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Background: Studies have identified a characteristic pulmonary function pattern in obesity. Obesity's association to respiratory pathologies, both contributive and causal, continues to be the subject of much research and analysis. These associations, often complicating the identification of the underlying clinical diagnosis, warrant special consideration in light of the growing obesity epidemic. Objectives: A review of published literature to describe the major effects of obesity on pulmonary function and its interaction with respiratory pathophysiology, in order to provide a differential diagnostic tool for clinicians. Results: A distinctly restrictive respiratory pattern is identified in the obese, evident by markedly reduced lung volumes, particularly the expiratory reserve volume (ERV). This is attributed to decreased chest wall compliance, and impaired respiratory muscle function. There is some degree of airflow impairment seen in obesity not attributable to decreased lung volumes, shown by decreaed expiratory flow rates. The association between chronic obstrutive lung disease and obesity is not well defined. Obesity and asthma are shown to have a stronger correlation, which may in part be due to mechanical, immunological, and a variety of other mechanisms. Conclusions: Clinicians must consider the degree of obesity and other objective data such as pulmonary function profiles in the diagnosis and treatment of obese patients exhibiting symptoms of respiratory compromise. [ABSTRACT FROM AUTHOR]

Since 1977, the Joint Public Affairs Committee for Older Adults (JPAC) has been educating and mobilizing older adults to take an active role in the public policy decisions affecting their lives. Recognizing the need to better train its members in the techniques of social action and in an effort to familiarize recent retirees with the world of senior advocacy, JPAC founded a comprehensive leadership training program called the Institute for Senior Action in 1994. JPAC's 10-week training Institute integrates critical aging policy issues with practical grassroots applications for action. In addition to honing the skills of longtime community activists, the Institute serves as a vehicle for recent retirees and others to become more involved in social action. [ABSTRACT FROM AUTHOR]

The oxidation of organic carbon contained within sedimentary rocks ("petrogenic" carbon, or hereafter OC petro ) emits nearly as much CO 2 as is released by volcanism, thereby playing a key role in the long-term global C budget. High erosion rates in mountains have been shown to increase OC petro oxidation. However, these settings also export unweathered material that may continue to react in downstream floodplains. The relative importance of OC petro oxidation in mountains versus floodplains remains difficult to assess as disparate methods have been used in the different environments. Here, we investigate the sources and fluxes of rhenium (Re) in the Rio Madre de Dios to quantify OC petro oxidation from the Andes to the Amazon floodplain using a common approach. Dissolved rhenium concentrations (n = 131) range from 0.01 to 63 pmol L -1 and vary depending on lithology and geomorphic setting. We find that >75% of the dissolved Re derives from OC petro oxidation and that this proportion increases downstream. We estimate that in the Andes, OC petro oxidation releases 11.2 +4.5 / -2.8 tC km -2 y -1 of CO 2 , which corresponds to ~41% of the total OC petro denudation (sum of oxidized and solid OC petro ). A Re mass balance across the Rio Madre de Dios shows that 46% of OC petro oxidation takes place in the Andes, 14% in the foreland-lowlands, and 40% in the Andean-fed floodplains. This doubling of OC petro oxidation flux downstream of the Andes demonstrates that, when present, floodplains can greatly increase OC petro oxidation and CO 2 release.

Wildfire alters the hydrologic cycle, with important implications for water supply and hazards including flooding and debris flows. In this study we use a combination of electrical resistivity and stable water isotope analyses to investigate the hydrologic response during storms in three catchments: one unburned and two burned during the 2020 Bobcat Fire in the San Gabriel Mountains, California, USA. Electrical resistivity imaging shows that in the burned catchments, rainfall infiltrated into the weathered bedrock and persisted. Stormflow isotope data indicate that the amount of mixing of surface and subsurface water during storms was similar in all catchments, despite higher streamflow post-fire. Therefore, both surface runoff and infiltration likely increased in tandem. These results suggest that the hydrologic response to storms in post-fire environments is dynamic and involves more surface-subsurface exchange than previously conceptualized, which has important implications for vegetation regrowth and post-fire landslide hazards for years following wildfire., (© 2023. The Author(s).)

Mosquito vector-borne diseases such as malaria and dengue pose a major threat to human health. Personal protection from mosquito blood feeding is mostly by treating clothing with insecticides and the use of repellents on clothing and skin. Here, we developed a low-voltage, mosquito-resistant cloth (MRC) that blocked all blood feeding across the textile and was flexible and breathable. The design was based on mosquito head and proboscis morphometrics, the development of a novel 3-D textile with the outer conductive layers insulated from each other with an inner, non-conductive woven mesh, and the use of a DC (direct current; extra-low-voltage) resistor-capacitor. Blockage of blood feeding was measured using host-seeking Aedes aegypti adult female mosquitoes and whether they could blood feed across the MRC and an artificial membrane. Mosquito blood feeding decreased as voltage increased from 0 to 15 volts. Blood feeding inhibition was 97.8% at 10 volts and 100% inhibition at 15 volts, demonstrating proof of concept. Current flow is minimal since conductance only occurs when the mosquito proboscis simultaneously touches the outside layers of the MRC and is then quickly repelled. Our results demonstrated for the first time the use of a biomimetic, mosquito-repelling technology to prevent blood feeding using extra-low energy consumption.

Gene expression levels are key molecular phenotypes at the interplay between genotype and environment. Mounting evidence suggests that short-term changes in environmental conditions, such as those encountered in captivity, can substantially affect gene expression levels. Yet, the exact magnitude of this effect, how general it is, and whether it results in parallel changes across populations are not well understood. Here, we take advantage of the well-studied cane toad, Rhinella marina, to examine the effect of short-term captivity on brain gene expression levels, and determine whether effects of captivity differ between long-colonized and vanguard populations of the cane toad's Australian invasion range. We compared the transcriptomes of wild-caught toads immediately assayed with those from toads captured from the same populations but maintained in captivity for seven months. We found large differences in gene expression levels between captive and wild-caught toads from the same population, with an over-representation of processes related to behaviour and the response to stress. Captivity had a much larger effect on both gene expression levels and gene expression variability in toads from vanguard populations compared to toads from long-colonized areas, potentially indicating an increased plasticity in toads at the leading edge of the invasion. Overall, our findings indicate that short-term captivity can induce large and population-specific transcriptomic changes, which has significant implications for studies comparing phenotypic traits of wild-caught organisms from different populations that have been held in captivity., (© 2022 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Pulmonary emphysema is associated with dysregulated innate immune responses that promote chronic pulmonary inflammation and alveolar apoptosis, culminating in lung destruction. However, the molecular regulators of innate immunity that promote emphysema are ill-defined. Here, we investigated whether innate immune inflammasome complexes, comprising the adaptor ASC, Caspase-1 and specific pattern recognition receptors (PRRs), promote the pathogenesis of emphysema. In the lungs of emphysematous patients, as well as spontaneous gp130 F/F and cigarette smoke (CS)-induced mouse models of emphysema, the expression (messenger RNA and protein) and activation of ASC, Caspase-1, and the inflammasome-associated PRR and DNA sensor AIM2 were up-regulated. AIM2 up-regulation in emphysema coincided with the biased production of the mature downstream inflammasome effector cytokine IL-1β but not IL-18. These observations were supported by the genetic blockade of ASC, AIM2, and the IL-1 receptor and therapy with AIM2 antagonistic suppressor oligonucleotides, which ameliorated emphysema in gp130 F/F mice by preventing elevated alveolar cell apoptosis. The functional requirement for AIM2 in driving apoptosis in the lung epithelium was independent of its expression in hematopoietic-derived immune cells and the recruitment of infiltrating immune cells in the lung. Genetic and inhibitor-based blockade of AIM2 also protected CS-exposed mice from pulmonary alveolar cell apoptosis. Intriguingly, IL-6 trans-signaling via the soluble IL-6 receptor, facilitated by elevated levels of IL-6, acted upstream of the AIM2 inflammasome to augment AIM2 expression in emphysema. Collectively, we reveal cross-talk between the AIM2 inflammasome/IL-1β and IL-6 trans-signaling axes for potential exploitation as a therapeutic strategy for emphysema.

Objective: The absent in melanoma 2 (AIM2) cytosolic pattern recognition receptor and DNA sensor promotes the pathogenesis of autoimmune and chronic inflammatory diseases via caspase-1-containing inflammasome complexes. However, the role of AIM2 in cancer is ill-defined., Design: The expression of AIM2 and its clinical significance was assessed in human gastric cancer (GC) patient cohorts. Genetic or therapeutic manipulation of AIM2 expression and activity was performed in the genetically engineered gp130 F/F spontaneous GC mouse model, as well as human GC cell line xenografts. The biological role and mechanism of action of AIM2 in gastric tumourigenesis, including its involvement in inflammasome activity and functional interaction with microtubule-associated end-binding protein 1 (EB1), was determined in vitro and in vivo., Results: AIM2 expression is upregulated by interleukin-11 cytokine-mediated activation of the oncogenic latent transcription factor STAT3 in the tumour epithelium of GC mouse models and patients with GC. Genetic and therapeutic targeting of AIM2 in gp130 F/F mice suppressed tumourigenesis. Conversely, AIM2 overexpression augmented the tumour load of human GC cell line xenografts. The protumourigenic function of AIM2 was independent of inflammasome activity and inflammation. Rather, in vivo and in vitro AIM2 physically interacted with EB1 to promote epithelial cell migration and tumourigenesis. Furthermore, upregulated expression of AIM2 and EB1 in the tumour epithelium of patients with GC was independently associated with poor patient survival., Conclusion: AIM2 can play a driver role in epithelial carcinogenesis by linking cytokine-STAT3 signalling, innate immunity and epithelial cell migration, independent of inflammasome activation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Understanding the mechanisms allowing invasive species to adapt to novel environments is a challenge in invasion biology. Many invaders demonstrate rapid evolution of behavioural traits involved in range expansion such as locomotor activity, exploration and risk-taking. However, the molecular mechanisms that underpin these changes are poorly understood. In 86 years, invasive cane toads (Rhinella marina) in Australia have drastically expanded their geographic range westward from coastal Queensland to Western Australia. During their range expansion, toads have undergone extensive phenotypic changes, particularly in behaviours that enhance the toads' dispersal ability. Common-garden experiments have shown that some changes in behavioural traits related to dispersal are heritable. At the molecular level, it is currently unknown whether these changes in dispersal-related behaviour are underlain by small or large differences in gene expression, nor is known the biological function of genes showing differential expression. Here, we used RNA-seq to gain a better understanding of the molecular mechanisms underlying dispersal-related behavioural changes. We compared the brain transcriptomes of toads from the Hawai'ian source population, as well as three distinct populations from across the Australian invasive range. We found markedly different gene expression profiles between the source population and Australian toads. By contrast, toads from across the Australian invasive range had very similar transcriptomic profiles. Yet, key genes with functions putatively related to dispersal behaviour showed differential expression between populations located at each end of the invasive range. These genes could play an important role in the behavioural changes characteristic of range expansion in Australian cane toads., (© 2022 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Inflammasomes are important multiprotein regulatory complexes of innate immunity and have recently emerged as playing divergent roles in numerous inflammation-associated cancers. Among these include gastric cancer (GC), the third leading cause of cancer-associated death worldwide, and we have previously discovered a pro-tumorigenic role for the key inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) in the spontaneous genetic gp130 F/F mouse model for GC. However, the identity of the specific pattern recognition receptors (PRRs) that activate tumor-promoting inflammasomes during GC is unknown. Here, we investigated the role of the best-characterized inflammasome-associated PRR, nucleotide-binding domain, and leucine-rich repeat containing receptor, pyrin domain-containing (NLRP) 3, in GC. In gastric tumors of gp130 F/F mice, although NLRP3 expression was elevated at the mRNA (qPCR) and protein (immunohistochemistry) levels, genetic ablation of NLRP3 in gp130 F/F : Nlrp3 -/- mice did not alleviate the development of gastric tumors. Similarly, cellular processes associated with tumorigenesis in the gastric mucosa, namely, proliferation, apoptosis, and inflammation, were comparable between gp130 F/F and gp130 F/F : Nlrp3 -/- mice. Furthermore, inflammasome activation levels, determined by immunoblotting and immunohistochemistry for cleaved Caspase-1, which along with ASC is another integral component of inflammasome complexes, were unchanged in gp130 F/F and gp130 F/F : Nlrp3 -/- gastric tumors. We also observed variable NLRP3 expression levels (mRNA and protein) among independent GC patient cohorts, and NLRP3 was not prognostic for survival outcomes. Taken together, these data suggest that NLRP3 does not play a major role in promoting inflammasome-driven gastric tumorigenesis, and thus pave the way for further investigations to uncover the key inflammasome-associated PRR implicated in GC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 West, Deswaerte, West, Gearing, Tan and Jenkins.)

Iron is a micronutrient critical to fundamental biological processes including respiration and photosynthesis, and it can therefore impact primary and heterotrophic productivity. Yet in oxic environments, iron is highly insoluble, rendering it, in principle, unavailable as a nutrient for biological growth. Life has "solved" this problem via the invention of iron chelates, known as siderophores, that keep iron available for microbial productivity. In this work, we examined the impact of siderophore synthesis on the speciation, mobility, and bioavailability of iron from rock-forming silicate minerals-shedding new light on the mechanisms by which microbes use mineral substrates to support primary productivity, as well as the consequent effects on silicate dissolution. Growth experiments were performed with Shewanella oneidensis MR-1 in an oxic, iron-depleted minimal medium, amended with olivine minerals as the sole source of iron. Experiments included the wild-type strain MR-1, and a siderophore synthesis gene deletion mutant strain (ΔMR-1). Relative to MR-1, ΔMR-1 exhibited a very pronounced growth penalty and an extended lag phase. However, substantial growth of ΔMR-1, comparable to MR-1 growth, was observed when the mutant strain was provided with siderophores in the form of either filtrate from a well-grown MR-1 culture, or commercially available deferoxamine. These observations suggest that siderophores are critical for S. oneidensis to acquire iron from olivine. Growth-limiting concentrations of deferoxamine amendments were observed to be ≤5-10 µM, concentrations significantly lower than previously recorded as necessary to impact mineral dissolution rates. X-ray photoelectric spectroscopy analyses of the incubated olivine surfaces suggest that siderophores deplete mineral surface layers of ferric iron. Combined, these results demonstrate that low micromolar concentrations of siderophores can effectively mobilize iron bound within silicate minerals, supporting very significant biological growth in limiting environments. The specific mechanism would involve siderophores removing a protective layer of nanometer-thick iron oxides, enhancing silicate dissolution and nutrient bioavailability., (© 2021 John Wiley & Sons Ltd.)

The Paleocene-Eocene Thermal Maximum (PETM; ~55.9 Ma) was a geologically rapid warming period associated with carbon release, which caused a marked increase in the hydrological cycle. Here, we use lithium (Li) isotopes to assess the global change in weathering regime, a critical carbon drawdown mechanism, across the PETM. We find a negative Li isotope excursion of ~3‰ in both global seawater (marine carbonates) and in local weathering inputs (detrital shales). This is consistent with a very large delivery of clays to the oceans or a shift in the weathering regime toward higher physical erosion rates and sediment fluxes. Our seawater records are best explained by increases in global erosion rates of ~2× to 3× over 100 ka, combined with model-derived weathering increases of 50 to 60% compared to prewarming values. Such increases in weathering and erosion would have supported enhanced carbon burial, as both carbonate and organic carbon, thereby stabilizing climate.

Permafrost soils store approximately twice the amount of carbon currently present in Earth's atmosphere and are acutely impacted by climate change due to the polar amplification of increasing global temperature. Many organic-rich permafrost sediments are located on large river floodplains, where river channel migration periodically erodes and redeposits the upper tens of meters of sediment. Channel migration exerts a first-order control on the geographic distribution of permafrost and floodplain stratigraphy and thus may affect microbial habitats. To examine how river channel migration in discontinuous permafrost environments affects microbial community composition, we used amplicon sequencing of the 16S rRNA gene on sediment samples from floodplain cores and exposed riverbanks along the Koyukuk River, a large tributary of the Yukon River in west-central Alaska. Microbial communities are sensitive to permafrost thaw: communities found in deep samples thawed by the river closely resembled near-surface active-layer communities in nonmetric multidimensional scaling analyses but did not resemble floodplain permafrost communities at the same depth. Microbial communities also displayed lower diversity and evenness in permafrost than in both the active layer and permafrost-free point bars recently deposited by river channel migration. Taxonomic assignments based on 16S and quantitative PCR for the methyl coenzyme M reductase functional gene demonstrated that methanogens and methanotrophs are abundant in older permafrost-bearing deposits but not in younger, nonpermafrost point bar deposits. The results suggested that river migration, which regulates the distribution of permafrost, also modulates the distribution of microbes potentially capable of producing and consuming methane on the Koyukuk River floodplain. IMPORTANCE Arctic lowlands contain large quantities of soil organic carbon that is currently sequestered in permafrost. With rising temperatures, permafrost thaw may allow this carbon to be consumed by microbial communities and released to the atmosphere as carbon dioxide or methane. We used gene sequencing to determine the microbial communities present in the floodplain of a river running through discontinuous permafrost. We found that the river's lateral movement across its floodplain influences the occurrence of certain microbial communities-in particular, methane-cycling microbes were present on the older, permafrost-bearing eroding riverbank but absent on the newly deposited river bars. Riverbank sediment had microbial communities more similar to those of the floodplain active-layer samples than permafrost samples from the same depth. Therefore, spatial patterns of river migration influence the distribution of microbial taxa relevant to the warming Arctic climate.

Garments treated with chemical insecticides are commonly used to prevent mosquito bites. Resistance to insecticides, however, is threatening the efficacy of this technology, and people are increasingly concerned about the potential health impacts of wearing insecticide-treated clothing. Here, we report a mathematical model for fabric barriers that resist bites from Aedes aegypti mosquitoes based on textile physical structure and no insecticides. The model was derived from mosquito morphometrics and analysis of mosquito biting behavior. Woven filter fabrics, precision polypropylene plates, and knitted fabrics were used for model validation. Then, based on the model predictions, prototype knitted textiles and garments were developed that prevented mosquito biting, and comfort testing showed the garments to possess superior thermophysiological properties. Our fabrics provided a three-times greater bite resistance than the insecticide-treated cloth. Our predictive model can be used to develop additional textiles in the future for garments that are highly bite resistant to mosquitoes.

The evolution of the global carbon and silicon cycles is thought to have contributed to the long-term stability of Earth's climate 1-3 . Many questions remain, however, regarding the feedback mechanisms at play, and there are limited quantitative constraints on the sources and sinks of these elements in Earth's surface environments 4-12 . Here we argue that the lithium-isotope record can be used to track the processes controlling the long-term carbon and silicon cycles. By analysing more than 600 shallow-water marine carbonate samples from more than 100 stratigraphic units, we construct a new carbonate-based lithium-isotope record spanning the past 3 billion years. The data suggest an increase in the carbonate lithium-isotope values over time, which we propose was driven by long-term changes in the lithium-isotopic conditions of sea water, rather than by changes in the sedimentary alterations of older samples. Using a mass-balance modelling approach, we propose that the observed trend in lithium-isotope values reflects a transition from Precambrian carbon and silicon cycles to those characteristic of the modern. We speculate that this transition was linked to a gradual shift to a biologically controlled marine silicon cycle and the evolutionary radiation of land plants 13,14 ., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Fly ash-the residuum of coal burning-contains a considerable amount of fossilized particulate organic carbon (FOC ash ) that remains after high-temperature combustion. Fly ash leaks into natural environments and participates in the contemporary carbon cycle, but its reactivity and flux remained poorly understood. We characterized FOC ash in the Chang Jiang (Yangtze River) basin, China, and quantified the riverine FOC ash fluxes. Using Raman spectral analysis, ramped pyrolysis oxidation, and chemical oxidation, we found that FOC ash is highly recalcitrant and unreactive, whereas shale-derived FOC (FOC rock ) was much more labile and easily oxidized. By combining mass balance calculations and other estimates of fly ash input to rivers, we estimated that the flux of FOC ash carried by the Chang Jiang was 0.21 to 0.42 Mt C⋅y -1 in 2007 to 2008-an amount equivalent to 37 to 72% of the total riverine FOC export. We attributed such high flux to the combination of increasing coal combustion that enhances FOC ash production and the massive construction of dams in the basin that reduces the flux of FOC rock eroded from upstream mountainous areas. Using global ash data, a first-order estimate suggests that FOC ash makes up to 16% of the present-day global riverine FOC flux to the oceans. This reflects a substantial impact of anthropogenic activities on the fluxes and burial of fossil organic carbon that has been made less reactive than the rocks from which it was derived., Competing Interests: The authors declare no competing interest.

Mosquito-borne malaria kills 429,000 people each year with the problem being acute in sub-Saharan Africa. The successes gained with long-lasting pyrethroid-treated bednets are now in jeopardy because of wide-spread, pyrethroid resistance in mosquitoes. Using crowd modeling theory normalized for standard bednet architecture, we were able to design an attract-trap-kill technology for mosquitoes that does not require insecticides. Using three-dimensional polyester knitting and heat fixation, trap funnels were developed with high capture efficacy with no egression under worst-case laboratory conditions. Field testing in Africa in WHO huts with Gen1-3 T (trap)-Nets validated our model, and as predicted, Gen3 had the highest efficacy with a 4.3-fold greater trap-kill rate with no deterrence or repellency compared to Permanet 2.0, the most common bednet in Africa. A T-Net population model was developed based on field data to predict community-level mosquito control compared to a pyrethroid bednet. This model showed the Gen3 non-insecticidal T-Net under field conditions in Africa against pyrethroid resistant mosquitoes was 12.7-fold more efficacious than single chemical, pyrethroid-treated nets.

Craniofacial microsomia is a congenital deformity caused by asymmetric development of the skull (cranium) and face before birth. Current treatments include corrective surgery and replacement of the deformed structure using autograft tissue, which results in donor site morbidity. An alternative therapy can be achieved by developing a resorbable scaffold for skeletal muscle regeneration which will help restore the symmetry and function of the facial muscles and reduce donor site morbidity. Two resorbable weft knitted scaffolds were fabricated using poly(ε-caprolactone) multifilament yarns with unique auxetic design structures possessing negative Poisson's ratio (NPR). These scaffolds exhibit their NPR elasticity through an increase in total volume as well as no lateral narrowing when stretched longitudinally, which can provide orientated mechanical supports to the cell growth of skeletal muscle regeneration. These scaffolds were evaluated for the required physical properties, mechanical performance and biocompatibility by culturing them with neonatal human dermal fibroblasts so as to determine their cell metabolic activity, cell attachment and proliferation. This study can facilitate the understanding and engineering of textile-based scaffolds for tissues/organs. The work also paves a pathway to emerge the NPR textiles into tissue engineering, which has an extensive potential for biomedical end-uses.

Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.

Gastric cancer is associated with chronic inflammation (gastritis) triggered by persistent Helicobacter pylori (H. pylori) infection. Elevated tyrosine phosphorylation of the latent transcription factor STAT3 is a feature of gastric cancer, including H. pylori-infected tissues, and aligns with nuclear transcriptional activity. However, the transcriptional role of STAT3 serine phosphorylation, which promotes STAT3-driven mitochondrial activities, is unclear. Here, by coupling serine-phosphorylated (pS)-STAT3-deficient Stat3 SA/SA mice with chronic H. felis infection, which mimics human H. pylori infection in mice, we reveal a key role for pS-STAT3 in promoting Helicobacter-induced gastric pathology. Immunohistochemical staining for infiltrating immune cells and expression analyses of inflammatory genes revealed that gastritis was markedly suppressed in infected Stat3 SA/SA mice compared with wild-type mice. Stomach weight and gastric mucosal thickness were also reduced in infected Stat3 SA/SA mice, which was associated with reduced proliferative potential of infected Stat3 SA/SA gastric mucosa. The suppressed H. felis-induced gastric phenotype of Stat3 SA/SA mice was phenocopied upon genetic ablation of signaling by the cytokine IL-11, which promotes gastric tumorigenesis via STAT3. pS-STAT3 dependency by Helicobacter coincided with transcriptional activity on STAT3-regulated genes, rather than mitochondrial and metabolic genes. In the gastric mucosa of mice and patients with gastritis, pS-STAT3 was constitutively expressed irrespective of Helicobacter infection. Collectively, these findings suggest an obligate requirement for IL-11 signaling via constitutive pS-STAT3 in Helicobacter-induced gastric carcinogenesis., (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Deregulated activation of the latent oncogenic transcription factor STAT3 in many human epithelial malignancies, including gastric cancer, has invariably been associated with its canonical tyrosine phosphorylation and enhanced transcriptional activity. By contrast, serine phosphorylation (pS) of STAT3 can augment its nuclear transcriptional activity and promote essential mitochondrial functions, yet the role of pS-STAT3 among epithelial cancers is ill-defined. Here, we reveal that genetic ablation of pS-STAT3 in the gp130 F/F spontaneous gastric cancer mouse model and human gastric cancer cell line xenografts abrogated tumor growth that coincided with reduced proliferative potential of the tumor epithelium. Microarray gene expression profiling demonstrated that the suppressed gastric tumorigenesis in pS-STAT3-deficient gp130 F/F mice associated with reduced transcriptional activity of STAT3-regulated gene networks implicated in cell proliferation and migration, inflammation, and angiogenesis, but not mitochondrial function or metabolism. Notably, the protumorigenic activity of pS-STAT3 aligned with its capacity to primarily augment RNA polymerase II-mediated transcriptional elongation, but not initiation, of STAT3 target genes. Furthermore, by using a combinatorial in vitro and in vivo proteomics approach based on the rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) assay, we identified RuvB-like AAA ATPase 1 (RUVBL1/Pontin) and enhancer of rudimentary homolog (ERH) as interacting partners of pS-STAT3 that are pivotal for its transcriptional activity on STAT3 target genes. Collectively, these findings uncover a hitherto unknown transcriptional role and obligate requirement for pS-STAT3 in gastric cancer that could be extrapolated to other STAT3-driven cancers. SIGNIFICANCE: These findings reveal a new transcriptional role and mandatory requirement for constitutive STAT3 serine phosphorylation in gastric cancer., (©2019 American Association for Cancer Research.)

Silicate minerals represent an important reservoir of nutrients at Earth's surface and a source of alkalinity that modulates long-term geochemical cycles. Due to the slow kinetics of primary silicate mineral dissolution and the potential for nutrient immobilization by secondary mineral precipitation, the bioavailability of many silicate-bound nutrients may be limited by the ability of micro-organisms to actively scavenge these nutrients via redox alteration and/or organic ligand production. In this study, we use targeted laboratory experiments with olivine and the siderophore deferoxamine B to explore how microbial ligands affect nutrient (Fe) release and the overall rate of mineral dissolution. Our results show that olivine dissolution rates are accelerated in the presence of micromolar concentrations of deferoxamine B. Based on the non-linear decrease in rates with time and formation of a Fe 3+ -ligand complex, we attribute this acceleration in dissolution rates to the removal of an oxidized surface coating that forms during the dissolution of olivine at circum-neutral pH in the presence of O 2 and the absence of organic ligands. While increases in dissolution rates are observed with micromolar concentrations of siderophores, it remains unclear whether such conditions could be realized in natural environments due to the strong physiological control on microbial siderophore production. So, to contextualize our experimental results, we also developed a feedback model, which considers how microbial physiology and ligand-promoted mineral dissolution kinetics interact to control the extent of biotic enhancement of dissolution rates expected for different environments. The model predicts that physiological feedbacks severely limit the extent to which dissolution rates may be enhanced by microbial activity, though the rate of physical transport modulates this limitation., (© 2019 John Wiley & Sons Ltd.)

Infrequent extreme events such as large earthquakes pose hazards and have lasting impacts on landscapes and biogeochemical cycles. Sediments provide valuable records of past events, but unambiguously identifying event deposits is challenging because of nonlinear sediment transport processes and poor age control. Here, we have been able to directly track the propagation of a tectonic signal into stratigraphy using reservoir sediments from before and after the 2008 Wenchuan earthquake. Cycles in magnetic susceptibility allow us to define a precise annual chronology and identify the timing and nature of the earthquake's sedimentary record. The grain size and Rb/Sr ratio of the sediments responded immediately to the earthquake. However, the changes were muted until 2 years after the event, when intense monsoonal runoff drove accumulation of coarser grains and lower Rb/Sr sediments. The delayed response provides insight into how climatic and tectonic agents interact to control sediment transfer and depositional processes.

The isotopic composition of iron, zinc, copper, and cadmium (δ 56 Fe, δ 66 Zn, δ 65 Cu, and δ 114 Cd) are novel and promising tools to study the metabolism and homeostasis of trace metals in the human body. Serum δ 65 Cu has been proposed as a potential tool for diagnosis of cancer in liquid biopsy, and other metals may have similar utility. However, accurate analysis of trace metal isotopes is challenging because of the difficulties in purifying the metals from biological samples. Here we developed a simple and rapid method for sequential purification of Cu, Fe, Zn, and Cd from a single blood plasma sample. By using a combination of 11 M acetic acid and 4 M HCl in the first steps of column chemistry on AG-MP1 resin, we dramatically improve the separation of Cu from matrix elements compared to previous methods which use concentrated HCl alone. Our new method achieves full recovery of Cu, Fe, Zn, and Cd to prevent column-induced isotope fractionation effects, and effectively separates analytes from the matrix in order to reduce polyatomic interferences during isotope analysis. Our methods were verified by the analysis of isotope standards, a whole blood reference material, and a preliminary sample set including five plasma samples from healthy individuals and five plasma samples from cancer patients. This new method simplifies preparation of blood samples for metal isotope analysis, accelerating multi-isotope approaches to medical studies and contributing to our understanding of the cycling of Fe, Zn, Cu, and Cd in the human body. Graphical abstract ᅟ.

Evidence for relationships between seismotectonic activity and dissolved weathering fluxes remains limited. Motivated by the occurrence of new springs emerging after the 2016 Kumamoto earthquake and supported by historical groundwater data, this study focuses on the long-term effect of near-surface structural deformation on the contribution of deep, highly saline fluids to the solute fluxes from the Aso caldera, Kyushu, Japan. Available hydrologic and structural data suggest that concentrated, over-pressured groundwaters migrate to the surface when new hydraulic pathways open during seismic deformation. These new springs have a hydrochemical fingerprint (including δD H2O , δ 18 O H2O , δ 7 Li, δ 11 B, δ 18 O SO4 , and δ 34 S SO4 ) indistinguishable from long-established confined groundwater that likely reflects a mixture of infiltrated meteoric water with high-sulfate hydrothermal fluids. A comparison of historical hydrochemistry data and patterns of past seismicity suggests that discharge of deep fluids is associated with similar deformation structures to those observed during the Kumamoto earthquake, and that seismic activity plays an important role over historic timescales in delivering the majority of the solutes to the caldera outlet, sustaining fluxes that are amongst the world's highest. This upwelling mechanism might be relevant for other systems too, and could contribute to the over-proportional share of active volcanic areas in global weathering fluxes.

Glioblastoma is the most common type of malignant brain tumor among adults and is currently a non-curable disease due primarily to its highly invasive phenotype, and the lack of successful current therapies. Despite surgical resection and post-surgical treatment patients ultimately develop recurrence of the tumour. Several signalling molecules have been implicated in the development, progression and aggressiveness of glioblastoma. The present study reviewed the role of interleukin (IL)-6, a cytokine known to be important in activating several pro-oncogenic signaling pathways in glioblastoma. The current study particularly focused on the contribution of IL-6 in recurrent glioblastoma, with particular focus on glioblastoma stem cells and resistance to therapy.

Mobile applications ("apps") designed for sexual health education have the potential to reach teens and young adults that are hard to reach through traditional platforms; however, little is known about availability of these apps and their adherence to existing guidelines. Following a search on the two major app stores, data from 2,693 apps were analyzed. Only 697 (25%) addressed sexual health, and only 15 (1%) of apps met inclusion criteria for comprehensive programs and their content was further analyzed. The content of most of these apps narrowly focused on sexually transmitted infections and pregnancy prevention and lacked information on puberty, sexual identity, and personal safety. Theoretically grounded strategies including self-efficacy and modeling behavior to strengthen behavior change efforts were largely absent. Last, we identified significant shortcomings in the literate design of these apps, including limited use of interactive features, such as videos, quizzes, or games. These findings indicate that the potential of apps as sexual health promotion tools has not yet been fully realized. We outline recommendations for developing theory- and evidence-based sexual education apps and provide suggestions for health educators on how to select relevant apps when working for youth.

Background: Cane toads (Rhinella marina) are an iconic invasive species introduced to 4 continents and well utilized for studies of rapid evolution in introduced environments. Despite the long introduction history of this species, its profound ecological impacts, and its utility for demonstrating evolutionary principles, genetic information is sparse. Here we produce a de novo transcriptome spanning multiple tissues and life stages to enable investigation of the genetic basis of previously identified rapid phenotypic change over the introduced range., Findings: Using approximately 1.9 billion reads from developing tadpoles and 6 adult tissue-specific cDNA libraries, as well as a transcriptome assembly pipeline encompassing 100 separate de novo assemblies, we constructed 62 202 transcripts, of which we functionally annotated ∼50%. Our transcriptome assembly exhibits 90% full-length completeness of the Benchmarking Universal Single-Copy Orthologs data set. Robust assembly metrics and comparisons with several available anuran transcriptomes and genomes indicate that our cane toad assembly is one of the most complete anuran genomic resources available., Conclusions: This comprehensive anuran transcriptome will provide a valuable resource for investigation of genes under selection during invasion in cane toads, but will also greatly expand our general knowledge of anuran genomes, which are underrepresented in the literature. The data set is publically available in NCBI and GigaDB to serve as a resource for other researchers., (© The Authors 2017. Published by Oxford University Press.)

Clinical simulation has gained prominence as an educational approach in many Canadian respiratory therapy programs and is strongly associated with improved learning, clinical and nonclinical skill, future performance, and patient outcomes. Traditionally, the primary assessment approach employed in clinical simulation has been formative debriefing for learning. Contextual factors, such as limited opportunities for learning in clinical practice and technologically oriented perspectives on learning in clinical simulation, are converging to prompt a move from using formative debriefing sessions that support learning in simulation to employing high-stakes testing intended to measure entry-to-practice competencies. We adopt the perspective that these factors are intricately linked to the profession's regulatory environment, which may strongly influence how simulation practices become embedded with respiratory therapy educational programs. Through this discussion we challenge the profession to consider how environmental factors, including externally derived requirements, may ultimately impact the effectiveness of simulation-based learning environments.

The cane toad ( Rhinella marina ) has undergone rapid evolution during its invasion of tropical Australia. Toads from invasion front populations (in Western Australia) have been reported to exhibit a stronger baseline phagocytic immune response than do conspecifics from range core populations (in Queensland). To explore this difference, we injected wild-caught toads from both areas with the experimental antigen lipopolysaccharide (LPS, to mimic bacterial infection) and measured whole-blood phagocytosis. Because the hypothalamic-pituitary-adrenal axis is stimulated by infection (and may influence immune responses), we measured glucocorticoid response through urinary corticosterone levels. Relative to injection of a control (phosphate-buffered saline), LPS injection increased both phagocytosis and the proportion of neutrophils in the blood. However, responses were similar in toads from both populations. This null result may reflect the ubiquity of bacterial risks across the toad's invaded range; utilization of this immune pathway may not have altered during the process of invasion. LPS injection also induced a reduction in urinary corticosterone levels, perhaps as a result of chronic stress., Competing Interests: Lee A. Rollins is an Academic Editor for PeerJ.

Despite the apparent centrality of fidelity to clinical simulation instructional design and practice in respiratory therapy education, it remains one of most contested constructs in the simulation literature. Fidelity has been described as educationally under-theorized resulting in an emphasis often being placed on technological sophistication rather than theory-informed design, particularly in respiratory therapy. This article critically examines various conceptualizations of fidelity in the field of clinical simulation in an effort to inform its instructional design practices. We adopt the perspective that a shift in the theoretic lens from individualistic to a more socio-cultural orientation may better support our understanding of learning in simulation environments. The instructional design framework (IDF) developed by the Canadian Network for Simulation in Healthcare provides a solid pedagogical foundation on which to base clinical simulations design. The IDF has also been a platform upon which designers can frame the characteristics of simulation environments. We propose an enhanced IDF informed by contemporary education theory describing the joint learning relationship that exists between learners and technology-enhanced learning environments. The enhanced IDF includes each of the interdependent design elements in the original model and incorporates a socio-culturally informed conceptualization of fidelity. The framework will be useful in fostering the relationships that support an effective clinical simulation learning environment. This will be of particular value to practitioners, researchers, and theorists in the clinical simulation-based respiratory therapy education field.

Connections between glaciation, chemical weathering, and the global carbon cycle could steer the evolution of global climate over geologic time, but even the directionality of feedbacks in this system remain to be resolved. Here, we assemble a compilation of hydrochemical data from glacierized catchments, use this data to evaluate the dominant chemical reactions associated with glacial weathering, and explore the implications for long-term geochemical cycles. Weathering yields from catchments in our compilation are higher than the global average, which results, in part, from higher runoff in glaciated catchments. Our analysis supports the theory that glacial weathering is characterized predominantly by weathering of trace sulfide and carbonate minerals. To evaluate the effects of glacial weathering on atmospheric pCO 2 , we use a solute mixing model to predict the ratio of alkalinity to dissolved inorganic carbon (DIC) generated by weathering reactions. Compared with nonglacial weathering, glacial weathering is more likely to yield alkalinity/DIC ratios less than 1, suggesting that enhanced sulfide oxidation as a result of glaciation may act as a source of CO 2 to the atmosphere. Back-of-the-envelope calculations indicate that oxidative fluxes could change ocean-atmosphere CO 2 equilibrium by 25 ppm or more over 10 ky. Over longer timescales, CO 2 release could act as a negative feedback, limiting progress of glaciation, dependent on lithology and the concentration of atmospheric O 2 Future work on glaciation-weathering-carbon cycle feedbacks should consider weathering of trace sulfide minerals in addition to silicate minerals., Competing Interests: The authors declare no conflict of interest.

Background: Breast cancer is one of the leading contributors to preventable illness and death among women. Although mobile phone apps provide unprecedented opportunity to engage women along the cancer continuum, little is known about the availability, content, and usability of breast cancer mobile phone apps., Objective: This study analyzed the content and adherence to literate design standards of all breast cancer-related apps available on the App Store and Google Play, as well as the relationship between their content, user ratings, and price., Methods: Following identification and downloading of all available breast cancer mobile phone apps in October 2015, 101 apps were confirmed as focusing on breast cancer. Based on prior research, we adapted and applied a content analysis scheme that was specific to breast cancer apps, including their main purpose, relevance to the cancer care continuum, and adherence to usability standards outlined by the Institute of Medicine (IOM)., Results: The most common aim of apps was educational (73/101, 72.3%), followed by behavior change (24/101, 23.9%), fundraising (20/101, 19.8%), and advocacy (14/101, 13.9%). On the cancer continuum, primary prevention (strategies to prevent cancer cells from occurring) was mentioned in almost one-third of the apps (30/101, 29.7%). Less than half of the apps (46/101, 45.5%) presented information about mammography and/or breast clinical exam, and 53 apps (52.5%) discussed breast self-exam (which is no longer recommended). Symptoms of cancer prediagnosis, such as a lump, were discussed in almost half of the apps (48/101, 47.5%) and a similar number of apps included information about genetic risk for breast cancer (47/101, 46.5%). Information about breast cancer diagnosis was included in 42 apps (41.58%) and 43 (42.6%) apps discussed treatment options. Survivorship issues were addressed in 17 (16.8%) apps. Only one (1.0%) app discussed hospice. Adherence to usability recommendations was low. The median composite score was 3 (mean 2.60, SD 1.20) of the six recommended usability items. With eight plain language items, the median of the composite health literacy score was 5 (mean 5.06, SD 2.00). Most apps did not use easy-to-understand words (44/101, 43.6%) and few (24/101, 23.8%) defined key terms., Conclusions: Current breast cancer apps provide important information about breast cancer, but the most common topic covered is breast self-examination, a non-evidence-based screening strategy. Apps that focus on evidence-based strategies on the cancer continuum are needed, with a notable pressing need for apps that would address survivorship and end of life. Finally, developers of breast cancer apps should adhere to IOM standards to meet the needs of diverse populations and reduce current disparities., (©Tamar Ginossar, Sayyed Fawad Ali Shah, Andrew J West, Joshua M Bentley, Charlene A Caburnay, Matthew W Kreuter, Anita Y Kinney. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 13.03.2017.)