Uniparental isodisomy of chromosome 2 causing MRPL44-related multisystem mitochondrial disease

Mutations in nuclear-encoded protein subunits of the mitochondrial ribosome are an increasingly recognised cause of oxidative phosphorylation system (OXPHOS) disorders. Among them, mutations in the MRPL44 gene, encoding a structural protein of the large subunit of the mitochondrial ribosome, have been identified in four patients with OXPHOS defects and early-onset hypertrophic cardiomyopathy with or without additional clinical features. A 23-year-old individual with cardiac and skeletal myopathy, neurological involvement, and combined deficiency of OXPHOS complexes in skeletal muscle was clinically and genetically investigated. Analysis of whole-exome sequencing data revealed a homozygous mutation in MRPL44 (c.467 T?>?G), which was not present in the biological father, and a region of homozygosity involving most of chromosome 2, raising the possibility of uniparental disomy. Short-tandem repeat and genome-wide SNP microarray analyses of the family trio confirmed complete maternal uniparental isodisomy of chromosome 2. Mitochondrial ribosome assembly and mitochondrial translation were assessed in patient derived-fibroblasts. These studies confirmed that c.467 T?>?G affects the stability or assembly of the large subunit of the mitochondrial ribosome, leading to impaired mitochondrial protein synthesis and decreased levels of multiple OXPHOS components. This study provides evidence of complete maternal uniparental isodisomy of chromosome 2 in a patient with MRPL44-related disease, and confirms that MRLP44 mutations cause a mitochondrial translation defect that may present as a multisystem disorder with neurological involvement.

     

Total neoadjuvant treatment in locally advanced rectal cancer

Locally advanced rectal cancer requires a multidisciplinary management, traditionally based on neo-adjuvant (chemo) radiotherapy, conservative surgery with total mesorectal excision and adjuvant chemotherapy. Despite effective in term of local control, this strategy is linked to a high risk of distant metastasis (up to 30%). In this context, recent published randomized phase III clinical trials have tested the potential benefits with a different sequencing and/or intensification of the standard components of the trimodal therapy.Here, we briefly assess the efficacy and discuss the clinical relevance of total neoadjuvant treatment with a focus on indications and results in the short-course radiotherapy followed by chemotherapy use for this setting of patients. Long term results and additional prospective studies are necessary to more accurately estimate the clinical benefit and further establish the role of total neoadjuvant therapy in locally advanced rectal cancer disease.     

Commercial lipase immobilization on Accurel MP 1004 porous polypropylene

Three commercial lipases (CLs), A Amano 6 (from Aspergillus niger), M Amano 10 (from Mucor javanicus), and R Amano (from Penicillium roqueforti) – called lipase A, M and R respectively – were characterized in terms of carbohydrate content, protein content and enzymatic activity (p-nitrophenylacetate assay). All the CL preparations contained different proteins as observed from electrophoresis. Lipases were immobilized on Accurel MP1004 porous polypropylene by physical adsorption.The Immobilization process caused a loss of enzymatic activity. The retained activity was similar for lipase M and R (about 15%). In contrast, lipase A retained only the 1.3% of the specific activity of the free lipase. The retained activity of lipases M and R seems to be due to a feature of the support, while the lower activity a of lipase A may be attributed to a strong structure distortion caused by lipase–support interaction.     

Contribuzione alla flora algologica del mare Adriatico

The specific species-rich high-altitude vegetation of the class Carici rupestris-Kobresietea bellardii Ohba 1974 (CK), with the occurrence of many arctic-alpine and endemic species, was chosen for a case study. The analyses were based on a dataset of 37,204 phytosociological relevés from the Slovak Vegetation Database. The traditional classification of the class CK, based on cluster analyses, was reproduced satisfactorily by means of formalised classification, based on the formal definitions created by the Cocktail method together with the frequency-positive fidelity index affiliation. Unequivocal assignment criteria for all eight associations of both alliances [Oxytropido-Elynion Br.-Bl. (1948) 1949 and Festucion versicoloris Krajina 1933] of the class CK were formulated. The formal delimitations followed the traditional ones very well. It was demonstrated that the results of applying the formal definitions created on the basis of a large, geographically stratified dataset capturing the occurrence of all vegetation types in Slovakia were highly similar in comparison with the traditional classification based on the results of cluster analysis. The reliability and the pros and cons of the expert system are also discussed.