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Abstract It is estimated that more than half of the world population has been infected with Helicobacter pylori. Most newly acquired H. pylori infections occur in children before 10 years of age. We hypothesized that early life H. pylori infection could influence the composition of the microbiome at mucosal sites distant to the stomach. To test this hypothesis, we utilized the infant rhesus macaque monkey as an animal model of natural H. pylori colonization to determine the impact of infection on the lung and oral microbiome during a window of postnatal development. From a cohort of 4–7 month-old monkeys, gastric biopsy cultures identified 44% of animals infected by H. pylori. 16S ribosomal RNA gene sequencing of lung washes and buccal swabs from animals showed distinct profiles for the lung and oral microbiome, independent of H. pylori infection. In order of relative abundance, the lung microbiome was dominated by the phyla Proteobacteria, Firmicutes, Bacteroidota, Fusobacteriota, Campilobacterota and Actinobacteriota while the oral microbiome was dominated by Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota. In comparison to the oral cavity, the lung was composed of more genera and species that significantly differed by H. pylori status, with a total of 6 genera and species that were increased in H. pylori negative infant monkey lungs. Lung, but not plasma IL-8 concentration was also associated with gastric H. pylori load and lung microbial composition. We found the infant rhesus macaque monkey lung harbors a microbiome signature that is distinct from that of the oral cavity during postnatal development. Gastric H. pylori colonization and IL-8 protein were linked to the composition of microbial communities in the lung and oral cavity. Collectively, these findings provide insight into how H. pylori infection might contribute to the gut-lung axis during early childhood and modulate future respiratory health.

Abstract Background Preterm birth is often associated with chorioamnionitis and leads to increased risk of neurodevelopmental disorders, such as autism. Preterm birth can lead to cerebellar underdevelopment, but the mechanisms of disrupted cerebellar development in preterm infants are not well understood. The cerebellum is consistently affected in people with autism spectrum disorders, showing reduction of Purkinje cells, decreased cerebellar grey matter, and altered connectivity. Methods Preterm rhesus macaque fetuses were exposed to intra-amniotic LPS (1 mg, E. coli O55:B5) at 127 days (80%) gestation and delivered by c-section 5 days after injections. Maternal and fetal plasma were sampled for cytokine measurements. Chorio-decidua was analyzed for immune cell populations by flow cytometry. Fetal cerebellum was sampled for histology and molecular analysis by single-nuclei RNA-sequencing (snRNA-seq) on a 10× chromium platform. snRNA-seq data were analyzed for differences in cell populations, cell-type specific gene expression, and inferred cellular communications. Results We leveraged snRNA-seq of the cerebellum in a clinically relevant rhesus macaque model of chorioamnionitis and preterm birth, to show that chorioamnionitis leads to Purkinje cell loss and disrupted maturation of granule cells and oligodendrocytes in the fetal cerebellum at late gestation. Purkinje cell loss is accompanied by decreased sonic hedgehog signaling from Purkinje cells to granule cells, which show an accelerated maturation, and to oligodendrocytes, which show accelerated maturation from pre-oligodendrocytes into myelinating oligodendrocytes. Conclusion These findings suggest a role of chorioamnionitis on disrupted cerebellar maturation associated with preterm birth and on the pathogenesis of neurodevelopmental disorders among preterm infants.

IntroductionIL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP).MethodsPregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation.ResultsIUI induced a robust expression of IL6 mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of IL6 mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, ADAM17 (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and IL6R mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced IL6 mRNAs in the AMC and variably decreased elements of IL6 trans-signaling.DiscussionThese data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.

Summary: Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.

Accurate estimate of fetal maturity could provide individualized guidance for delivery of complicated pregnancies. However, current methods are invasive, have low accuracy, and are limited to fetal lung maturation. To identify diagnostic gestational biomarkers, we performed transcriptomic profiling of lung and brain, as well as cell-free RNA from amniotic fluid of preterm and term rhesus macaque fetuses. These data identify potentially new and prior-associated gestational age differences in distinct lung and neuronal cell populations when compared with existing single-cell and bulk RNA-Seq data. Comparative analyses found hundreds of genes coincidently induced in lung and amniotic fluid, along with dozens in brain and amniotic fluid. These data enable creation of computational models that accurately predict lung compliance from amniotic fluid and lung transcriptome of preterm fetuses treated with antenatal corticosteroids. Importantly, antenatal steroids induced off-target gene expression changes in the brain, impinging upon synaptic transmission and neuronal and glial maturation, as this could have long-term consequences on brain development. Cell-free RNA in amniotic fluid may provide a substrate of global fetal maturation markers for personalized management of at-risk pregnancies.

The Canadian Arctic is warming at three times the rate of the rest of the planet and the effects of climate change on the Arctic marine carbon cycle remains unconstrained. Baffin Bay is a semi-enclosed, Arctic basin that connects the Arctic Ocean to the north to the Labrador Sea to the south. While the physical oceanography of surface Baffin Bay is well characterized, less is known about deep water formation mechanisms within the Basin. Only a few residence-time estimates for Baffin Bay Deep Water (BBDW) exist and range from 20 to 1450 years. Better residence time estimates are needed to understand the oceanographic significance of Baffin Bay. Here we report stable carbon (δ13C) and radiocarbon (Δ14C) values of dissolved inorganic carbon (DIC) collected aboard the CCGS Amundsen in 2019. DIC δ13C and Δ14C values between ranged between -0.7‰ to +1.9‰ and -90.0‰ to +29.8‰, respectively. Surface DIC δ13C values were between +0.7‰ to +1.9‰, while deep (>100m) values were 0.0 to -0.7‰. Surface DIC Δ14C values ranged between -5.4‰ to +22.9‰, while deep DIC (>1400m) DIC Δ14C averaged -82.2 ± 8.5‰ (n = 9). To constrain natural DIC Δ14C values, we quantified the amount of atmospheric “bomb” 14C in DIC (Δ14Cbomb; using the potential alkalinity method; Palk) and anthropogenic DIC (DICanth; using the ΔC* method). Both proxies indicate an absence of Δ14Cbomb and DICanth below 1000m. Using two previously proposed deep water formation mechanisms and our corrected DIC Δ14Cnatural values, we estimated a 14C-based residence time of 360-690 years for BBDW. Based on these residence times, we infer carbon is likely stored for centuries in deep Baffin Bay.

Background: Wildfire smoke is responsible for around 20% of all particulate emissions in the U.S. and affects millions of people worldwide. Children are especially vulnerable, as ambient air pollution exposure during early childhood is associated with reduced lung function. Most studies, however, have focused on the short-term impacts of wildfire smoke exposures. We aimed to identify long-term baseline epigenetic changes associated with early-life exposure to wildfire smoke. We collected nasal epithelium samples for whole genome bisulfite sequencing (WGBS) from two groups of adult female rhesus macaques: one group born just before the 2008 California wildfire season and exposed to wildfire smoke during early-life (n = 8), and the other group born in 2009 with no wildfire smoke exposure during early-life (n = 14). RNA-sequencing was also performed on a subset of these samples. Results: We identified 3370 differentially methylated regions (DMRs) (difference in methylation ≥ 5%, empirical p

Introduction: Wildfire smoke (WFS) exposure is a growing threat to human health, and lower socioeconomic position (SEP) has been shown to increase pollution susceptibility. Studies of SEP-related susceptibility, however, are often compromised due to spatial confounding between lower-SEP and pollution. Here we examine outdoor-housed nonhuman primates, living in natural social hierarchy in a common location, born during years of high vs. low WFS, to examine the separate and combined effects of WFS and social rank, an analog to SEP, on lung and immune function. Methods: Twenty-one females were born during extreme WFS events in summer 2008; 22 were born in summer 2009, during low WFS. Pulmonary function and circulating cytokines were measured three years later, in adolescence. We estimated fine particulate (PM2.5) and ozone exposures during each animal's first 90 days and three years of age using regulatory data. Early-life social status was estimated using maternal rank at birth, as rank in females is relatively stable throughout life, and closely approximates mother's rank. We tested associations among WFS exposure, rank, and endpoints using linear regression and ANOVA. Results: Higher WFS exposure in infancy was, on average, associated with lower functional residual capacity (FRC), residual volume (RV), tissue compliance (Ct), and IL-8 secretion in adolescence. Higher social rank conferred significantly higher expiratory reserve volume (ERV) and functional residual capacity (FRC) solely among those born in the high-WFS year (2008). Differences in effects of rank between years were not significant after adjustment for multiple comparisons. Conclusions: Exposure to WFS in infancy generally conferred lower adolescent respiratory volumes and inflammatory cytokines. Higher rank conferred higher respiratory volumes only among females born during WFS, suggesting the possibility that the health benefits of rank may be more apparent under environmental challenge.

The epithelium-associated cytokine thymic stromal lymphopoietin (TSLP) can induce OX40L and CCL17 expression by myeloid dendritic cells (mDCs), which contributes to aberrant Th2-type immune responses. Herein, we report that such TSLP-induced Th2-type immune response can be effectively controlled by Dectin-1, a C-type lectin receptor expressed by mDCs. Dectin-1 stimulation induced STAT3 activation and decreased the transcriptional activity of p50-RelB, both of which resulted in reduced OX40L expression on TSLP-activated mDCs. Dectin-1 stimulation also suppressed TSLP-induced STAT6 activation, resulting in decreased expression of the Th2 chemoattractant CCL17. We further demonstrated that Dectin-1 activation was capable of suppressing ragweed allergen (Amb a 1)-specific Th2-type T cell response in allergy patients ex vivo and house dust mite allergen (Der p 1)-specific IgE response in non-human primates in vivo. Collectively, this study provides a molecular explanation of Dectin-1-mediated suppression of Th2-type inflammatory responses and suggests Dectin-1 as a target for controlling Th2-type inflammation.

Respiratory complications are the major cause of morbidity and mortality among preterm infants, which is partially prevented by the administration of antenatal corticosteroids (ACS). Most very preterm infants are exposed to chorioamnionitis, but short- and long-term effects of ACS treatment in this setting are not well defined. In low-resource settings, ACS increased neonatal mortality by perhaps increasing infection. We report that treatment with low-dose ACS in the setting of inflammation induced by intraamniotic lipopolysaccharide (LPS) in rhesus macaques improves lung compliance and increases surfactant production relative to either exposure alone. RNA sequencing shows that these changes are mediated by suppression of proliferation and induction of mesenchymal cellular death via TP53. The combined exposure results in a mature-like transcriptomic profile with inhibition of extracellular matrix development by suppression of collagen genes COL1A1, COL1A2, and COL3A1 and regulators of lung development FGF9 and FGF10. ACS and inflammation also suppressed signature genes associated with proliferative mesenchymal progenitors similar to the term gestation lung. Treatment with ACS in the setting of inflammation may result in early respiratory advantage to preterm infants, but this advantage may come at a risk of abnormal extracellular matrix development, which may be associated with increased risk of chronic lung disease.

Accumulation of activated neutrophils at the feto-maternal interface is a defining hallmark of intrauterine inflammation (IUI) that might trigger an excessive immune response during pregnancy. Mechanisms responsible of this massive neutrophil recruitment are poorly investigated. We have previously showed that intraamniotic injection of LPS in rhesus macaques induced a neutrophil predominant inflammatory response similar to that seen in human IUI. Here, we demonstrate that anti-TNF antibody (Adalimumab) inhibited ~80% of genes induced by LPS involved in inflammatory signaling and innate immunity in chorio-decidua neutrophils. Consistent with the gene expression data, TNF-blockade decreased LPS-induced neutrophil accumulation and activation at the feto-maternal interface. We also observed a reduction in IL-6 and other pro-inflammatory cytokines but not prostaglandins concentrations in the amniotic fluid. Moreover, TNF-blockade decreased mRNA expression of inflammatory cytokines in the chorio-decidua but not in the uterus, suggesting that inhibition of TNF-signaling decreased the inflammation in a tissue-specific manner within the uterine compartment. Taken together, our results demonstrate a predominant role for TNF-signaling in modulating the neutrophilic infiltration at the feto-maternal interface during IUI and suggest that blockade of TNF-signaling could be considered as a therapeutic approach for IUI, the major leading cause of preterm birth.

As ocean acidification (OA) sensor technology develops and improves, in situ deployment of such sensors is becoming more widespread. However, the scientific value of these data depends on the development and application of best practices for calibration, validation, and quality assurance as well as on further development and optimization of the measurement technologies themselves. Here, we summarize the results of a 2-day workshop on OA sensor best practices held in February 2018, in Victoria, British Columbia, Canada, drawing on the collective experience and perspectives of the participants. The workshop on in situ Sensors for OA Research was organized around three basic questions: 1) What are the factors limiting the precision, accuracy and reliability of sensor data? 2) What can we do to facilitate the quality assurance/quality control (QA/QC) process and optimize the utility of these data? and 3) What sort of data or metadata are needed for these data to be most useful to future users? A synthesis of the discussion of these questions among workshop participants and conclusions drawn is presented in this paper.

Controlled laboratory experiments have shed new light on the potential importance of brine rejection during sea-ice formation for carbon dioxide sequestration in the ocean. We grew ice in an experimental seawater tank (1 m3) under abiotic conditions at three different air temperatures (−40°C, −25°C, −15°C) to determine how different ice growth rates affect the allocation of carbon to ice, water, or air. Carbonate system parameters were determined by discrete sampling of ice cores and water, as well as continuous measurements by multiple sensors deployed mainly in the water phase. A budgetary approach revealed that of the initial total inorganic carbon (TIC) content of the water converted to ice, only 28–29% was located in the ice phase by the end of the experiments run at the warmest temperature, whereas for the coldest ambient temperature, 46–47% of the carbon remained in the ice. Exchange with air appeared to be negligible, with the majority of the TIC remaining in the under-ice water (53–72%). Along with a good correlation between salinity and TIC in the ice and water samples, these observations highlight the importance of brine drainage to TIC redistribution during ice formation. For experiments without mixing of the under-ice water, the sensor data further suggested stronger stratification, likely related to release of denser brine, and thus potentially larger carbon sequestration for ice grown at a colder temperature and faster growth rate.

Earth observing systems have proven to be a unique source of long-term synoptic information on numerous physical, chemical and biological parameters on a global scale. Merging this information for integrated studies that peruse key questions about the ocean-atmosphere interface is, however, very challenging. Such studies require interdisciplinary frameworks and novel insights into ways to address the problem. We present here a perspective review on how current and emerging remote sensing technologies could help address two scientific questions within the Surface Ocean-Lower Atmosphere Study (SOLAS) science plan: (1) to what extent does upper-ocean biology affect the composition and radiative properties of the marine boundary layer; and (2) to what extent does upper-ocean turbulence drive fluxes of mass and energy at the air-sea interface. We provide a thorough review of how these questions have been addressed and discuss novel potential avenues using multiplatform space-borne missions, from visible to microwave, active and passive sensors.

With the Arctic summer sea-ice extent in decline, questions are arising as to how changes in sea-ice dynamics might affect biogeochemical cycling and phenomena such as carbon dioxide (CO2) uptake and ocean acidification. Recent field research in these areas has concentrated on biogeochemical and CO2 measurements during spring, summer or autumn, but there are few data for the winter or winter–spring transition, particularly in the High Arctic. Here, we present carbon and nutrient data within and under sea ice measured during the Catlin Arctic Survey, over 40 days in March and April 2010, off Ellef Ringnes Island (78° 43.11′ N, 104° 47.44′ W) in the Canadian High Arctic. Results show relatively low surface water (1–10 m) nitrate (

A recently recovered and compiled set of inorganic carbon data collected in the Canadian Arctic since the 1970s has revealed substantial change, as well as variability, in the carbonate system of the Beaufort Sea and Canada Basin. Whereas the role of this area as a net atmospheric carbon sink has been confirmed, high pCO2 values in the upper halocline underscore the potential for CO2 outgassing as sea ice retreats and upwelling increases. In addition, increasing total inorganic carbon and decreasing alkalinity are increasing pCO2 and decreasing CaCO3 saturation states, such that undersaturation with respect to aragonite now occurs regularly in both deep waters and the upper halocline.

Abstract Numerical models can be a powerful tool helping to understand the role biogeochemical processes play in local and global systems and how this role may be altered in a changing climate. With respect to sea-ice biogeochemical models, our knowledge is severely limited by our poor confidence in numerical model parameterisations representing those processes. Improving model parameterisations requires communication between observers and modellers to guide model development and improve the acquisition and presentation of observations. In addition to more observations, modellers need conceptual and quantitative descriptions of the processes controlling, for example: primary production and diversity of algal functional types in sea ice, ice algal growth, release from sea ice, heterotrophic remineralisation, transfer and emission of gases (e.g., DMS, CH4, BrO), incorporation of seawater components in growing sea ice (including Fe, organic and inorganic carbon, and major salts) and subsequent release; CO2 dynamics (including CaCO3 precipitation), flushing and supply of nutrients to sea-ice ecosystems; and radiative transfer through sea ice. These issues can be addressed by focused observations, as well as controlled laboratory and field experiments that target specific processes. The guidelines provided here should help modellers and observers improve the integration of measurements and modelling efforts and advance toward the common goal of understanding biogeochemical processes in sea ice and their current and future impacts on environmental systems.

The porous nature of sea ice not only provides a habitat for ice algae but also opens a pathway for exchanges of organic matter, nutrients, and gases with the seawater below and the atmosphere above. These constituents permeate the ice cover through air-ice gas exchange, brine drainage, seawater entrainment into the ice, and air-sea gas exchange within leads and polynyas. The central goal in sea ice biogeochemistry since the 1980s has been to discover the physical, biological, and chemical rates and pathways by which sea ice affects the distribution and storage of biogenic gases (namely CO2, O2, and dimethyl sulfide) between the ocean and the atmosphere. Historically, sea ice held the fascination of scientists for its role in the ocean heat budget, and the resulting view of sea ice as a barrier to heat and mass transport became its canonical representation. However, the recognition that sea ice contains a vibrant community of ice-tolerant organisms and strategic reserves of carbon has brought forward a more nuanced view of the "barrier" as an active participant in polar biogeochemical cycles. In this context, the organisms and their habitat of brine and salt crystals drive material fluxes into and out of the ice, regulated by liquid and gas permeability. Today, scientists who study sea ice are acutely focused on determining the flux pathways of inorganic carbon, particulate organics, climate-active gases, excess carbonate alkalinity, and ultimately, the role of all of these constituents in the climate system. Thomas and Dieckmann (2010) recently reviewed sea ice biogeochemistry, and so we do not attempt a comprehensive review here. Instead, our goal is to provide a historical perspective, along with some recent discoveries and observations to highlight the most outstanding questions and possibly useful avenues for future research.

Abstract Over the past two decades, with recognition that the ocean’s sea-ice cover is neither insensitive to climate change nor a barrier to light and matter, research in sea-ice biogeochemistry has accelerated significantly, bringing together a multi-disciplinary community from a variety of fields. This disciplinary diversity has contributed a wide range of methodological techniques and approaches to sea-ice studies, complicating comparisons of the results and the development of conceptual and numerical models to describe the important biogeochemical processes occurring in sea ice. Almost all chemical elements, compounds, and biogeochemical processes relevant to Earth system science are measured in sea ice, with published methods available for determining biomass, pigments, net community production, primary production, bacterial activity, macronutrients, numerous natural and anthropogenic organic compounds, trace elements, reactive and inert gases, sulfur species, the carbon dioxide system parameters, stable isotopes, and water-ice-atmosphere fluxes of gases, liquids, and solids. For most of these measurements, multiple sampling and processing techniques are available, but to date there has been little intercomparison or intercalibration between methods. In addition, researchers collect different types of ancillary data and document their samples differently, further confounding comparisons between studies. These problems are compounded by the heterogeneity of sea ice, in which even adjacent cores can have dramatically different biogeochemical compositions. We recommend that, in future investigations, researchers design their programs based on nested sampling patterns, collect a core suite of ancillary measurements, and employ a standard approach for sample identification and documentation. In addition, intercalibration exercises are most critically needed for measurements of biomass, primary production, nutrients, dissolved and particulate organic matter (including exopolymers), the CO2 system, air-ice gas fluxes, and aerosol production. We also encourage the development of in situ probes robust enough for long-term deployment in sea ice, particularly for biological parameters, the CO2 system, and other gases.

An unlicensed injectable medicine sold as adrenal cortex extract (ACE*) and distributed in the alternative medicine community led to the largest outbreak of Mycobacterium abscessus infections reported in the United States. Records from the implicated distributor from January 1, 1995, to August 18, 1996, were used to identify purchasers; purchasers and public health alerts were used to identify patients. Purchasers and patients were interviewed, and available medical records were reviewed. Vials of ACE* were tested for mycobacterial contamination, and the product was recalled by the U.S. Food and Drug Administration. ACE* had been distributed to 148 purchasers in 30 states; 87 persons with postinjection abscesses attributable to the product were identified. Patient and vial cultures contained M. abscessus identical by enzymatic and molecular typing methods. Unusual infectious agents and alternative health practices should be considered in the diagnosis of infections that do not respond to routine treatment.