Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.

Natural-killer receptor group 2, member D (NKG2D) is a well characterized natural killer (NK) cell activating receptor that recognizes several ligands poorly expressed on healthy cells but up-regulated upon stressing stimuli in the context of cancer or viral infection. Although NKG2D ligands represent danger signals that render target cells more susceptible to NK cell lysis, accumulating evidence demonstrates that persistent exposure to ligand-expressing cells causes the decrease of NKG2D surface expression leading to a functional impairment of NKG2D-dependent NK cell functions. Upon ligand binding, NKG2D is internalized from the plasma membrane and sorted to lysosomes for degradation. However, receptor endocytosis is not only a mechanism of receptor clearance from the cell surface, but is also required for the proper activation of signalling events leading to the functional program of NK cells. This review is aimed at providing a summary of current literature relevant to the molecular mechanisms leading to NKG2D down-modulation with particular emphasis given to the role of NKG2D endocytosis in both receptor degradation and signal propagation. Examples of chronic ligand-induced down-regulation of NK cell activating receptors other than NKG2D, including natural cytotoxicity receptors (NCRs), DNAX accessory molecule-1 (DNAM1) and CD16, will be also discussed

Apoptotic signaling through CD95 (Fas/Apo-1) activates an acidic sphingomyelinase.

Intracellular pathways leading from membrane receptor engagement to apoptotic cell death are still poorly characterized. We investigated the intracellular signaling generated after cross-linking of CD95 (Fas/Apo-1 antigen), a broadly expressed cell surface receptor whose engagement results in triggering of cellular apoptotic programs. DX2, a new functional anti-CD95 monoclonal antibody was produced by immunizing mice with human CD95-transfected L cells. Crosslinking of CD95 with DX2 resulted in the activation of a sphingomyelinase (SMase) in promyelocytic U937 cells, as well as in other human tumor cell lines and in CD95-transfected murine cells, as demonstrated by induction of in vivo sphingomyelin (SM) hydrolysis and generation of ceramide. Direct in vitro measurement of enzymatic activity within CD95-stimulated U937 cell extracts, using labeled SM vesicles as substrates, showed strong SMase activity, which required pH 5.0 for optimal substrate hydrolysis. Finally, all CD95-sensitive cell lines tested could be induced to undergo apoptosis after exposure to cell-permeant C2-ceramide. These data indicate that CD95 cross-linking induces SM breakdown and ceramide production through an acidic SMase, thus providing the first information regarding early signal generation from CD95, and may be relevant in defining the biochemical nature of intracellular messengers leading to apoptotic cell death

Advanced radar absorbing ceramic-based materials for multifunctional applications in space environment

In this review, some results of the experimental activity carried out by the authors on advanced composite materials for space applications are reported. Composites are widely employed in the aerospace industry thanks to their lightweight and advanced thermo-mechanical and electrical properties. A critical issue to tackle using engineered materials for space activities is providing two or more specific functionalities by means of single items/components. In this scenario, carbon-based composites are believed to be ideal candidates for the forthcoming development of aerospace research and space missions, since a widespread variety of multi-functional structures are allowed by employing these materials. The research results described here suggest that hybrid ceramic/polymeric structures could be employed as spacecraft-specific subsystems in order to ensure extreme temperature withstanding and electromagnetic shielding behavior simultaneously. The morphological and thermo-mechanical analysis of carbon/carbon (C/C) three-dimensional (3D) shell prototypes is reported; then, the microwave characterization of multilayered carbon-filled micro-/nano-composite panels is described. Finally, the possibility of combining the C/C bulk with a carbon-reinforced skin in a synergic arrangement is discussed, with the aid of numerical and experimental analyses

APOBEC3G-Depleted Resting CD4+ T Cells Remain Refractory to HIV1 Infection

Background: CD4+ T lymphocytes are the primary targets of HIV1 but cannot be infected when fully quiescent, due to a post-entry block preventing the completion of reverse transcription. Chiu et al. recently proposed that this restriction reflects the action of APOBEC3G (A3G). They further suggested that T cell activation abrogates the A3G-mediated block by directing this protein to a high molecular mass complex. Methodology/Principal Findings: In the present work, we sought to explore further this model. However, we found that effective suppression of A3G by combined RNA interference and expression of HIV1 Vif does not relieve the restrictive phenotype of post-activation resting T cells. We also failed to find a correlation between HIV resistance and the presence of A3G in a low molecular complex in primary T cells. Conclusions/Significance: We conclude that A3G is unlikely to play a role in the HIV restrictive phenotype of quiescent T lymphocytes

Effects of atomic oxygen and UV rays ageing on the reflection coefficient of carbon/carbon plates in the 12-18 GHz frequency range

Advanced carbon-based ceramic materials, such as Carbon/Carbon (C/C) are commonly employed in aerospace industry to face the thermo-mechanical stress suffered by the spacecraft external structures during re-entry in earth atmosphere. Thanks to very low thermal expansion and outstanding chemical stability at extreme temperatures, in fact, such materials represent the ideal candidates for re-usable space integrated systems, such as TPS, nozzles and ablation thermal-proof structures. In long-time missions, on the other hand, issues related to continuous and extended exposure of the spacecraft surfaces to the detrimental space environment must be carefully considered. In this frame, also the tracking of satellites by mean of radar systems is a vital aspect for a safe stay in space. In LEO working conditions, the combined effects induced by severe thermal cycles, ultra-high vacuum and UV/Atomic Oxygen(AO) irradiation can be of impediment for the use of C/C as re-entry protection material, since a significant surface oxidation leads to so high TPS damaging as to compromise its main functionality. This surface oxidation can also affect the radar visibility of satellites. Aim of this paper is to evaluate the effects of the AO/UV ageing on C/C plates reflection coefficient, in order to avoid misfunctioning in the radar visibility

Hypofractionated stereotactic radiotherapy in combination with whole brain radiotherapy for brain metastases

Background The efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) in combination with whole brain radiotherapy (WBRT), for the treatment of 1-4 brain metastases, using a non invasive fixation of the skull, was investigated. Methods Between 04/2001 and 01/2006 30 patients with 44 brain metastases underwent irradiation. Every patient received WBRT (10 x 3 Gy); 41/44 lesions received HSRT boost with a median dose fraction of 6 Gy, the fractionation schemes were 3 x 6 Gy and 4 x 8 Gy; a median total dose of 18 Gy was delivered to the tumor isocenter. Results The median survival period was 9.15 months, the actuarial 1-year overall survival and freedom from new brain metastases were 36.6% and 87.9%, respectively; at univariate analysis Karnofsky Performance Status (KPS) was statistically significant (P = 0.05); the actuarial 1-year local control for the 41/44 lesions was 86.1%. No patient had acute or late complications. Conclusions HSRT as a concomitant boost during WBRT is a safe and well tolerated treatment for selected patients with brain metastases

Tinjauan Geografis Perumahan Gading Jaya Kotabaru Kecamatan Tanjung Karang Timur Bandar Lampung Tahun 2016

The research aimed to find out geographical review of Gading Jaya Residence Kotabaru, East Tanjung Karang Sub-district, Bandar Lampung in 2016.The data collecting technique was done through field observation technique and documentation.The research method used in the research was explorative description. Results of the research showed that: (1) the topography of Gading Jaya Residence is appropriate since its height difference is 18 mand its slope is 2% - 15%, (2) the soil type of Gading Jaya Residence is Mediterranean (lime) and Latosol which are appropriate for residence construction, (3) the average rainfall at Gading Jaya residence is average since yearly average rainfall is below 4.000 mm, (4) the land use for housing at Gading Jaya is based on the criteria issued by PU (Pekerjaan Umum) department, and (5) the depth of ground water at Gading Jaya Residence is 100% or entirely considered deep.Penelitian ini dilakukan bertujuan untuk mengetahui tinjauan geografis Perumahan Gading Jaya Kotabaru Kecamatan Tanjung Karang Timur Bandar LampungTahun 2016. Pengumpulan data dilakukan dengan menggunakan teknik observasi lapangan dan dokumentasi.Teknik analisis deskriptif eksploratif. Hasil penelitian menunjukan bahwa: (1) Topografi Perumahan Gading Jaya sesuai karena memiliki beda tinggi 18 meter serta memiliki kemiringan lereng 2% - 15%. (2) Jenis tanah Perumahan Gading Jaya adalah mediteranian (kapur) dan latosol sesuai untuk dibangun Perumahan. (3) Rata-rata curah hujan di Perumahan Gading Jaya sesuai karena rata-rata curah hujan per tahunnya < 4.000 mm. (4) Penggunaan lahan di Perumahan Gading Jaya sudah sesuai dengan kriteria penggunaan lahan untuk Perumahan yang dikeluarkan kementerian Pekerjaan Umum (PU) serta,(5) Kedalaman air tanah di Perumahan Gading Jaya 100% atau seluruhnya termasuk dalam kriteria dalam