Mechanisms to Evade the Phagocyte Respiratory Burst Arose by Convergent Evolution in Typhoidal Salmonella Serovars.

Typhoid fever caused by Salmonella enterica serovar (S.) Typhi differs in its clinical presentation from gastroenteritis caused by S. Typhimurium and other non-typhoidal Salmonella serovars. The different clinical presentations are attributed in part to the virulence-associated capsular polysaccharide (Vi antigen) of S. Typhi, which prevents phagocytes from triggering a respiratory burst by preventing antibody-mediated complement activation. Paradoxically, the Vi antigen is absent from S. Paratyphi A, which causes a disease that is indistinguishable from typhoid fever. Here, we show that evasion of the phagocyte respiratory burst by S. Paratyphi A required very long O antigen chains containing the O2 antigen to inhibit antibody binding. We conclude that the ability to avoid the phagocyte respiratory burst is a property distinguishing typhoidal from non-typhoidal Salmonella serovars that was acquired by S. Typhi and S. Paratyphi A independently through convergent evolution

Fostering Teacher-Student Relationships: A Case Study Connecting Middle School Teachers, Authentic Local History, and Empathetic Competence

TThis co-authored qualitative case study explores the challenge of teachers connecting with their students at the middle school level, especially when White teachers serve predominantly African-American students in large urban metropolitan areas like St. Louis, Missouri. While research has established the need for teachers to better understand the background experiences of their students, more research is needed to explore the value of place-based professional development in promoting more effective teacher-student relationships (TSRs). Using a psychological theory known as Relational-Cultural Theory (RCT), we sought to examine the following research questions while also applying this theory to the field of education: What insights does RCT offer as teachers engage in challenging local history? How does a teacher’s knowledge and awareness of a student’s neighborhood of origin influence the teacher-student relationship? What impact does an immersive experience in local history have toward increasing teacher’s empathetic competence? This case study examined the impact of a place-based professional development experience, i.e., a two-hour bus tour offered by the Missouri History Museum that explores St. Louis\u27 history of racial segregation and urban development, for middle school teachers at a small charter school in urban St. Louis. Through a series of in-depth interviews, classroom observations, and a focus group interview, data were collected to further study this phenomenon. We used reflexive thematic analysis (Terry & Hayfield, 2021) to derive themes and overall patterns of meaning. The study yielded the following findings: Teachers want better connections to their students. They also see how local history and knowledge of place can help strengthen the teacher-student relationship by building reciprocity and shared knowledge. Teachers can use local history as an entry point or pathway to building a relationship with students and families. Teachers see the value of adding local history to their professional development experiences, and advocate for student learning opportunities that incorporate authentic local history

Polysaccharide Processing and Presentation by the MHCII Pathway

AbstractThe adaptive immune system functions through the combined action of antigen-presenting cells (APCs) and T cells. Specifically, class I major histocompatibility complex antigen presentation to CD8+ T cells is limited to proteosome-generated peptides from intracellular pathogens while the class II (MHCII) endocytic pathway presents only proteolytic peptides from extracellular pathogens to CD4+ T cells. Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria can activate CD4+ T cells. Here we show that ZPSs are processed to low molecular weight carbohydrates by a nitric oxide-mediated mechanism and presented to T cells through the MHCII endocytic pathway. Furthermore, these carbohydrates bind to MHCII inside APCs for presentation to T cells. Our observations begin to elucidate the mechanisms by which some carbohydrates induce important immunologic responses through T cell activation, suggesting a fundamental shift in the MHCII presentation paradigm

Varied Response of Western Pacific Hydrology to Climate Forcings over the Last Glacial Period

Atmospheric deep convection in the west Pacific plays a key role in the global heat and moisture budgets, yet its response to orbital and abrupt climate change events is poorly resolved. Here, we present four absolutely dated, overlapping stalagmite oxygen isotopic records from northern Borneo that span most of the last glacial cycle. The records suggest that northern Borneo’s hydroclimate shifted in phase with precessional forcing but was only weakly affected by glacial-interglacial changes in global climate boundary conditions. Regional convection likely decreased during Heinrich events, but other Northern Hemisphere abrupt climate change events are notably absent. The new records suggest that the deep tropical Pacific hydroclimate variability may have played an important role in shaping the global response to the largest abrupt climate change events

Transformation of ENSO-related rainwater to dripwater δ^(18)O variability by vadose water mixing

Speleothem oxygen isotopes (δ^(18)O) are often used to reconstruct past rainfall δ^(18)O variability, and thereby hydroclimate changes, in many regions of the world. However, poor constraints on the karst hydrological processes that transform rainfall signals into cave dripwater add significant uncertainty to interpretations of speleothem-based reconstructions. Here we present several 6.5 year, biweekly dripwater δ^(18)O time series from northern Borneo and compare them to local rainfall δ^(18)O variability. We demonstrate that vadose water mixing is the primary rainfall-to-dripwater transformation process at our site, where dripwater δ^(18)O reflects amount-weighted rainfall δ^(18)O integrated over the previous 3–10 months. We document large interannual dripwater δ^(18)O variability related to the El Niño–Southern Oscillation (ENSO), with amplitudes inversely correlated to dripwater residence times. According to a simple stalagmite forward model, asymmetrical ENSO extremes produce significant offsets in stalagmite δ^(18)O time series given different dripwater residence times. Our study highlights the utility of generating multiyear, paired time series of rainfall and dripwater δ^(18)O to aid interpretations of stalagmite δ^(18)O reconstructions

Northern Borneo stalagmite records reveal West Pacific hydroclimate across MIS 5 and 6

Over the past decades, tropical stalagmite δ^(18)O records have provided valuable insight on glacial and interglacial hydrological variability and its relationship to a variety of natural climate forcings. The transition out of the penultimate glaciation (MIS 6) represents an important target for tropical hydroclimate reconstructions, yet relatively few such reconstructions resolve this transition. Particularly, comparisons between Termination 1 and 2 provide critical insight on the extent and influence of proposed climate mechanisms determined from paleorecords and model experiments spanning the recent deglaciation. Here we present a new compilation of western tropical Pacific hydrology spanning 0–160 ky BP, constructed from eleven different U/Th-dated stalagmite δ^(18)O records from Gunung Mulu National Park in northern Borneo. The reconstruction exhibits significant precessional power in phase with boreal fall insolation strength over the 0–160 ky BP period, identifying precessional insolation forcing as the dominant driver of hydroclimate variability in northern Borneo on orbital timescales. A comparison with a network of paleoclimate records from the circum-Pacific suggests the insolation sensitivity may arise from changes in the Walker circulation system. Distinct millennial-scale increases in stalagmite δ^(18)O, indicative of reduced regional convection, occur within glacial terminations and may reflect a response to shifts in inter-hemispheric temperature gradients. Our results imply that hydroclimate in this region is sensitive to external forcing, with a response dominated by large-scale temperature gradients

A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2

Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A (PSA), which is produced by the intestinal commensal Bacteroides fragilis, activates CD4+ T cells, resulting in a Th1 response correcting the Th2 cell skew of germ-free mice. We identify Toll-like receptors as crucial to the convergence of innate and adaptive responses stimulated by PSA. Optimization of the Th1 cytokine interferon-γ in PSA-stimulated dendritic cell–CD4+ T cell co-cultures depends on both Toll-like receptor (TLR) 2 and antigen presentation. Synergy between the innate and adaptive responses was also shown when TLR2−/− mice exhibited impaired intraabdominal abscess formation in response to B. fragilis. Commensal bacteria, using molecules like PSA, potentially modulate the Th1/Th2 cell balance and the response to infection by coordinating both the innate and adaptive pathways

Trace metal and carbon isotopic variations in cave dripwater and stalagmite geochemistry from northern Borneo

We investigate stalagmite trace metal ratios and carbon isotopic composition (δ^(13)C) as potential paleoclimate proxies by comparing cave dripwaters, stalagmites, and bedrock composition from Gunung Mulu and Gunung Buda National Parks in northern Borneo, a tropical rainforest karst site. Three year long, biweekly time series of dripwater Mg/Ca, Sr/Ca, and δ^(13)C from several drips at our site are not correlated with rainfall variability, indicative of a relatively weak relationship between hydroclimate and dripwater geochemistry at our site. However, combining all of the dripwater geochemical data gathered over four field trips to our site (N > 300 samples), we find that drips with highly variable Mg[Sr]/Ca have relatively invariable δ^(18)O values close to the mean. We hypothesize that increased residence times translate into reduced variance in dripwater δ^(18)O through mixing in the epikarst as well as increased Mg[Sr]/Ca values through increased calcite precipitation in the epikarst. Mg/Ca, Sr/Ca, and δ^(13)C time series from three overlapping stalagmites that grew over the last 27 kyrs are characterized by strong centennial-scale variations, and bear little resemblance to previously published, well-reproduced δ^(18)O time series from the same stalagmites. The only shared signal among the three stalagmites' geochemical time series is a relative decrease of 1‰ in δ^(13)C from the Last Glacial Maximum to the Holocene, consistent with a transition from savannah (C4) to rainforest (C3) conditions documented in nearby records. Taken together, our study indicates that stalagmite Mg[Sr]/Ca ratios are poor indicators of hydroclimate conditions at our site, while stalagmite δ^(13)C exhibits some reproducible signals on glacial-interglacial timescales

Acute and chronic lung inflammation drives changes in epithelial glycans

IntroductionAsthma is the most common chronic inflammatory disease and it is characterized by leukocyte infiltration and tissue remodeling, with the latter generally referring to collagen deposition and epithelial hyperplasia. Changes in hyaluronin production have also been demonstrated, while mutations in fucosyltransferases reportedly limit asthmatic inflammation.MethodsGiven the importance of glycans in cellular communication and to better characterize tissue glycosylation changes associated with asthma, we performed a comparative glycan analysis of normal and inflamed lungs from a selection of murine asthma models.ResultsWe found that among other changes, the most consistent was an increase in fucose-α1,3-N-acetylglucosamine (Fuc-α1,3-GlcNAc) and fucose-α1,2-galactose (Fuc-α1,2-Gal) motifs. Increases in terminal galactose and N-glycan branching were also seen in some cases, whereas no overall change in O-GalNAc glycans was observed. Increased Muc5AC was found in acute but not chronic models, and only the more human-like triple antigen model yielded increased sulfated galactose motifs. We also found that human A549 airway epithelial cells stimulated in culture showed similar increases in Fuc-α1,2-Gal, terminal galactose (Gal), and sulfated Gal, and this matched transcriptional upregulation of the α1,2-fucosyltransferase Fut2 and the α1,3-fucosyltransferases Fut4 and Fut7.ConclusionsThese data suggest that airway epithelial cells directly respond to allergens by increasing glycan fucosylation, a known modification important for the recruitment of eosinophils and neutrophils

MHCII glycosylation modulates Bacteroides fragilis carbohydrate antigen presentation

N-linked glycans on class II MHC molecules are required for the presentation of glycoantigens, but not peptide antigens