Cytokine Profiles of Stimulated Blood Lymphocytes in Asthmatic and Healthy Adolescents Cross the School Year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-γ (IFN-γ), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th 1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-γ:IL-4 and IFN-γ:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation

Virulence of the emerging pathogen, Burkholderia pseudomallei, depends upon the O-linked oligosaccharyltransferase, PglL.

Aim: We sought to characterize the contribution of the O-OTase, PglL, to virulence in two Burkholderia spp. by comparing isogenic mutants in Burkholderia pseudomallei with the related species, Burkholderia thailandensis. Materials & methods: We utilized an array of in vitro assays in addition to Galleria mellonella and murine in vivo models to assess virulence of the mutant and wild-type strains in each Burkholderia species. Results: We found that pglL contributes to biofilm and twitching motility in both species. PglL uniquely affected morphology; cell invasion; intracellular motility; plaque formation and intergenus competition in B. pseudomallei. This mutant was attenuated in the murine model, and extended survival in a vaccine-challenge experiment. Conclusion: Our data support a broad role for pglL in bacterial fitness and virulence, particularly in B. pseudomallei

Educating Future Nursing Scientists: Recommendations for Integrating Omics Content in PhD Programs

Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science\u27s Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals

Skeletal accumulation of fluorescently-tagged zoledronate is higher in animals with early stage chronic kidney disease

This work examines the skeletal accumulation of fluorescently-tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation 24-hours post-dose in animals with lower kidney function due to greater amounts of binding at individual surfaces.NIH F30 DK115162; NIH T32 AR065971; NIH P30 DK 07931

The effect of polyploidy and hybridization on the evolution of floral colour in Nicotiana (Solanaceae)

Background and Aims: We investigate whether changes in floral colour accompany polyploid and homoploid hybridisation, important processes in angiosperm evolution. Potentially, changes in floral colour can facilitate speciation through pollinator shifts. Methods: We examined spectral reflectance of corolla tissue from 60 Nicotiana (Solanaceae) accessions (41 taxa) based on spectral shape (corresponding to pigmentation) as well as bee and hummingbird colour perception to assess patterns of floral colour evolution. We compared polyploid and homoploid hybrid spectra to those of their progenitors to evaluate whether hybridisation has resulted in floral colour shifts. Key Results: Floral colour categories in Nicotiana seem to have arisen multiple times independently during the evolution of the genus. Polyploid and homoploid hybrids can display a floral colour: 1) intermediate between progenitors, 2) like one or other progenitor, or 3) a transgressive or divergent colour not present in either progenitor. Conclusions: Floral colour evolution in Nicotiana is weakly constrained by phylogeny, but colour shifts occur and are sometimes associated with allopolyploid or homoploid speciation. Transgressive floral colour in N. tabacum has arisen by inheritance of anthocyanin pigmentation from its paternal progenitor while having a plastid phenotype like its maternal progenitor. Potentially, floral colour evolution has been driven by, or resulted in, pollinator shifts

Antibody mediated activation of natural killer cells in malaria exposed pregnant women

Immune effector responses against Plasmodium falciparum include antibody-mediated activation of innate immune cells, which can induce Fc effector functions, including antibody-dependent cellular cytotoxicity, and the secretion of cytokines and chemokines. These effector functions are regulated by the composition of immunoglobulin G (IgG) Fc N-linked glycans. However, a role for antibody-mediated natural killer (NK) cells activation or Fc N-linked glycans in pregnant women with malaria has not yet been established. Herein, we studied the capacity of IgG antibodies from pregnant women, with placental malaria or non-placental malaria, to induce NK cell activation in response to placental malaria-associated antigens DBL2 and DBL3. Antibody-mediated NK cell activation was observed in pregnant women with malaria, but no differences were associated with susceptibility to placental malaria. Elevated anti-inflammatory glycosylation patterns of IgG antibodies were observed in pregnant women with or without malaria infection, which were not seen in healthy non-pregnant controls. This suggests that pregnancy-associated anti-inflammatory Fc N-linked glycans may dampen the antibody-mediated activation of NK cells in pregnant women with malaria infection. Overall, although anti-inflammatory glycans and antibody-dependent NK cell activation were detected in pregnant women with malaria, a definitive role for these antibody features in protecting against placental malaria remains to be proven

Three Lyman-alpha Emitters at z approx 6: Early GMOS/Gemini Data from the GLARE Project

We report spectroscopic detection of three z~6 Lyman-alpha emitting galaxies, in the vicinity of the Hubble Ultra Deep Field, from the early data of the Gemini Lyman-$\alpha$ at Reionisation Era (GLARE) project. Two objects, GLARE#3001 (z =5.79) and GLARE#3011 (z =5.94), are new detections and are fainter in $z'$ (z'_{AB} =26.37 and 27.15) than any Lyman break galaxy previously detected in Lyman-alpha. A third object, GLARE#1042 (z =5.83) has previously been detected in line emission from the ground; we report here a new spectroscopic continuum detection. Gemini/GMOS-S spectra of these objects, obtained using nod & shuffle, are presented together with a discussion of their photometric properties. All three objects were selected for spectroscopy via the i-drop Lyman Break technique, the two new detections from the GOODS v1.0 imaging data. The red i'-z' colors and high equivalent widths of these objects suggest a high-confidence z>5 Lyman-alpha identification of the emission lines. This brings the total number of known z>5 galaxies within 9 arcmin of the Hubble Ultra Deep Field to four, of which three are at the same redshift (z=5.8 within 2000 km/s suggesting the existence of a large-scale structure at this redshift.Comment: 5 pages, 2 figures. Revised to match accepted versio

Methylphenidate and Sleep Difficulties in Children and Adolescents With ADHD: Results From the 2-Year Naturalistic Pharmacovigilance ADDUCE Study

Objective: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. Methods: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children’s-Sleep-Habits-Questionnaire (CSHQ). Results: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. Conclusion: Our findings support that sleep-problems are common in ADHD, but don’t suggest significant negative long-term effects of MPH on sleep

Sunyaev-Zel'dovich observations of galaxy clusters out to the virial radius with the Arcminute Microkelvin Imager

We present observations using the Small Array of the Arcminute Microkelvin Imager (AMI; 14-18 GHz) of four Abell and three MACS clusters spanning 0.171-0.686 in redshift. We detect Sunyaev-Zel'dovich (SZ) signals in five of these without any attempt at source subtraction, although strong source contamination is present. With radio-source measurements from high-resolution observations, and under the assumptions of spherical $\beta$-model, isothermality and hydrostatic equilibrium, a Bayesian analysis of the data in the visibility plane detects extended SZ decrements in all seven clusters over and above receiver noise, radio sources and primary CMB imprints. Bayesian evidence ratios range from 10^{11}:1 to 10^{43}:1 for six of the clusters and 3000:1 for one with substantially less data than the others. We present posterior probability distributions for, e.g., total mass and gas fraction averaged over radii internal to which the mean overdensity is 1000, 500 and 200, r_200 being the virial radius. Reaching r_200 involves some extrapolation for the nearer clusters but not for the more-distant ones. We find that our estimates of gas fraction are low (compared with most in the literature) and decrease with increasing radius. These results appear to be consistent with the notion that gas temperature in fact falls with distance (away from near the cluster centre) out to the virial radius.Comment: 18 pages, 10 figures, submitted to MNRAS (updated authors and fixed Figure 1

Reports of Perceived Adverse Events of Stimulant Medication on Cognition, Motivation, and Mood:Qualitative Investigation and the Generation of Items for the Medication and Cognition Rating Scale

Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects)