Borrelia burgdorferi stimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis

Introduction: Joint fluid in patients with Lyme arthritis often contains high levels of CCL4 and CCL2, which are chemoattractants for monocytes and some T cells, and CXCL9 and CXCL10, which are chemoattractants for CD4+ and CD8+ T effector cells. These chemokines are produced primarily by cells of monocyte lineage in TH1-type immune responses. Our goal was to begin to learn how infection with Borrelia burgdorferi leads to the secretion of these chemokines, using patient cell samples. We hypothesized that B. burgdorferi stimulates chemokine secretion from monocytes/macrophages in multiple ways, thereby linking innate and adaptive immune responses. Methods: Peripheral blood mononuclear cells (PBMC) from 24 Lyme arthritis patients were stimulated with B. burgdorferi, interferon (IFN)-γ, or both, and the levels of CCL4, CCL2, CXCL9 and CXCL10 were measured in culture supernatants. CD14+ monocytes/macrophages from PBMC and synovial fluid mononuclear cells (SFMC) were stimulated in the same way, using available samples. CXCR3, the receptor for CXCL9 and CXCL10, and CCR5, the receptor for CCL4, were assessed on T cells from PBMC and SFMC. Results: In patients with Lyme arthritis, B. burgdorferi but not IFN-γ induced PBMC to secrete CCL4 and CCL2, and B. burgdorferi and IFN-γ each stimulated the production of CXCL9 and CXCL10. However, with the CD14+ cell fraction, B. burgdorferi alone stimulated the secretion of CCL4; B. burgdorferi and IFN-γ together induced CCL2 secretion, and IFN-γ alone stimulated the secretion of CXCL9 and CXCL10. The percentage of T cells expressing CXCR3 or CCR5 was significantly greater in SFMC than PBMC, confirming that $T_H1$ effector cells were recruited to inflamed joints. However, when stimulated with B. burgdorferi or IFN-γ, SFMC and PBMC responded similarly. Conclusions: B. burgdorferi stimulates PBMC or CD14+ monocytes/macrophages directly to secrete CCL4, but spirochetal stimulation of other intermediate cells, which are present in PBMC, is required to induce CD14+ cells to secrete CCL2, CXCL9 and CXCL10. We conclude that B. burgdorferi stimulates monocytes/macrophages directly and indirectly to guide innate and adaptive immune responses in patients with Lyme arthritis

Complement-Like Protein TEP1 Is a Determinant of Vectorial Capacity in the Malaria Vector Anopheles gambiae

AbstractAnopheles mosquitoes are major vectors of human malaria in Africa. Large variation exists in the ability of mosquitoes to serve as vectors and to transmit malaria parasites, but the molecular mechanisms that determine vectorial capacity remain poorly understood. We report that the hemocyte-specific complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei. The dsRNA knockdown of TEP1 in adults completely abolishes melanotic refractoriness in a genetically selected refractory strain. Moreover, in susceptible mosquitoes this knockdown increases the number of developing parasites. Our results suggest that the TEP1-dependent parasite killing is followed by a TEP1-independent clearance of dead parasites by lysis and/or melanization. Further elucidation of the molecular mechanisms of TEP1-mediated parasite killing will be of great importance for our understanding of the principles of vectorial capacity in insects

Direct observation of active material concentration gradients and crystallinity breakdown in LiFePO4 electrodes during charge/discharge cycling of lithium batteries

The phase changes that occur during discharge of an electrode comprised of LiFePO4, carbon, and PTFE binder have been studied in lithium half cells by using X-ray diffraction measurements in reflection geometry. Differences in the state of charge between the front and the back of LiFePO4 electrodes have been visualized. By modifying the X-ray incident angle the depth of penetration of the X-ray beam into the electrode was altered, allowing for the examination of any concentration gradients that were present within the electrode. At high rates of discharge the electrode side facing the current collector underwent limited lithium insertion while the electrode as a whole underwent greater than 50% of discharge. This behavior is consistent with depletion at high rate of the lithium content of the electrolyte contained in the electrode pores. Increases in the diffraction peak widths indicated a breakdown of crystallinity within the active material during cycling even during the relatively short duration of these experiments, which can also be linked to cycling at high rate

The Flint Food Store Survey: combining spatial analysis with a modified Nutrition Environment Measures Survey in Stores (NEMS-S) to measure the community and consumer nutrition environments

Objective The goal of the present study was to use a methodology that accurately and reliably describes the availability, price and quality of healthy foods at both the store and community levels using the Nutrition Environment Measures Survey in Stores (NEMS-S), to propose a spatial methodology for integrating these store and community data into measures for defining objective food access. Setting Two hundred and sixty-five retail food stores in and within 2 miles (3·2 km) of Flint, Michigan, USA, were mapped using ArcGIS mapping software. Design A survey based on the validated NEMS-S was conducted at each retail food store. Scores were assigned to each store based on a modified version of the NEMS-S scoring system and linked to the mapped locations of stores. Neighbourhood characteristics (race and socio-economic distress) were appended to each store. Finally, spatial and kernel density analyses were run on the mapped store scores to obtain healthy food density metrics. Results Regression analyses revealed that neighbourhoods with higher socio-economic distress had significantly lower dairy sub-scores compared with their lower-distress counterparts (β coefficient=−1·3; P=0·04). Additionally, supermarkets were present only in neighbourhoods with \u3c60 % African-American population and low socio-economic distress. Two areas in Flint had an overall NEMS-S score of 0. Conclusions By identifying areas with poor access to healthy foods via a validated metric, this research can be used help local government and organizations target interventions to high-need areas. Furthermore, the methodology used for the survey and the mapping exercise can be replicated in other cities to provide comparable results

KMT-2016-BLG-1107: A New Hollywood-Planet Close/Wide Degeneracy

We show that microlensing event KMT-2016-BLG-1107 displays a new type of degeneracy between wide-binary and close-binary Hollywood events in which a giant-star source envelops the planetary caustic. The planetary anomaly takes the form of a smooth, two-day "bump" far out on the falling wing of the light curve, which can be interpreted either as the source completely enveloping a minor-image caustic due to a close companion with mass ratio $q=0.036$, or partially enveloping a major-image caustic due to a wide companion with $q=0.004$. The best estimates of the companion masses are both in the planetary regime ($3.3^{+3.5}_{-1.8}\,M_{\rm jup}$ and $0.090^{+0.096}_{-0.037}\,M_{\rm jup}$) but differ by an even larger factor than the mass ratios due to different inferred host masses. We show that the two solutions can be distinguished by high-resolution imaging at first light on next-generation ("30m") telescopes. We provide analytic guidance to understand the conditions under which this new type of degeneracy can appear.Comment: 23 pages, 7 figures, accepted for publication in A

KMT-2018-BLG-1990Lb: A Nearby Jovian Planet From A Low-Cadence Microlensing Field

We report the discovery and characterization of KMT-2018-BLG-1990Lb, a Jovian planet $(m_p=0.57_{-0.25}^{+0.79}\,M_J)$ orbiting a late M dwarf $(M=0.14_{-0.06}^{+0.20}\,M_\odot)$, at a distance (D_L=1.23_{-0.43}^{+1.06}\,\kpc), and projected at $2.6\pm 0.6$ times the snow line distance, i.e., a_{\rm snow}\equiv 2.7\,\au (M/M_\odot), This is the second Jovian planet discovered by KMTNet in its low cadence ($0.4\,{\rm hr}^{-1}$) fields, demonstrating that this population will be well characterized based on survey-only microlensing data.Comment: 24 pages, 7 figures, 4 table

A case study in adaptable and reusable infrastructure at the Keck Observatory Archive: VO interfaces, moving targets, and more

The Keck Observatory Archive (KOA) (https://koa.ipac.caltech.edu) curates all observations acquired at the W. M. Keck Observatory (WMKO) since it began operations in 1994, including data from eight active instruments and two decommissioned instruments. The archive is a collaboration between WMKO and the NASA Exoplanet Science Institute (NExScI). Since its inception in 2004, the science information system used at KOA has adopted an architectural approach that emphasizes software re-use and adaptability. This paper describes how KOA is currently leveraging and extending open source software components to develop new services and to support delivery of a complete set of instrument metadata, which will enable more sophisticated and extensive queries than currently possible. In August 2015, KOA deployed a program interface to discover public data from all instruments equipped with an imaging mode. The interface complies with version 2 of the Simple Imaging Access Protocol (SIAP), under development by the International Virtual Observatory Alliance (IVOA), which defines a standard mechanism for discovering images through spatial queries. The heart of the KOA service is an R-tree-based, database-indexing mechanism prototyped by the Virtual Astronomical Observatory (VAO) and further developed by the Montage Image Mosaic project, designed to provide fast access to large imaging data sets as a first step in creating wide-area image mosaics (such as mosaics of subsets of the 4.7 million images of the SDSS DR9 release). The KOA service uses the results of the spatial R-tree search to create an SQLite data database for further relational filtering. The service uses a JSON configuration file to describe the association between instrument parameters and the service query parameters, and to make it applicable beyond the Keck instruments. The images generated at the Keck telescope usually do not encode the image footprints as WCS fields in the FITS file headers. Because SIAP searches are spatial, much of the effort in developing the program interface involved processing the instrument and telescope parameters to understand how accurately we can derive the WCS information for each instrument. This knowledge is now being fed back into the KOA databases as part of a program to include complete metadata information for all imaging observations. The R-tree program was itself extended to support temporal (in addition to spatial) indexing, in response to requests from the planetary science community for a search engine to discover observations of Solar System objects. With this 3D-indexing scheme, the service performs very fast time and spatial matches between the target ephemerides, obtained from the JPL SPICE service. Our experiments indicate these matches can be more than 100 times faster than when separating temporal and spatial searches. Images of the tracks of the moving targets, overlaid with the image footprints, are computed with a new command-line visualization tool, mViewer, released with the Montage distribution. The service is currently in test and will be released in late summer 2016