A parametric model for the changes in the complex valued conductivity of a lung during tidal breathing

Classical homogenization theory based on the Hashin-Shtrikman coated ellipsoids is used to model the changes in the complex valued conductivity (or admittivity) of a lung during tidal breathing. Here, the lung is modeled as a two-phase composite material where the alveolar air-filling corresponds to the inclusion phase. The theory predicts a linear relationship between the real and the imaginary parts of the change in the complex valued conductivity of a lung during tidal breathing, and where the loss cotangent of the change is approximately the same as of the effective background conductivity and hence easy to estimate. The theory is illustrated with numerical examples, as well as by using reconstructed Electrical Impedance Tomography (EIT) images based on clinical data from an ongoing study within the EU-funded CRADL project. The theory may be potentially useful for improving the imaging algorithms and clinical evaluations in connection with lung EIT for respiratory management and monitoring in neonatal intensive care units

Viral Interactions with the Nuclear Transport Machinery: Discovering and Disrupting Pathways

Viruses have been invaluable tools for discovering key pathways of nucleocytoplasmic transport. Conversely, disruption of specific nuclear transport pathways, are crucial for the productive life cycle of some viruses. The major cellular mRNA export pathway, which uses TAP (NXF1)/p15(NXT) as receptor, was discovered as a result of TAP interaction with CTE-containing RNAs from Mason-Pfizer Monkey Virus. In addition, CRM1 or exportin 1, which is a transport receptor that mediates nuclear export of proteins, snRNAs, rRNAs and a small subset of mRNAs, was discovered as an interacting partner of the Rev protein of HIV1. Viruses may disrupt the nuclear transport machinery to prevent host antiviral response. VSV Matrix (M) protein inhibits mRNA export by forming a complex with the mRNA export factor Rae1 whereas poliovirus inhibits nuclear import of proteins by probably degrading Nup62 and Nup153. Hence, this review focuses on viruses as tools and as disruptors of nucleocytoplasmic trafficking

Vesicular stomatitis virus inhibits mitotic progression and triggers cell death

Vesicular stomatitis virus (VSV) infects and kills a wide range of cell types; however, the mechanisms involved in VSV-mediated cell death are not fully understood. Here we show that VSV infection interferes with mitotic progression, resulting in cell death. This effect requires the interaction of VSV matrix (M) protein with the Rae1–Nup98 complex in mitosis, which is associated with a subset of ribonucleoproteins (RNPs). VSV displaced Rae1 from spindle poles, caused spindle abnormalities and triggered substantial cell death during metaphase. These effects were attenuated in cells infected with VSV expressing a mutant M protein that does not bind efficiently to the Rae1–Nup98–RNP complex. In cells that progressed to late mitosis, M protein prevented proper nuclear formation and chromatin decondensation. VSV is an oncolytic (anti-tumour) agent as it preferentially replicates and kills tumour cells. As tumour cells have a high mitotic index, VSV-mediated mitotic cell death probably contributes to its oncolytic activity

The Nucleoporin Nup96 Is Required for Proper Expression of Interferon-Regulated Proteins and Functions

Nup98 and Nup96 are components of the nuclear transport machinery and are induced by interferons (IFN). Nup98 is a constituent of an mRNA export pathway that is targeted by viruses and regulated by IFN. However, the role of Nup96 in IFN-related mechanisms has not been established. To investigate the function of Nup96 in vivo, we generated Nup96 +/− mice that express low levels of Nup96, as Nup96 −/− mice are lethal. The Nup96 +/− mice presented selective alterations of the immune system, which resulted in downregulation and impaired IFN α- and γ-mediated induction of MHC I and IFNγ induction of MHC II, ICAM-1, and other proteins. Frequency of TCRαβ+ and CD4+ T cells, which depends on MHC function, is reduced in NUP96 +/− mice. Upon immunization, Nup96 +/− mice showed impaired antigen presentation and T cell proliferation. Nup96 +/− cells and mice were highly susceptible to viral infection, demonstrating a role for Nup96 in innate and adaptive immunity