Palmoplantar Keratoderma: A Molecular Genetic Analysis of Family Cases.

Palmoplantar keratoderma is a clinically polymorphic disorder with a heterogeneous etiology characterized by marked hyperkeratotic lesions on the surface of palms and soles. Hereditary forms of palmoplantar keratoderma usually have autosomal dominant inheritance and are caused by mutations in dozens of genes, most of which belong to the keratin family. We carried out clinical and molecular genetic analysis of the affected and healthy members of four families with autosomal dominant palmoplantar keratoderma. In three out of four family cases of autosomal dominant palmoplantar keratoderma, the following molecular genetic causes were established: in two families­previously non-described missense mutations in the AQP5 gene (NM_001651.4): c.369C>G (p.(Asn123Lys)) and c.103T>G (p.(Trp35Gly)); in one family­a described splice site mutation in the KRT9 gene (NM_000226.4): c.31T>G. In one family, the possible cause of palmoplantar keratoderma was detected­a variant in the KRT1 gene (NM_006121.4): c.931G>A (p.(Glu311Lys)).

Towards sustainable diagnostics: replacing unstable H2O2 by photoactive TiO2 in testing systems for visible and tangible diagnostics for use by blind people.

Blind and color blind people cannot use colorimetric diagnostics; the problem is especially severe in rural areas where high temperatures and the absence of electricity challenge modern diagnostics. Here we propose to replace the unstable component of a diagnostic test, H2O2, with stable TiO2. Under UV irradiation, TiO2 forms reactive oxygen species that initiate polymerization of acrylamide causing liquid-to-gel transition in an analyte-dependent manner. We demonstrate that specific DNA sequences can be detected using this approach. This development may enable the detection of biological molecules by users with limited resources, for example in developing countries or for travelers in remote areas.

Liquid-to-gel transition for visual and tactile detection of biological analytes.

So far all visual and instrument-free methods have been based on a color change. However, colorimetric assays cannot be used by blind or color-blind people. Here we introduce a liquid-to-gel transition as a general output platform. The signal output (a piece of gel) can be unambiguously distinguished from liquid both visually and by touch. This approach promises to contribute to the development of an accessible environment for visually impaired persons.

Nonequilibrium Hybridization Enables Discrimination of a Point Mutation within 5-40 °C.

Detection of point mutations and single nucleotide polymorphisms in DNA and RNA has a growing importance in biology, biotechnology, and medicine. For the application at hand, hybridization assays are often used. Traditionally, they differentiate point mutations only at elevated temperatures (>40 °C) and in narrow intervals (ΔT = 1-10 °C). The current study demonstrates that a specially designed multistranded DNA probe can differentiate point mutations in the range of 5-40 °C. This unprecedentedly broad ambient-temperature range is enabled by a controlled combination of (i) nonequilibrium hybridization conditions and (ii) a mismatch-induced increase of equilibration time in respect to that of a fully matched complex, which we dub "kinetic inversion".

Bioelectronic Interface Connecting Reversible Logic Gates Based on Enzyme and DNA Reactions.

It is believed that connecting biomolecular computation elements in complex networks of communicating molecules may eventually lead to a biocomputer that can be used for diagnostics and/or the cure of physiological and genetic disorders. Here, a bioelectronic interface based on biomolecule-modified electrodes has been designed to bridge reversible enzymatic logic gates with reversible DNA-based logic gates. The enzyme-based Fredkin gate with three input and three output signals was connected to the DNA-based Feynman gate with two input and two output signals-both representing logically reversible computing elements. In the reversible Fredkin gate, the routing of two data signals between two output channels was controlled by the control signal (third channel). The two data output signals generated by the Fredkin gate were directed toward two electrochemical flow cells, responding to the output signals by releasing DNA molecules that serve as the input signals for the next Feynman logic gate based on the DNA reacting cascade, producing, in turn, two final output signals. The Feynman gate operated as the controlled NOT gate (CNOT), where one of the input channels controlled a NOT operation on another channel. Both logic gates represented a highly sophisticated combination of input-controlled signal-routing logic operations, resulting in redirecting chemical signals in different channels and performing orchestrated computing processes. The biomolecular reaction cascade responsible for the signal processing was realized by moving the solution from one reacting cell to another, including the reacting flow cells and electrochemical flow cells, which were organized in a specific network mimicking electronic computing circuitries. The designed system represents the first example of high complexity biocomputing processes integrating enzyme and DNA reactions and performing logically reversible signal processing.

Comparative analysis of age dynamics of average values of body dimensions in children from birth to 7 years.

Mean values of different body dimensions in different age cohorts of children make it possible to learn a lot about their dynamic changes. Their comparative analysis, as is usually practiced, in fact leads to a simple description of changes in measurement units (mm or cm) at the average level of some body dimension during a shorter or longer period of time. To estimate comparative intensity of the growth process of different body dimensions, the authors use the analogue of Mahalanobis distance, the so-called Kullback divergence (1967), which does not demand stability of dispersion or correlation coefficients of dimensions in compared cohorts of children. Most of the dimensions, excluding skinfolds, demonstrate growth dynamics with gradually reducing increments from birth to 7 years. Body length has the highest integrative increment, leg length about 94% of body length, body mass 77%, and trunk and extremities circumferences 56%. Skinfolds have a non-monotonic pattern of accumulated standardized increments with some increase until 1-2 years of age.