Role of endolysosomes in HIV-1 Tat-induced neurotoxicity

Combined anti-retroviral therapeutic drugs effectively increase the lifespan of HIV-1-infected individuals who then have a higher prevalence of HAND (HIV-1 associated neurocognitive disorder). Soluble factors including HIV-1 proteins released from HIV-1-infected cells have been implicated in the pathogenesis of HAND, and particular attention has been paid to the HIV-1 Tat (transactivator of transcription) protein because of its ability to directly excite neurons and cause neuronal cell death. Since HIV-1 Tat enters cells by receptor-mediated endocytosis and since endolysosomes play an important role in neuronal cell life and death, we tested here the hypothesis that HIV-1 Tat neurotoxicity is associated with changes in the endolysosome structure and function and also autophagy. Following the treatment of primary cultured rat hippocampal neurons with HIV-1 Tat or as controls mutant-Tat or PBS, neuronal viability was determined using a triple staining method. Preceding observations of HIV-1 Tat-induced neuronal cell death, we observed statistically significant changes in the structure and membrane integrity of endolysosomes, endolysosome pH and autophagy. As early as 24 h after HIV-1 Tat was applied to neurons, HIV-1 Tat accumulated in endolysosomes, endolysosome morphology was affected and their size increased, endolysosome membrane integrity was disrupted, endolysosome pH increased, specific activities of endolysosome enzymes decreased and autophagy was inhibited, as indicated by the significant changes in three markers for autophagy. In contrast, statistically significant levels of HIV-1 Tat-induced neuronal cell death were observed only after 48 h of HIV-1 Tat treatment. Our findings suggest that endolysosomes are involved in HIV-1 Tat-induced neurotoxicity and may represent a target for therapeutic intervention against HAND

Moving from evidence-based medicine to evidence-based health.

While evidence-based medicine (EBM) has advanced medical practice, the health care system has been inconsistent in translating EBM into improvements in health. Disparities in health and health care play out through patients' limited ability to incorporate the advances of EBM into their daily lives. Assisting patients to self-manage their chronic conditions and paying attention to unhealthy community factors could be added to EBM to create a broader paradigm of evidence-based health. A perspective of evidence-based health may encourage physicians to consider their role in upstream efforts to combat socially patterned chronic disease

GeSn lasers for CMOS integration

In search of a suitable CMOS compatible light source many routes and materials are under investigation. Si-based group IV (Si)GeSn alloys offer a tunable bandgap from indirect to direct, making them ideal candidates for on-chip photonics and nano-electronics. An overview of recent achievements in material growth and device developments will be given. Optically pumped waveguide and microdisk structures with different strain and various Sn concentrations provide direct evidence of gain in these alloys and the width of the emission wavelength range that can be covered. Towards the aim of electrically pumped lasers, a set of different homojunction light emitting diodes and more complex heterostructure SiGeSn/GeSn LEDs is presented. Detailed investigation of electroluminescence spectra indicate that GeSn/SiGeSn heterostructures will be advantageous for future laser fabrication

Direct bandgap GeSn microdisk lasers at 2.5 μm for monolithic integration on Si-platform

We report on the first experimental demonstration of direct bandgap group IV GeSn microdisk (MD) lasers (λem=2.5 μm) grown on Si(001). The evidence of lasing is supported by a detailed analysis of strain-dependent emission characteristics of GeSn alloys with xSn ≥ 12 at.%. Residual compressive strain within the layer is relieved via under-etching of the MD enabling increased energy offsets up to EL-EΓ=80 meV. The lasing threshold and max. temperature amount to 220 kW/cm2 and 135 K, respectively

Anomalous Features of EMT during Keratinocyte Transformation

During the evolution of epithelial cancers, cells often lose their characteristic features and acquire a mesenchymal phenotype, in a process known as epithelial-mesenchymal transition (EMT). In the present study we followed early stages of keratinocyte transformation by HPV16, and observed diverse cellular changes, associated with EMT. We compared primary keratinocytes with early and late passages of HF1 cells, a cell line of HPV16-transformed keratinocytes. We have previously shown that during the progression from the normal cells to early HF1 cells, immortalization is acquired, while in the progression to late HF1, cells become anchorage independent. We show here that during the transition from the normal state to late HF1 cells, there is a progressive reduction in cytokeratin expression, desmosome formation, adherens junctions and focal adhesions, ultimately leading to poorly adhesive phenotype, which is associated with anchorage-independence. Surprisingly, unlike “conventional EMT”, these changes are associated with reduced Rac1-dependent cell migration. We monitored reduced Rac1-dependent migration also in the cervical cancer cell line SiHa. Therefore we can conclude that up to the stage of tumor formation migratory activity is eliminated

Necator americanus and Helminth Co-Infections: Further Down-Modulation of Hookworm-Specific Type 1 Immune Responses

Parasitic infections in humans are common in tropical regions and under bad housing and sanitation conditions multiple parasitic infections are the rule rather than the exception. For helminth infections, which are thought to affect almost a quarter of the world's population, most common combinations include soil-transmitted helminths, such as hookworm, roundworm, and whipworm, as well as extra-intestinal infections by schistosomes. In order to develop and test a hookworm vaccine in endemic areas, the understanding of the impact of multiple helminth infections (co-infection) on the immune response against hookworm in infected individuals is crucial. The authors report in their article, that several parameters of the cellular (T cell markers, cytokines, chemokines) and humoral immune response (e.g. IgG4 and IgE antibodies) against hookworm are significantly affected or modulated in individuals co-infected with hookworm, roundworm and/or schistosomes. These results imply that the immune response against components of a hookworm vaccine might be altered by previous contact with other helminth species in endemic areas

GeSn lasers for monolithic integration on Si

Lasing under optical pumping is shown in suspended GeSn microdisks fabricated on a Ge virtual substrate with a lasing threshold below 1 mW at 20K

PUGeo-Net: A Geometry-centric Network for 3D Point Cloud Upsampling

This paper addresses the problem of generating uniform dense point clouds to describe the underlying geometric structures from given sparse point clouds. Due to the irregular and unordered nature, point cloud densification as a generative task is challenging. To tackle the challenge, we propose a novel deep neural network based method, called PUGeo-Net, that learns a $3\times 3$ linear transformation matrix $\bf T$ for each input point. Matrix $\mathbf T$ approximates the augmented Jacobian matrix of a local parameterization and builds a one-to-one correspondence between the 2D parametric domain and the 3D tangent plane so that we can lift the adaptively distributed 2D samples (which are also learned from data) to 3D space. After that, we project the samples to the curved surface by computing a displacement along the normal of the tangent plane. PUGeo-Net is fundamentally different from the existing deep learning methods that are largely motivated by the image super-resolution techniques and generate new points in the abstract feature space. Thanks to its geometry-centric nature, PUGeo-Net works well for both CAD models with sharp features and scanned models with rich geometric details. Moreover, PUGeo-Net can compute the normal for the original and generated points, which is highly desired by the surface reconstruction algorithms. Computational results show that PUGeo-Net, the first neural network that can jointly generate vertex coordinates and normals, consistently outperforms the state-of-the-art in terms of accuracy and efficiency for upsampling factor $4\sim 16$.Comment: 17 pages, 10 figure