Brendan meets Columbus: A more commodious islescape

This paper proposes that we can reimagine insular literatures and medieval islescapes as commodious seas of cultural and intellectual loci that span time, culture, and text alike. By moving beyond the rhetoric of insular separation or connectivity, we can see that islands connect even when medieval minds saw separation. The essay focuses on the Brendan legend and the commodious cultural ‘sea of islands’ that it inhabits, a space that connects the modern reader to a history of other connections, fact to fancy, and the real and the imaginary. When sailing in this sea, Brendan meets Columbus, and the late medieval idea of a lost island spreads though space and time

Emergent dynamic chirality in a thermally driven artificial spin ratchet

Modern nanofabrication techniques have opened the possibility to create novel functional materials, whose properties transcend those of their constituent elements. In particular, tuning the magnetostatic interactions in geometrically frustrated arrangements of nanoelements called artificial spin ice1, 2 can lead to specific collective behaviour3, including emergent magnetic monopoles4, 5, charge screening6, 7 and transport8, 9, as well as magnonic response10, 11, 12. Here, we demonstrate a spin-ice-based active material in which energy is converted into unidirectional dynamics. Using X-ray photoemission electron microscopy we show that the collective rotation of the average magnetization proceeds in a unique sense during thermal relaxation. Our simulations demonstrate that this emergent chiral behaviour is driven by the topology of the magnetostatic field at the edges of the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a bias field can be used to modify the sense of rotation of the average magnetization. This opens the possibility of implementing a magnetic Brownian ratchet13, 14, which may find applications in novel nanoscale devices, such as magnetic nanomotors, actuators, sensors or memory cells

Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain.

BACKGROUND: Chlamydia trachomatis is the most common cause of sexually transmitted infections globally and the leading cause of preventable blindness in the developing world. There are two biovariants of C. trachomatis: 'trachoma', causing ocular and genital tract infections, and the invasive 'lymphogranuloma venereum' strains. Recently, a new variant of the genital tract C. trachomatis emerged in Sweden. This variant escaped routine diagnostic tests because it carries a plasmid with a deletion. Failure to detect this strain has meant it has spread rapidly across the country provoking a worldwide alert. In addition to being a key diagnostic target, the plasmid has been linked to chlamydial virulence. Analysis of chlamydial plasmids and their cognate chromosomes was undertaken to provide insights into the evolutionary relationship between chromosome and plasmid. This is essential knowledge if the plasmid is to be continued to be relied on as a key diagnostic marker, and for an understanding of the evolution of Chlamydia trachomatis. RESULTS: The genomes of two new C. trachomatis strains were sequenced, together with plasmids from six C. trachomatis isolates, including the new variant strain from Sweden. The plasmid from the new Swedish variant has a 377 bp deletion in the first predicted coding sequence, abolishing the site used for PCR detection, resulting in negative diagnosis. In addition, the variant plasmid has a 44 bp duplication downstream of the deletion. The region containing the second predicted coding sequence is the most highly conserved region of the plasmids investigated. Phylogenetic analysis of the plasmids and chromosomes are fully congruent. Moreover this analysis also shows that ocular and genital strains diverged from a common C. trachomatis progenitor. CONCLUSION: The evolutionary pathways of the chlamydial genome and plasmid imply that inheritance of the plasmid is tightly linked with its cognate chromosome. These data suggest that the plasmid is not a highly mobile genetic element and does not transfer readily between isolates. Comparative analysis of the plasmid sequences has revealed the most conserved regions that should be used to design future plasmid based nucleic acid amplification tests, to avoid diagnostic failures

Artemisinin Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Inhibiting NF-κB Pathway in Microglia Cells

Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemisinin has the ability to inhibit NF-κB activation. In this study, the inhibitory effects of artemisinin on the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated primary microglia. Our results show that artemisinin significantly inhibited LPS-induced production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO). Artemisinin significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) and increased the protein levels of IκB-α, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex. Artemisinin treatment significantly inhibited basal and LPS-induced migration of BV-2 microglia. Electrophoretic mobility shift assays revealed increased NF-κB binding activity in LPS-stimulated primary microglia, and this increase could be prevented by artemisinin. The inhibitory effects of artemisinin on LPS-stimulated microglia were blocked after IκB-α was silenced with IκB-α siRNA. Our results suggest that artemisinin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The data provide direct evidence of the potential application of artemisinin for the treatment of neuroinflammatory diseases

Human cytomegalovirus latency-associated proteins elicit immune-suppressive IL-10 producing CD4⁺ T cells.

Human cytomegalovirus (HCMV) is a widely prevalent human herpesvirus, which, after primary infection, persists in the host for life. In healthy individuals, the virus is well controlled by the HCMV-specific T cell response. A key feature of this persistence, in the face of a normally robust host immune response, is the establishment of viral latency. In contrast to lytic infection, which is characterised by extensive viral gene expression and virus production, long-term latency in cells of the myeloid lineage is characterised by highly restricted expression of viral genes, including UL138 and LUNA. Here we report that both UL138 and LUNA-specific T cells were detectable directly ex vivo in healthy HCMV seropositive subjects and that this response is principally CD4⁺ T cell mediated. These UL138-specific CD4⁺ T cells are able to mediate MHC class II restricted cytotoxicity and, importantly, show IFNγ effector function in the context of both lytic and latent infection. Furthermore, in contrast to CDCD4⁺ T cells specific to antigens expressed solely during lytic infection, both the UL138 and LUNA-specific CD4⁺ T cell responses included CD4⁺ T cells that secreted the immunosuppressive cytokine cIL-10. We also show that cIL-10 expressing CD4⁺ T-cells are directed against latently expressed US28 and UL111A. Taken together, our data show that latency-associated gene products of HCMV generate CD4⁺ T cell responses in vivo, which are able to elicit effector function in response to both lytic and latently infected cells. Importantly and in contrast to CD4⁺ T cell populations, which recognise antigens solely expressed during lytic infection, include a subset of cells that secrete the immunosuppressive cytokine cIL-10. This suggests that HCMV skews the T cell responses to latency-associated antigens to one that is overall suppressive in order to sustain latent carriage in vivo

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

Background: VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings: Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion: Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab

The mediating role of self/everyday creativity and depression on the relationship between creative personality traits and problematic social media use among emerging adults

Personality is one of the important contributory factors in the development of problematic technology use. The purpose of the present study was to investigate the direct and indirect associations of creative personality traits with problematic social media use via self/everyday creativity, depression, and loneliness. A total of 460 Turkish emerging adults aged between 18 and 26 years (61% female) were surveyed. Findings indicated that (i) task-orientedness was indirectly associated with problematic social media use via self/everyday creativity, (ii) self-confidence was directly and indirectly associated with problematic social media use via self/everyday creativity and depression, (iii) risk-taking was indirectly associated with problematic social media use via depression, and (iv) self/everyday creativity and depression were directly associated with problematic social media use. The present study is the first to suggest that creative personality traits (i.e., task-orientedness, self-confidence, and risk-taking) and self/everyday creativity are associated with problematic social media use and that these factors should be taken into account when considering the etiology of problematic social media use

Backpack-mounted satellite transmitters do not affect reproductive performance in a migratory bustard

Backpack-mounted satellite transmitters (PTTs) are used extensively in the study of avian habitat use and of the movements and demography of medium- to large-bodied species, but can affect individuals’ performance and fitness. Transparent assessment of potential transmitter effects is important for both ethical accountability and confidence in, or adjustment to, life history parameter estimates. We assessed the influence of transmitters on seven reproductive parameters in Asian houbara Chlamydotis macqueenii, comparing 114 nests of 38 females carrying PTTs to 184 nests of untagged birds (non-PTT) over seven breeding seasons (2012‒2018) in Uzbekistan. There was no evidence of any influence of PTTs on: lay date (non-PTT x̅ = 91.7 Julian day ± 12.3 SD; PTT x̅ = 95.1 Julian day ± 15.7 SD); clutch size (non-PTT x̅ = 3.30 ± 0.68 SD; PTT x̅ = 3.25 ± 0.65 SD); mean egg weight at laying (non-PTT x̅ = 66.1g ± 5.4 SD; PTT x̅ = 66.4g ± 5.4 SD); nest success (non-PTT x̅ = 57.08% ± 4.3 SE; PTT x̅ = 58.24% ± 4.5 SE for nests started 2 April); egg hatchability (non-PTT x̅ = 88.3% ± 2.2 SE; PTT x̅ = 88.3% ± 2.6 SE); or chick survival to fledging from broods that had at least one surviving chick (non-PTT x̅ = 63.4% ± 4.2 SE; PTT x̅= 64.4% ± 4.7 SE). High nesting propensity (97.3% year-1 ± 1.9% SE) of tagged birds indicated minimal PTT effect on breeding probability. These findings show harness-mounted transmitters can give unbiased measures of demographic parameters of this species, and are relevant to other large-bodied, cursorial, ground-nesting birds of open habitats, particularly other bustards

Soil Respiration in Relation to Photosynthesis of Quercus mongolica Trees at Elevated CO2

Knowledge of soil respiration and photosynthesis under elevated CO2 is crucial for exactly understanding and predicting the carbon balance in forest ecosystems in a rapid CO2-enriched world. Quercus mongolica Fischer ex Ledebour seedlings were planted in open-top chambers exposed to elevated CO2 (EC = 500 µmol mol−1) and ambient CO2 (AC = 370 µmol mol−1) from 2005 to 2008. Daily, seasonal and inter-annual variations in soil respiration and photosynthetic assimilation were measured during 2007 and 2008 growing seasons. EC significantly stimulated the daytime soil respiration by 24.5% (322.4 at EC vs. 259.0 mg CO2 m−2 hr−1 at AC) in 2007 and 21.0% (281.2 at EC vs. 232.6 mg CO2 m−2 hr−1 at AC) in 2008, and increased the daytime CO2 assimilation by 28.8% (624.1 at EC vs. 484.6 mg CO2 m−2 hr−1 at AC) across the two growing seasons. The temporal variation in soil respiration was positively correlated with the aboveground photosynthesis, soil temperature, and soil water content at both EC and AC. EC did not affect the temperature sensitivity of soil respiration. The increased daytime soil respiration at EC resulted mainly from the increased aboveground photosynthesis. The present study indicates that increases in CO2 fixation of plants in a CO2-rich world will rapidly return to the atmosphere by increased soil respiration