mTORC1 activity is supported by spatial association with focal adhesions

The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Activation of mTORC1 by amino acids and growth factors involves recruitment of the complex to the lysosomal membrane and is further supported by lysosome distribution to the cell periphery. Here, we show that translocation of lysosomes toward the cell periphery brings mTORC1 into proximity with focal adhesions (FAs). We demonstrate that FAs constitute discrete plasma membrane hubs mediating growth factor signaling and amino acid input into the cell. FAs, as well as the translocation of lysosome-bound mTORC1 to their vicinity, contribute to both peripheral and intracellular mTORC1 activity. Conversely, lysosomal distribution to the cell periphery is dispensable for the activation of mTORC1 constitutively targeted to FAs. This study advances our understanding of spatial mTORC1 regulation by demonstrating that the localization of mTORC1 to FAs is both necessary and sufficient for its activation by growth-promoting stimuli.     

VPS13D bridges the ER to mitochondria and peroxisomes via Miro

Mitochondria, which are excluded from the secretory pathway, depend on lipid transport proteins for their lipid supply from the ER, where most lipids are synthesized. In yeast, the outer mitochondrial membrane GTPase Gem1 is an accessory factor of ERMES, an ER–mitochondria tethering complex that contains lipid transport domains and that functions, partially redundantly with Vps13, in lipid transfer between the two organelles. In metazoa, where VPS13, but not ERMES, is present, the Gem1 orthologue Miro was linked to mitochondrial dynamics but not to lipid transport. Here we show that Miro, including its peroxisome-enriched splice variant, recruits the lipid transport protein VPS13D, which in turn binds the ER in a VAP-dependent way and thus could provide a lipid conduit between the ER and mitochondria. These findings reveal a so far missing link between function(s) of Gem1/Miro in yeast and higher eukaryotes, where Miro is a Parkin substrate, with potential implications for Parkinson’s disease pathogenesis.     

Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction

Peptidoglycan is the major structural component of the Staphylococcus aureus cell wall, in which it maintains cellular integrity, is the interface with the host, and its synthesis is targeted by some of the most crucial antibiotics developed. Despite this importance, and the wealth of data from in vitro studies, we do not understand the structure and dynamics of peptidoglycan during infection. In this study we have developed methods to harvest bacteria from an active infection in order to purify cell walls for biochemical analysis ex vivo. Isolated ex vivo bacterial cells are smaller than those actively growing in vitro, with thickened cell walls and reduced peptidoglycan crosslinking, similar to that of stationary phase cells. These features suggested a role for specific peptidoglycan homeostatic mechanisms in disease. As S. aureus missing penicillin binding protein 4 (PBP4) has reduced peptidoglycan crosslinking in vitro its role during infection was established. Loss of PBP4 resulted in an increased recovery of S. aureus from the livers of infected mice, which coincided with enhanced fitness within murine and human macrophages. Thicker cell walls correlate with reduced activity of peptidoglycan hydrolases. S. aureus has a family of 4 putative glucosaminidases, that are collectively crucial for growth. Loss of the major enzyme SagB, led to attenuation during murine infection and reduced survival in human macrophages. However, loss of the other three enzymes Atl, SagA and ScaH resulted in clustering dependent attenuation, in a zebrafish embryo, but not a murine, model of infection. A combination of pbp4 and sagB deficiencies resulted in a restoration of parental virulence. Our results, demonstrate the importance of appropriate cell wall structure and dynamics during pathogenesis, providing new insight to the mechanisms of disease.     

A dynamic task scheduler tolerant to multiple hibernations in cloud environments

Cluster Computing - Cloud platforms usually offer several types of Virtual Machines (VMs) with different guarantees in terms of availability and volatility, provisioning the same resource through...     

Notes on the genus Orobanche in Italy: 3. Taxa described by A. Bertoloni

Abstract

Original material of the 12 taxa described as new by Bertoloni has been examined, and typification of their names is discussed. Lectotypes are designated for 11 of Bertoloni's names, one (O. densiflora Bertol.) had been lectotypified before. Orobanche bicolor Bertol. (non C. A. Mey.) belongs to O. cernua L., O. cruenta Bertol. to O. gracilis Sm., O. stricta Moris ex Bertol. to O. schultzii Mutel, O. thyrsoidea Moris ex Bertol to O. rigens Loisel., O. crithmi Bertol. to O. minor Sm., O. vitalbae Bertol. to O. artemisiae-campestris Gaudin, O. fragrantissima Bertol. to O. lutea Baumg., O. laurina Bertol. to O. hederae Duby, O. yuccae Savi f. ex Bertol. to O. hederae Duby (not to O. minor Sm.), O. centaurina Bertol. to O. litorea Guss. (not to O. artemisiae-campestris Gaudin). O. australis Moris ex Bertol., included by Beck in O. canescens C. Presl, is a good species restricted to Sardinia. O. densiflora Bertol. must not, as is customary, be ascribed to Reuter who republished it later.     

A phytosociological analysis of abandoned terraced olive grove shrublands in the Tyrrhenian district of Central Italy

ABSTRACT

A phytosociological study of the shrubland communities which colonise abandoned terraced olive groves in the Tyrrhenian district of Central Italy is presented here. The vegetational analysis was carried out using the Braun Blanquet phytosociological approach. Two main types of shrubland communities characterising distinct environmental conditions occur within abandoned terraced olive groves. On the one hand, there are those scrub types which tend to occupy the central part of the terrace; on the other hand, there are the scrubs types which develop along the stone walls bordering the terrace. Different phytosociological associations, sub-associations, and variants ranging from Pistacio-Rhamnetalia alaternii to Prunetalia spinosae are recognised and described. In the warm dry areas, both Myrto-Lentiscetum and Rhamno-Euphorbietum dendroidis occur. Also, a new Oleo-Ceratonion sub-association (Myrto-Lentiscetum spartietosum junceii) is presented here for the first time. In the inner zones of the study area, a range of aspects characterising a new Pruno-Rubion ulmifolii community type (Roso-Rubetum ulmifolii ass. nova) are identified.     

Analisi citologica di alcune specie del genere Vicia

Abstract

Karyology of some species of Vicia. The species studied are: Vicia articulata, Vicia monantha, Vicia narbonensis and Vicia ervilia.

The chromosome number 2n = 14 counted for the first three species agrees with that reported in literature; that of Vicia monantha (2n=14) agrees with that quoted by Heitz, while Senn finds 2n=12.

Karyotypes of V. narbonensis and V. ervilia show appreciable differences from those reported in literature.     

Modification of chromatin organisation at low water potential in cultured cells of Solanum tuberosum: Possible involvement of dehydrins

ABSTRACT

To understand the mechanisms which enable the nucleus to function under low water potential, the morphology and biochemistry of potato cell nuclei were studied. Conformational modifications were observed in the chromatin of nuclei of cells growing under low water potential. These modifications include a higher number of heterochromatic centres, enlargement of the nuclear diameter, and a different accessibility of DNA to the action of restriction enzymes. Biochemical analyses showed that these chromatin modifications may coincide with quantitative and qualitative variations of several nuclear proteins, some of which may belong to the dehydrin family. We especially focussed our attention on a 45-kDa protein that is heat-stable and is recognised by an antibody raised against the conserved domain of dehydrins. The survival of potato cells in an environment where water availability is low may depend on several simultaneous events regarding the nucleus. The accumulation in the nucleus of specific proteins such as dehydrins could be required to stabilise the chromatin by means of their molecule-salvation action. Further studies are in progress to check whether or not variations in chromatin organisation may be one of the numerous traits that a cell must acquire to become water-stress resistant.     

Iron Release in Erythrocytes and Plasma Non Protein-bound Iron in Hypoxic and Non Hypoxic Newborns

Iron is released in a desferrioxamine (DFO)-chelatable form (DCI) when erythrocytes are challenged by an oxidative stress. In &#103 -thalassemic erythrocytes, both DCI content and release (after aerobic incubation for 24 h) are increased and correlated with the fetal hemoglobin (HbF) levels. Since erythrocytes from newborns have an extremely high content of HbF and are exposed to conditions of oxidative stress, the release of iron in these erythrocytes was investigated. The erythrocyte DCI content was increased in preterm but not in term newborns as compared to adults, while the release was increased in both preterm and term erythrocytes. The level of plasma non protein-bound iron (NPBI), which was not detectable in adults, was much higher in preterm than in term newborns. When term plus preterm newborns were divided in two groups, normoxic and hypoxic, according to cord blood pH, it was found that both iron release and NBPI were markedly higher in the hypoxic newborns compared to normoxic ones. Similar results were also obtained when the preterm and term infants were considered separately on the basis of cord blood pH. Therefore, iron release and NPBI are higher when conditions of hypoxia occur. In fact, when the values for iron release and NPBI were separately plotted against cord blood pH values, significant negative correlations were seen in both cases. NPBI was correlated with iron release seen in all the newborns and a significant part of the released iron could be recovered into the incubation medium at the end of the incubation.