The molecular pathogenesis of endotoxic shock and organ failure

Sepsis is still associated with a high mortality rate. Septic shock and sequential multiple organ failure have a strong correlation with poor outcome. Lipopolysaccharide (LPS) plays a pivotal role in the initiation of host responses to Gram-negative infection. A number of mediators, such as cytokines, nitric oxide and eicosanoids, are responsible for most of the manifestations caused by LPS, and circulatory failure, leukocyte-induced tissue injury and coagulation disorder appear to be critical determinants in the development of sequential organ failure. Although several anti-LPS or anti-cytokine clinical trials have been attempted, none of them has so far been successful.     

Endogenous activity rhythm in Talitrus saltator,Britorchestia brito (Crustacea,Amphipoda) and Tylos europaeus (Crustacea,Isopoda) from Barkoukech Beach (Tabarka,Tunisia)

The locomotor activity rhythm of three supralittoral crustacean species, Tylos europaeus (terrestrial isopod) and Britorchestia brito and Talitrus saltator (amphipod, Talitridea), was investigated in Barkoukech Beach. The rhythm was monitored in individual animals in spring under continuous darkness and constant temperature. Results revealed that whatever the species, actograms and mean activity curves showed that specimens of T. europaeus and T. saltator concentrated their activity during the subjective night; whereas, B. brito concentrated its activity during the subjective day. The three species exhibited a circadian locomotor rhythm with mean circadian period, respectively, equal to 24h41′ ± 0h44′, 24h46′ ± 0h55′ and 25h21′ ± 1h16′. The most stable locomotor rhythm was found in T. saltator (0.444 ± 0.246). Furthermore, individuals of T. europaeus were significantly more active (10h47′ ± 2h52′) than the two amphipods. Differences in the activity patterns of the three species will be discussed as an adaptative strategy to respond to interspecific competitive interactions.     

Diversity of terrestrial isopods in the northern Tunisian wetlands

To evaluate the influence of wetland types on the distribution of terrestrial isopods, species richness, relative abundance and diversity indices were studied in the supralittoral zone of 95 wetlands in the north‐western of Tunisian dorsal, belonging to six types: lagoon, hill reservoir, river, dam, lake and sebkha. We tested the following hypothesis: (i) is isopod diversity influenced by wetland types? (ii) is isopod diversity influenced by bioclimatic zones? and (iii) what are the environmental factors influencing isopod distribution? A total of 3255 individuals belonging to twenty species of terrestrial isopods were captured. Species richness differs significantly between wetland types. A highly significant positive relationship between species richness and both humidity and altitudinal gradient was described. The dendrogram of similarities showed a divergence of the lagoons compared to the remaining wetland types.     

Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress

Background  

Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT), within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein.     

Helicobacter pylori Genotypes Associated with Gastric Histo-Pathological Damages in a Moroccan Population

H. pylori persistent infection induces chronic gastritis and is associated with peptic ulcer disease and gastric carcinoma development. The severity of these diseases is related to human’s genetic diversity, H. pylori genetic variability and environmental factors. To identify the prevalence of histo-pathological damages caused by H. pylori infection in Moroccan population, and to determine their association to H. pylori genotypes, a prospective study has been conducted during 3 years on patients attending the gastroenterology department of Hassan II University Hospital (CHU) of Fez, Morocco. A total of 801 Moroccan adults’ patients were recruited; H. pylori was diagnosed and genotyped by PCR in biopsy specimens and histological exam was performed. We found a high rate of glandular atrophy. Chronic inflammation, neutrophil activity and glandular atrophy showed statistically significant association with H. pylori infection. However, intestinal metaplasia was inversely associated to this infection and no association was observed with gastric cancer cases. A statistically significant association was found between intestinal metaplasia and vacAs1 and vac Am1 genotypes in patients aged 50 years and more but not in younger. This last genotype is also associated to gastric cancer. In this study, gastric cancer showed no significant association with H. pylori. Further studies are warranted to determine the role of other etiological agents such as Epstein-Barr virus, human papillomavirus and possibly environmental and dietetic factors in the occurrence of this pathology.     

Cytisus villosus from Northeastern Algeria is nodulated by genetically diverse Bradyrhizobium strains

Fifty-one rhizobial strains isolated from root nodules of Cytisus villosus growing in Northeastern Algeria were characterized by genomic and phenotypic analyses. Isolates were grouped into sixteen different patterns by PCR-RAPD. The phylogenetic status of one representative isolate from each pattern was examined by multilocus sequence analyses of four housekeeping genes (16S rRNA, glnII, recA, and atpD) and one symbiotic gene (nodC). Analysis of 16S rRNA gene sequences showed that all the isolates belonged to the genus Bradyrhizobium. Phylogenetic analyses based on individual or concatenated genes glnII, recA, and atpD indicated that strains cluster in three distinct groups. Ten out of the sixteen strains grouped together with Bradyrhizobium japonicum, while a second group of four clustered with Bradyrhizobium canariense. The third group, represented by isolates CTS8 and CTS57, differed significantly from all other bradyrhizobia known to nodulate members of the Genisteae tribe. In contrast with core genes, sequences of the nodC symbiotic gene from all the examined strains form a homogeneous group within the genistearum symbiovar of Bradyrhizobium. All strains tested nodulated Lupinus angustifolius, Lupinus luteus, and Spartium junceum but not Glycine max. From these results, it is concluded that C. villosus CTS8 and CTS57 strains represent a new lineage within the Bradyrhizobium genus.     

M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity

Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.     

Esthesioneuroblastoma metastatic to the breast in a young woman

BACKGROUND: Metastases to the breast are rare and can be missed without knowledge of the clinical history. We report an unusual breast metastasis originating in an olfactory neuroblastoma. CASE: A breast metastasis from esthesioneuroblastoma occurred in a 20-year-old woman 2 years after the onset of the disease. The aspirates were hypercellular and composed of cellular aggregates and single cells with a monomorphic appearance. The cytoplasm was scanty and inconspicuous. The nucleus was large, with granular, hyperchromatic chromatin. Mitoses and apoptotic bodies were numerous. Because we were unaware of the past history at the time of the cytologic analysis, a definitive diagnosis was made only after pathologic study. CONCLUSION: Esthesioneuroblastoma metastatic to the breast must be considered in the differential diagnosis of breast metastases. Fine needle aspiration, in conjunction with clinical information, can be effective in the diagnosis of esthesioneuroblastoma metastatic to the breast.     

Defective Lamin A-Rb Signaling in Hutchinson-Gilford Progeria Syndrome and Reversal by Farnesyltransferase Inhibition

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by a de novo heterozygous point mutation G608G (GGC>GGT) within exon 11 of LMNA gene encoding A-type nuclear lamins. This mutation elicits an internal deletion of 50 amino acids in the carboxyl-terminus of prelamin A. The truncated protein, progerin, retains a farnesylated cysteine at its carboxyl terminus, a modification involved in HGPS pathogenesis. Inhibition of protein farnesylation has been shown to improve abnormal nuclear morphology and phenotype in cellular and animal models of HGPS. We analyzed global gene expression changes in fibroblasts from human subjects with HGPS and found that a lamin A-Rb signaling network is a major defective regulatory axis. Treatment of fibroblasts with a protein farnesyltransferase inhibitor reversed the gene expression defects. Our study identifies Rb as a key factor in HGPS pathogenesis and suggests that its modulation could ameliorate premature aging and possibly complications of physiological aging.