Mutations in the EGR2 cause demyelinating, but also axonal neuropathies and, except for one family, all reported cases have autosomal dominant inheritance with mutations within the ZNF domains. We ...described here 3 siblings with a demyelinating neuropathy carrying the second novel recessive mutation (c.791C>T, p.P264L) reported in the R1 domain of EGR2. Our data indicate that both the p.I268N and p.P264L recessive mutations inhibit interaction of EGR2 with NAB corepressors, which are required for myelination.
Background and purpose
Mutations in the early growth response 2 gene (EGR2) cause demyelinating, but also axonal, neuropathies differing in severity and age of onset. Except for one family, all reported cases have autosomal dominant inheritance and mutations are localized within the three zinc finger (ZNF) DNA‐binding domain. The aim of this study was to provide a clinical and molecular analysis of a novel recessive mutation in EGR2.
Methods
Clinical and electrophysiological assessments of three affected patients, from a consanguineous family, were performed. Genetic analyses of EGR2 were carried out by Sanger sequencing. Functional effects of clinical recessive mutations were assessed using a mammalian two‐hybrid assay.
Results
A novel missense mutation (c.791C>T; p.P264L) in the homozygous state was detected outside the ZNF domains of the EGR2 gene. Three affected siblings presented with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. Respiratory compromise and cranial nerve dysfunction were also found. Our data indicate that the p.P264L mutation prevents interaction of EGR2 transcription factor with NAB corepressors, suggesting that a disruption of the NAB‐EGR2 protein interactions can result in dramatic neuropathy.
Conclusion
Mutations in, or next to, the R1 domain of EGR2 should be considered with extreme caution for genetic counseling, since these could cause a severe neuropathy with an autosomal recessive manner of transmission.
Sánchez‐Ferrero E, Coto E, Beetz C, Gámez J, Corao A, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual‐Pascual SI, López de Munaín A, Garcia‐Barcina MJ, Alvarez V on behalf ...of the Genetics of Spastic Paraplegia study group. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.
Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.
Background and purpose
Pompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in ...adult patients were developed and reported here.
Methods
Three consensus meetings were organized through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. A systematic review of the literature was undertaken to determine the effectiveness of ERT in adult patients on a range of clinical outcome measures and quality of life. A narrative synthesis is presented.
Results
Consensus was reached on how the diagnosis of Pompe disease should be confirmed, when treatment should be started, reasons for stopping treatment and the use of ERT during pregnancy. This was based on expert opinion and supported by the literature. One clinical trial and 43 observational studies, covering a total of 586 individual adult patients, provided evidence of a beneficial effect of ERT at group level. At individual patient level, the response to treatment varied, but factors associated with a patient's response to ERT were not described in many studies. Eleven observational studies focused on more severely affected patients, suggesting that ERT can also be beneficial in these patients. There are no studies on the effects of ERT in pre‐symptomatic patients.
Conclusions
This is the first European consensus recommendation for starting and stopping ERT in adult patients with Pompe disease, based on the extensive experience of experts from different countries.
Abstract
The Astropy Project supports and fosters the development of open-source and openly developed
Python
packages that provide commonly needed functionality to the astronomical community. A key ...element of the Astropy Project is the core package
astropy
, which serves as the foundation for more specialized projects and packages. In this article, we provide an overview of the organization of the Astropy project and summarize key features in the core package, as of the recent major release, version 2.0. We then describe the project infrastructure designed to facilitate and support development for a broader ecosystem of interoperable packages. We conclude with a future outlook of planned new features and directions for the broader Astropy Project.
Muscle gross lesions, associated to parasites, were routinely found during self-inspection in a Spanish fish plant processing Atlantic swordfish. To determine the taxonomic status of these parasites, ...molecular analysis was performed based on 18S, ITS1, 5.8S, ITS2 and 28S rDNA sequences, obtaining a consensus sequences of 4581 bp for the cestode and 4200 bp for the trematode. Taxonomic affiliation was determined by phylogenetic analysis of combined SSU + LSU rDNA regions using maximum likelihood models. Molecular characterization allows us to identify the trematode Maccallumtrema xiphiados and the cestode Molicola sp. infecting the musculature of the Atlantic swordfish. Both parasites are responsible of significant economic loss to fish industry due to commercial rejection of parasitized products.
•The occurrence of parasites infecting edible muscle of swordfish was investigated.•A trematode and a cestode are responsible of swordfish commercial rejection.•Novel sequence data of rRNA gene of the cestode Molicola sp. were obtained.•The first genetic identification of the trematode Maccallumtrema xiphiados was performed.•The new added data will help fish industry and inspectors to identify these parasites.
Calcium-looping thermochemical energy storage associated to concentrating solar plants appears as promising technology given its potential to increase the storage period and energy density of the ...stored material. Up to now, research efforts focused on the global efficiency of the TCES associated to different power cycles under fixed modes of operation: day or night. However, TCES will never operate under a stationary situation but will experience different operation points to adapt to solar availability and energy demand from the power cycle. The aim is to analyse the influence of those variables which define the operation points, under energy storage and release modes, in the design of the heat exchangers network, storage tanks and reactors involved in the TCES system. The equipment in the conceptual plant have been modelled accounting variable storage/discharge fractions in the mass balances. The results show a suitable capture efficiency, quantifies the stored power and define the size and performance of the heat exchangers required to operate the system. The behaviour of each heat exchanger and their relevance in heat integration with a power plant is derived. The novelty relies in the analysis of potential situations arising from different combinations of charge/discharge fractions of storage tanks.
•A CaL – CSP model is analysed under two operation modes: energy storage/release.•The stored power, up to 20 MW, is quantified in a large number of situations.•The required size to store CaO and CO2 during 15 h is 1280–10,436 m3.•The carbon capture efficiency limited by operational restrictions is 96.15%.•The heat exchangers size is influenced by storage tanks charge/discharge fractions.
Sustainability of agroecosystems depends on the ecosystem services, provided by beneficial organisms, such as the syrphids (Diptera: Syrphidae) acting as other‐insect predators and pollinators in ...different crops. In the case of olive groves, syrphids are predators of important pests and are endangered by the continuous intensification of agriculture, including landscape simplification. In this work, the effect of landscape structure on the abundance and species richness of syrphids in the olive agroecosystem of central Spain is assessed.
Adult syrphids were sampled in 2015 and 2016 in the centre of circular areas of 15 olive grove landscapes (from 250 to 1500 m radius) representing a gradient of landscape complexity, in the province of Madrid, central Spain.
The syrphid assemblage was made up of 57 species, although Eupeodes corollae, Eristalis tenax, Eristalis similis and Chrysotoxum intermedium made up 76% of the captures.
Syrphid abundance and species richness were favoured in complex landscapes, with low olive grove area (CAO). Other landscape indices showed also this trend although their effect was not as strong and consistent as that of CAO. The area of scrublands (CAS) favoured syrphids in spring, but was unfavourable in autumn. The effect of Shannon's Evenness Index (SHEI) and mean shape index (MSI) was less consistent. The effect of CAO increased with increasing buffers radii, while the effect of CAS, SHEI and MSI was detected in general at smaller radii, indicating these indices affect different processes.
Redundancy analysis (RDA) detected some differences between species regarding their abundance in spring versus autumn, and their relationship with landscape indices.
This work provides new evidence that maintenance of complex landscapes is essential for maintaining functional biodiversity in the olive agroecosystem.
Landscapes dominated by olive groves do not encourage syrphid population.
Syrphids can help pest control in olive groves.
A complex landscape structure can contribute to the ecosystem service biological pest control.
This paper examines the link between reliance on Facebook for news, political knowledge, and political engagement in the Philippines. We tested five hypotheses using data gathered from an online ...survey of 978 Filipinos conducted from February 1 to March 31, 2016. Findings support the hypothesis that those who rely less on social media as a news source exhibit higher levels of perceived knowledge about politics than those who rely more on it for news. Controlling for traditional news use, following political officials or institutions on social media is associated with higher levels of political interest and engagement, those with more politically active friends on Facebook have higher levels of exposure to political content online, and there is a positive correlation between Facebook being a source of information about politics and discussing politics more often with others. However, the hypothesis that those with more friends on their network who are politically active, will have greater political knowledge and more political engagement than those who have few politically active friends on their Facebook network is not supported.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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