UV absorption of Criegee intermediates: quantitative cross sections from high-level ab initio theory.

Criegee intermediates (CIs) are increasingly recognized as important intermediates in atmospheric and combustion chemistry. Modelling in these fields requires reliable characterization of the CI's UV absorption cross sections. Different experimental approaches provided seemingly contradictory results both for the simplest CI as well as for higher analogues. To resolve these discrepancies, we model simultaneously the positions, widths, shapes and absolute intensities of the first absorption bands of CIs using the semiclassical reflection principle approach based on the path integral molecular dynamics. The UV spectra were efficiently processed via the kernel density estimation method. We show that the multireference character complicates the description of the system and the appropriate treatment of the electron correlation is vital. Multi-reference methods with dynamical correlation are problematic due to high sensitivity of the results with respect to the active space. Single-reference based methods become reliable once the triple excitations components are included. Interestingly, the very similar CC2 and ADC(2) methods provide highly conflicting results which are, however, reconciled at the CC3 and ADC(3) levels. To calculate the spectra of higher CIs, we introduce composite EOM-CCSD/T and CC2/3 methods providing excellent absorption cross sections at an acceptable computational cost. We provide the first absolute intensities for individual conformers of the CH3CHOO molecule.

Allelic heterogeneity of alkaptonuria in Central Europe.

Defects of the homogentisate 1,2 dioxygenase (HGO; E.C. No. 1.13.11.5) have been identified as the molecular cause of alkaptonuria in humans (AKU) and the aku mouse. Here, we report on the genetic basis of 30 AKU patients from Central Europe. In addition to five mutations described previously, we have detected five novel HGO mutations. Recombinant expression of mutated HGO enzymes in E. coli demonstrates the inactivating effect of three of these mutations. A genetic epidemiologic study in Slovakia, the country with the highest incidence of alkaptonuria, demonstrates that two recurrent mutations (c.183-1G > A and Glyl61Arg) are found on more than 50% of AKU chromosomes. An analysis of the allelic association with intragenic DNA markers and of the geographic origins of the AKU chromosomes suggests that several independent founders have contributed to the gene pool, and that subsequent genetic isolation is likely to be responsible for the high prevalence of alkaptonuria in Slovakia.

[Congenital developmental defects of the cardiovascular system from the aspect of genetic factors and dysmorphogenesis]. / Vrodené vývinové chyby kardiovaskulárneho systému z hl'adiska genetických faktorov a dysmorfogenézy.

Congenital defects of cardiovascular system have marked impact on the morbidity, invalidization and mortality of human population. Genetic factors are the most important factors in their etiology. The authors analyze the role of genetic factors and some problems of cardiovascular dysmorphogenesis important for evaluation of the reasons and risk of repeated congenital heart diseases family occurrence using clinical data and professional literature. (Tab. 7, Ref. 19.)

Molecular defects in alkaptonuria.

At the dawn of human genetics Sir Archibald Garrod used alkaptonuria as a paradigm to demonstrate the applicability of the Mendelian laws to men and to develop the concept of inborn errors of metabolism. The human cDNA for homogentisate 1,2 dioxygenase was identified due to its homology to the corresponding mouse enzyme and was screened for mutations in alkaptonuric patients from Slovakia. Homozygous mutations were found in four unrelated families and their segregation with the disease was demonstrated. One of the mutations, observed in two families, leads to a frame-shift and thus is unlikely to produce functional protein. The data formally establish the homogentisate 1,2 dioxygenase gene (HGD) as the molecular cause of alkaptonuria and allow for the development of molecular carrier tests in populations at risk.

The human gene for alkaptonuria (AKU) maps to chromosome 3q.

Alkaptonuria (AKU; McKusick no. 203500) is a rare autosomal recessive disorder caused by the lack of homogentisic acid oxidase activity. Patients excrete large amounts of homogentisic acid in their urine and a black ochronotic pigment is deposited in their cartilage and collagenous tissues. Ochronosis is the predominant clinical complication of the disease leading to ochronotic arthropathy, dark urine, pigment changes of the skin, and other clinical features. A mutation causing alkaptonuria in the mouse has mapped to chromosome 16. Considering conserved synteny, we were able to map the human gene to chromosome 3q in six alkaptonuria pedigrees of Slovak origin.

[Disorders of the cardiovascular system in congenital lentiginosis]. / Poruchy kardiovaskulárneho systému pri vrodenej lentiginóze.

The authors investigated during the last 10 years four patients with lentiginosis and affection of the heart. In none of them the symptoms were complete enough to include it under the leopard syndrome. In two patients the authors found changes in the outflow portion of the right ventricle which was in their opinion caused by hypertrophy of the interventricular septum and musculature of the right ventricle. The authors consider the term lentiginocardiomyopathic syndrome suitable for this rare clinical and genetic entity. The authors check patients with lentiginocardiomyopathic syndrome regularly after 6-month intervals. In two children they recorded progression of the heart disease.

Stable isotope dilution analysis of N-acetylaspartic acid in CSF, blood, urine and amniotic fluid: accurate postnatal diagnosis and the potential for prenatal diagnosis of Canavan disease.

A sensitive and selective analytical technique is described for the determination of N-acetylaspartic acid in body fluids using stable isotope dilution in combination with positive chemical ionization mass spectrometry with selected ion monitoring. Control mean and ranges have been established: in urine 19.5 and 6.6-35.4 mumol/mmol creat.; in plasma 0.44 and 0.17-0.81 mumol/L; in cerebrospinal fluid 1.51 and 0.25-2.83 mumol/L; and in amniotic fluid 1.27 and 0.30-2.55 mumol/L. In a patient with Canavan disease, N-acetylaspartic acid concentration was elevated 80-fold in urine and 20-fold in plasma compared to the control means. A subsequent pregnancy of the mother was monitored and the N-acetylaspartic acid concentration in the amniotic fluid was within the control range and a healthy child was born.

[Let us cure our planet!]. / Vyliecme nasu planétu!

Ideas of the moral code of nuclear age selected from IPPNW sessions at the 8th World Congress (Montreal 1988) and the 4th Regional Rhineland Symposium (1988). The proclamation of these sessions was adopted also by the newly established Czechoslovak Medical Society for the prevention of nuclear war.

[Chromosome aberrations in a group of mentally retarded persons]. / Chromozómové aberácie v súbore mentálne retardovaných jedincov.

Mental retardation (MR) is a frequent manifestation in patients referred to departments of medical genetics (OLG). At the OLG in Martin their number in the years 1981-1985 was 324, i.e. 21.22% of the total number of examined subjects. MR was found as one of the pathological symptoms (symptomatic MR) in 86.73% and as the only pathological manifestation (isolated MR) in 13.27%. Genetic factors were revealed in 59%, exogenous ones in 19%, and in 22% the aetiology was not unequivocally resolved. As to genetic factors, the most frequent cause were chromosomal aberrations (in 104 patients-53%), a monogenic character was found in 68 subjects (35%) and a multifactorial one in 24 (12%). As to chromosomal aberrations, in 102 cases autosomes were affected (91 times numerical and 11 times structural affection), in four subjects a numerical anomaly of genosomes was involved and once a combined aberration of an autosomal and gonosomal character. The authors give the character and number of different types of aberrations and the incidence of so-called chromosomal markers (12 cases) and they evaluate their causal relationship with MR. Further advances in the aetiological evaluation of genetic factors will be made possible by the introduction of strip methods with a high resolution technique (use of prophasic chromosomes), combined with hybridization in situ, cytogenetic methods for the detection of individuals with the fragile X-chromosome syndrome, and in particular the application of the technology of recombinant DNA for the diagnosis of clinical and genetic units at the gene level.