Asthma in Children and Adults-What Are the Differences and What Can They Tell us About Asthma

Asthma varies considerably across the life course. Childhood asthma is known for its overall high prevalence with a male predominance prior to puberty, common remission, and rare mortality. Adult asthma is known for its female predominance, uncommon remission, and unusual mortality. Both childhood and adult asthma have variable presentations, which are described herein. Childhood asthma severity is associated with duration of asthma symptoms, medication use, lung function, low socioeconomic status, racial/ethnic minorities, and a neutrophilic phenotype. Adult asthma severity is associated with increased IgE, elevated FeNO, eosinophilia, obesity, smoking, and low socioeconomic status. Adult onset disease is associated with more respiratory symptoms and asthma medication use despite higher prebronchodilator FEV1/FVC. There is less quiescent disease in adult onset asthma and it appears to be less stable than childhood-onset disease with more relapses and less remissions

Treg Cells and CTLA-4: The Ball and Chain of the Germinal Center Response

The mechanism by which regulatory T cells control the germinal center response is unknown. In this issue of Immunity, Wing et al. (2014) and Sage et al. (2014) demonstrate that CTLA-4 is a critical effector molecule used by regulatory T cells to control the germinal center

Social class and academic achievement in college: The interplay of rejection sensitivity and entity beliefs.

Undergraduates, especially those from lower income backgrounds, may perceive their social class background as different or disadvantaged relative to that of peers and worry about negative social treatment. We hypothesized that concerns about discrimination based on one's social class (i.e., class-based rejection sensitivity or RS-class) would be damaging to undergraduates' achievement outcomes particularly among entity theorists, who perceive their personal characteristics as fixed. We reasoned that a perceived capacity for personal growth and change, characteristic of incremental theorists, would make the pursuit of a college degree and upward mobility seem more worthwhile and attainable. We found evidence across 3 studies that dispositionally held and experimentally primed entity (vs. incremental) beliefs predicted college academic performance as a function of RS-class. Studies 1a and 1b documented that high levels of both entity beliefs and RS-class predicted lower self-reported and official grades, respectively, among undergraduates from socioeconomically diverse backgrounds. In Study 2, high entity beliefs and RS-class at matriculation predicted decreased year-end official grades among lower class Latino students. Study 3 established the causal relationship of entity (vs. incremental) beliefs on academic test performance as a function of RS-class. We observed worse test performance with higher RS-class levels following an entity (vs. incremental) prime, an effect driven by lower income students. Findings from a 4th study suggest that entity theorists with RS-class concerns tend to believe less in upward mobility and, following academic setbacks, are prone to personal attributions of failure, as well as hopelessness. Implications for education and intervention are discussed

Long‐lived plasmaspheric drainage plumes: Where does the plasma come from?

Long‐lived (weeks) plasmaspheric drainage plumes are explored. The long‐lived plumes occur during long‐lived high‐speed‐stream‐driven storms. Spacecraft in geosynchronous orbit see the plumes as dense plasmaspheric plasma advecting sunward toward the dayside magnetopause. The older plumes have the same densities and local time widths as younger plumes, and like younger plumes they are lumpy in density and they reside in a spatial gap in the electron plasma sheet (in sort of a drainage corridor). Magnetospheric‐convection simulations indicate that drainage from a filled outer plasmasphere can only supply a plume for 1.5–2 days. The question arises for long‐lived plumes (and for any plume older than about 2 days): Where is the plasma coming from? Three candidate sources appear promising: (1) substorm disruption of the nightside plasmasphere which may transport plasmaspheric plasma outward onto open drift orbits, (2) radial transport of plasmaspheric plasma in velocity‐shear‐driven instabilities near the duskside plasmapause, and (3) an anomalously high upflux of cold ionospheric protons from the tongue of ionization in the dayside ionosphere, which may directly supply ionospheric plasma into the plume. In the first two cases the plume is drainage of plasma from the magnetosphere; in the third case it is not. Where the plasma in long‐lived plumes is coming from is a quandary: to fix this dilemma, further work and probably full‐scale simulations are needed. Key Points Plasmaspheric drainage plumes can persist for weeks The source of the plasma supplying the long‐lived plumes is unknown Candidate sources include outflow from the tongue of ionizationPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108632/1/jgra51234.pd

Discovery, Characterization, and Structure–Activity Relationships of an Inhibitor of Inward Rectifier Potassium (Kir) Channels with Preference for Kir2.3, Kir3.X, and Kir7.1

The inward rectifier family of potassium (Kir) channels is comprised of at least 16 family members exhibiting broad and often overlapping cellular, tissue, or organ distributions. The discovery of disease-causing mutations in humans and experiments on knockout mice has underscored the importance of Kir channels in physiology and in some cases raised questions about their potential as drug targets. However, the paucity of potent and selective small-molecule modulators targeting specific family members has with few exceptions mired efforts to understand their physiology and assess their therapeutic potential. A growing body of evidence suggests that G protein-coupled inward rectifier K (GIRK) channels of the Kir3.X subfamily may represent novel targets for the treatment of atrial fibrillation. In an effort to expand the molecular pharmacology of GIRK, we performed a thallium (Tl+) flux-based high-throughput screen of a Kir1.1 inhibitor library for modulators of GIRK. One compound, termed VU573, exhibited 10-fold selectivity for GIRK over Kir1.1 (IC50 = 1.9 and 19 μM, respectively) and was therefore selected for further study. In electrophysiological experiments performed on Xenopus laevis oocytes and mammalian cells, VU573 inhibited Kir3.1/3.2 (neuronal GIRK) and Kir3.1/3.4 (cardiac GIRK) channels with equal potency and preferentially inhibited GIRK, Kir2.3, and Kir7.1 over Kir1.1 and Kir2.1.Tl+ flux assays were established for Kir2.3 and the M125R pore mutant of Kir7.1 to support medicinal chemistry efforts to develop more potent and selective analogs for these channels. The structure–activity relationships of VU573 revealed few analogs with improved potency, however two compounds retained most of their activity toward GIRK and Kir2.3 and lost activity toward Kir7.1. We anticipate that the VU573 series will be useful for exploring the physiology and structure–function relationships of these Kir channels

Influence of epoch time selection on the results of superposed epoch analysis using ACE and MPA data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94710/1/jgra19440.pd

The dopamine D2 receptor gene and depressive and anxious symptoms in childhood: Associations and evidence for gene-environment correlation and gene-environment interaction

ObjectiveS: Research implicates the A1 allele of the dopamine D2 receptor gene (DRD2) Taq1A polymorphism in the development of depression and anxiety. Furthermore, recent papers suggest that children with A1 allele of this gene may receive less positive parenting, and that the effects of this gene on child symptoms may be moderated by parenting. We sought to replicate and extend these findings using behavioral measures in a nonclinical sample of young children. Methods: In a sample of 473 preschool-aged children and their mothers, structured clinical interview measures and maternal reports of child symptoms were collected, and standardized observations of parent-child interactions were conducted. Results: An association was detected between the DRD2 A1 allele and symptoms of depression and anxiety indexed using interview and parent report methods. As found in previous reports, children with the DRD2 A1 allele received less supportive parenting and displayed higher levels of negative emotionality during parent-child interactions. Tests of mediation and moderation were conducted. Conclusion: We found associations between the DRD2 A1 allele and early-emerging anxious and depressive symptoms in a community sample of preschool-aged children, and evidence of a gene-environment correlation and moderation of the main effect of child genotype on child symptoms by parenting. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Type I interferon induces CXCL13 to support ectopic germinal center formation.

Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection-induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation

Understanding storm‐time ring current development through data‐model comparisons of a moderate storm

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94635/1/jgra18489.pd