Studies on the metabolic effects of methylthioformycin

1. 5′-Methylthioformycin, a structural analog of 5′-methylthioadenosine in which the N-C glycosidic bond is substituted by a C-C bond, has been synthesized by a newly developed procedure. 2. Membrane permeability of the molecule has been compared to that of methylthioadenosine in intact human erythrocytes and Friend erythroleukemia cells. The formycinyl compound is taken up with a rate significantly lower than that of 5′-methylthioadenosine and is not metabolized by the cells. 3. 5′-Methylthioformycin inhibits Friend erythroleukemia cells' growth: the effect is dose-dependent, fully reversible and not caused by cytotoxicity. 4. Several enzymes related to methylthioadenosine metabolism are inhibited by methylthioformycin. Rat liver methylthioadenosine phosphorylase is competitively inhibited with a K_i value of 2 μM. Among the propylamine transferases tested only rat brain spermine synthase is significantly inhibited, while rat brain spermidine synthase is less sensitive. Rat liver S-adenosylhomocysteine hydrolase is irreversibly inactivated with 50% inhibition at 400 μM methylthioformycin. 5′-Methylthioformycin does not exert any significant effect on protein carboxyl-O-methyltransferase. Inferences about the mechanism of the antiproliferative effect of the drug have been drawn from the above results.     

Conformational Studies on Two FtsZ Targeting Cyclic Peptides

International Journal of Peptide Research and Therapeutics - Two FtsZ targeting cyclic peptides 1 (Ac-[Orn-Leu-Met-Asp]-Ala-Phe-Arg-Ser-NH2) and 2 (Ac-Ser-Leu-Met-[Asp-Ala-Phe-Arg-Orn]-NH2) were...     

Ataxic gait and mental retardation with absence of the paternal chromosome 8 and an idic(8)(p23.3): imprinting effect or nullisomy for distal 8p genes?

A female child with mild dysmorphisms, motor and mental retardation had a 45,XX,-8,-8,+psu dic(8)(p23.3) karyotype in blood lymphocytes, skin fibroblasts and in a lymphoblastoid cell line. DNA analysis showed that the proposita was nullisomic for the 8pter region distal to D8S264, at less than 1 cM from the telomere. Analysis of DNA polymorphisms of 38 loci spread along the entire chromosome 8 revealed that only maternal alleles were present, distributed in four heterozygous and four homozygous regions. This finding indicated that the rearrangement occurred during maternal meiosis in a chromosome recombinant with a minimum of seven crossovers. To our knowledge this is the first case of uniparental maternal disomy for chromosome 8 and of nullisomy for the distal 1-cM portion of the short arm. The available data are in favour of the assumption that no imprinted genes are present on chromosome 8. Thus, dysmorphisms, motor and mental retardation of the proposita are likely to be caused by the nullisomy for the region distal to D8S264, a region in which a recessive gene for epilepsy with progressive mental retardation is known to be located. Received: 16 December 1996 / Revised: 24 January 1997     

Nitrogen regulation of transport operons: analysis of promoters argTr and dhuA

Summary In Salmonella typhimurium the periplasmic permeases for histidine and for lysine-arginine-ornithine are regulated by nitrogen availability. The nature of the dhuA and argTr promoters of the operons coding for these permeases was analyzed by placing the galactokinase gene under their control (in vector pKO-1). argTr was found to respond to nitrogen regulation. We investigated the involvement of a mirror symmetry in argTr in its regulation by nitrogen. It had been postulated previously (Higgins and Ames 1982) that mirror symmetries might act as protein recognition sites important in regulation of gene expression. Here we demonstrate that the mirror symmetry in argTr is not involved in nitrogen control. Contrary to expectation, the galK gene was not regulated by nitrogen when it was placed under dhuA control. Here we propose a possible explanation for this finding.     

Mapping malaria risk among children in Côte d’Ivoire using Bayesian geo-statistical models

ABSTRACT: BACKGROUND: In Cote d'Ivoire, an estimated 767,000 disability-adjusted life years are due to malaria, placing the country at position number 14 with regard to the global burden of malaria. Risk maps are important to guide control interventions, and hence, the aim of this study was to predict the geographical distribution of malaria infection risk in children aged <16 years in Cote d'Ivoire at high spatial resolution. METHODS: Using different data sources, a systematic review was carried out to compile and georeference survey data on Plasmodium spp. infection prevalence in Cote d'Ivoire, focusing on children aged <16 years. The period from 1988 to 2007 was covered. A suite of Bayesian geo-statistical logistic regression models was fitted to analyse malaria risk. Non-spatial models with and without exchangeable random effect parameters were compared to stationary and non-stationary spatial models. Non-stationarity was modelled assuming that the underlying spatial process is a mixture of separate stationary processes in each ecological zone. The best fitting model based on the deviance information criterion was used to predict Plasmodium spp. infection risk for entire Cote d'Ivoire, including uncertainty. RESULTS: Overall, 235 data points at 170 unique survey locations with malaria prevalence data for individuals aged <16 years were extracted. Most data points (n = 182, 77.4%) were collected between 2000 and 2007. A Bayesian non-stationary regression model showed the best fit with annualized rainfall and maximum land surface temperature identified as significant environmental covariates. This model was used to predict malaria infection risk at nonsampled locations. High-risk areas were mainly found in the north-central and western area, while relatively low-risk areas were located in the north at the country border, in the northeast, in the south-east around Abidjan, and in the central-west between two high prevalence areas. CONCLUSION: The malaria risk map at high spatial resolution gives an important overview of the geographical distribution of the disease in Cote d'Ivoire. It is a useful tool for the national malaria control programme and can be utilized for spatial targeting of control interventions and rational resource allocation.