Metastatic small bowel occlusion as initial presentation of squamous cell carcinoma of the lung

info:eu-repo/semantics/publishedVersio

Local seismic cultures: the use of timber frame structures in the south of Portugal

Given the fact that using timber frame structures has proven to improve the seismic behavior of vernacular architecture, as has been reported in past earthquakes in many countries, its preservation as a traditional earthquake resistant practice is important. This paper firstly intends to evaluate whether the use of timber frames as a traditional seismic resistant technique for vernacular architecture in the South of Portugal, traditionally a seismic region, is still active. Secondly, the city of Vila Real de Santo António was selected as a case study because it also followed a Pombaline development contemporary to the reconstruction of Lisbon. The plan included the provision of timber frame partition walls for some of the buildings and, thus, an overview of the type of constructions originally conceived is provided. Finally, the alterations done in the original constructions and the current state of the city center are described and the effect of these changes on the seismic vulnerability of the city is discussed.The authors wish to express their gratitude to the Portuguese Science and Technology Foundation (FCT) for the scholarship granted in the scope of the research project 'SEISMIC-V-Vernacular Seismic Culture in Portugal' (PTDC/ATP-AQI/3934/2012)

Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter

KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation (K+ and Na+) transport proteins that closely resemble K+ channels. These proteins underlie a plethora of cellular functions that are crucial for environmental adaptation in plants, fungi, archaea, and bacteria. The activation mechanism of the Trk/Ktr/HKT proteins remains unknown. It has been shown that ATP stimulates the activity of KtrAB while ADP does not. Here, we present X-ray structural information on the KtrAB complex with bound ADP. A comparison with the KtrAB-ATP structure reveals conformational changes in the ring and in the membrane protein. In combination with a biochemical and functional analysis, we uncover how ligand- dependent changes in the KtrA ring are propagated to the KtrB membrane protein and conclude that, despite their structural similarity, the activation mechanism of KtrAB is markedly different from the activation mechanism of K+ channels

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition