Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder.

Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders

Removal of Amitraz insecticide by heterogeneous UV-Fenton process using metals supported on chitosan beads as a catalyst

International audiencePhotocatalytic degradation of Amitraz insecticide in a heterogeneous phase was studied at neutral pH using several types of metals supported on chitosan beads (Fe-CS, Fe3O4-CS, Mn-CS, MnO2-CS, and TiO2-CS). Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared (FTIR), and Brunauer Emmett Teller (BET) analysis were used to characterize the prepared catalysts. Parameters, including the type of catalyst, UV irradiation, the method of hydrogen peroxide addition, and the presence of dissolved oxygen were investigated in order to evaluate the performance of the heterogeneous Fenton process. The optimal conditions were achieved when using 1 g L−1 of Fe3O4-CS catalyst under UV irradiation with the sequential addition of 12 mM of H2O2 and a continuous bubbling of air in the reactional medium. The degradation of the pollutant follows a pseudo-first-order kinetic. The catalyst stability was evaluated and confirmed in four repeated runs with a control of the amount of leached iron in the aqueous solution. © 2020 American Institute of Chemical Engineer

Natural language processing and expert follow-up establishes tachycardia association with CDKL5 deficiency disorder

Purpose: CDKL5 deficiency disorder (CDD) is a developmental and epileptic encephalopathy with multisystemic comorbidities. Cardiovascular involvement in CDD was shown in animal models but is yet poorly described in CDD cohorts. Methods: We identified 38 individuals with genetically confirmed CDD through the Cleveland Clinic CDD specialty clinic and matched 190 individuals with non-genetic epilepsy to them as a comparison group. Natural language processing was applied to yield Human Phenotype Ontology (HPO) terms from medical records. We conducted HPO association testing and manual chart review to explore cardiovascular comorbidities associated with CDD. Results: We extracted 243,541 HPO terms from 30,512 medical encounters. Phenome-wide analysis confirmed well-established CDD phenotypes and identified association of tachycardia with CDD (Odds ratio 4.2, 95% confidence interval (CI) 1.75-9.93, Padj < .001). We found a 99.6-fold enrichment of supraventricular tachycardia (SVT) in CDD encounter notes (Padj < .001), which led to identification of 2 cases of fetal/neonatal onset SVT previously undescribed in CDD. Tachycardia in CDD individuals was associated with the presence of other autonomic symptoms (Odds ratio 5.63, 95% CI 1.08-40.3, P = .038). Conclusion: CDD is associated with tachycardia, potentially including early-onset SVT. Alongside prospective validation studies, semiautomated genotype-phenotype analysis with matched controls is a scalable, rapid, and efficient approach for validating known and identifying novel phenotype associations

Language-driven engineering: from general-purpose to purpose-specific languages

In this paper, we present the paradigm of Language-Driven Engineering (LDE), which is characterized by its unique support for division of labour on the basis of Domain-Specific Languages (DSLs) targeting different stakeholders. LDE allows the involved stakeholders, including the application experts, to participate in the system development and evolution process using dedicated DSLs, while at the same time establishing new levels of reuse that are enabled by powerful model transformations and code generation. Technically, the interplay between the involved DSLs is realized in a service-oriented fashion. This eases a product line approach and system evolution by allowing to introduce and exchange entire DSLs within corresponding Mindset-Supporting Integrated Development Environments (mIDEs). The impact of this approach is illustrated along the development and evolution of a profilebased email distribution system. Here we do not want to emphasize the precise choice of DSLs, but rather the flexible DSL-based modularization of the development process, which allows one to freely introduce and exchange DSLs as needed to optimally capture the mindsets of the involved stakeholders

The utility of statoliths and bell size to elucidate age and condition of a scyphomedusa (Cassiopea sp.)

Scyphomedusae play important roles in marine ecosystems and are of economic significance. However, no reliable techniques for estimating scyphomedusa age have been documented. This study focused on the utility of Cassiopea sp. (Cnidaria: Scyphozoa) statoliths, statocysts, and body size as proxies for age of medusae. Reared medusae of known age and a manipulative experiment were used to assess the accuracy and reliability of four measures of age: number of statoliths, size (diameter) of statoliths, area of statocyst (housing statoliths), and bell diameter. Bell diameter provided the most accurate measure of age under constant conditions, but was increasingly inaccurate under varying environmental conditions. In contrast, the average number of statoliths per medusa reflected age with relatively low accuracy, but did not vary with changes in food availability and salinity. Only temperature influenced the average number of statoliths. Comparisons of bell diameter to the number of statoliths in medusae under low food availability to those fed well showed that the ratio of medusa size to the number of statoliths can be used to recognise medusae that are relatively poorly conditioned. Statoliths, therefore, provide a tool for studying both population ecology and the influence of environmental variation on medusa growth

Impacts of temperature and acidification on larval calcium incorporation of the spider crab Hyas araneus from different latitudes (54° vs. 79°N)

The combined effects of ocean warming and acidification were compared in larvae from two populations of the cold-eurythermal spider crab Hyas araneus, from one of its southernmost populations (around Helgoland, southern North Sea, 54A degrees N, habitat temperature 3-18A degrees C; collection: January 2008, hatch: January-February 2008) and from one of its northernmost populations (Svalbard, North Atlantic, 79A degrees N, habitat temperature 0-6A degrees C; collection: July 2008, hatch: February-April 2009). Larvae were exposed to temperatures of 3, 9 and 15A degrees C combined with present-day normocapnic (380 ppm CO(2)) and projected future CO(2) concentrations (710 and 3,000 ppm CO(2)). Calcium content of whole larvae was measured in freshly hatched Zoea I and after 3, 7 and 14 days during the Megalopa stage. Significant differences between Helgoland and Svalbard Megalopae were observed at all investigated temperatures and CO(2) conditions. Under 380 ppm CO(2), the calcium content increased with rising temperature and age of the larvae. At 3 and 9A degrees C, Helgoland Megalopae accumulated more calcium than Svalbard Megalopae. Elevated CO(2) levels, especially 3,000 ppm, caused a reduction in larval calcium contents at 3 and 9A degrees C in both populations. This effect set in early, at 710 ppm CO(2) only in Svalbard Megalopae at 9A degrees C. Furthermore, at 3 and 9A degrees C Megalopae from Helgoland replenished their calcium content to normocapnic levels and more rapidly than Svalbard Megalopae. However, Svalbard Megalopae displayed higher calcium contents under 3,000 ppm CO(2) at 15A degrees C. The findings of a lower capacity for calcium incorporation in crab larvae living at the cold end of their distribution range suggests that they might be more sensitive to ocean acidification than those in temperate regions