Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities

PURPOSE: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency. METHODS: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously. We add 21 individuals with similar PRR12 variants identified via matchmaking platforms, bringing the total number to 24. RESULTS: We observed 12 frameshift, 6 nonsense, 1 splice-site, and 2 missense variants and one patient with a gross deletion involving PRR12. Three individuals had additional genetic findings, possibly confounding the phenotype. All patients had developmental impairment. Variable structural eye defects were observed in 12/24 individuals (50%) including anophthalmia, microphthalmia, colobomas, optic nerve and iris abnormalities. Additional common features included hypotonia (61%), heart defects (52%), growth failure (54%), and kidney anomalies (35%). PrediXcan analysis showed that phecodes most strongly associated with reduced predicted PRR12 expression were enriched for eye- (7/30) and kidney- (4/30) phenotypes, such as wet macular degeneration and chronic kidney disease. CONCLUSION: These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities

Highlights from the Faraday Discussion on Ionic Liquids:From Fundamental Properties to Practical Applications, Cambridge, UK, September 2017

For the third time, a Faraday Discussion addressed ionic liquids.</p

Hafnium-Oxide 3‑D Nanofilms via the Anodizing of Al/Hf Metal Layers

Hafnium-oxide films with self-organized nanostructured 3-D architectures and variable dimension (10 to 400 nm) are synthesized via the high-current anodizing of thin aluminum-on-hafnium layers in phosphoric, malonic, and oxalic acid electrolytes. In the approach, the self-organized growth of a porous anodic alumina (PAA) film is immediately followed by the fast PAA-assisted reanodizing of the hafnium underlayer. The PAA-dissolved films consist of arrays of upright-standing hafnium-oxide nanorods held on the substrate by the tiny needle-like “nanoroots” widespread over a continuous hafnium-oxide bottom layer. The roots are amorphous Hf₂O₃, while the rods are amorphous HfO₂–Hf₂O₃–Al₂O₃ mixed oxides, the bottom layer being, however, highly textured nanocrystalline HfO₂. The calculated transport numbers for O^2– and Hf⁴⁺⁽³⁾⁺ ions are, respectively, ∼0.55 and ∼0.45, which is a unique situation for anodic hafnium oxide, which normally grows by O^2– transport only. Annealing the films in air at 600 °C oxidizes the remaining Hf metal to polycrystalline HfO₂, still leaving the roots and rods amorphous. The annealing in vacuum results in partial oxide reduction and crystallization of the roots and rods to stable orthorhombic and monoclinic HfO₂ phases. A model of the anodic film growth and solid-state ionic transport is proposed and experimentally justified. Potential applications of the 3-D hafnium-oxide nanofilms are in advanced electronic, photonic, or magnetic micro- and nanodevices

Dohled nad trhem: analýza parfémů na přítomnost alergenů a zakázaných látek

The market surveillance study was based on chemical analysis of 166 commercially available perfuming products in order to identify the presence of 24 regulated allergens and 21 prohibited substances. For this purpose, several GC methods were tested. The analytical approach for determination of 24 regulated allergens was based on GC-MS and GC-MS/MS analysis. Analyses were performed on two different GC columns to avoid potentially overestimated results due to matrix component co-elutions. Allergens determined by the chemical analyses were compared with the allergens declared on the product label to verify whether these products comply with the requirements of the Regulation No 1223/2009 of the European Parliament and of the Council. A specific proportion of the tested cosmetic products (43%) was found as non-compliant either due to a missing list of ingredients or due to the presence of undeclared allergens that were found to be present in the product above limits (0.001%) for required labelling. The GC-MS/MS analysis of 21 prohibited substances did not reveal any of the prohibited compounds in a concentration above LOQ except safrole, which was found in 12 out of 166 tested samples. The concentration of safrole did not exceed the concentration limit permitted by legislation for the presence from natural sources in any of these samples.Studie byla založena na chemické analýze 166 komerčně dostupných parfémovacích produktů s cílem identifikovat přítomnost 24 regulovaných alergenů a 21 zakázaných látek. Za tímto účelem bylo testováno několik metod GC. Analytický přístup pro stanovení 24 regulovaných alergenů byl založen na analýze GC-MS a GC-MS/MS. Analýzy byly provedeny na dvou různých GC kolonách, aby se zabránilo potenciálně nadhodnoceným výsledkům v důsledku společných elucí složek matrice. Alergeny stanovené chemickými rozbory byly porovnány s alergeny deklarovanými na etiketě výrobku, aby se ověřilo, zda tyto výrobky splňují požadavky Nařízení Evropského parlamentu a Rady č. 1223/2009. Konkrétní část testovaných kosmetických přípravků (43 %) byla shledána jako nevyhovující buď kvůli chybějícímu seznamu složek, nebo kvůli přítomnosti nedeklarovaných alergenů, které byly ve výrobku nalezeny nad limity (0,001 %) pro požadované označení. GC-MS/MS analýza 21 zakázaných látek neodhalila žádnou ze zakázaných sloučenin v koncentraci nad LOQ kromě safrolu, který byl nalezen ve 12 ze 166 testovaných vzorků. Koncentrace safrolu v žádném z těchto vzorků nepřekročila koncentrační limit povolený legislativou pro přítomnost z přírodních zdrojů

Electrical Properties of Hybrid Nanomembrane/Nanoparticle Heterojunctions: The Role of Inhomogeneous Arrays

Investigation of charge transport mechanisms across inhomogeneous nanoparticle (NP) layers in heterojunctions is one of the key technological challenges nowadays for developing novel hybrid nanostructured functional elements. Here, we successfully demonstrate for the first time the fabrication and characterization of a novel hybrid organic/inorganic heterojunction, which combines free-standing metallic nanomembranes with self-assembled mono- and sub-bilayers of commercially available colloidal NPs with no more than ∼10⁵ NPs. The low-temperature conductance–voltage spectra exhibit Coulomb features that correlate with various interface’s configurations, including the presence of inhomogeneities at the nano- and micrometer scale owing to the NP size, the micrometer-sized voids, and the thickness of the layers. The charge transport features observed can be explained by a superposition of conductance characteristics of each individual type of NPs. The procedure adopted to fabricate the heterojunctions as well as the theoretical approach employed to study the charge transport mechanisms across the NP layers may be of interest for investigating different types of NPs and commonly obtained inhomogeneous layers. In addition, the combination of metallic nanomembranes with self-assembled layers of NPs makes such a hybrid organic/inorganic heterostructure an interesting platform and building block for future nanoelectronics, especially after intentional tuning of its electronic behavior