Simulated microgravity induces nuclear translocation of Bax and BCL-2 in glial cultured C6 cells

Alterations in the control of apoptotic processes were observed in cells during space flight or under simulated microgravity, the latter obtained with the 3D-Random Positioning Machine (3D-RPM). Usually the proteins Bax and Bcl-2, act as pro- or anti-apoptotic regulators. Here we investigated the effects of simulated microgravity obtained by the 3D-RPM on cell viability, localization and expression of Bax and Bcl-2 in cultures of glial cancerous cells. We observed for the first time a transient cytoplasmic/nuclear translocation of Bax and Bcl-2 triggered by changing gravity vector. Bax translocates into the nucleus after 1 h, is present simultaneously in the cytoplasm after 6 h and comes back to the cytoplasm after 24 h. Bcl-2 translocate into the nucleus only after 6 h and comes back to the cytoplasm after 24 h. Physiological meaning, on the regulation of apoptotic event and possible applicative outcomes of such finding are discussed

New miRNA Signature Heralds Human NK Cell Subsets at Different Maturation Steps: Involvement of miR-146a-5p in the Regulation of KIR Expression

Natural killer cells are cytotoxic innate lymphoid cells that play an important role for early host defenses against infectious pathogens and surveillance against tumor. In humans, NK cells may be divided in various subsets on the basis of the relative CD56 expression and of the low-affinity FcγRIIIA CD16. In particular, the two main NK cell subsets are represented by the CD56bright/CD16−/dim and the CD56dim/CD16bright NK cells. Experimental evidences indicate that CD56bright and CD56dim NK cells represent different maturative stages of the NK cell developmental pathway. We identified multiple miRNAs differentially expressed in CD56bright/CD16− and CD56dim/CD16bright NK cells using both univariate and multivariate analyses. Among these, we found a few miRNAs with a consistent differential expression in the two NK cell subsets, and with an intermediate expression in the CD56bright/CD16dim NK cell subset, representing a transitional step of maturation of NK cells. These analyses allowed us to establish the existence of a miRNA signature able to efficiently discriminate the two main NK cell subsets regardless of their surface phenotype. In addition, by analyzing the putative targets of representative miRNAs we show that hsa-miR-146a-5p, may be involved in the regulation of killer Ig-like receptor (KIR) expression. These results contribute to a better understanding of the physiologic significance of miRNAs in the regulation of the development/function of human NK cells. Moreover, our results suggest that hsa-miR-146a-5p targeting, resulting in KIR down-regulation, may be exploited to generate/increment the effect of NK KIR-mismatching against HLA-class I+ tumor cells and thus improve the NK-mediated anti-tumor activity

Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition

Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognizing the widest array of HLA-I ligands. These differences were further reflected in functional studies using NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005, and *015 polymorphisms are remote from the KIR3DL1-HLA-I interface, the structures of these three KIR3DL1-HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs

Geological map of the eastern sector of the Gorgoglione Basin (southern Italy)

In this paper we report new stratigraphic data related to a new geological map of the Miocene Gorgoglione Basin of southern Italy, traditionally considered as a piggy-back or wedge-top basin filled by a turbidite-like succession. Well exposed outcrops in the study area (eastern sector of the basin) show four unconformities in the Castelmezzano-Pietrapertosa area. Two of these unconformities pass to paraconformities southeastward, in the Cirigliano-Gorgoglione area. Based on new stratigraphic data the "succession of the Gorgoglione Flysch" can be divided into different informal units: Val Miletta formation and Gorgoglione supersynthem. The latter can be subdivided into the Cirigliano and Castelmezzano synthems. The previously established Cirigliano synthem is here divided into three subsynthems. The lowermost sediments of the Gorgoglione Flysch on the eastern sectors correspond to a complex unit (Val Miletta formation) including Numidian-like quartzarenites, Gorgoglionelike sandstones, and, at the top of the formation, an olistostrome of varicoloured clays, belonging to the Argille Variegate Group. The stratigraphic analyses and the biostratigraphic results based on calcareous plankton assemblage, improve the reconstruction of the geometries of the sedimentary bodies and the time-space facies evolution of the synthems. Sedimentologic and petrographic characters of the upper part of the Castelmezzano synthem show a clear fining and thinning upward trend. Medium- and fine-grained arenites, varying in composition from quartz sandstones to siltstones and shales, are locally marked by abundant planktonic foraminifera and are interpreted as contourites. Moreover, the relationships between tectonics and sedimentation are analyzed. The data are used to propose a scheme of the Burdigalian to Tortonian tectono-stratigrafiphic evolution of the eastern sector of the basin

GEOLOGICAL MAP OF THE GORGOGLIONE BASIN (EASTERN SECTOR)

In this paper we report new stratigraphic data related to a new geological map of the Miocene Gorgoglione Basin of southern Italy, traditionally considered as a piggy-back or wedge-top basin filled by a turbidite-like succession. Well exposed outcrops in the study area (eastern sector of the basin) show four unconformities in the Castelmezzano-Pietrapertosa area. Two of these unconformities pass to paraconformities southeastward, in the Cirigliano-Gorgoglione area. Based on new stratigraphic data the “succession of the Gorgoglione Flysch” can be divided into different informal units: Val Miletta formation and Gorgoglione supersynthem. The latter can be subdivided into the Cirigliano and Castelmezzano synthems. The previously established Cirigliano synthem is here divided into three subsynthems. The lowermost sediments of the Gorgoglione Flysch on the eastern sectors correspond to a complex unit (Val Miletta formation) including Numidian-like quartzarenites, Gorgoglionelike sandstones, and, at the top of the formation, an olistostrome of varicoloured clays, belonging to the Argille Variegate Group. The stratigraphic analyses and the biostratigraphic results based on calcareous plankton assemblage, improve the reconstruction of the geometries of the sedimentary bodies and the time-space facies evolution of the synthems. Sedimentologic and petrographic characters of the upper part of the Castelmezzano synthem show a clear fining and thinning upward trend. Medium- and fine-grained arenites, varying in composition from quartz sandstones to siltstones and shales, are locally marked by abundant planktonic foraminifera and are interpreted as contourites. Moreover, the relationships between tectonics and sedimentation are analyzed. The data are used to propose a scheme of the Burdigalian to Tortonian tectono-stratigrafiphic evolution of the eastern sector of the basin

GEOLOGICAL MAP OF THE GORGOGLIONE BASIN (EASTERN SECTOR)

In this paper we report new stratigraphic data related to a new geological map of the Miocene Gorgoglione Basin of southern Italy, traditionally considered as a piggy-back or wedge-top basin filled by a turbidite-like succession. Well exposed outcrops in the study area (eastern sector of the basin) show four unconformities in the Castelmezzano-Pietrapertosa area. Two of these unconformities pass to paraconformities southeastward, in the Cirigliano-Gorgoglione area. Based on new stratigraphic data the "succession of the Gorgoglione Flysch" can be divided into different informal units: Val Miletta formation and Gorgoglione supersynthem. The latter can be subdivided into the Cirigliano and Castelmezzano synthems. The previously established Cirigliano synthem is here divided into three subsynthems. The lowermost sediments of the Gorgoglione Flysch on the eastern sectors correspond to a complex unit (Val Miletta formation) including Numidian-like quartzarenites, Gorgoglionelike sandstones, and, at the top of the formation, an olistostrome of varicoloured clays, belonging to the Argille Variegate Group. The stratigraphic analyses and the biostratigraphic results based on calcareous plankton assemblage, improve the reconstruction of the geometries of the sedimentary bodies and the time-space facies evolution of the synthems. Sedimentologic and petrographic characters of the upper part of the Castelmezzano synthem show a clear fining and thinning upward trend. Medium- and fine-grained arenites, varying in composition from quartz sandstones to siltstones and shales, are locally marked by abundant planktonic foraminifera and are interpreted as contourites. Moreover, the relationships between tectonics and sedimentation are analyzed. The data are used to propose a scheme of the Burdigalian to Tortonian tectono-stratigrafiphic evolution of the eastern sector of the basin

Role of pericytes in blood–brain barrier preservation during ischemia through tunneling nanotubes

Crosstalk mechanisms between pericytes, endothelial cells, and astrocytes preserve integrity and function of the blood-brain-barrier (BBB) under physiological conditions. Long intercellular channels allowing the transfer of small molecules and organelles between distant cells called tunneling nanotubes (TNT) represent a potential substrate for energy and matter exchanges between the tripartite cellular compartments of the BBB. However, the role of TNT across BBB cells under physiological conditions and in the course of BBB dysfunction is unknown. In this work, we analyzed the TNT's role in the functional dialog between human brain endothelial cells, and brain pericytes co-cultured with human astrocytes under normal conditions or after exposure to ischemia/reperfusion, a condition in which BBB breakdown occurs, and pericytes participate in the BBB repair. Using live time-lapse fluorescence microscopy and laser-scanning confocal microscopy, we found that astrocytes form long TNT with pericytes and endothelial cells and receive functional mitochondria from both cell types through this mechanism. The mitochondria! transfer also occurred in multicellular assembloids of human BBB that reproduce the three-dimensional architecture of the BBB. Under conditions of ischemia/reperfusion, TNT formation is upregulated, and astrocytes exposed to oxygen-glucose deprivation were rescued from apoptosis by healthy pericytes through TNT-mediated transfer of functional mitochondria, an effect that was virtually abolished in the presence of TNT-destroying drugs. The results establish a functional role of TNT in the crosstalk between BBB cells and demonstrate that TNT-mediated mitochondrial transfer from pericytes rescues astrocytes from ischemia/reperfusion-induced apoptosis. Our data confirm that the pericytes might play a pivotal role in preserving the structural and functional integrity of BBB under physiological conditions and participate in BBB repair in brain diseases

Scalable FPGA Graph model to detect routing faults

The SRAM cells that form the configuration memory of an SRAM-based FPGA make such FPGAs particularly vulnerable to soft errors. A soft error occurs when ionizing radiation corrupts the data stored in a circuit. The error persists until new data is written. Soft errors have long been recognized as a potential problem as radiation can come from a variety of sources. This paper presents an FPGA fault model focusing on routing aspects. A graph model of SRAM nodes behavior in case of fault, starting from netlist description of well known FPGA models, is presented. It is also performed a classification of possible logical effects of a soft error in the configuration bit controlling, providing statistics on the possible numbers of faults. Finally it is reported the definition of fault metrics computed on a set of complex benchmarks proving the effectiveness of our approach

IL-1β inhibits ILC3 while favoring NK-cell maturation of umbilical cord blood CD34(+) precursors

NK cells are innate lymphocytes characterized by the expression of nuclear factor interleukin 3 regulated (NFIL3 or E4BP4), eomesodermin (EOMES) transcription factors (TFs), and by the ability to exert cytolytic activity and release IFN‐γ. In the haploidentical‐hematopoietic stem cell transplantation (haplo‐HSCT) setting, CD34+ donor derived NK cells play a major role in the control of leukemic relapses. Therefore, it is important to better define cytokines that influence NK‐cell differentiation from CD34+ precursors. We analyzed the effects of IL‐1β on NK‐cell differentiation from umbilical cord blood (UCB) CD34+ cells. While IL‐1β inhibited CD161+CD56+ cell proliferation, an increased expression of LFA‐1, CD94/NKG2A, KIRs, and perforin on CD56+ cells was detected. In addition, within the CD161+CD56+IL‐1RI+LFA‐1− cell fraction (representing group 3 innate lymphoid cells, ILC3‐like cells), a significant increase of EOMES, NKp46, and CD94/NKG2A receptors, cytolytic granules, and IFN‐γ was detected. This increase was paralleled by a decrease of related orphan receptors (RORγt) TF, NKp44 expression, and IL‐22 production. These data suggest that IL‐1β inhibits ILC3‐ while favoring NK‐cell maturation. Since in haplo‐HSCT conditioning regimen, infections or residual leukemia cells may induce IL‐1β production, this may influence the NK/ILC3 development from donor‐derived CD34+ precursor

Secure Embedded Architectures: Taint Properties Verification

Nowadays embedded devices collect various kinds of information and provide it to communication networks for further processing. These devices often provide critical functionalities that could be exploited by malicious parties. Using formal techniques is a natural way to increase the confidence in the overall embedded system security. However, the major research focus is on verifying only the correctness of encryption algorithms and their implementation in software and hardware and not the whole security process. Following novel research studies, many security requirements of an embedded architecture can be specified as Taint Properties, expressing properties related to information flow and access control. In this paper we define Taint Properties as a way to find out whether there is a path from src to dest, where src is an RTL signal seeded with the Taint and dest is a signal not to be reached by the Taint in order to satisfy the security requirements. In our scenario a Taint is an untrusted code following an illegal path from src to dest. We present a systematic approach to formalize generic security requirements, referring to a model abstraction, and their related Taint Properties of an embedded architecture. First, we present our model abstraction of two selected embedded secure architectures, then we define a portfolio of Taint Properties to verify key secrecy, isolation, attestation, confidentiality and availability features. We finally perform verification of previously defined formal security properties, hence presenting results on two selected embedded architectures proving the effectiveness of our approach