Determinants of lung health across the life course in sub-Saharan Africa

Lung health across the life course is influenced by factors affecting airway and alveolar development and growth during antenatal and perinatal periods, throughout childhood and adolescence, and into adulthood. Lung function trajectories are set in early life and childhood deficits may predispose to non-communicable respiratory diseases, such as asthma and chronic obstructive pulmonary disease, in later years. Potential risk factors are common in many sub-Saharan African (sSA) countries; adverse antenatal environments cause in utero growth restriction and prematurity; HIV and respiratory infections, including TB are common; exposure to air pollution is widespread, including household air pollution from biomass fuel use, traffic-related pollution in rapidly expanding cities, and tobacco smoke exposure. Multiple disadvantages experienced in early life require an integrated approach that addresses reproductive, maternal and child health. Public health strategies need to tackle multiple risk factors, emphasising Universal Health Coverage, to maximise lung health in the world’s poorest, most vulnerable populations. This review explores potential determinants of lung health across the life course. Due to the extensive topic and wide range of related literature, we prioritised more recent citations, especially those from sSA, focusing on risk factors for which there is most information, and which are most prevalent in the region

Noncommunicable Respiratory Disease and Air Pollution Exposure in Malawi (CAPS). A Cross-Sectional Study.

RationaleNoncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults.ObjectivesWe set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi.MethodsWe performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter <2.5 μm in aerodynamic diameter [PM2.5] and carbon monoxide [CO]). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done.Measurements and main resultsOne thousand four hundred eighty-one participants (mean [SD] age, 43.8 [17.8] yr; 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction, and restriction were 13.6% (95% confidence interval [CI], 11.9-15.4), 8.7% (95% CI, 7.0-10.7), and 34.8% (95% CI, 31.7-38.0), respectively. Median 48-hour personal PM2.5 and CO exposures were 71.0 μg/m3 (interquartile range [IQR], 44.6-119.2) and 1.23 ppm (IQR, 0.79-1.93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (odds ratio [OR], 1.59; 95% CI, 1.05-2.39), previous tuberculosis (OR, 2.50; 95% CI, 1.04-15.58), and CO exposure (OR, 1.46; 95% CI, 1.04-2.05). Exposure to PM2.5 was not associated with any demographic, clinical, or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes.ConclusionsThe burden of chronic respiratory symptoms, abnormal spirometry, and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for noncommunicable respiratory disease in sub-Saharan Africa are needed. Clinical trial registered with www.isrctn.com (ISRCTN 59448623)

Controlling the activation and inhibition of human natural killer cells

Natural Killer (NK) cells are innate lymphocytes that play an essential role in host defence against viral infection and tumours. The activation and function of NK cells is regulated by cytokines, in particular IL-15, which promotes their differentiation, survival and activation. IL-10 is a potent immunosuppressive cytokine; however, some studies report immunostimulatory activity towards NK cells. The aim of this study was to investigate the immunomodulatory effects of IL-10 on NK cell activity. Using an in vitro system of primary human NK cells, the effect of IL-10 stimulation on key NK cell activating pathways, such as cytotoxicity, receptor expression and proliferation was explored. IL-10 stimulation of NK cells enhanced granzyme B expression and NK cell cytotoxicity in a STAT3-dependent manner. Unlike the prototypical NK cell activator, IL-15, IL-10 stimulation did not alter the expression of NK cell activating receptors, induce proliferation or activate the mTOR pathway. The immunosuppressive cytokine TGF-β inhibits IL-15-mediated NK cell activation by inhibiting mTOR signalling. Interestingly, although this study does not show IL-10 activation of mTOR signalling, IL-10 mediated NK cell activation was susceptible to TGF-β-mediated inhibition. Moreover, this TGF-β mediated inhibition was independent of STAT3 signalling, suggesting the involvement of other, as yet undefined pathways. This study highlights distinct pathways of NK cell activation by IL-15 and IL-10, and defines an IL-10 mediated, mTOR-independent, activation pathway. Observations in this study suggest that the complex mechanisms leading to activation of NK cells can be induced independently of one another, providing further insight into immune cell regulation

Conflicting Ideologies of Mexican Immigrant English Across Levels of Schooling

This article explores how language ideologies—beliefs about immigrant students’ language use—carry conflicting images of Spanish speakers in one New Latino Diaspora town. We describe how teachers and students encounter, negotiate, and appropriate divergent ideologies about immigrant students’ language use during routine schooling practices, and we show how these ideologies convey different messages about belonging to the community and to the nation. Although the concept of language ideology often assumes stable macrolevel beliefs, our data indicate that ideologies can vary dramatically in one town. Elementary educators and students had a positive, “bilinguals-in-the-making” ideology about Spanish-speaking students, while secondary educators used more familiar deficit accounts. Despite their differences, we argue that both settings tended toward subtractive schooling, and we offer suggestions for how educators could more effectively build upon emergent bilinguals’ language skills and practices

Primers for Castilleja and their Utility Across Orobanchaceae: II. Single‐copy nuclear loci

Premise of the study: We developed primers targeting nuclear loci in Castilleja with the goal of reconstructing the evolutionary history of this challenging clade. These primers were tested across other major clades in Orobanchaceae to assess their broader utility.Methods and Results: We assembled low-coverage genomes for three taxa in Castilleja and developed primer combinations for the single-copy conserved ortholog set (COSII) and the pentatricopeptide repeat (PPR) gene family. These primer combinations were designed to take advantage of the Fluidigm microfluidic PCR platform and are well suited for high-throughput sequencing applications. Eighty-seven primers were designed for Castilleja, and 27 were found to have broader utility in Orobanchaceae.Conclusions: These results demonstrate the utility of these primers, not only across Castilleja, but for other lineages within Orobanchaceae as well. This expanded molecular toolkit will be an asset to future phylogenetic studies in Castilleja and throughout Orobanchaceae

Generating genome browsers to facilitate undergraduate-driven collaborative genome annotation

Scientists are sequencing new genomes at an increasing rate with the goal of associating genome contents with phenotypic traits. After a new genome is sequenced and assembled, structural gene annotation is often the first step in analysis. Despite advances in computational gene prediction algorithms, most eukaryotic genomes still benefit from manual gene annotation. Undergraduates can become skilled annotators, and in the process learn both about genes/genomes and about how to utilize large datasets. Data visualizations provided by a genome browser are essential for manual gene annotation, enabling annotators to quickly evaluate multiple lines of evidence (e.g., sequence similarity, RNA-Seq, gene predictions, repeats). However, creating genome browsers requires extensive computational skills; lack of the expertise required remains a major barrier for many biomedical researchers and educators.To address these challenges, the Genomics Education Partnership (GEP; https://gep.wustl.edu/) has partnered with the Galaxy Project (https://galaxyproject.org) to develop G-OnRamp (http://g-onramp.org), a web-based platform for creating UCSC Assembly Hubs and JBrowse genome browsers. G-OnRamp can also convert a JBrowse instance into an Apollo instance for collaborative genome annotations in research and educational settings. G-OnRamp enables researchers to easily visualize their experimental results, educators to create Course-based Undergraduate Research Experiences (CUREs) centered on genome annotation, and students to participate in genomics research.Development of G-OnRamp was guided by extensive user feedback from in-person workshops. Sixty-five researchers and educators from over 40 institutions participated in these workshops, which produced over 20 genome browsers now available for research and education. For example, genome browsers for four parasitoid wasp species were used in a CURE engaging 142 students taught by 13 faculty members —producing a total of 192 gene models. G-OnRamp can be deployed on a personal computer or on cloud computing platforms, and the genome browsers produced can be transferred to the CyVerse Data Store for long-term access

Primers for Castilleja and their utility across Orobanchaceae: I. Chloroplast primers1

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141726/1/aps31700020.pd