Optimisation of UAVs‐SfM data collection in aeolian landform morphodynamics : a case study from the Gonghe Basin, China

UAVs‐SfM (Unmanned Aerial Vehicles‐ Structure from Motion) systems can generate high‐resolution 3D topographic models of aeolian landforms. To explore the optimisation of UAVs‐SfM for use in aeolian landform morphodynamics, this study tested flight parameters for two contrasting aeolian landform areas (free dune and blowout) to assess the 3D reconstruction accuracy of the UAVs survey compared with field point measurements using differential RTK‐GPS (Real‐time Kinematic‐Global Positioning System). The results reveal the optimum UAVs‐SfM flight set‐up at the free‐dune site was: flying height = 74 m, camera tilt angle = ‐90°, photo overlap ratio = 85%/70% (heading/sideways). The horizontal/vertical location error was around 0.028~0.055 m and 0.053‐0.069 m respectively, and a point cloud density of 463/m3 was found to generate a clear texture using these flying parameters. For the <20m deep blowout the optimum set‐up with highest accuracy and the lowest cliff texture distortion was: flying height = 74 m combined camera tilt angle = ‐90° and ‐60°, photo overlap ratio = 85%/70% (heading/sideways), and an evenly distributed GCPs (Ground Control Points) density of 42/km2 using these flying parameters. When the depth of the blowouts exceeded 40 m, the optimum flight/survey parameters changed slightly to account for more challenging cliff texture generation: flying height = 80 m (with ‐90° and ‐60°combined camera tilt angle), GCPs density = 63/km2 to generate horizontal and vertical location error of 0.024 m and 0.050 m respectively, and point cloud density of 2597.11/m3. The main external factors that affect the successful 3D reconstruction of aeolian landforms using UAVs‐SfM are the weather conditions, manipulation errors, and instrument system errors. The UAVs‐SfM topographic monitoring results demonstrate that UAVs provide a viable and robust means for aeolian landform morphodynamics monitoring. Importantly, the rapid and high precision 3D reconstruction processes were significantly advanced using the optimal flight parameters reported here

Antamanide, a Derivative of Amanita phalloides, Is a Novel Inhibitor of the Mitochondrial Permeability Transition Pore

Antamanide is a cyclic decapeptide derived from the fungus Amanita phalloides. Here we show that antamanide inhibits the mitochondrial permeability transition pore, a central effector of cell death induction, by targeting the pore regulator cyclophilin D. Indeed, (i) permeability transition pore inhibition by antamanide is not additive with the cyclophilin D-binding drug cyclosporin A, (ii) the inhibitory action of antamanide on the pore requires phosphate, as previously shown for cyclosporin A; (iii) antamanide is ineffective in mitochondria or cells derived from cyclophilin D null animals, and (iv) abolishes CyP-D peptidyl-prolyl cis-trans isomerase activity. Permeability transition pore inhibition by antamanide needs two critical residues in the peptide ring, Phe6 and Phe9, and is additive with ubiquinone 0, which acts on the pore in a cyclophilin D-independent fashion. Antamanide also abrogates mitochondrial depolarization and the ensuing cell death caused by two well-characterized pore inducers, clotrimazole and a hexokinase II N-terminal peptide. Our findings have implications for the comprehension of cyclophilin D activity on the permeability transition pore and for the development of novel pore-targeting drugs exploitable as cell death inhibitors

Histone Deacetylase 3 Depletion in Osteo/Chondroprogenitor Cells Decreases Bone Density and Increases Marrow Fat

Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health

Using death to one's advantage: HIV modulation of apoptosis

Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of opportunistic infections associated with acquired immune deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV viral proteins that modulate apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors. Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing anti-apoptotic proteins and down- regulating cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV proteins perform in the progressive T cell depletion observed in AIDS pathogenesis. Originally published Leukemia, Vol. 15, No. 3, Mar 200

HCV NS5A and IRF9 compete for CypA binding

BACKGROUND: Cyclophilin A (CypA) is vital for HCV replication. Cyp inhibitors successfully decrease viral loads in HCV-infected patients. However, their mechanisms of action remain unknown. Since interferon (IFN) can also suppress HCV replication, we asked whether a link between CypA and the IFN response exists. METHODS: We used cellular and recombinant pulldown approaches to investigate the possibility of a specific association of CypA with host ligands. RESULTS: We found for the first time that CypA binds to a major component of the IFN response – the IFN regulatory factor 9 (IRF9). IRF9 is the DNA-binding component of the transcriptional IFN-stimulated gene factor 3 (ISGF3). CypA binds directly IRF9 via its peptidyl-prolyl isomerase (PPIase) pocket. Cyp inhibitors such as cyclosporine A (CsA) or non-immunosuppressive derivates such as alisporivir and SCY-635, prevent IRF9-CypA complex formation. CypA binds to the C-terminal IRF-association-domain (IAD), but not to the DNA-binding or linker domains of IRF9. Remarkably, CypA associates with the multimeric ISGF3 complex. We also obtained evidence that CypA neutralization enhances IFN-induced transcription. Interestingly, the hepatitis C virus (HCV) nonstructural 5A (NS5A) protein, which is known to modulate the IFN response, competes with IRF9 for CypA binding and can prevent the formation of IRF9-CypA complexes. CONCLUSIONS: This study demonstrates for the first time that CypA binds specifically to a component of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway - IRF9. This study also reveals a novel opportunity of HCV to modulate the IFN response via NS5A