follow the spectral evolution as the source fades from outburst. The spectrum is arguably best characterized by a two-temperature blackbody whose luminosities are decreasing exponentially with tau_1 = 870 days and tau_2 = 280 days, respectively. The temperatures of these components are currently cooling at a rate of 22% per year from a nearly constant value recorded at earlier epochs of kT_1 = 0.25 keV and kT_2 = 0.67 keV, respectively. The new data show that the temperature T_1 and luminosity of that component have nearly returned to their historic quiescent levels and that its pulsed fraction, which has steadily decreased with time, is now consistent with the previous lack of detected pulsations in quiescence. We also summarize the detections of radio emission from XTE J1810-197, the first confirmed for any AXP. We consider possible models for the emission geometry and mechanisms of XTE J1810-197.Comment: 8 pages, 7 figures, 1 table, latex. To appear in the proceedings of "Isolated Neutron Stars", Astrophysics & Space Science, in pres

The first multi-wavelength campaign of AXP 4U 0142+61 from radio to hard X-rays

For the first time a quasi-simultaneous multi-wavelength campaign has been performed on an Anomalous X-ray Pulsar from the radio to the hard X-ray band. 4U 0142+61 was an INTEGRAL target for 1 Ms in July 2005. During these observations it was also observed in the X-ray band with Swift and RXTE, in the optical and NIR with Gemini North and in the radio with the WSRT. In this paper we present the source-energy distribution. The spectral results obtained in the individual wave bands do not connect smoothly; apparently components of different origin contribute to the total spectrum. Remarkable is that the INTEGRAL hard X-ray spectrum (power-law index 0.79 +/- 0.10) is now measured up to an energy of ~230 keV with no indication of a spectral break. Extrapolation of the INTEGRAL power-law spectrum to lower energies passes orders of magnitude underneath the NIR and optical fluxes, as well as the low ~30 microJy (2 sigma) upper limit in the radio band.Comment: 6 pages, 1 figure. To be published in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 24-28, 2006, London, UK), eds. S. Zane, R. Turolla and D. Pag

Vortex dynamics and states of artificially layered superconducting films with correlated defects

Linear resistances and $IV$-characteristics have been measured over a wide range in the parameter space of the mixed phase of multilayered a-TaGe/Ge films. Three films with varying interlayer coupling and correlated defects oriented at an angle $\approx 25$ from the film normal were investigated. Experimental data were analyzed within vortex glass models and a second order phase transition from a resistive vortex liquid to a pinned glass phase. Various vortex phases including changes from three to two dimensional behavior depending on anisotropy have been identified. Careful analysis of $IV$-characteristics in the glass phases revealed a distinctive $T$ and $H$-dependence of the glass exponent $\mu$. The vortex dynamics in the Bose-glass phase does not follow the predicted behavior for excitations of vortex kinks or loops.Comment: 16 pages, 10 figures, 3 table

Functional organisation for verb generation in children with developmental language disorder

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10–15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance.</p