Group A Streptococcus M1T1 Intracellular Infection of Primary Tonsil Epithelial Cells Dampens Levels of Secreted IL-8 Through the Action of SpyCEP.

Streptococcus pyogenes (Group A Streptococcus; GAS) commonly causes pharyngitis in children and adults, with severe invasive disease and immune sequelae being an infrequent consequence. The ability of GAS to invade the host and establish infection likely involves subversion of host immune defenses. However, the signaling pathways and innate immune responses of epithelial cells to GAS are not well-understood. In this study, we utilized RNAseq to characterize the inflammatory responses of primary human tonsil epithelial (TEpi) cells to infection with the laboratory-adapted M6 strain JRS4 and the M1T1 clinical isolate 5448. Both strains induced the expression of genes encoding a wide range of inflammatory mediators, including IL-8. Pathway analysis revealed differentially expressed genes between mock and JRS4- or 5448-infected TEpi cells were enriched in transcription factor networks that regulate IL-8 expression, such as AP-1, ATF-2, and NFAT. While JRS4 infection resulted in high levels of secreted IL-8, 5448 infection did not, suggesting that 5448 may post-transcriptionally dampen IL-8 production. Infection with 5448ΔcepA, an isogenic mutant lacking the IL-8 protease SpyCEP, resulted in IL-8 secretion levels comparable to JRS4 infection. Complementation of 5448ΔcepA and JRS4 with a plasmid encoding 5448-derived SpyCEP significantly reduced IL-8 secretion by TEpi cells. Our results suggest that intracellular infection with the pathogenic GAS M1T1 clone induces a strong pro-inflammatory response in primary tonsil epithelial cells, but modulates this host response by selectively degrading the neutrophil-recruiting chemokine IL-8 to benefit infection

Insights Gained into Marginalized Students Access Challenges During the COVID-19 Academic Response

The American Chemical Society (ACS) Committee on Minority Affairs (CMA) endeavors to support all chemistry faculty and staff as they educate all of our students during this pandemic. While the chemistry education community and the ACS have both provided resources as most institutions transitioned to virtual platforms, this pandemic disproportionally affects our students of color, lower socio-economic and rural backgrounds, and students with disabilities. Specifically, these students must overcome hurdles of technology access, environmental disruptions, and cultural pressures in order to be successful. Therefore, CMA has formulated partnerships with both academic and industrial institutions to highlight some best practices to improve future virtual learning experiences of these oftentimes marginalized students. Specifically, the work presented here examines programs and policies at three academic institutions with very different student body demographics and surrounding learning environments (Indiana University Purdue University Indianapolis (IUPUI), The College of New Jersey (TCNJ), and Los Angeles Community College District (LACCD)) with an attempt to identify variables that enhance marginalized student success in chemistry courses. The combination of their results suggests elements such as access to technology, home responsibility, and impostor syndrome, that other learning programs should consider to increase virtual learning success. Furthermore, other stopgap measures implemented at industrial partners give insight as to how these considerations can be implemented during virtual internship programs to meet their learning objectives associated with entering their institutional pipeline

Comparison of Trihalomethanes in Tap Water and Blood: A Case Study in the United States

Background: Epidemiological studies have used various measures to characterize trihalomethane (THM) exposures, but the relationship of these indicators to exposure biomarkers remains unclear

Multi-Domain Cognitive Assessment of Male Mice Shows Space Radiation Is Not Harmful to High-Level Cognition and Actually Improves Pattern Separation

Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56Fe and 28Si. Earth-based preclinical studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as 56Fe and 28Si irradiation led to faster context discrimination in a non-touchscreen task and 56Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition

Comparing antigenaemia- and microfilaraemia as criteria for stopping decisions in lymphatic filariasis elimination programmes in Africa

BACKGROUND: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires \u3c2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole. METHODOLGY/PRINCIPAL FINDINGS: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (\u3e95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV \u3c95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies. CONCLUSIONS/SIGNIFICANCE: For African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission

Mathematical Modeling of Epicardial RF Ablation of Atrial Tissue with Overlying Epicardial Fat

The efficacy of treating atrial fibrillation by RF ablation on the epicardial surface is currently under question due to the presence of epicardial adipose tissue interposed between the ablation electrode and target site (atrial wall). The problem is probably caused by the electrical conductivity of the fat (0.02 S/m) being lower than that of the atrial tissue (0.4-0.6 S/m). Since our objective is to improve epicardial RF ablation techniques, we planned a study based on a two-dimensional mathematical model including an active electrode, a fragment of epicardial fat over a fragment of atrial tissue, and a section of atrium with circulating blood. Different procedures for applying RF power were studied, such as varying the frequency, using a cooled instead of a dry electrode, and different modes of controlling RF power (constant current, temperature and voltage) for different values of epicardial fat thickness. In general, the results showed that the epicardial fat layer seriously impedes the passage of RF current, thus reducing the effectiveness of atrial wall RF ablation

Whole brain 31P MRSI at 7T with a dual-tuned receive array

Purpose: The design and performance of a novel head coil setup for 31P spectroscopy at ultra‐high field strengths (7T) is presented. The described system supports measurements at both the 1H and 31P resonance frequencies. Methods: The novel coil consists of 2, actively detunable, coaxial birdcage coils to give homogeneous transmit, combined with a double resonant 30 channel receive array. This allows for anatomical imaging combined with 31P acquisitions over the whole head, without changing coils or disturbing the subject. A phosphate buffer phantom and 3 healthy volunteers were scanned with a pulse acquire CSI sequence using both the novel array coil and a conventional transceiver birdcage. Four different methods of combining the array channels were compared at 3 different levels of SNR. Results: The novel coil setup delivers significantly increased 31P SNR in the peripheral regions of the brain, reaching up to factor 8, while maintaining comparable performance relative to the birdcage in the center. Conclusions: The new system offers the potential to acquire whole brain 31P MRSI with superior signal relative to the standard options

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit