Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM ) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules – CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p<0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase). Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p<0.0073). Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44+CD62L− differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4+ and CD8+ T cells accumulated in the brain vasculature is approximately equal

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Spin asymmetry in electron impact ionization of caesium

Baum G, Granitza B, Grau L, et al. Spin asymmetry in electron impact ionization of caesium. J. Phy. B. 1993;26(2):331-336.We measured the total ionization asymmetry A in dependence on the incident electron energy E Here 'total' refers to integration over all emission angles and energy partitions of the outgoing electrons. From a threshold value of A = 0.1 25 the A(E) curve rises smoothly toward a broad maximum of A(max) = 0.31 at E(max) = 8.3 eV. The fall-off towards higher energies is quite similar to that of the other one-electron atoms. However, it shows a structure which can be explained by contributions from autoionizing P states. Bartschat has made a theoretical estimate of A(E) for various atoms. At low energies the agreement with our data is satisfactory, at higher energies the experimental A values are considerably smaller than the theoretical ones. In the threshold region measurements were performed with small electron energy width (0.1 eV). No structure in the A(E) curve was found. The slope at threshold was determined as dA/dE = (0.136+/-0.005) eV-1

Correction: Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations.

[This corrects the article DOI: 10.1371/journal.pone.0173580.]

Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations.

Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators

Implementing policy on next-generation broadband networks and implications for equity of access to high speed broadband: A case study of Australia's NBN

Next generation telecommunications infrastructure is expanding and supporting rapid growth of broadband technologies and a digital economy. In this context, digital information and communications technologies (ICTs) are of increasing importance as a means for people to gain access to health or social services, employment opportunities, information and social networks. In this article we draw on our recent case study research to examine the policy (and politics) shaping implementation of Australia's National Broadband Network (NBN) and its likely effects on equity of access to high speed broadband (HSB) services. We monitored NBN policy and implementation from 2015 to 2018 through policy documents, reports, and media. To assess likely effects of NBN policy on implementation and subsequently on equity of access to HSB we: a) applied a framework defining four elements of equity of access; and b) analysed stakeholder views drawn from media articles and 22 interviews with experts on NBN policy including politicians, government staff, and industry representatives. We found that equity considerations competed with political and commercial imperatives during the rollout of the NBN. This resulted in positive and negative consequences for equity of access to HSB, with a change in policy and implementation in 2013 bringing greater risks to equity of access. The case study provides a framework for considering equity in the implementation of next generation telecommunications infrastructure and highlights the importance of considering equity in the evaluation of telecommunications infrastructure.The research reported in this article was conducted through the NHMRC Centre of Research Excellence on the Social Determinants of Health Equity