MW 775 Christian Witness and Other Faiths

Richard Plantinga, ed. Christianity and Plurality: Classic and Contemporary Readings. Oxford: Blackwell, 1999. 379 pages. ISBN: 0-631-20915-8 (paperback) Wesley Pluralism Packet David Bosch. A Spirituality of the Road. Eugene, Oregon: Wipf and Stock, 2000 (1979). 92 pages. ISBN: 1-57910-795-8 (paperback) Paul Hiebert. Missiological Implications of Epistemological Shifts. Harrisburg, PA: Trinity Press, International, 1999. 135 pages. ISBN: 1-56338-259-8 (paperback)https://place.asburyseminary.edu/syllabi/2452/thumbnail.jp

Identification and in vivo characterization of a brain-penetrating nanobody

BACKGROUND: Preclinical models to determine blood to brain transport ability of therapeutics are often ambiguous. In this study a method is developed that relies on CNS target-engagement and is able to rank brain-penetrating capacities. This method led to the discovery of an anti-transferrin receptor nanobody that is able to deliver a biologically active peptide to the brain via receptor-mediated transcytosis. METHODS: Various nanobodies against the mouse transferrin receptor were fused to neurotensin and injected peripherally in mice. Neurotensin is a neuropeptide that causes hypothermia when present in the brain but is unable to reach the brain from the periphery. Continuous body temperature measurements were used as a readout for brain penetration of nanobody-neurotensin fusions after its peripheral administration. Full temperature curves were analyzed using two-way ANOVA with Dunnett multiple comparisons tests. RESULTS: One anti-transferrin receptor nanobody coupled to neurotensin elicited a drop in body temperature following intravenous injection. Epitope binning indicated that this nanobody bound a distinct transferrin receptor epitope compared to the non-crossing nanobodies. This brain-penetrating nanobody was used to characterize the in vivo hypothermia model. The hypothermic effect caused by neurotensin is dose-dependent and could be used to directly compare peripheral administration routes and various nanobodies in terms of brain exposure. CONCLUSION: This method led to the discovery of an anti-transferrin receptor nanobody that can reach the brain via receptor-mediated transcytosis after peripheral administration. This method could be used to assess novel proteins for brain-penetrating capabilities using a target-engaging readout

Why the idea of framework propositions cannot contribute to an understanding of delusions

One of the tasks that recent philosophy of psychiatry has taken upon itself is to extend the range of understanding to some of those aspects of psychopathology that Jaspers deemed beyond its limits. Given the fundamental difficulties of offering a literal interpretation of the contents of primary delusions, a number of alternative strategies have been put forward including regarding them as abnormal versions of framework propositions described by Wittgenstein in On Certainty. But although framework propositions share some of the apparent epistemic features of primary delusions, their role in partially constituting the sense of inquiry rules out their role in helping to understand delusions

Existential Communication and Leadership

The aim of this article is to introduce and explain a number of important existentialist philosophers and concepts that we believe can contribute to a critical approach to leadership theory. Emphasis is placed on understanding the nature of communication from an existentialist perspective and so Jaspers' conceptualization of existential communication is introduced along with important related concepts that may be regarded as important facets of leader communication including Being-in-the-world, the Other, intersubjectivity, dialogue and indirect communication. Particular attention is paid to Buber's ideas on communication as relationship and dialogue. Throughout, reference is made to contemporary, and what is often regarded as orthodox, thinking regarding the centrality of communication to leadership practice as a means by which to highlight the salience of an existentialist analysis

Characterisation of detachment in the MAST-U Super-X divertor using multi-wavelength imaging of 2D atomic and molecular emission processes

In this work, we provide the first 2D spatially resolved description of radiative detachment in MAST-U Super-X L-mode divertor plasmas. The Super-X magnetic configuration was designed to achieve reduced heat- and particle loads at the divertor target compared to conventional exhaust solutions. We use filtered camera imaging to reconstruct 2D emissivity profiles in the poloidal plane for multiple atomic and molecular emission lines and bands. A set of deuterium fuelling scans is discussed that, together, span attached to deeply detached divertor states observed in MAST-U. Emissivity profiles facilitate separate analysis of locked-mode induced split branches of the scrape-off layer. Molecular deuterium Fulcher band emission front tracking reveals that the deuterium electron-impact ionisation front, for which it serves a proxy, detaches at different upstream electron densities in the split branches. Upon detachment of this ionisation front, Balmer emission attributed to molecular activated recombination appears near-target. We report a simultaneous radial broadening of the emission leg, consistent with previous SOLPS-ITER modelling. With increased fuelling this emission region detaches, implying electron temperatures below ∼ 1 eV. In this phase, 2D Balmer line ratio reconstruction indicates an onset of volumetric direct electron-ion recombination near-target. At the highest fuelling rates this emission region moves off-target, suggesting a drop in near-wall electron density accompanying the low temperatures.</p

Novel Human/Non-Human Primate Cross-Reactive Anti-Transferrin Receptor Nanobodies for Brain Delivery of Biologics

The blood-brain barrier (BBB), while being the gatekeeper of the central nervous system (CNS), is a bottleneck for the treatment of neurological diseases. Unfortunately, most of the biologicals do not reach their brain targets in sufficient quantities. The antibody targeting of receptor-mediated transcytosis (RMT) receptors is an exploited mechanism that increases brain permeability. We previously discovered an anti-human transferrin receptor (TfR) nanobody that could efficiently deliver a therapeutic moiety across the BBB. Despite the high homology between human and cynomolgus TfR, the nanobody was unable to bind the non-human primate receptor. Here we report the discovery of two nanobodies that were able to bind human and cynomolgus TfR, making these nanobodies more clinically relevant. Whereas nanobody BBB00515 bound cynomolgus TfR with 18 times more affinity than it did human TfR, nanobody BBB00533 bound human and cynomolgus TfR with similar affinities. When fused with an anti-beta-site amyloid precursor protein cleaving enzyme (BACE1) antibody (1A11AM), each of the nanobodies was able to increase its brain permeability after peripheral injection. A 40% reduction of brain Aβ1–40 levels could be observed in mice injected with anti-TfR/BACE1 bispecific antibodies when compared to vehicle-injected mice. In summary, we found two nanobodies that could bind both human and cynomolgus TfR with the potential to be used clinically to increase the brain permeability of therapeutic biologicals

Cultivable microbiota associated with Aurelia aurita and Mnemiopsis leidyi

The associated microbiota of marine invertebrates plays an important role to the host in relation to fitness, health, and homeostasis. Cooperative and competitive interactions between bacteria, due to release of, for example, antibacterial substances and quorum sensing (QS)/quorum quenching (QQ) molecules, ultimately affect the establishment and dynamics of the associated microbial community. Aiming to address interspecies competition of cultivable microbes associated with emerging model species of the basal animal phyla Cnidaria (Aurelia aurita) and Ctenophora (Mnemiopsis leidyi), we performed a classical isolation approach. Overall, 84 bacteria were isolated from A. aurita medusae and polyps, 64 bacteria from M. leidyi, and 83 bacteria from ambient seawater, followed by taxonomically classification by 16S rRNA gene analysis. The results show that A. aurita and M. leidyi harbor a cultivable core microbiome consisting of typical marine ubiquitous bacteria also found in the ambient seawater. However, several bacteria were restricted to one host suggesting host-specific microbial community patterns. Interbacterial interactions were assessed by (a) a growth inhibition assay and (b) QS interference screening assay. Out of 231 isolates, 4 bacterial isolates inhibited growth of 17 isolates on agar plates. Moreover, 121 of the 231 isolates showed QS-interfering activities. They interfered with the acyl-homoserine lactone (AHL)-based communication, of which 21 showed simultaneous interference with autoinducer 2. Overall, this study provides insights into the cultivable part of the microbiota associated with two environmentally important marine non-model organisms and into interbacterial interactions, which are most likely considerably involved in shaping a healthy and resilient microbiota

Disruption of MicroRNA Expression in Human Airway Cells by Diesel Exhaust Particles Is Linked to Tumorigenesis-Associated Pathways

BackgroundParticulate matter (PM) is associated with adverse airway health effects; however, the underlying mechanism in disease initiation is still largely unknown. Recently, microRNAs (miRNAs; small noncoding RNAs) have been suggested to be important in maintaining the lung in a disease-free state through regulation of gene expression. Although many studies have shown aberrant miRNA expression patterns in diseased versus healthy tissue, little is known regarding whether environmental agents can induce such changes.ObjectivesWe used diesel exhaust particles (DEP), the largest source of emitted airborne PM, to investigate pollutant-induced changes in miRNA expression in airway epithelial cells. We hypothesized that DEP exposure can lead to disruption of normal miRNA expression patterns, representing a plausible novel mechanism through which DEP can mediate disease initiation.MethodsHuman bronchial epithelial cells were grown at air–liquid interface until they reached mucociliary differentiation. After treating the cells with 10 μg/cm2 DEP for 24 hr, we analyzed total RNA for miRNA expression using microarray profile analysis and quantitative real-time polymerase chain reaction.ResultsDEP exposure changed the miRNA expression profile in human airway epithelial cells. Specifically, 197 of 313 detectable miRNAs (62.9%) were either up-regulated or down-regulated by 1.5-fold. Molecular network analysis of putative targets of the 12 most altered miRNAs indicated that DEP exposure is associated with inflammatory responses pathways and a strong tumorigenic disease signature.ConclusionsAlteration of miRNA expression profiles by environmental pollutants such as DEP can modify cellular processes by regulation of gene expression, which may lead to disease pathogenesis

Differences in the microbiota of native and non-indigenous gelatinous zooplankton organisms in a low saline environment

Highlights: • Non-indigenous species (NIS) are increasingly recognized as a matter of concern. • The microbiome of native and NIS gelatinous zooplankton organisms are compared. • Next generation sequencing confirms sign. Species specific microbiome differences. • Indicator OTUs include bacteria which contain known pathogenic strains. • Microbiome monitoring of NIS should be considered for aquaculture risk assessments. Abstract: The translocation of non-indigenous species (NIS) around the world, especially in marine systems, is increasingly being recognized as a matter of concern. Species translocations have been shown to lead to wide ranging changes in food web structure and functioning. In addition to the direct effects of NIS, they could facilitate the accumulation or translocation of bacteria as part of their microbiomes. The Baltic Sea harbours many non-indigenous species, with most recent detection of the jellyfish Blackfordia virginica and the comb jelly Mnemiopsis leidyi in the low saline southwestern Baltic Sea. In this study, we used a multidisciplinary approach and investigated three gelatinous zooplankton species that co-occur in the same environment and feed on similar zooplankton food sources but show different histories of origin. The aim was to conduct a comparative microbiome analysis of indigenous and non-indigenous gelatinous zooplankton species in the low-saline southwestern Baltic Sea. Next-generation 16S rRNA marker gene sequencing of the V1/V2 region was employed to study the bacterial microbiome compositions. All tested species showed significant differences in their microbiome compositions (one way ANOSIM, R = 1, P < 0.008) with dissimilarities ranging from 85 to 92%. The indigenous jellyfish Aurelia aurita showed the highest bacterial operational taxonomic unit (OTU) richness. The overall differentiation between microbiomes was driven by eight indicator OTUs, which included Mycoplasma and Vibrio species. These bacteria can be problematic, as they include known pathogenic strains that are relevant to human health and aquaculture activities. Our results suggest that the impact assessment of NIS should consider potential pathogenic bacteria, enriched in the environment due to invasion, as potential risks to aquaculture activities