Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.     

The Formation of Mn-Ce Oxide Catalysts for CO Oxidation by Oxalate Route: The Role of Annealing Conditions

Catalysis Letters - A series of Mn-Ce oxide catalysts with Mn:Ce?=?1 was synthesized by oxalate route under different annealing conditions. The physicochemical properties were...     

Thermal prehistory,structure and high-temperature thermodynamic properties of Y2O3-CeO2 and Y2O3-ZrO2-CeO2 solid solutions

Ceria-based solid solutions are important materials for high- and medium-temperature electrochemical applications. However, the stabilities of both binary and ternary ceria-based solid solutions are insufficient at elevated temperatures, which limits their application as solid electrolytes or SOFC cathodes. Data on the high-temperature stability of ceria-based ceramics are unavailable in the literature. In the present study, we report a thermodynamic stability investigation of Y₂O₃-CeO₂ and Y₂O₃-ZrO₂-CeO₂ solid solutions. The thermal prehistories of binary and ternary systems were investigated using STA, XRD, and ESCA techniques. The vaporization processes were investigated in the temperature range of 1577–2227°С via the Knudsen effusion mass spectrometry technique. Using data on the component activity in solid-phase thermodynamic properties of Y₂O₃-CeO₂ solid solutions, which is represented as the Gibbs energy, the excess Gibbs energy was calculated as a function of the ceria mol. %. It was shown that the reduction of Ce⁴⁺ to Ce³⁺ in Y₂O₃-CeO₂ and Y₂O₃-ZrO₂-CeO₂ solid solutions corresponds to less-negative Gibbs energy compared to ZrO₂-CeO₂ solid solutions.     

Direct energy transfer to study the 3D structure of non-native proteins: AGH complex in molten globule state of apomyoglobin

The direct energy transfer technique was modified and appliedto probe the relative localization of apomyoglobin A-, G- andH-helixes, which are partly protected from deuterium exchangein the equilibrium molten globule state and in the molten globule-likekinetic intermediate. The non-radiative transfer of tryptophanelectronic energy to 3-nitrotyrosine was studied in differentconformational states of apomyoglobin (native, molten globule,unfolded) and interpreted in terms of average distances betweengroups of the protein chain. The experimental data show thatthe distance between the middle of A-helix and the N-terminusof G-helix as well as the distance between the middle of theA-helix and the C-terminus of the H-helix in the molten globulestate are close to those in the native state. This is a strongargument in favor of similarity of the overall architectureof the molten globule and native states.     

An analysis of students’ spontaneous computer-mediated help seeking: A step toward the design of ecologically valid supporting tools

This study analyzes middle school students’ spontaneous mathematics-related help-seeking behavior, in view of making ecologically valid recommendations for the design of supporting tools or “help systems”. Our aim was to investigate the content of students’ help-seeking messages – Are there different forms of help-seeking messages and do they evolve with age? We used the archives of a French forum that provides students with free individualized help in mathematics. The data consisted of 206 messages sent by French middle school students over a period of 42 months. The constituent categories of the messages were identified. The results showed that not all middle school students use the same help-seeking “format”. Compared to sixth graders, ninth graders wrote messages containing more constituent categories, i.e., they provided the online expert with more kinds of information. A detailed analysis of the categories further showed that older students’ messages more often contained explicit help requests and contextual information than did younger students’ messages. Thus, the messages of the oldest students (age 15) were both cognitively more understandable and socially more acceptable than those of the youngest students (age 11). The interpretation of these findings and their implications for designing help systems are discussed.     

S-map and tracial states

The notion of s-map introduced in quantum logics to define conditional expectations for non-compatible events is studied in projection lattices of von Neumann algebras. It is shown that every tracial state gives rise to an s-map, and conversely, every s-map defines a tracial state.     

Study of Evaporative Convection in an Open Cavity under Shear Stress Flow

When a layer of volatile liquid is exposed to a shear flow of inert gas, thermal patterns, in the form of interfacial ripples and bulk plumes, are created by the combined action of evaporative, shear-driven and surface-tension-driven instabilities. The topology of the interfacial thermal patterns is mainly influenced by the geometry of the evaporating surface, the thickness of the evaporating layer, the intensity of the shear flow and by the physic-chemical properties of the working fluid. In this paper, by means of numerical simulations, we focused our attention on the dynamics of the interfacial thermal patterns for different working fluids and thicknesses of the volatile liquid layer. This study has been performed in the frame of the ESA sponsored Space Program on heat and mass transfer CIMEX-1. The choice of the fluids—ethyl alcohol and FC72 (n-perfluorohexane)—the reference values for the inert gas flow rate, the thickness of the liquid layer as well as the geometrical features of the computational domain correspond exactly to the ones foreseen for the CIMEX-1 experiment. However, the main conclusions can be considered of more general validity.     

Surface area production during grinding

During grinding, in cascading mills, the mass distribution of the material moves continuously to finer sizes. Grinding models are usually designed to predict the size distribution of the mill products either as a function of effective breakage events and the time or the energy consumed by the mill. Mill products are always tested for their size analysis and their fineness is usually expressed as the size d through which a certain amount of material passes, i.e. d₈₀. However, particulate materials have some supplementary properties that a grinding model should predict as well. The specific surface area is such an important supplementary property. Initially, the present work examines the relationship between mass distribution and the surface area of ground materials and determines the conditions under which, mass distribution can be used to determine the surface area. Based on these findings the work further examines the operating conditions of a cascading mill under which the surface area of the material increases at the highest rate. The operating parameter examined is the mill load ratio expressed as the mass ratio of mill grinding media and the material present in the mill.     

Impaired timing precision produced by striatal D2 receptor overexpression is mediated by cognitive and motivational deficits.

Increased striatal dopamine D2 receptor activity is thought to contribute to the pathophysiology of schizophrenia. To model this condition in mice, Kellendonk et al. (2006) generated transgenic mice that selectively overexpress the D2 receptor in striatum (D2OE). Drew et al. (2007) reported that D2OE mice display deficits in interval timing and motivation. The present study further explored the impaired timing in D2OE mice. Experiment 1 assessed the role of motivation in producing timing deficits in the peak procedure and found that performance in D2OE mice was improved by increasing motivation. In addition, performance was impaired in control mice when motivation was decreased. In Experiment 2, we found that D2OE mice have no timing impairment when tested using the bisection task, a procedure in which the measure of timing performance is less influenced by motivation to respond. In Experiment 3, we also used the bisection task and found selective impairment in timing of long durations in D2OE mice. These results suggest that striatal D2 overexpression impairs timing by decreasing motivation and through its impact on working memory and/or sustained attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)