Clinical,Molecular, and Computational Analysis in two cases with mitochondrial encephalomyopathy associated with SUCLG1 mutation in a consanguineous family

Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (α subnit) and SUCLA2 (β subnit). We report here, two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy, hearing loss, lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria. Mutational analysis of SUCLG1 gene showed, for the first time, the presence of c.41T > C in the exon 1 at homozygous state. In-silico analysis revealed that this mutation substitutes a conserved methionine residue to a threonine at position 14 (p.M14T) located at the SUCLG1 protein mitochondrial targeting sequence. Moreover, these analysis predicted that this mutation alter stability structure and mitochondrial translocation of the protein. In Addition, a decrease in mtDNA copy number was revealed by real time PCR in the peripheral blood leukocytes in the two patients compared with controls.     

Analysis of monomeric mutants of HSC70: a possible relationship between oligomerization and functional properties

Data of this study showed that alphaD-alphaE helices and the conserved interdomain linker are two interfaces essential not only for the self-association but also for the functional properties of rat HSC70. Self-association which is a conserved property of HSP70 seems to be important for the activity of these proteins.     

A whole mitochondrial genome screening in a MELAS patient: a novel mitochondrial tRNA(Val) mutation

Mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder characterized by a wide variety of clinical presentations and a multisystemic organ involvement. In this study, we report a Tunisian girl with clinical features of MELAS syndrome who was negative for the common m.3243A>G mutation, but also for the reported mitochondrial DNA (mtDNA) mutations and deletions. Screening of the entire mtDNA genome showed several known mitochondrial variants besides to a novel transition m.1640A>G affecting a wobble adenine in the anticodon stem region of the tRNA(Val). This nucleotide was conserved and it was absent in 150 controls suggesting its pathogenicity. In addition, no mutations were found in the nuclear polymerase gamma-1 gene (POLG1). These results suggest further investigation nuclear genes encoding proteins responsible for stability and structural components of the mtDNA or to the oxidative phosphorylation machinery to explain the phenotypic variability in the studied family.     

The epistatic interrelationships of IL-1, IL-1 receptor antagonist,and the type I IL-1 receptor

Mice lacking the gene for the IL-1R antagonist (IL-1ra) show abnormal development and homeostasis as well as altered responses to infectious and inflammatory stimuli. A reduction in the level of IL-1 signaling, either by deletion of the receptor or increased expression of IL-1ra, does not affect development or homeostasis, but does alter immune responses. In this study we use genetic epistasis to investigate the interdependence of selected genes in the IL-1 family in the regulation of these developmental and immunological processes. Deletion of the gene encoding the type I IL-1R (IL-1RI) is epistatic to deletion of the IL-1ra gene. Therefore, all functions of IL-1ra depend upon the presence of a functional receptor; there is no other target. Similarly, overexpression of the mRNA encoding the secreted form of IL-1ra is epistatic to deletion of the receptor antagonist, leaving the role of the intracellular splice variants of IL-1ra unknown. The abnormal development of IL-1ra-deficient mice is probably due to chronic overstimulation of the proinflammatory pathway via IL-1, but a clear single pathological defect is not apparent. These results support the model that the only essential function of IL-1ra in both health and disease is competitive inhibition of the IL-1RI.     

Effect of inoculation of lactic acid bacteria on proteolytic activity of psychrotrophic Gram-negative bacteria in fresh farmed sea bass (Dicentrarchus labrax) fillets during storage at 4 °C under vacuum-packed conditions

The effect of two strains of lactic acid bacteria (LAB) (Lactococcus lactis and Carnobacterium piscicola) on the proteolytic activity of four strains of Psychrotrophic Gram-negative bacteria [Psy G(?)] (Pseudomonas fluorescens, Aeromonas hydrophila, Pseudomonas putida and Photobacterium damselae) has been determined using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), in fresh vacuum-packed farmed sea bass (Dicentrarchus labrax) fillets artificially contaminated, during 21 days of chilled storage. The profiles of sarcoplasmic (SP) and myofibrillar (MP) proteins indicated that the major changes were produced with Pseudomonas fluorescens, Aeromonas hydrophila, and Pseudomonas putida starters. The results also showed that LAB strains presented a weak proteolytic activity against MP and SP proteins in muscle of fresh sea bass. In fact, we noted the less pronounced degradation of protein fractions in samples inoculated with LAB combination. Moreover, a significant bacteriostatic effect of LAB strains was demonstrated against all microflora, particularly mesophilic aerobic plate counts (MAPC) and psychrotrophic bacterial counts (PBC), with fillets remaining unspoiled until the end of storage, against values of 7 and 8 log CFU/g, respectively; control fish fillets exceeded the upper acceptability limit.     

Improving performance of olive trees by the enhancement of key physiological parameters of olive leaves in response to foliar fertilization

Most of the studies investigated the effects of nutrient-based fertilizers on olive fruits and oil quality; few studies have been interested in the modification of the chemical composition of olive leaves in response to fertilization. Thus, the current study aims to examine the effects of foliar fertilization on the mineral profile of olive leaves as well as the concentrations of chlorophyll, antioxidants (phenolic compounds) and carbohydrates. Experimentation consists of the annual application of six treatments during two successive growing seasons (2009–2010): TC (untreated trees), P1 (nitrogen-based fertilizer), P2 (contains boron, magnesium and manganese), P3 (phosphorus and potassium based fertilizer), P4 (rich in calcium and phosphorus), T5 (P1 and P2 application) and T6 (P1, P2, P3 and P4 application). At the end of the experiment, mineral analysis of olive leaves showed an increase in the concentrations of most nutrients which induced changes in biochemical composition: an increase of chlorophyll content, a reduction of total phenols and oleuropein concentrations coupled with an increase of hydroxytyrosol level. Moreover, an increase of total sugar content and most individual sugars, principally translocated forms of sugars (mannitol, sucrose and raffinose), was also observed. The accumulation of these key physiological parameters by foliar fertilization suggests an improvement of physiological performance and photosynthetic capacity of olive trees. Moreover, from a biological point of view, the results of the study revealed the possibility to improve plants of medicinal interest by enhancing the accumulation of some bio-active compounds, such as hydroxytyrosol and mannitol, via foliar nutrient supply.     

Autosomal single-gene disorders involved in human infertility

Human infertility, defined as the inability to conceive after 1?year of unprotected intercourse, is a healthcare problem that has a worldwide impact. Genetic causes of human infertility are manifold. In addition to the chromosomal aneuploidies and rearrangements, single-gene defects can interfere with human fertility. This paper provides a review of the most common autosomal recessive and autosomal dominant single-gene disorders involved in human infertility. The genes reviewed are CFTR, SPATA16, AURKC, CATSPER1, GNRHR, MTHFR, SYCP3, SOX9, WT1 and NR5A1 genes. These genes may be expressed throughout the hypothalamic-pituitary–gonadal-outflow tract axis, and the phenotype of affected individuals varies considerably from varying degrees of spermatogenic dysfunction leading to various degrees of reduced sperm parameters, through hypogonadotropic hypogonadism reslting in pubertal deficiencies, until gonadal dysgenesis and XY and XX sex reversal. Furthermore, congenital bilateral absence of the vas deferens, as well as premature ovarian failure, have been reported to be associated with some single-gene defects.     

Hypercapnia slows down proliferation and apoptosis of human bone marrow promyeloblasts

Stem cells are being applied in increasingly diverse fields of research and therapy; as such, growing and culturing them in scalable quantities would be a huge advantage for all concerned. Gas mixtures containing 5 % CO₂ are a typical concentration for the in vitro culturing of cells. The effect of varying the CO₂ concentration on promyeloblast KG-1a cells was investigated in this paper. KG-1a cells are characterized by high expression of CD34 surface antigen, which is an important clinical surface marker for human hematopoietic stem cells (HSCs) transplantation. KG-1a cells were cultured in three CO₂ concentrations (1, 5 and 15 %). Cells were batch-cultured and analyzed daily for viability, size, morphology, proliferation, and apoptosis using flow cytometry. No considerable differences were noted in KG-1a cell morphological properties at all three CO₂ levels as they retained their myeloblast appearance. Calculated population doubling time increased with an increase in CO₂ concentration. Enhanced cell proliferation was seen in cells cultured in hypercapnic conditions, in contrast to significantly decreased proliferation in hypocapnic populations. Flow cytometry analysis revealed that apoptosis was significantly (p = 0.0032) delayed in hypercapnic cultures, in parallel to accelerated apoptosis in hypocapnic ones. These results, which to the best of our knowledge are novel, suggest that elevated levels of CO₂ are favored for the enhanced proliferation of bone marrow (BM) progenitor cells such as HSCs.     

Primary malignant non-Hodgkin's lymphoma of the breast: a study of seven cases and literature review

ABSTRACT: INTRODUCTION: Primary breast lymphoma is an uncommon disease with poor clinical outcome. Breast lymphomas present less than 0.5% of malignant breast neoplasms and 2.2% of extranodal lymphomas. This study investigated the clinicopathological features and optimal treatment of PBL. Case presentations Clinical records of seven Moroccan PBL patients, treated at the National Institute of Oncology, Rabat, Morocco, from 2002 to 2010, were reviewed. Six of the patients were women and one a man, with ages ranging from 32 to 76. Five patients had stage IE and two stage IIE. All of the patients were classified with DLBCL. Of seven patients, one received a mastectomy and three excision of the breast lesion. Axillary dissection was performed in three patients. Two patients received chemotherapy followed by radiotherapy, while four received chemotherapy alone. Complete remission (CR) following primary treatment for all patients with PBL except in two cases was obtained. In one patient, recurrence occurred. CONCLUSIONS: There is no consensus on the question of how to best treat PBL: Mastectomy offers no benefit in the treatment of PBL. The combined therapy approach, with chemotherapy and radiotherapy, is the most successful treatment. PBL is poorly represented in rituximab-containing trials in DLBCL patients; there is not much experience with this agent in breast DLBCL. Because of the high incidence of central nervous system (CNS) involvement in PBL patients, many authors strongly believe that patients with aggressive forms of PBL should receive CNS infiltration prophylaxis.     

A new concept of olfactory biosensor based on interdigitated microelectrodes and immobilized yeasts expressing the human receptor OR17-40

This work shows the feasibility of an olfactory biosensor based on the immobilization of Saccharomyces cerevisiae yeast cells genetically modified to express the human olfactory receptor OR17-40 onto interdigitated microconductometric electrodes. This olfactory biosensor has been applied to the detection of its specific odorant (helional) with a high sensitivity (threshold 10⁻¹⁴ M). In contrast, no significant response was observed using a non-specific odorant (heptanal), which suggests a good selectivity. Thus, this work may represent a first step towards a new kind of bioelectronic noses based on whole yeast cells and allowing a real time monitoring of olfactory receptor activation. Presented at the joint biannual meeting of the SFB-GEIMM-GRIP, Anglet, France, 14–19 October, 2006.