46 research outputs found
Mutations in MAP3K1 tilt the balance from SOX9/FGF9 to WNT/β-catenin signaling
In-frame missense and splicing mutations (resulting in a 2 amino acid insertion or a 34 amino acid deletion) dispersed through the MAP3K1 gene tilt the balance from the male to female sex-determining pathway, resulting in 46,XY disorder of sex development. These MAP3K1 mutations mediate this balance by enhancing WNT/β-catenin/FOXL2 expression and β-catenin activity and by reducing SOX9/FGF9/FGFR2/SRY expression. These effects are mediated at multiple levels involving MAP3K1 interaction with protein co-fact
Psychopathological features of irritable bowel syndrome patients with and without functional dyspepsia: a cross sectional study
Background: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) show considerable overlap and are both associated with psychiatric comorbidity. The present study aimed to investigate whether IBS patients with FD show higher levels of psychopathology than those without FD. As a preliminary analysis, it also evaluated the psychopathological differences, if any, between IBS patients featuring the two Rome III-defined FD subtypes, i.e. postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).Methods: Consecutive outpatients (n = 82, F = 67, mean age 41.6 ± 12.7 years) referred to our third level gastroenterological centre, matching the Rome III criteria for IBS and, if present, for concurrent FD, were recruited. They were asked to complete a 90-item self-rating questionnaire, the Symptom Checklist 90 Revised (SCL-90-R), in order to assess the psychological status. Comparisons between groups were carried out using the non-parametric Mann-Whitney U test.Results: Patients with IBS only were 56 (68.3%, F = 43, mean age 41.6 ± 13.3 years) and patients with both IBS and FD were 26 (31.7%, F = 24, mean age 41.8 ± 11.5 years), 17 of whom had PDS and 9 EPS. Patients with both IBS and FD scored significantly higher on the SCL-90-R GSI and on eight out of the nine subscales than patients with IBS only (P ranging from 0.000 to 0.03). No difference was found between IBS patients with PDS and IBS patients with EPS (P ranging from 0.07 to 0.97), but this result has to be considered provisional, given the small sample size of the two subgroups.Conclusions: IBS-FD overlap is associated with an increased severity of psychopathological features. This finding suggests that a substantial subset of patients of a third level gastroenterological centre with both IBS and FD may benefit from psychological assessment and treatment. © 2011 Piacentino et al; licensee BioMed Central Ltd
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy
We measure the energy emitted by extensive air showers in the form of radio
emission in the frequency range from 30 to 80 MHz. Exploiting the accurate
energy scale of the Pierre Auger Observatory, we obtain a radiation energy of
15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV
arriving perpendicularly to a geomagnetic field of 0.24 G, scaling
quadratically with the cosmic-ray energy. A comparison with predictions from
state-of-the-art first-principle calculations shows agreement with our
measurement. The radiation energy provides direct access to the calorimetric
energy in the electromagnetic cascade of extensive air showers. Comparison with
our result thus allows the direct calibration of any cosmic-ray radio detector
against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI.
Supplemental material in the ancillary file
Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice
Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice