An Ethnographic Inquiry into Prudent Behavior and Culturally Correct Attitudes of Ethnodoxologists Living among the Lakota Oyate

For centuries, the indigenous people of North America have been plagued by white encroachment. People of European descent have come among Native Americans in almost every form imaginable. They have been treasure seekers, soldiers, bearers of horrific diseases, liars, rapists, murderers, missionaries, anthropologists, government workers, doctors, and teachers. In the summer of 2004, in spite of my own reluctance, I became part of this historically menacing group. Still, I am somewhat different than the others I’ve already mentioned–I came as an ethnodoxologist. Other ethnomusicologists have come among the Lakota people to study music and culture including Frances Densmore, R.D. Theisz, William W. Paige, and William K. Powers. Nonetheless, I may be one of the first non-Native ethnomusicologists whose research focuses primarily on Lakota music and culture in the context of Christian life and worship. It is this focus that sets ethnodoxology apart from secular ethnomusicology. (The efforts of Richard Twiss and Dr. Gerald Yellowhawk–who are both Lakota–could also be considered ethnodoxological.) Since I am one of the first of my kind, this work is an attempt to lay groundwork for other ethnodoxologists that may follow my lead. Using the data from eleven in-depth interviews that I’ve conducted with Will Peters–Lakota father, musician, traditionalist, teacher, and believer in Jesus Christ–I attempt to answer the following question: How should ethnodoxologists act when they come to live among Native Americans and what attitudes should they most appropriately harbor inside

Radiation pressure instability driven variability in the accreting black holes

The time dependent evolution of the accretion disk around black hole is computed. The classical description of the $\alpha$-viscosity is adopted so the evolution is driven by the instability operating in the innermost radiation-pressure dominated part of the accretion disk. We assume that the optically thick disk always extends down to the marginally stable orbit so it is never evacuated completely. We include the effect of the advection, coronal dissipation and vertical outflow. We show that the presence of the corona and/or the outflow reduce the amplitude of the outburst. If only about half of the energy is dissipated in the disk (with the other half dissipated in the corona and carried away by the outflow) the outburst amplitude and duration are consistent with observations of the microquasar GRS 1915+105. Viscous evolution explains in a natural way the lack of direct transitions from the state C to the state B in color-color diagram of this source. Further reduction of the fraction of energy dissipated in the optically thick disk switches off the outbursts which may explain why they are not seen in all high accretion rate sources being in the Very High State.Comment: 31 pages, 14 figures; accepted to Ap

Radiation pressure instability as a variability mechanism in the microquasar GRS 1915+105

Physical mechanism responsible for high viscosity in accretion disks is still under debate. Parameterization of the viscous stress as $\alpha P$ proved to be a successful representation of this mechanism in the outer parts of the disk, explaining the dwarf novae and X-ray novae outbursts as due to ionization instability. We show that this parameterization can be also adopted in the innermost part of the disk where the adoption of the $\alpha$-viscosity law implies the presence of the instability in the radiation pressure dominated region. We study the time evolution of such disks. We show that the time-dependent behavior of GRS 1915+105 can be well reproduced if $\alpha$-viscosity disk model is calculated accurately (with proper numerical coefficients in vertically averaged equations and with advection included), and if the model is supplemented with (i) moderate corona dissipating 50% of energy (ii) jet carrying luminosity-dependent fraction of energy. These necessary modifications in the form of the presence of a corona and a jet are well justified observationally. The model predicts outbursts at luminosity larger than 0.16$\dot M_{Edd}$, as required, correct outburst timescales and amplitudes, including the effect of increasing outburst timescale with mean luminosity. This result strongly suggests that the $\alpha$-viscosity law is a good description of the actual mechanism responsible for angular momentum transfer also in the innermost, radiation pressure dominated part of the disk around a black hole.Comment: 6 pages, 2 figures; accepted for publication in ApJ Letter

The 'new majority' and the academization of journalism

The academization of journalism is reliant on the development of the field founded in scholarship demonstrated through the publication of research in peer-reviewed specialist journals. Given the profile of journalism faculty, this means inducting practitioners into a culture of critical research. In Australia at least, this cohort of neophytes is predominantly comprised of middle-aged women who were surveyed about their personal attitudes to research. They were mostly open to the idea of becoming researchers but were inclined to proceed cautiously without necessarily severing their ties with practice. There was evidence to suggest that a generally positive orientation to research was not capitalized on and that they remained uncertain about the role of research. On the other hand, they appeared not to have adopted the orthodoxy of implacable opposition to scholarly inquiry. The change in gender composition in the academy may provide, contrary to historical, but more in line with contemporary, evidence, a renewed impetus to the project of academizing the field

Replication and Virus-Induced Transcriptome of HAdV-5 in Normal Host Cells versus Cancer Cells - Differences of Relevance for Adenoviral Oncolysis

Adenoviruses (Ads), especially HAdV-5, have been genetically equipped with tumor-restricted replication potential to enable applications in oncolytic cancer therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients, but their anti-tumor efficacy needs to be enhanced. In this regard, it should be considered that cancer cells, dependent on their tissue of origin, can differ substantially from the normal host cells to which Ads are adapted by complex virus-host interactions. Consequently, viral replication efficiency, a key determinant of oncolytic activity, might be suboptimal in cancer cells. Therefore, we have analyzed both the replication kinetics of HAdV-5 and the virus-induced transcriptome in human bronchial epithelial cells (HBEC) in comparison to cancer cells. This is the first report on genome-wide expression profiling of Ads in their native host cells. We found that E1A expression and onset of viral genome replication are most rapid in HBEC and considerably delayed in melanoma cells. In squamous cell lung carcinoma cells, we observed intermediate HAdV-5 replication kinetics. Infectious particle production, viral spread and lytic activity of HAdV-5 were attenuated in melanoma cells versus HBEC. Expression profiling at the onset of viral genome replication revealed that HAdV-5 induced the strongest changes in the cellular transcriptome in HBEC, followed by lung cancer and melanoma cells. We identified prominent regulation of genes involved in cell cycle and DNA metabolism, replication and packaging in HBEC, which is in accord with the necessity to induce S phase for viral replication. Strikingly, in melanoma cells HAdV-5 triggered opposing regulation of said genes and, in contrast to lung cancer cells, no weak S phase induction was detected when using the E2F promoter as reporter. Our results provide a rationale for improving oncolytic adenoviruses either by adaptation of viral infection to target tumor cells or by modulating tumor cell functions to better support viral replication

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Exosomes Derived from M. Bovis BCG Infected Macrophages Activate Antigen-Specific CD4+ and CD8+ T Cells In Vitro and In Vivo

Activation of both CD4+ and CD8+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4+ and CD8+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4+ and CD8+ T cells. The isolated T cells also produced IFN-γ upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate

SNARE Protein Mimicry by an Intracellular Bacterium

Many intracellular pathogens rely on host cell membrane compartments for their survival. The strategies they have developed to subvert intracellular trafficking are often unknown, and SNARE proteins, which are essential for membrane fusion, are possible targets. The obligate intracellular bacteria Chlamydia replicate within an intracellular vacuole, termed an inclusion. A large family of bacterial proteins is inserted in the inclusion membrane, and the role of these inclusion proteins is mostly unknown. Here we identify SNARE-like motifs in the inclusion protein IncA, which are conserved among most Chlamydia species. We show that IncA can bind directly to several host SNARE proteins. A subset of SNAREs is specifically recruited to the immediate vicinity of the inclusion membrane, and their accumulation is reduced around inclusions that lack IncA, demonstrating that IncA plays a predominant role in SNARE recruitment. However, interaction with the SNARE machinery is probably not restricted to IncA as at least another inclusion protein shows similarities with SNARE motifs and can interact with SNAREs. We modelled IncA's association with host SNAREs. The analysis of intermolecular contacts showed that the IncA SNARE-like motif can make specific interactions with host SNARE motifs similar to those found in a bona fide SNARE complex. Moreover, point mutations in the central layer of IncA SNARE-like motifs resulted in the loss of binding to host SNAREs. Altogether, our data demonstrate for the first time mimicry of the SNARE motif by a bacterium

Legionella Metaeffector Exploits Host Proteasome to Temporally Regulate Cognate Effector

Pathogen-associated secretion systems translocate numerous effector proteins into eukaryotic host cells to coordinate cellular processes important for infection. Spatiotemporal regulation is therefore important for modulating distinct activities of effectors at different stages of infection. Here we provide the first evidence of “metaeffector,” a designation for an effector protein that regulates the function of another effector within the host cell. Legionella LubX protein functions as an E3 ubiquitin ligase that hijacks the host proteasome to specifically target the bacterial effector protein SidH for degradation. Delayed delivery of LubX to the host cytoplasm leads to the shutdown of SidH within the host cells at later stages of infection. This demonstrates a sophisticated level of coevolution between eukaryotic cells and L. pneumophila involving an effector that functions as a key regulator to temporally coordinate the function of a cognate effector protein