Identification of a novelABCD1 mutation in a family with Adrenoleukodistrophy

X-linked adrenoleukodistrophy (X-ALD) is the most common peroxisomal disorder. The disease is caused by muta>ons in the ABCD1 gene that encodes the peroxisomal membrane protein ALDP which is involved in the transmembrane transport of very long-chain faGy acids (VLCFA; >22). A defect in ALDP results in elevated levels of VLCFA in plasma and >ssues. The clinical spectrum in males with X-ALD ranges from isolated adrenocor>cal insufficiency and slowly progressive myelopathy to devasta>ng cerebral demyelina>on. The majority of heterozygous females will develop symptoms by the age of 60 years. We describe a family with six members carrying a novel heterozygous muta>on IVS4+2T>A (c.1393+2T>A) of the ABCD1 gene highligh>ng the wide range of phenotypic manifesta>ons of ALD

Detection of enteric viral and bacterial pathogens associated with paediatric diarrhoea in Goroka, Papua New Guinea

Objectives: The aim of this study was to investigate the viral and bacterial causes of acute watery diarrhoea in hospitalized children in Papua New Guinea. Methods: A retrospective analysis was conducted on stool samples collected from 199 children (age < 5 years) admitted to the paediatric ward of Goroka General Hospital from August 2009 through November 2010. A large range of viral and bacterial enteric pathogens were targeted using real-time PCR/RT-PCR assays. Results: Young children were much more likely to be admitted with acute gastroenteritis, with 62.8% of patients aged <1 year and 88.4% aged <2 years. An enteric pathogen was detected in 69.8% (n = 138) of patients. The most commonly detected pathogens were Shigella spp (26.6%), rotavirus (25.6%), adenovirus types 40/41 (11.6%), enterotoxigenic Escherichia coli (11.1%), enteropathogenic E. coli (8.5%), norovirus G2 (6.0%), and Campylobacter spp (4.0%). Norovirus G1, sapovirus, and Salmonella spp were also detected, but below our statistical limit of detection. Vibrio cholerae and astrovirus were not detected in any patients. Mixed infections were detected in 22.1% of patients, with Shigella and rotavirus most commonly detected in co-infections with other pathogens. Conclusions: This study demonstrates that Shigella and rotavirus are the major pathogens associated with acute paediatric gastroenteritis in this setting

Recurrent NF1 gene variants and their genotype/phenotype correlations in patients with Neurofibromatosis type I

Neurofibromatosis type I, a genetic condition due to pathogenic variants in the NF1 gene, is burdened by a high rate of complications, including neoplasms, which increase morbidity and mortality for the disease. We retrospectively re-evaluated the NF1 gene variants found in the period 2000\u20132019 and we studied for genotype/phenotype correlations of disease complications and neoplasms 34 variants, which were shared by at least two unrelated families (range 2\u201311) for a total 141 of probands and 21 relatives affected by Neurofibromatosis type I. Recurrent variants could be ascribed to the most common mutational mechanisms (C to T transition, microsatellite slippage, non-homologous recombination). In genotype/phenotype correlations, the variants p.Arg440*, p.Tyr489Cys, and p.Arg1947*, together with the gross gene deletions, displayed the highest rates of complications. When considering neoplasms, carriers of variants falling in the extradomain region at the 5\u2032 end of NF1 had a lower age-related cancer frequency than the rest of the gene sequence, showing a borderline significance (p&nbsp;=&nbsp;0.045), which was not conserved after correction with covariates. We conclude that (1) hotspots in NF1 occur via different mutational mechanisms, (2) several variants are associated with high rates of complications and cancers, and (3) there is an initial evidence toward a lower cancer risk for carriers of variants in the 5\u2032 end of the NF1 gene although not significant at the multivariate analysis

The AGILE Mission

AGILE is an Italian Space Agency mission dedicated to observing the gamma-ray Universe. The AGILE's very innovative instrumentation for the first time combines a gamma-ray imager (sensitive in the energy range 30 MeV-50 GeV), a hard X-ray imager (sensitive in the range 18-60 keV), a calorimeter (sensitive in the range 350 keV-100 MeV), and an anticoincidence system. AGILE was successfully launched on 2007 April 23 from the Indian base of Sriharikota and was inserted in an equatorial orbit with very low particle background. Aims. AGILE provides crucial data for the study of active galactic nuclei, gamma-ray bursts, pulsars, unidentified gamma-ray sources, galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. Methods. An optimal sky angular positioning (reaching 0.1 degrees in gamma- rays and 1-2 arcmin in hard X-rays) and very large fields of view (2.5 sr and 1 sr, respectively) are obtained by the use of Silicon detectors integrated in a very compact instrument. Results. AGILE surveyed the gamma- ray sky and detected many Galactic and extragalactic sources during the first months of observations. Particular emphasis is given to multifrequency observation programs of extragalactic and galactic objects. Conclusions. AGILE is a successful high-energy gamma-ray mission that reached its nominal scientific performance. The AGILE Cycle-1 pointing program started on 2007 December 1, and is open to the international community through a Guest Observer Program

The time course of auditory and language-specific mechanisms in compensation for sibilant assimilation

Models of spoken-word recognition differ on whether compensation for assimilation is language-specific or depends on general auditory processing. English and French participants were taught words that began or ended with the sibilants /s/ and /∫/. Both languages exhibit some assimilation in sibilant sequences (e.g., /s/ becomes like [∫] in dress shop and classe chargée), but they differ in the strength and predominance of anticipatory versus carryover assimilation. After training, participants were presented with novel words embedded in sentences, some of which contained an assimilatory context either preceding or following. A continuum of target sounds ranging from [s] to [∫] was spliced into the novel words, representing a range of possible assimilation strengths. Listeners' perceptions were examined using a visual-world eyetracking paradigm in which the listener clicked on pictures matching the novel words. We found two distinct language-general context effects: a contrastive effect when the assimilating context preceded the target, and flattening of the sibilant categorization function (increased ambiguity) when the assimilating context followed. Furthermore, we found that English but not French listeners were able to resolve the ambiguity created by the following assimilatory context, consistent with their greater experience with assimilation in this context. The combination of these mechanisms allows listeners to deal flexibly with variability in speech forms