Identification of a novel IVD mutation in a consanguineous family with isovaleric acidemia

Isovaleric acidemia (IVA) is a rare autosomal recessive disorder caused by a deficiency of isovaleryl-CoA dehydrogenase encoded by IVD gene. In this case study we report the first Saudi IVA patients from a consanguineous family with a novel transversion (p.G362V) and briefly discuss likely phenotype–genotype correlation of the disease in the Saudi population. We explored the functional consequences of the mutation by using various bioinformatics prediction algorithms and discussed the likely mechanism of the disease caused by the mutation.     

Alginate Films Containing Viable Lactobacillus Plantarum: Preparation and In Vitro Evaluation

The objective of the study was to develop calcium alginate films, containing Lactobacillus plantarum ATCC 8040 with preserved and stable viability and antibacterial activity. L. plantarum-loaded films containing different calcium concentrations were physically characterized for mechanical and bioadhesive properties and lactobacilli release. The viability and antibacterial activity of L. plantarum was studied before and after processing, and during 6 months of storage. A multiresistant clinical isolate, VIM-2-metalo-β-lactamase producing Pseudomonas aeruginosa, was used as an indicator strain. Interference between L. plantarum and films enhanced films elasticity, water absorption ability, release of lactobacilli, and decreased films adherence. A decrease of L. plantarum viability in alginate films (≤1 log unit) was observed after freeze drying. L. plantarum, at cell concentrations of 108 cfu/ml, was inhibitory active. The viability and antibacterial activity of the immobilized lactobacilli remained stable during 6 months of storage. The study has proved the potential of alginate films to deliver L. plantarum in high numbers to individuals.     

Taxonomical Properties of a Producer of Viral-neuraminidase Inhibitor,No. 289 Strain,and Culture Conditions for Inhibitor Production

Taxonomical properties of an actinomycete, strain No. 289, a potent producer of viral-neuraminidase inhibitor, and culture conditions for the production of the inhibitor have been studied. It belongs to the genus Streptomyces and is characterized mainly by spiral formation, smooth spore surface, Gray color-series and chromogenicity. A high yield of the inhibitor was achieved when it was cultured in a medium containing lactose, peptone and yeast extract at 27° under aerobic condition; the inhibitory activity of the broth reached as high as 2⁴ deHAI units/ml at the fifth day of the main culture.     

A prevalent POLG CAG microsatellite length allele in humans and African great apes

The human nuclear gene for the catalytic subunit of mitochondrial DNA polymerase (POLG) contains within its coding region a CAG microsatellite encoding a polyglutamine repeat. Previous studies demonstrated an association between length variation at this repeat and male infertility, suggesting a mechanism whereby the prevalent (CAG)₁₀ allele, which occurs at a frequency of >80% in different populations, could be maintained by selection. Sequence analysis of the POLG CAG microsatellite region of more than 1000 human chromosomes reveals that virtually all allelic variation at the locus is accounted for by length variation of the CAG repeat. Analysis of POLG from African great apes shows that a prevalent length allele is present in each species, although its exact length is species-specific. In common chimpanzee (Pan troglodytes) a number of different sequence variants contribute to the prevalent length allele, strongly supporting the idea that the length of the POLG microsatellite region, rather than its exact nucleotide or amino acid sequence, is what is maintained. Analysis of POLG in other primates indicates that the repeat has expanded from a shorter, glutamine-rich sequence, present in the common ancestor of Old and New World monkeys.     

The tripeptide feG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis

Background  

Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG), which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction.     

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.     

Cellular integrity plus: organelle-related and protein-targeting functions of intermediate filaments

Intermediate filament proteins (IFs) maintain cell and tissue integrity, based on evidence of their polymerization and mechanical properties, abundance and disease-associated phenotypes. This 'traditional' function is now augmented by organelle-related and protein-targeting roles. Mitochondrial location and function depend on intact IFs, as demonstrated for desmin, keratins and neurofilaments. Golgi positioning is regulated by several IFs, and endosomal/lysosomal protein distribution by vimentin. IFs dramatically affect nuclear function and shape and play a role in subcellular and membrane targeting of proteins. These functions have been noted in tissues but in some cases only in cell culture. The IF-related organelle-specific and protein-targeting roles, which are likely interrelated, provide functions beyond cell scaffolding and integrity and contribute to the cytoprotective and tissue-specific functions of IF proteins.     

The cross-road between the mechanisms of protein folding and aggregation; study of human stefin B and its H75W mutant

The role of the aromatic residue at site 75 to protein stability, the mechanism of folding and the mechanism of amyloid-fibril formation were investigated for the human stefin B variant (bearing Y at site 31) and its point mutation H75W. With an aim to reveal the conformation at the cross-road between folding and aggregation, first, the kinetics of folding and oligomer formation by human stefin B(Y31) variant were studied. It was found to fold in three kinetic phases at pH 4.8 and 10% TFE; the pH and solvent conditions that transform the protein into amyloid fibrils at longer times. The same pH leads to the formation of native-like intermediate (known from previous studies of this variant), meaning that the process of folding and amyloid-fibril formation share the same structural intermediate, which is in this case native-like and dimeric. At pH 5.8 and 7.0 stefin B folded to the native state in four kinetic phases over two intermediates. In distinction, the mutant H75W did not fold to completion, ending in intermediate states at all pH values studied: 4.8, 5.8 and 7.0. At pH 4.8 and 5.8, the mutant folded in one kinetic phase to the intermediate of the “molten globule” type, which leads to the conclusion that its mechanism of folding differs from the one of the parent stefin B at the same pH. At pH 7.0 the mutant H75W folded in three kinetic phases to a native-like intermediate, analogous to folding of stefin B at pH 4.8.