Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women

ContextObesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity.ObjectivesWe compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development.Methods30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression.ResultsSystemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR.ConclusionOur results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.     

Traditional Banana Diversity in Oceania: An Endangered Heritage

This study aims to understand the genetic diversity of traditional Oceanian starchy bananas in order to propose an efficient conservation strategy for these endangered varieties. SSR and DArT molecular markers are used to characterize a large sample of Pacific accessions, from New Guinea to Tahiti and Hawaii. All Pacific starchy bananas are shown of New Guinea origin, by interspecific hybridization between Musa acuminata (AA genome), more precisely its local subspecies M. acuminata ssp. banksii, and M. balbisiana (BB genome) generating triploid AAB Pacific starchy bananas. These AAB genotypes do not form a subgroup sensu stricto and genetic markers differentiate two subgroups across the three morphotypes usually identified: Iholena versus Popoulu and Maoli. The Popoulu/Maoli accessions, even if morphologically diverse throughout the Pacific, cluster in the same genetic subgroup. However, the subgroup is not strictly monophyletic and several close, but different genotypes are linked to the dominant genotype. One of the related genotypes is specific to New Caledonia (NC), with morphotypes close to Maoli, but with some primitive characters. It is concluded that the diffusion of Pacific starchy AAB bananas results from a series of introductions of triploids originating in New Guinea area from several sexual recombination events implying different genotypes of M. acuminata ssp. banksii. This scheme of multiple waves from the New Guinea zone is consistent with the archaeological data for peopling of the Pacific. The present geographic distribution suggests that a greater diversity must have existed in the past. Its erosion finds parallels with the erosion of cultural traditions, inexorably declining in most of the Polynesian or Melanesian Islands. Symmetrically, diversity hot spots appear linked to the local persistence of traditions: Maoli in New Caledonian Kanak traditions or Iholena in a few Polynesian islands. These results will contribute to optimizing the conservation strategy for the ex-situ Pacific Banana Collection supported collectively by the Pacific countries.     

The roles of Centrin 2 and Dynein Light Chain 8a in apical secretory organelles discharge of Toxoplasma gondii

To efficiently enter host cells, apicomplexan parasites such as Toxoplasma gondii rely on an apical complex composed of tubulin‐based structures as well as two sets of secretory organelles named micronemes and rhoptries. The trafficking and docking of these organelles to the apical pole of the parasite is crucial for the discharge of their contents. Here, we describe two proteins typically associated with microtubules, Centrin 2 (CEN2) and Dynein Light Chain 8a (DLC8a), that are required for efficient host cell invasion. CEN2 localizes to four different compartments, and remarkably, conditional depletion of the protein occurs in stepwise manner, sequentially depleting the protein pools from each location. This phenomenon allowed us to discern the essential function of the apical pool of CEN2 for microneme secretion, motility, invasion and egress. DLC8a localizes to the conoid, and its depletion also perturbs microneme exocytosis in addition to the apical docking of the rhoptry organelles, causing a severe defect in host cell invasion. Phenotypic characterization of CEN2 and DLC8a indicates that while both proteins participate in microneme secretion, they likely act at different steps along the cascade of events leading to organelle exocytosis.     

PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress

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So Close Yet So Different: Cultural Differences Among Farmers in Central Kenya Affect Their Knowledge of Sorghum (Sorghum bicolor [L.] Moench) Landrace Identification

Economic Botany - So Close Yet So Different: Cultural Differences among Farmers in Central Kenya Affect Their Knowledge of Sorghum (Sorghum bicolor [L.] Moench) Landrace Identification. Whether...     

Distinction between major and minor Bacillus signal peptidases based on phylogenetic and structural criteria

The processing of secretory preproteins by signal peptidases (SPases) is essential for cell viability. As previously shown for Bacillus subtilis, only certain SPases of organisms containing multiple paralogous SPases are essential. This allows a distinction between SPases that are of major and minor importance for cell viability. Notably, the functional difference between major and minor SPases is not reflected clearly in sequence alignments. Here, we have successfully used molecular phylogeny to predict major and minor SPases. The results were verified with SPases from various bacilli. As predicted, the latter enzymes behaved as major or minor SPases when expressed in B. subtilis. Strikingly, molecular modeling indicated that the active site geometry is not a critical parameter for the classification of major and minor Bacillus SPases. Even though the substrate binding site of the minor SPase SipV is smaller than that of other known SPases, SipV could be converted into a major SPase without changing this site. Instead, replacement of amino-terminal residues of SipV with corresponding residues of the major SPase SipS was sufficient for conversion of SipV into a major SPase. This suggests that differences between major and minor SPases are based on activities other than substrate cleavage site selection.     

The phylogenetic position of "Acomyinae" (Rodentia, Mammalia) as sister group of a Murinae + Gerbillinae clade: evidence from the nuclear ribonuclease gene.

The phylogenetic relationships of Acomys and Uranomys within Muridae were investigated using nuclear pancreatic ribonuclease A gene sequences. The various kinds of substitutions in the data matrix (15 taxa x 375 nucleotides) were examined for saturation, in order to apply a weighted parsimony approach. Phylogenies were derived by maximum parsimony (weighted and unweighted) and maximum likelihood procedures, using a dormouse (Gliridae) as outgroup. Maximum likelihood gave the most robust results. All analyses cluster some traditional taxa with a strong robustness, such as three species of the genus Mus, two South-East Asian rats, and two genera in each of the gerbil and vole families. When analyzed with those of other murid rodents representing Murinae, Gerbillinae, Arvicolinae, Cricetinae, and Sigmodontinae, sequences of the ribonuclease gene suggest that Acomys and Uranomys constitute a monophyletic clade at the subfamily level, denoted "Acomyinae." The relationships between the six subfamilies of Muridae appear poorly resolved, except for a clade uniting Murinae, Acomyinae, and Gerbillinae. Within this clade, the sister group of Acomyinae could not be identified, as the branch length defining a Gerbillinae + Murinae cluster is extremely short. The poor resolution of our phylogenetic inferences is probably the result of two confounding factors, namely the limited size of the pancreatic ribonuclease sequence and the probable short time intervals during the radiation of the six murid subfamilies involved in this study.