Ascending aortic remodelling in Fabry disease after long-term enzyme replacement therapy.

Previous cross-sectional studies reported a high prevalence of ascending aorta dilations/aneurysms in male adults with Fabry disease, independently of cardiovascular risk factors. To characterise the remodelling of the ascending aorta in classic Fabry disease under long-term enzyme replacement therapy. Diameter of the ascending aorta was measured with magnetic resonance imaging at the sino-tubular junction (STJ), and proximal (pAsAo), and distal ascending aorta (dAsAo) at baseline, and after 5 and 10 years of enzyme replacement therapy in 15 adult Fabry patients (10 males; 5 females). Over a mean follow-up of 9.5 years, the annual expansion rates measured in 10 males with Fabry disease were 0.41 ± 0.16, 0.36 ± 0.25 and 0.41 ± 0.26 mm/y at the STJ, pAsAo and dAsAo, respectively. Expansion rate at the pAsAo level in male patients was significantly higher than the expected expansion projected from theoretical normal values: 0.36 ± 0.25 vs 0.13 ± 0.05, p = 0.017. In 5 females, the annual expansion rates at the STJ, pAsAo and dAsAo were 0.14 ± 0.11, 0.21 ± 0.18 and 0.26 ± 0.24 mm/y, respectively. There was no significant difference from the projected normal expansion rate at the level of the pAsAo: 0.21 ± 0.18 vs 0.13 ± 0.04, p = 0.39. Our data suggest that the remodelling of the ascending aorta is more pronounced in male patients with Fabry disease under long-term enzyme replacement therapy compared with the progression observed in a large population study

TomograPy: A Fast, Instrument-Independent, Solar Tomography Software

Solar tomography has progressed rapidly in recent years thanks to the development of robust algorithms and the availability of more powerful computers. It can today provide crucial insights in solving issues related to the line-of-sight integration present in the data of solar imagers and coronagraphs. However, there remain challenges such as the increase of the available volume of data, the handling of the temporal evolution of the observed structures, and the heterogeneity of the data in multi-spacecraft studies. We present a generic software package that can perform fast tomographic inversions that scales linearly with the number of measurements, linearly with the length of the reconstruction cube (and not the number of voxels) and linearly with the number of cores and can use data from different sources and with a variety of physical models: TomograPy (http://nbarbey.github.com/TomograPy/), an open-source software freely available on the Python Package Index. For performance, TomograPy uses a parallelized-projection algorithm. It relies on the World Coordinate System standard to manage various data sources. A variety of inversion algorithms are provided to perform the tomographic-map estimation. A test suite is provided along with the code to ensure software quality. Since it makes use of the Siddon algorithm it is restricted to rectangular parallelepiped voxels but the spherical geometry of the corona can be handled through proper use of priors. We describe the main features of the code and show three practical examples of multi-spacecraft tomographic inversions using STEREO/EUVI and STEREO/COR1 data. Static and smoothly varying temporal evolution models are presented.Comment: 21 pages, 6 figures, 5 table

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly

We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debr,-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A > G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. Conclusion: Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period.Peer reviewe

The effectiveness of emergency obstetric referral interventions in developing country settings : a systematic review

Peer reviewedPublisher PD

WearCam: A head mounted wireless camera for monitoring gaze attention and for the diagnosis of developmental disorders in young children

Autism covers a large spectrum of disorders that affect the individual’s way of interacting socially and is often revealed by the individual’s lack of interest in gazing at human faces. Currently Autism is diagnosed in children no younger than 2 years old. This paper presents a new monitoring device, the WearCam, to help forming a diagnosis of this neurodevelopmental disorder at an earlier age than currently possible. The WearCam consists of a wireless camera located on the forefront of the child. The WearCam collects videos from the viewpoint of the child’s head. Color detection, face detection and gaze detection are run on the data in order to locate the approximate gaze direction of the child and determine where her attention is drawn to (persons, objects, etc.). We report on early tests of the camera within normally developing children. Firstly the technical characteristics of the current prototype of the WearCam will be described. Afterwards the type of data collected with this device with young children will be shown

Fabry Disease Caused by the GLA p.Phe113Leu (p.F113L) Variant: Natural History in Males

Background, aims and methods: The α-galactosidase gene (GLA) c.337T>C/p.Phe113Leu variant was originally described in patients with late-onset cardiac forms of Fabry disease (FD), who had residual α-galactosidase activity. It has since emerged as the most commonly reported GLA variant in Portuguese subjects diagnosed with FD but is also prevalent in the Italian population, where two boys carrying the GLA Leu113 allele were identified in a large-scale newborn screening program, the variant allele segregating in both cases with the same surrounding haplotype. To further delineate the genotype-phenotype correlations of this GLA variant, we have reviewed the natural history and clinical phenotypes of 11 symptomatic Portuguese males, from 10 unrelated families originating from several different areas in mainland Portugal and Madeira Island, who were diagnosed with FD associated with the GLA Leu113 allele in a diversity of clinical and screening settings. Nine of the patients were the probands of their respective families. To test whether the GLA Leu113 allele inherited by the 10 Portuguese and the two Italian families resulted from independent mutational events, we have additionally performed a haplotype analysis with 5 highly polymorphic, closely linked microsatellite markers surrounding the GLA gene. Results and conclusions: Hemizygosity for the GLA Leu113 variant allele is associated with a late-onset form of FD, invariably presenting with severe cardiac involvement. Clinically relevant cerebrovascular and kidney involvement may also occur in some patients but the pathogenic relationship between the incomplete α-galactosidase deficiency and the risks of stroke and of chronic kidney disease is not straightforward. The observation that the Leu113 allele segregated within the same GLA microsatellite haplotype in both the Portuguese and Italian families suggests its inheritance from a common ancestor.info:eu-repo/semantics/publishedVersio

Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses

<p>Abstract</p> <p>Background</p> <p>In circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development.</p> <p>Results</p> <p>We have developed an epitope-based method to identify the antigenic drift of influenza A utilizing the conformation changes on epitopes. A changed epitope, an antigenic site on HA with an accumulated conformation change to escape from neutralizing antibody, can be considered as a "key feature" for representing the antigenic drift. According to hemagglutination inhibition (HI) assays and HA/antibody complex structures, we statistically measured the conformation change of an epitope by considering the number of critical position mutations with high genetic diversity and antigenic scores. Experimental results show that two critical position mutations can induce the conformation change of an epitope to escape from the antibody recognition. Among five epitopes of HA, epitopes A and B, which are near to the receptor binding site, play a key role for neutralizing antibodies. In addition, two changed epitopes often drive the antigenic drift and can explain the selections of 24 WHO vaccine strains.</p> <p>Conclusions</p> <p>Our method is able to quantify the changed epitopes on HA for predicting the antigenic variants and providing biological insights to the vaccine updates. We believe that our method is robust and useful for studying influenza virus evolution and vaccine development.</p

Magnetic and Electrical Properties of Ordered 112-type Perovskite LnBaCoMnO5+\delta (Ln = Nd, Eu)

Investigation of the oxygen-deficient 112-type ordered oxides of the type LnBaCoMnO5+\delta (Ln = Nd, Eu) evidences certain unusual magnetic behavior at low temperatures, compared to the LnBaCo2O5+\delta cobaltites. One observes that the substitution of manganese for cobalt suppresses the ferromagnetic state and induces strong antiferromagnetic interactions. Importantly, NdBaCoMnO5.9 depicts a clear paramagnetic to antiferromagnetic type transition around 220 K, whereas for EuBaCoMnO5.7 one observes an unusual magnetic behavior below 177 K which consists of ferromagnetic regions embedded in an antiferromagnetic matrix. The existence of two sorts of crystallographic sites for Co/Mn and their mixed valence states favor the ferromagnetic interaction whereas antiferromagnetism originates from the Co3+-O-Co3+ and Mn4+-O-Mn4+ interactions. Unlike the parent compounds, the present Mn-substituted phases do not exhibit prominent magnetoresistance effects in the temperature range 75-400K.Comment: 23 pages including figure

Allelic Variation of MYB10 Is the Major Force Controlling Natural Variation in Skin and Flesh Color in Strawberry (Fragaria spp.) Fruit

Independent mutations in the transcription factor MYB10 cause most of the anthocyanin variation observed in diploid woodland strawberry (Fragaria vesca) and octoploid cultivated strawberry (Fragaria x ananassa). The fruits of diploid and octoploid strawberry (Fragaria spp) show substantial natural variation in color due to distinct anthocyanin accumulation and distribution patterns. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among which MYB10 is the main activator in strawberry fruit. Here, we show that mutations in MYB10 cause most of the variation in anthocyanin accumulation and distribution observed in diploid woodland strawberry (F. vesca) and octoploid cultivated strawberry (F. xananassa). Using a mapping-by-sequencing approach, we identified a gypsy-transposon in MYB10 that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruited F. vesca ecotype. Two additional loss-of-function mutations in MYB10 were identified among geographically diverse white-fruited F. vesca ecotypes. Genetic and transcriptomic analyses of octoploid Fragaria spp revealed that FaMYB10-2, one of three MYB10 homoeologs identified, regulates anthocyanin biosynthesis in developing fruit. Furthermore, independent mutations in MYB10-2 are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon (FaEnSpm-2) insertion in the MYB10-2 promoter of red-fleshed accessions that was associated with enhanced expression. Our findings suggest that cis-regulatory elements in FaEnSpm-2 are responsible for enhanced MYB10-2 expression and anthocyanin biosynthesis in strawberry fruit flesh.Peer reviewe