| 1. |
- Nava, C, et al.
(författare)
-
Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE.
- 2012
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- The striking excess of affected males in autism spectrum disorders (ASD) suggests that genes located on chromosome X contribute to the etiology of these disorders. To identify new X-linked genes associated with ASD, we analyzed the entire chromosome X exome by next-generation sequencing in 12 unrelated families with two affected males. Thirty-six possibly deleterious variants in 33 candidate genes were found, including PHF8 and HUWE1, previously implicated in intellectual disability (ID). A nonsense mutation in TMLHE, which encodes the ɛ-N-trimethyllysine hydroxylase catalyzing the first step of carnitine biosynthesis, was identified in two brothers with autism and ID. By screening the TMLHE coding sequence in 501 male patients with ASD, we identified two additional missense substitutions not found in controls and not reported in databases. Functional analyses confirmed that the mutations were associated with a loss-of-function and led to an increase in trimethyllysine, the precursor of carnitine biosynthesis, in the plasma of patients. This study supports the hypothesis that rare variants on the X chromosome are involved in the etiology of ASD and contribute to the sex-ratio disequilibrium.
|
|
| 2. |
- Longo, F., et al.
(författare)
-
Upper limits on the high-energy emission from gamma-ray bursts observed by AGILE-GRID
- 2012
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. A95-
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The detection and the characterization of the highenergy emission component from individual gamma-ray bursts (GRBs) is one of the key science objectives of the currently operating gamma-ray satellite AGILE, launched in April 2007. In its first two years of operation AGILE detected three GRBs with photons of energy larger than 30 MeV. One more GRB was detected in AGILE third operation year, while operating in spinning mode. Aims. For the 64 other GRBs localized during the period July 2007 to October 2009 in the field of view of the AGILE Gamma-Ray Imaging Detector (GRID), but not detected by this instrument, we estimate the count and flux upper limits on the GRB high energy emission in the AGILE-GRID energy band (30 MeV-3 GeV). Methods. To calculate the count upper limits, we adopted a Bayesian approach. The flux upper limits are derived using several assumptions on the high-energy spectral behavior. For 28 GRBs with available prompt spectral information, a flux upper limit and the comparison with the expected flux estimated from spectral extrapolation of the Band spectrum to the 30 MeV-3 GeV band are provided. Moreover, upper limits on the flux under the assumption of an extra power law component dominating the 30 MeV-3 GeV band are calculated for all GRBs and considering four different values for the spectral photon index. Finally, we performed a likelihood upper limit on the possible delayed emission up to 1 h after the GRB. Results. The estimated flux upper limits range between 1 × 10 -4 and ∼2 × 10 -2 photons cm -2 s -1 and generally lie above the flux estimated from the extrapolation of the prompt emission in the 30 MeV-3 GeV band. A notable case is GRB 080721, where the AGILE-GRID upper limit suggests a steeper spectral index or the presence of a cut-off in the high energy part of the Band prompt spectrum. The four GRBs detected by AGILE-GRID show high-energy (30 MeV-3 GeV) to low-energy (1 keV-10 MeV) fluence ratios similar to those estimated in this paper for the 64 GRBs without GRID detection, favoring the possibility that AGILE-GRID detected only high-fluence, hard GRBs. From the flux upper limits derived in this work we put some constraint on high-energy radiation from the afterglow emission and from synchrotron self Compton emission in internal shocks.
|
|
| 3. |
|
|
