Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Exoplanets and SETI

The discovery of exoplanets has both focused and expanded the search for extraterrestrial intelligence. The consideration of Earth as an exoplanet, the knowledge of the orbital parameters of individual exoplanets, and our new understanding of the prevalence of exoplanets throughout the galaxy have all altered the search strategies of communication SETI efforts, by inspiring new "Schelling points" (i.e. optimal search strategies for beacons). Future efforts to characterize individual planets photometrically and spectroscopically, with imaging and via transit, will also allow for searches for a variety of technosignatures on their surfaces, in their atmospheres, and in orbit around them. In the near-term, searches for new planetary systems might even turn up free-floating megastructures.Comment: 9 page invited review. v2 adds some references and v3 has other minor additions and modification

Application of volumetric modulated arc therapy (VMAT) in a dual-vendor environment

Background and Purpose The purpose of this study was to assess plan quality and treatment time achievable with the new VMAT optimization tool implemented in the treatment planning system Oncentra MasterPlan® as compared to IMRT for Elekta SynergyS® linear accelerators. Materials and methods VMAT was implemented on a SynergyS® linear accelerator (Elekta Ltd., Crawley, UK) with Mosaiq® record and verify system (IMPAC Medical Systems, Sunnyvale, CA) and the treatment planning system Oncentra MasterPlan® (Nucletron BV, Veenendaal, the Netherlands). VMAT planning was conducted for three typical target types of prostate cancer, hypopharynx/larynx cancer and vertebral metastases, and compared to standard IMRT with respect to plan quality, number of monitor units (MU), and treatment time. Results For prostate cancer and vertebral metastases single arc VMAT led to similar plan quality as compared to IMRT. For treatment of the hypopharynx/larynx cancer, a second arc was necessary to achieve sufficient plan quality. Treatment time was reduced in all cases to 35% to 43% as compared to IMRT. Times required for optimization and dose calculation, however, increased by a factor of 5.0 to 6.8. Conclusion Similar or improved plan quality can be achieved with VMAT as compared to IMRT at reduced treatment times but increased calculation times

Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection

Abstract: Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo). While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1), which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-XL, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells. Author Summary: A variety of physiological death signals, as well as pathological insults, trigger apoptosis, a genetically programmed form of cell death. Pathogens often induce host cell apoptosis to establish a successful infection. Neisseria gonorrhoeae (Ngo), the etiological agent of the sexually transmitted disease gonorrhoea, is a highly adapted obligate human-specific pathogen and has been shown to induce apoptosis in infected cells. Here we unveil the molecular mechanisms leading to apoptosis of infected cells. We show that Ngo-mediated apoptosis requires a special subset of proapoptotic proteins from the group of BH3-only proteins. BH3-only proteins act as stress sensors to translate toxic environmental signals to the initiation of apoptosis. In a siRNA-based miniscreen, we found Bim and Bmf, BH3-only proteins associated with the cytoskeleton, necessary to induce host cell apoptosis upon infection. Bim and Bmf inactivated different inhibitors of apoptosis and thereby induced cell death in response to infection. Our data unveil a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic cell death

The smaller vesicomyid bivalves in the genus Isorropodon (Bivalvia, Vesicomyidae, Pliocardiinae) also harbour chemoautotrophic symbionts

Species of Isorropodon are vesicomyid bivalves for which little information is available regarding host phylogeny and bacterial symbioses. In this study we investigated the symbioses in three Isorropodon species from three cold seep areas: Isorropodon bigoti (Gulf of Guinea), Isorropodon megadesmus (Gulf of Cadiz) and Isorropodon perplexum (Eastern Mediterranean). Analysis of bacterial 16S ribosomal RNA gene sequences demonstrated that each vesicomyid species harbours a single symbiont phylotype, that symbionts from the three species cluster together, and that they are closely related to other known vesicomyid symbionts. These results are confirmed by other marker genes (encoding 23S rRNA and APS reductase) and by fluorescence in situ hybridization. Due to their extended depth range and transoceanic distribution Isorropodon species are interesting examples to further study evolutionary processes in bivalve hosts and their associated symbionts

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA

Search for Higgs bosons of the Universal Extra Dimensions at the Large Hadron Collider

The Higgs sector of the Universal Extra Dimensions (UED) has a rather involved setup. With one extra space dimension, the main ingredients to the construct are the higher Kaluza-Klein (KK) excitations of the Standard Model Higgs boson and the fifth components of the gauge fields which on compactification appear as scalar degrees of freedom and can mix with the former thus leading to physical KK-Higgs states of the scenario. In this work, we explore in detail the phenomenology of such a Higgs sector of the UED with the Large Hadron Collider (LHC) in focus. We work out relevant decay branching fractions involving the KK-Higgs excitations. Possible production modes of the KK-Higgs bosons are then discussed with an emphasis on their associated production with the third generation KK-quarks and that under the cascade decays of strongly interacting UED excitations which turn out to be the only phenomenologically significant modes. It is pointed out that the collider searches of such Higgs bosons face generic hardship due to soft end-products which result from severe degeneracies in the masses of the involved excitations in the minimal version of the UED (MUED). Generic implications of either observing some or all of the KK-Higgs bosons at the LHC are discussed.Comment: 25 pages, 9 figures and 1 tabl

Thermopile detector of light ellipticity

Polarimetric imaging is widely used in applications from material analysis to biomedical diagnostics, vision and astronomy. The degree of circular polarization, or light ellipticity, is associated with the S3 Stokes parameter which is defined as the difference in the intensities of the left- and right-circularly polarized components of light. Traditional way of determining this parameter relies on using several external optical elements, such as polarizers and wave plates, along with conventional photodetectors, and performing at least two measurements to distinguish left- and right-circularly polarized light components. Here we theoretically propose and experimentally demonstrate a thermopile photodetector element that provides bipolar voltage output directly proportional to the S3 Stokes parameter of the incident light.ope