mTOR Complex 1 Plays Critical Roles in Hematopoiesis and Pten-Loss-Evoked Leukemogenesis

The mechanistic target of rapamycin (mTOR) pathway serves as a key sensor of cellular-energetic state?and functions to maintain tissue homeostasis. Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) function and is associated with leukemogenesis. However, the roles of the unique mTOR complexes (mTORCs) in hematopoiesis and leukemogenesis have not been adequately elucidated. We deleted the mTORC1 component, regulatory-associated protein of mTOR (Raptor), in mouse HSCs and its loss causes a nonlethal phenotype characterized by pancytopenia, splenomegaly, and the accumulation of monocytoid cells. Furthermore, Raptor is required for HSC regeneration, and plays largely nonredundant roles with rapamycin-insensitive companion of mTOR (Rictor) in these processes. Ablation of Raptor also significantly extends survival of mice in models of leukemogenesis evoked by Pten deficiency. These data delineate critical roles for mTORC1 in hematopoietic function and leukemogenesis and inform clinical strategies based on chronic mTORC1 inhibition.     

Monte Carlo simulation of myoglobin primary to helical structure

A Monte Carlo simulation is presented of the formation of the individual helices of myoglobin from their primary to their helical structures. A simplified model in which each amino acid residue is replaced by a single interaction center is used. The small helices formed are in good agreement with experiment, while the larger helices are moderately well reproduced.     

Cell-wall-bound proteinase of Lactobacillus delbrueckii subsp. lactis ACA-DC 178: characterization and specificity for beta-casein

Lactobacillus delbrueckii subsp. lactis ACA-DC 178, which was isolated from Greek Kasseri cheese, produces a cell-wall-bound proteinase. The proteinase was removed from the cell envelope by washing the cells with a Ca2+-free buffer. The crude proteinase extract shows its highest activity at pH 6.0 and 40 degrees C. It is inhibited by phenylmethylsulfonyl fluoride, showing that the enzyme is a serine-type proteinase. Considering the substrate specificity, the enzyme is similar to the lactococcal PI-type proteinases, since it hydrolyzes beta-casein mainly and alpha- and kappa-caseins to a much lesser extent. The cell-wall-bound proteinase from L. delbrueckii subsp. lactis ACA-DC 178 liberates four main peptides from beta-casein, which have been identified.     

Acquisition through Horizontal Gene Transfer of Plasmid pSMA198 by Streptococcus macedonicus ACA-DC 198 Points towards the Dairy Origin of the Species

Background

Streptococcus macedonicus is an intriguing streptococcal species whose most frequent source of isolation is fermented foods similarly to Streptococcus thermophilus. However, S. macedonicus is closely related to commensal opportunistic pathogens of the Streptococcus bovis/Streptococcus equinus complex.

Methodology/Principal Findings

We analyzed the pSMA198 plasmid isolated from the dairy strain Streptococcus macedonicus ACA-DC 198 in order to provide novel clues about the main ecological niche of this bacterium. pSMA198 belongs to the narrow host range pCI305/pWV02 family found primarily in lactococci and to the best of our knowledge it is the first such plasmid to be reported in streptococci. Comparative analysis of the pSMA198 sequence revealed a high degree of similarity with plasmids isolated from Lactococcus lactis strains deriving from milk or its products. Phylogenetic analysis of the pSMA198 Rep showed that the vast majority of closely related proteins derive from lactococcal dairy isolates. Additionally, cloning of the pSMA198 ori in L. lactis revealed a 100% stability of replication over 100 generations. Both pSMA198 and the chromosome of S. macedonicus exhibit a high percentage of potential pseudogenes, indicating that they have co-evolved under the same gene decay processes. We identified chromosomal regions in S. macedonicus that may have originated from pSMA198, also supporting a long co-existence of the two replicons. pSMA198 was also found in divergent biotypes of S. macedonicus and in strains isolated from dispersed geographic locations (e.g. Greece and Switzerland) showing that pSMA198’s acquisition is not a recent event.

Conclusions/Significance

Here we propose that S. macedonicus acquired plasmid pSMA198 from L. lactis via an ancestral genetic exchange event that took place most probably in milk or dairy products. We provide important evidence that point towards the dairy origin of this species.     

The association between glycemia and endothelial function in nondiabetic individuals: the importance of body weight

The aim of this study was to examine the association between glycemia and markers of early atherosclerosis in healthy nondiabetic individuals. In 309 individuals without diabetes or symptomatic cardiovascular disease, we assessed long-term glycemia by glycosylated hemoglobin (HbA1c) and endothelial function by flow-mediated dilatation (FMD) in the brachial artery. HbA1c was negatively associated with FMD (r = -0.162, P = 0.004). Multivariate linear regression analysis after adjusting for common risk factors of cardiovascular disease showed that BMI was an effect modifier of the association between HbA1c and FMD (P = 0.034 for the HbA1c x BMI interaction). We stratified the FMD outcome data into two groups separated by the median BMI (group 1: BMI < or = 26.1 kg/m(2) and group 2: BMI > 26.1 kg/m(2)). In the lower BMI group, HbA1c was an independent predictor of FMD even when adjusted for confounding factors associated with impaired glucose metabolism (r = -0.215, P = 0.009), but in the higher BMI group HbA1c was not associated with FMD (r = -0.051, P = 0.5). In a nondiabetic population, long-term glycemia was associated with endothelial dysfunction only in lean individuals. In the overweight individuals, this association was not apparent, possibly because some of the mechanisms that mediate the effect of glycemia on vascular function are shared by obesity.     

The secretory glands of <Emphasis Type="Italic">Asphodelus aestivus</Emphasis> flower

Various secretory glands are observed on Asphodelus aestivus flower, a common geophyte of Mediterranean type ecosystem. The floral nectary has the form of individual slits between the gynecium carpels (septal nectary). The septal slits extend downwards to the ascidiate zone of the carpels. The nectar is secreted by the epidermal cells of the slits, which differentiate into epithelial cells. The latter contain numerous organelles, among which endoplasmic reticulum elements and golgi bodies predominate. Nectar secretion results in an expansion of the space between the septa. The nectar becomes discharged through small holes on the ovary wall. Six closely packed stamens surround the ovary and bear numerous papillae at their basis. These papillae are actually osmophores, i.e. secretory structures responsible for the manufacture, secretion and dispersion of terpenic scent. A mucilage gland (obturator) exists between the lateral ovule and the ovary septa, giving a positive reaction with Schiff’s reagent. This gland secretes a mucoproteinaceous product to nourish the pollen tube and to facilitate its penetration into the ovary.