A Highly Potent and Cellularly Active β‐Peptidic Inhibitor of the p53/hDM2 Interaction

New and improved : The incorporation of a 6‐chlorotryptophan (6‐Cl‐Trp) into a β‐peptide (M)‐3₁₄ helix leads to a high‐affinity hDM2 inhibitor, as demonstrated by fluorescence fluctuation analysis at single molecule resolution. When conjugated to penetratin, the newly derived hDM2 binder specifically inhibits tumour cell growth in vitro.

     

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.     

De Novo Missense Mutations in TNNC1 and TNNI3 Causing Severe Infantile Cardiomyopathy Affect Myofilament Structure and Function and Are Modulated by Troponin Targeting Agents

Rare pediatric non-compaction and restrictive cardiomyopathy are usually associated with a rapid and severe disease progression. While the non-compaction phenotype is characterized by structural defects and is correlated with systolic dysfunction, the restrictive phenotype exhibits diastolic dysfunction. The molecular mechanisms are poorly understood. Target genes encode among others, the cardiac troponin subunits forming the main regulatory protein complex of the thin filament for muscle contraction. Here, we compare the molecular effects of two infantile de novo point mutations in TNNC1 (p.cTnC-G34S) and TNNI3 (p.cTnI-D127Y) leading to severe non-compaction and restrictive phenotypes, respectively. We used skinned cardiomyocytes, skinned fibers, and reconstituted thin filaments to measure the impact of the mutations on contractile function. We investigated the interaction of these troponin variants with actin and their inter-subunit interactions, as well as the structural integrity of reconstituted thin filaments. Both mutations exhibited similar functional and structural impairments, though the patients developed different phenotypes. Furthermore, the protein quality control system was affected, as shown for TnC-G34S using patient’s myocardial tissue samples. The two troponin targeting agents levosimendan and green tea extract (-)-epigallocatechin-3-gallate (EGCg) stabilized the structural integrity of reconstituted thin filaments and ameliorated contractile function in vitro in some, but not all, aspects to a similar degree for both mutations.     

Stray current-induced corrosion in cathodic protection installations of steel-reinforced concrete structures: FEM study of the critical parameters

A wide range of parameters was investigated by numerical calculations concerning their impact on DC stray current corrosion of reinforced concrete (RC) structures. A simplified model geometry was used to extract the relevant parameters and their interaction in terms of stray current-affected structures. This study mainly focuses on RC structures that are fitted with cathodic protection installations. The findings reveal a complex interaction between the investigated parameters. The possible relevance of further parameters, which is not the subject of this study, was emphasised.     

Gas Responsive Nanoswitch: Copper Oxide Composite for Highly Selective H2S Detection

A nanocomposite material based on copper(II) oxide (CuO) and its utilization as a highly selective and stable gas‐responsive electrical switch for hydrogen sulphide (H₂S) detection is presented. The material can be applied as a sensitive layer for H₂S monitoring, e.g., in biogas gas plants. CuO nanoparticles are embedded in a rigid, nanoporous silica (SiO₂) matrix to form an electrical percolating network of low conducting CuO and, upon exposure to H₂S, highly conducting copper(II) sulphide (CuS) particles. By steric hindrance due to the silica pore walls, the structure of the network is maintained even though the reversible reaction of CuO to CuS is accompanied by significant volume expansion. The conducting state of the percolating network can be controlled by a variety of parameters, such as temperature, electrode layout, and network topology of the porous silica matrix. The latter means that this new type of sensing material has a structure‐encoded detection limit for H₂S, which offers new application opportunities. The fabrication process of the mesoporous CuO@SiO₂ composite as well as the sensor design and characteristics are described in detail. In addition, theoretical modeling of the percolation effect by Monte‐Carlo simulations yields deeper insight into the underlying percolation mechanism and the observed response characteristics.     

Influence of sputter deposition parameters on the properties of tunable barium strontium titanate thin films for microwave applications

Barium strontium titanate (BST) thin films are studied with respect to their application as tunable dielectric at microwave frequencies. BST thin films are deposited by means of radio-frequency magnetron sputtering on platinized Si substrates. The substrate to target distance during sputter deposition is varied and the effect on structure, topology, composition and electronic properties is monitored using X-ray diffraction, atomic force microscopy, Rutherford backscattering spectrometry and X-ray photoelectron spectroscopy. These findings are related to the dielectric measurements, which are carried out at 1 MHz and in the microwave range up to 8 GHz using metal-insulator-metal structures with Pt electrodes. For further device evaluation, leakage current measurements are carried out. Changing the process parameter strongly affects the composition of the films. The results emphasize the possibility for enhancing the microwave properties by fine-tuning of the chosen process parameter.     

The impacts of power boating and water skiing on lakes and reservoirs

Over the last 30 years, the use of motorised recreational craft on inland waters has increased significantly, and it is likely that this trend will continue. This growing use of rivers, lakes and water storage reservoirs for recreational purposes has led to concerns about increasing anthropological pressures on freshwater environments. As a result, numerous studies focusing on the possible impact of power boats on inland waterbodies have been undertaken since the early 1970s, when attention started to be drawn to environmental impacts associated with this type of recreation. This paper presents an overview of identified and documented physical, chemical and biological impacts as a result of motorised recreational activities on lakes and reservoirs. Relevant literature, including research papers, government reports and bibliographies, was consulted in the preparation of this review. It has become obvious that in the past, biological impacts have been underestimated. Thus, there is a need for further, more focused, research into the impacts on not only freshwater ecosystems but on terrestrial biota surrounding recreational waters.     

The impact of tourism on dune lakes on Fraser Island, Australia

In view of the increasing tourism to Fraser Island, Queensland, a tourist pressure index (TPI) was developed to assess the potential threat of tourism to 15 of the most accessible dune lakes on the island. Tourist pressure index scores indicated that the two clear lakes on the island, Lake McKenzie and Lake Birrabeen, are most threatened by tourist activities owing to their accessibility, facilities and prominence in advertising campaigns. In addition, limnological investigations of the same 15 lakes were conducted in February 1999 to determine their current trophic status and potential susceptibility to adverse impacts from tourism, particularly with reference to eutrophication. On the basis of nutrient and chlorophyll a concentrations, the two water table window lakes, Ocean Lake and Lake Wabby, were classed as mesotrophic and oligo‐mesotrophic, while all of the perched dune lakes were oligotrophic. Lake McKenzie and Lake Birrabeen, the two most threatened lakes according to TPI scores, had the lowest nutrient concentrations of all of the lakes examined and, consequently, we suggest that nutrient additions might elicit rapid algal growth responses in these systems. Comparisons between current data and historical data from Arthington et al. (1990 ) indicate that increases in planktonic chlorophyll a concentrations were not always directly mirrored by increases in total phosphorus concentrations. We found that while chlorophyll a concentrations were significantly higher in the 1999 samples than in the 1990 samples for all lakes, total phosphorus concentrations were higher in Ocean Lake, lower in Lake Jennings and similar in lakes McKenzie, Birrabeen and Wabby.     

Liquid chromatography with accurate mass measurement on a triple quadrupole mass-spectrometer for the identification and quantification of N-lactoyl ethanolamine in wine

In this study a specific taste-modulating flavor ingredient, N-lactoyl ethanolamine, was determined in two Beerenauslese wines using preparative LC, as a first isolation and concentration step, followed by LC-MS/MS on a triple quadrupole in accurate mass (AM) mode. The accurate masses of the analyte and three characteristic fragments were determined with mass accuracies between 8 and 20 ppm. N-lactoyl ethanolamine concentrations in the wines were 0.4 and 2.5 mg/L.