603 research outputs found
Long-term storage and age‐biased export of fluvial organic carbon: field evidence from West Iceland
Terrestrial organic carbon (OC) plays an important role in the carbon cycle, but questions remain regarding the controls and timescale(s) over which atmospheric CO₂ remains sequestered as particulate OC (POC). Motivated by observations that terrestrial POC is physically stored within soils and other shallow sedimentary deposits, we examined the role that sediment storage plays in the terrestrial OC cycle. Specifically, we tested the hypothesis that sediment storage impacts the age of terrestrial POC. We focused on the Efri Haukadalsá River catchment in Iceland as it lacks ancient sedimentary bedrock that would otherwise bias radiocarbon‐based determinations of POC storage duration by supplying pre‐aged “petrogenic” POC.
Our radiocarbon measurements of riverine suspended sediments and deposits implicated millennial‐scale storage times. Comparison between the sample types (suspended and deposits) suggested an age offset between transported (suspended sediments) and stored (deposits) POC at the time of sampling, which is predicted by theory for the sediment age distribution in floodplains. We also observed that POC in suspended sediments is younger than the predicted mean storage duration generated from independent geomorphological data, which suggested an additional role for OC cycling. Consistent with this, we observed interparticle heterogeneity in the composition of POC by imaging our samples at the microscale using X‐ray absorption spectroscopy. Specifically, we found that particles within individual samples differed in their sulfur oxidation state, which is indicative of multiple origins and/or diagenetic histories. Altogether, our results support recent coupled sediment storage and OC cycling models and indicate that the physical drivers of sediment storage are important factors controlling the cadence of carbon cycling
estMOI: estimating multiplicity of infection using parasite deep sequencing data.
Individuals living in endemic areas generally harbour multiple parasite strains. Multiplicity of infection (MOI) can be an indicator of immune status and transmission intensity. It has a potentially confounding effect on a number of population genetic analyses, which often assume isolates are clonal. Polymerase chain reaction-based approaches to estimate MOI can lack sensitivity. For example, in the human malaria parasite Plasmodium falciparum, genotyping of the merozoite surface protein (MSP1/2) genes is a standard method for assessing MOI, despite the apparent problem of underestimation. The availability of deep coverage data from massively parallizable sequencing technologies means that MOI can be detected genome wide by considering the abundance of heterozygous genotypes. Here, we present a method to estimate MOI, which considers unique combinations of polymorphisms from sequence reads. The method is implemented within the estMOI software. When applied to clinical P.falciparum isolates from three continents, we find that multiple infections are common, especially in regions with high transmission
AVALIANDO JULGAMENTOS NÃO VERBAIS DE IGUALDADE/DIFERENÇA ENTRE ESTÍMULOS AUDITIVOS EM INDIVÍDUOS COM DEFICIÊNCIAS INTELECTUAIS: UMA INVESTIGAÇÃO METODOLÓGICA
This methodological paper reports an initial attempt to evaluate the feasibility and utility of a nonverbal task for assessing generalized same/different judgments of auditory stimuli in individuals with intellectual disabilities. Study 1 asked whether participants could readily acquire a baseline of auditory same/different, go-left/go-right performance with minimal prompting. Sample stimuli consisted of pairs of successively presented sine-wave tones. If the tones were identical, selections of a visual stimulus on the left side of the computer screen were reinforced. If the tones were different, selections of a visual stimulus on the right side of the computer screen were reinforced. Two of five participants readily acquired the task, generalized performance to other stimuli, and completed a rudimentary protocol for examining auditory discriminations that are potentially more difficult than those used to establish the initial task. In Study 2, two participants who could not perform the “go-left/go-right” task with tone stimuli, but could do so with spoken-word stimuli, successfully transferred control by spoken words to tones via an auditory superimposition-and-fading procedure. The findings support the feasibility of using the task as a general-purpose auditory discrimination assessment.Keywords: auditory discrimination, go-left/go-right, intellectual disabilities, matching to sample, superimposition and fading.O presente artigo metodológico relata uma tentativa inicial de avaliar a viabilidade e a utilidade de uma tarefa não verbal para avaliar o julgamento generalizado de igualdade/diferença entre estímulos auditivos em indivíduos com deficiências intelectuais. O Estudo 1 investigou se os participantes poderiam prontamente adquirir uma linha de base de desempenho discriminativo de igualdade/diferença, em tarefa de “go-left/go-right” (responder à esquerda/responder à direita) com ajuda mínima. Os estímulos-modelo consistiam em pares de sons de frequência única apresentados sucessivamente. Se os sons fossem idênticos, seleções de um estímulo visual no lado esquerdo da tela do computador eram reforçadas. Se os sons fossem diferentes, seleções de um estímulo visual no lado direito da tela do computador eram reforçadas. Dois dos cinco participantes aprenderam prontamente a tarefa, generalizaram o desempenho para outros estímulos e completaram um protocolo rudimentar para avaliar discriminações auditivas que são potencialmente mais difíceis do que aquelas usadas para estabelecer a tarefa inicial. No Estudo 2, dois participantes que não puderam desempenhar a tarefa “go-left/go-right” com os sons de única frequência, mas puderam fazê-lo com palavras faladas como estímulos, transferiram com sucesso o controle das palavras faladas para os sons via um procedimento de esmaecimento e sobreposição de estímulos auditivos. Os achados apoiam a viabilidade de se usar a tarefa como uma avaliação de discriminação auditiva em geral. Palavras-chave: discriminação auditiva, procedimento de resposta à esquerda/resposta à direita, deficiência intelectual, emparelhamento ao modelo, sobreposição e esmaecimento
The identification of markers of macrophage differentiation in PMA-stimulated THP-1 Cells and monocyte-derived macrophages
Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the composite of environmental and differentiation-dependent imprinting. Phorbol-12-myristate-13-acetate (PMA) and 1,25-dihydroxyvitamin D3 (VD3) are stimuli commonly used to induce macrophage differentiation in monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear. We have compared the phenotype of the promonocytic THP-1 cell line after various protocols of differentiation utilising VD3 and PMA in comparison to primary human monocytes or monocyte-derived macrophages (MDM). Both stimuli induced changes in cell morphology indicative of differentiation but neither showed differentiation comparable to MDM. In contrast, PMA treatment followed by 5 days resting in culture without PMA (PMAr) increased cytoplasmic to nuclear ratio, increased mitochondrial and lysosomal numbers and altered differentiation-dependent cell surface markers in a pattern similar to MDM. Moreover, PMAr cells showed relative resistance to apoptotic stimuli and maintained levels of the differentiation-dependent anti-apoptotic protein Mcl-1 similar to MDM. PMAr cells retained a high phagocytic capacity for latex beads, and expressed a cytokine profile that resembled MDM in response to TLR ligands, in particular with marked TLR2 responses. Moreover, both MDM and PMAr retained marked plasticity to stimulus-directed polarization. These findings suggest a modified PMA differentiation protocol can enhance macrophage differentiation of THP-1 cells and identify increased numbers of mitochondria and lysosomes, resistance to apoptosis and the potency of TLR2 responses as important discriminators of the level of macrophage differentiation for transformed cells
Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria
Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio
Integration of magnetic bearings in the design of advanced gas turbine engines
Active magnetic bearings provide revolutionary advantages for gas turbine engine rotor support. These advantages include tremendously improved vibration and stability characteristics, reduced power loss, improved reliability, fault-tolerance, and greatly extended bearing service life. The marriage of these advantages with innovative structural network design and advanced materials utilization will permit major increases in thrust to weight performance and structural efficiency for future gas turbine engines. However, obtaining the maximum payoff requires two key ingredients. The first key ingredient is the use of modern magnetic bearing technologies such as innovative digital control techniques, high-density power electronics, high-density magnetic actuators, fault-tolerant system architecture, and electronic (sensorless) position estimation. This paper describes these technologies. The second key ingredient is to go beyond the simple replacement of rolling element bearings with magnetic bearings by incorporating magnetic bearings as an integral part of the overall engine design. This is analogous to the proper approach to designing with composites, whereby the designer tailors the geometry and load carrying function of the structural system or component for the composite instead of simply substituting composites in a design originally intended for metal material. This paper describes methodologies for the design integration of magnetic bearings in gas turbine engines
Long-term storage and age‐biased export of fluvial organic carbon: field evidence from West Iceland
Terrestrial organic carbon (OC) plays an important role in the carbon cycle, but questions remain regarding the controls and timescale(s) over which atmospheric CO₂ remains sequestered as particulate OC (POC). Motivated by observations that terrestrial POC is physically stored within soils and other shallow sedimentary deposits, we examined the role that sediment storage plays in the terrestrial OC cycle. Specifically, we tested the hypothesis that sediment storage impacts the age of terrestrial POC. We focused on the Efri Haukadalsá River catchment in Iceland as it lacks ancient sedimentary bedrock that would otherwise bias radiocarbon‐based determinations of POC storage duration by supplying pre‐aged “petrogenic” POC.
Our radiocarbon measurements of riverine suspended sediments and deposits implicated millennial‐scale storage times. Comparison between the sample types (suspended and deposits) suggested an age offset between transported (suspended sediments) and stored (deposits) POC at the time of sampling, which is predicted by theory for the sediment age distribution in floodplains. We also observed that POC in suspended sediments is younger than the predicted mean storage duration generated from independent geomorphological data, which suggested an additional role for OC cycling. Consistent with this, we observed interparticle heterogeneity in the composition of POC by imaging our samples at the microscale using X‐ray absorption spectroscopy. Specifically, we found that particles within individual samples differed in their sulfur oxidation state, which is indicative of multiple origins and/or diagenetic histories. Altogether, our results support recent coupled sediment storage and OC cycling models and indicate that the physical drivers of sediment storage are important factors controlling the cadence of carbon cycling
The linked survival prospects of siblings : evidence for the Indian states
This paper reports an analysis of micro-data for India that shows a high correlation in infant mortality
among siblings. In 13 of 15 states, we identify a causal effect of infant death on the risk of infant death of the
subsequent sibling (a scarring effect), after controlling for mother-level heterogeneity. The scarring effects
are large, the only other covariate with a similarly large effect being mother’s (secondary or higher)
education. The two states in which evidence of scarring is weak are Punjab, the richest, and Kerala, the
socially most progressive. The size of the scarring effect depends upon the sex of the previous child in three
states, in a direction consistent with son-preference. Evidence of scarring implies that policies targeted at
reducing infant mortality will have social multiplier effects by helping avoid the death of subsequent
siblings. Comparison of other covariate effects across the states offers some interesting new insights
Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors
Mammals express the sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). Neu5Gc is synthesized from Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the Carnivora. Interactions between two human strains of IAV with the sialyllactose receptor (sialic acid—α2,6Gal) confirm that the type of terminal sialic acid contributes significantly to IAV receptor specificity. Our results indicate that exclusive expression of Neu5Ac contributes to the susceptibility of ferrets to human-adapted IAV strains
- …