The Nef protein of the human immunodeficiency virus is as important for disease progression as it is perplexing in its plethora of target molecules and functions. In this article, it is proposed that ...the complex biology of Nef is regulated through conformational changes of the protein that are triggered by cellular location and specific interactions as Nef traffics through the infected cell.
When studying how HIV‐1 Nef can promote packaging of the proinflammatory transmembrane protease TACE (tumor necrosis factor‐α converting enzyme) into extracellular vesicles (EVs) we have revealed a ...novel tyrosine kinase‐regulated unconventional protein secretion (UPS) pathway for TACE. When TACE was expressed without its trafficking cofactor iRhom allosteric Hck activation by Nef triggered translocation of TACE into EVs. This process was insensitive to blocking of classical secretion by inhibiting endoplasmic reticulum (ER) to Golgi transport, and involved a distinct form of TACE devoid of normal glycosylation and incompletely processed for prodomain removal. Like most other examples of UPS this process was Golgi reassembly stacking protein (GRASP)‐dependent but was not associated with ER stress. These data indicate that Hck‐activated UPS provides an alternative pathway for TACE secretion that can bypass iRhom‐dependent ER to Golgi transfer, and suggest that tyrosine phosphorylation might have a more general role in regulating UPS.
Src family tyrosine kinases, in particular Hck, can induce an unconventional protein secretion (UPS) pathway leading to Golgi‐bypass secretion of a transmembrane protein into extracellular vesicles (EVs). These results reveal an iRhom‐independent alternative secretion route for the proinflammatory protease TACE (tumor necrosis factor‐α converting enzyme), and have general implications for understanding the regulation of UPS and EV biogenesis (ER, endoplasmic reticulum; MVE, multivesicular endosome; pTyr, phosphotyrosine).
The potential of
super
critical
water
oxidation (SCWO) lies in the complete destruction of persistent, anthropogenic waste material. The obstacles in the technical application are due to the highly ...corrosive reaction medium and the precipitation of salts. The concept of the SUWOX facility is based on a corrosion resistant double-wall reactor the material of which is adapted to the respective compounds of the waste water, and a system pressure of 70
MPa at temperatures of 470–490
°C to obtain high fluid densities which lead to high salt solubility.
The investigations were carried out over a period of 3 years within the scope of an industrial cooperation sponsored by the German Federal Ministry of Education and Research (BMBF). The aim is the development of the SUWOX process into an industrial scale application. After proof of the successful destruction of pollutants dissolved in industrial waste water the investigations concentrated on the development of an application-oriented plant as well as on an economic oxidant supply.
This report reviews the concept, the steps of development for application and the results obtained. Based on these results a technological plant has been developed and constructed, which is to be regarded as the preliminary stage of an industrial pilot plant for the disposal of waste water containing biocides.
After two decades of research the Nef protein of human immunodeficiency virus (HIV) remains a mysterious protein with an indisputable role in HIV pathogenesis. The ability to downregulate CD4 and ...major histocompatibility complex class I (MHC-I) was the first ascribed function of Nef and, whereas the number of downmodulated receptors by Nef is rising, so are the explanations for how their downregulation could contribute to HIV pathogenesis. At the same time there is increasing evidence that Nef not only induces endocytosis but also exocytosis, namely of cytokines and microvesicles that contain Nef itself. Because endocytosis and exocytosis are connected events, this is not surprising – and raises the intriguing possibility that HIV aims at secretion rather than ingestion. Have we therefore barked up the wrong tree over the past two decades? In this opinion article I argue that Nef-induced secretion is most probably the pathogenesis-relevant function behind this elusive viral effector.
The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and ...function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells. The Nef-induced translocation of Eed led to a potent stimulation of Tat-dependent HIV transcription, implying that Eed removal from the nucleus is required for optimal Tat function. Similar to Nef action, activation of integrin receptors recruited Eed to the plasma membrane, also leading to enhanced Tat/Nef-mediated transcription. Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism.
Correspondence: 1 Corresponding Author: Pascal Chaubert, Institut für Tierpathologie, Länggassstrasse 122, CH-3001 Berne, Switzerland, e-mail: pascalchaubert{at}msn.com
In the dog, early-stage ...epitheliotropic T-cell lymphoma (ETCL) can clinically and histologically mimic a large range of inflammatory dermatoses and often progresses rapidly to a more aggressive tumor stage. Early diagnosis of ETCL is essential to proceed with a specific oncologic therapy that is favorable for the prognosis. In the present study, an improved method for the detection of T-cell receptor gamma (TCR ) rearrangement was developed by designing a new set of consensus primers to amplify the different forms of rearranged canine TCR gene sequences by polymerase chain reaction. The amplicons were analyzed by conventional polyacrylamide gel electrophoresis, which requires minimal specific equipment and may be performed in almost every pathology laboratory at low costs. The method proved to be highly specific and sensitive to detect early ETCL in formalin-fixed, paraffin-embedded biopsy specimens, providing an efficient tool for veterinary pathologists to distinguish early neoplastic from reactive cutaneous T-cell infiltrates (tumor-specific marker) or to discriminate T-cell lymphoma from B-cell lymphomas or nonlymphoid neoplasms (T-cell lineage marker). By direct sequencing analysis of amplified TCR gene sequences, ETCL was found to rearrange exclusively the joining (J) 4 region, which suggests specific biology for primary cutaneous T-cell lymphomas. Also, a novel (seventh) functional J region in the TCR gene, localized approximately 2.3 kb upstream of J5, was identified.
Key Words: Dogs epitheliotropic T-cell lymphoma gene rearrangement mycosis fungoides T-cell receptor
Raytheon Vision Systems (RVS, Goleta, CA) in collaboration with HRL Laboratories (Malibu, CA) is contributing to the maturation and manufacturing readiness of third-generation, dual-color, HgCdTe ...infrared staring focal plane arrays (FPAs). This paper will highlight data from the routine growth and fabrication of 256 × 256 30-µm unit-cell staring FPAs that provide dual-color detection in the mid-wavelength infrared (MWIR) and long wavelength infrared (LWIR) spectral regions. The FPAs configured for MWIR/MWIR, MWIR/LWIR, and LWIR/LWIR detection are used for target identification, signature recognition, and clutter rejection in a wide variety of space and ground-based applications. Optimized triple-layer heterojunction (TLHJ) device designs and molecular beam epitaxy (MBE) growth using in-situ controls has contributed to individual bands in all dual-color FPA configurations exhibiting high operability (>99%) and both performance and FPA functionality comparable to state-of-the-art, single-color technology. The measured spectral cross talk from out-of-band radiation for either band is also typically less than 10%. An FPA architecture based on a single-mesa, single-indium bump, and sequential-mode operation leverages current single-color processes in production while also providing compatibility with existing second-generation technologies. PUBLICATION ABSTRACT Key words: Dual-color, focal plane array (FPA), mid-wavelength infrared (MWIR), long-wavelength infrared (LWIR), molecular beam epitaxy (MBE)
The HIV Nef protein mediates endocytosis of surface receptors that correlates with disease progression, but the link between this Nef function and HIV pathogenesis is not clear. Here, we report that ...Nef-mediated activation of membrane trafficking is bidirectional, connecting endocytosis with exocytosis as occurs in activated T cells. Nef expression induced an extensive secretory activity in infected and, surprisingly, also in noninfected T cells, leading to the massive release of microvesicle clusters, a phenotype observed in vitro and in 36%-87% of primary CD4 T cells from HIV-infected individuals. Consistent with exocytosis in noninfected cells, Nef is transferred to bystander cells upon cell-to-cell contact and subsequently induces secretion in an Erk1/2-dependent manner. Thus, HIV Nef alters membrane dynamics, mimicking those of activated T cells and causing a transfer of infected cell signaling (TOS) to bystander cells. This mechanism may help explain the detrimental effect on bystander cells seen in HIV infection.
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