The early stages of heart development: insights from chicken embryos

The heart is the first functioning organ in the developing embryo and the detailed understanding of the molecular and cellular mechanisms involved in its formation provides insights into congenital malformations affecting its function and therefore the survival of the organism. Because many developmental mechanisms are highly conserved, it is possible to extrapolate from observations made in invertebrate and vertebrate model organisms to human. This review will highlight the contributions made through studying heart development in avian embryos, particularly the chicken. The major advantage of chick embryos is their accessibility for surgical manipulations and functional interference approaches, both gain- and loss-of-function. In addition to experiments performed in ovo, the dissection of tissues for ex vivo culture, genomic or biochemical approaches, is straightforward. Furthermore, embryos can be cultured for time-lapse imaging, which enables tracking of fluorescently labeled cells and detailed analyses of tissue morphogenesis. Owing to these features, investigations in chick embryos have led to important discoveries, often complementing genetic studies in mouse and zebrafish. As well as including some historical aspects, we cover here some of the crucial advances made in understanding of early heart development using the chicken model

The FHI FEL Upgrade Design

Since coming on-line in November 2013, the Fritz-Haber-Institut (FHI) der Max-Planck-Gesellschaft (MPG) Free-Electron Laser (FEL) has provided intense, tunable infrared radiation to FHI user groups. It has enabled experiments in diverse fields ranging from bio-molecular spectroscopy to studies of clusters and nanoparticles, nonlinear solid-state spectroscopy, and surface science, resulting in 50 peer-reviewed publications so far. The MPG has now funded a significant upgrade to the original FHI FEL. A second short Rayleigh range undulator FEL beamline is being added that will permit lasing from 160 microns. Additionally, a 500 MHz kicker cavity will permit simultaneous two-color operation of the FEL from both FEL beamlines over an optical range of 5 to 50 microns by deflecting alternate 1 GHz pulses into each of the two undulators. We will describe the upgraded FHI FEL physics and engineering design and present the plans for two-color FEL operations in November 2020

The FHI FEL Upgrade Design

Since coming on-line in November 2013, the Fritz-Haber-Institut (FHI) der Max-Planck-Gesellschaft (MPG) Free-Electron Laser (FEL) has provided intense, tunable infrared radiation to FHI user groups. It has enabled experiments in diverse fields ranging from bio-molecular spectroscopy to studies of clusters and nanoparticles, nonlinear solid-state spectroscopy, and surface science, resulting in 50 peer-reviewed publications so far. A significant upgrade of the FHI FEL is now being prepared. A second short Rayleigh range undulator FEL beamline is being added that will permit lasing from 160 microns. Additionally, a 500 MHz kicker cavity will permit simultaneous two-color operation of the FEL from both FEL beamlines over an optical range of 5 to 50 microns by deflecting alternate 1 GHz pulses into each of the two undulators. We will describe the upgraded FHI FEL physics and engineering design and present the plans for two-color FEL operations in November 2020

Safety Implications of High-Field MRI: Actuation of Endogenous Magnetic Iron Oxides in the Human Body

Background: Magnetic Resonance Imaging scanners have become ubiquitous in hospitals and high-field systems (greater than 3 Tesla) are becoming increasingly common. In light of recent European Union moves to limit high-field exposure for those working with MRI scanners, we have evaluated the potential for detrimental cellular effects via nanomagnetic actuation of endogenous iron oxides in the body.Methodology: Theoretical models and experimental data on the composition and magnetic properties of endogenous iron oxides in human tissue were used to analyze the forces on iron oxide particles.Principal Finding and Conclusions: Results show that, even at 9.4 Tesla, forces on these particles are unlikely to disrupt normal cellular function via nanomagnetic actuation

Simple preparation of plant epidermal tissue for laser microdissection and downstream quantitative proteome and carbohydrate analysis

The outwardly directed cell wall and associated plasma membrane of epidermal cells represent the first layers of plant defense against intruding pathogens. Cell wall modifications and the formation of defense structures at sites of attempted pathogen penetration are decisive for plant defense. A precise isolation of these stress-induced structures would allow a specific analysis of regulatory mechanism and cell wall adaption. However, methods for large-scale epidermal tissue preparation from the model plant Arabidopsis thaliana, which would allow proteome and cell wall analysis of complete, laser-microdissected epidermal defense structures, have not been provided. We developed the adhesive tape - liquid cover glass technique (ACT) for simple leaf epidermis preparation from A. thaliana, which is also applicable on grass leaves. This method is compatible with subsequent staining techniques to visualize stress-related cell wall structures, which were precisely isolated from the epidermal tissue layer by laser microdissection (LM) coupled to laser pressure catapulting. We successfully demonstrated that these specific epidermal tissue samples could be used for quantitative downstream proteome and cell wall analysis. The development of the ACT for simple leaf epidermis preparation and the compatibility to LM and downstream quantitative analysis opens new possibilities in the precise examination of stress- and pathogen-related cell wall structures in epidermal cells. Because the developed tissue processing is also applicable on A. thaliana, well-established, model pathosystems that include the interaction with powdery mildews can be studied to determine principal regulatory mechanisms in plant-microbe interaction with their potential outreach into crop breeding

Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease?: A Systematic Review

BACKGROUND: Oral 5-aminosalicylic acid (5-ASA, mesalazine) is the first choice therapeutic agent for treating mild-to-moderate ulcerative colitis (UC). Unfortunately a significant group of patients fail to respond. Therapeutic drug monitoring might help to maintain or induce remission by providing a tool for optimization of 5-ASA therapy. However, plasma and urine concentrations of 5-ASA reflect systemic uptake and are not useful to evaluate therapeutic effect. OBJECTIVES: To explore if mucosal and faecal 5-ASA values correlate with disease activity and/or therapeutic effects in patients with inflammatory bowel disease, especially UC. METHOD: We identified studies that analysed 5-ASA in faeces or mucosa of humans using an oral 5-ASA formulation, using PubMed and Embase. RESULTS: In total, 39 studies (n = 939) were included, 27 on faecal 5-ASA, 9 on mucosal concentrations, and 3 on both faecal and mucosal values. We included 33 cross-sectional studies, 3 randomised clinical trials, 2 longitudinal cohorts and 1 randomized cross-over study. Mucosal 5-ASA concentrations in healthy subjects and patients on equivalent doses of 5-ASA were not found to differ remarkably. In the sub-analysis of mucosal 5-ASA concentrations in patients with active or quiescent UC, a higher concentration was seen during remission. Faecal concentrations were associated with 5-ASA doses but not with disease activity. Differences in faecal or mucosal 5-ASA values could not be ascribed to different 5-ASA formulations. CONCLUSIONS: An increase of the mucosal 5-ASA concentrations was observed during remission in patients with UC. No clear relationship between the faecal 5-ASA excretion and the therapeutic efficacy was identified

Metabolic alterations: A biomarker for radiation-induced normal brain injury—an MR spectroscopy study

Purpose To assess if interval changes in metabolic status in normal cerebral tissue after radiation therapy (RT) can be detected by 2D CSI (chemical shift imaging) proton spectroscopy. Materials and Methods Eleven patients with primary brain tumors undergoing cranial radiation therapy (RT) were included. 2D-CSI MRS was performed before, during, and after the course of RT with the following parameters: TE/TR 144/1500 ms, field of view (FOV) 24, thickness 10 mm, matrix 16 × 16. The metabolic ratios choline/creatine (Cho/Cr), N-acetylaspartate (NAA)/Cr, and NAA/Cho in normal brain tissue were calculated. Results NAA/Cr and Cho/Cr were significantly decreased at week 3 during RT and at 1 month and 6 months after RT compared to values prior to RT ( P < 0.01). The NAA/Cr ratio decreased by −0.19 ± 0.05 (mean ± standard error [SE]) at week 3 of RT, −0.14 ± 0.06 at the last week of RT, −0.14 ± 0.05 at 1 month after RT, and −0.30 ± 0.08 at 6 months after RT compared to the pre-RT value of 1.43 ± 0.04. The Cho/Cr ratio decreased by −0.27 ± 0.05 at week 3 of RT, −0.11 ± 0.05 at the last week of RT, −0.26 ± 0.05 at 1 month after RT and −0.25 ± 0.07 at 6 months after RT from the pre-RT value of 1.29 ± 0.03. Changes in Cho/Cr were correlated with the interaction of the radiation dose and dose-volume at week 3 of RT, during the last week of RT ( P < 0.005), and at 1 month after RT ( P = 0.017). Conclusion The results of this study suggest that MRS can detect early metabolic changes in normal irradiated brain tissue. J. Magn. Reson. Imaging 2009;29:291–297. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61530/1/21657_ftp.pd

Outcome of Reverse Switching From CT-P13 to Originator Infliximab in Patients With Inflammatory Bowel Disease

BACKGROUND: Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are "reverse switched" to treatment with the originator. Here we assess the prevalence of reverse switching, including its indication and outcomes. METHODS: In this retrospective multicenter cohort study, data on patients with IBD from 9 hospitals in the Netherlands were collected. All adult patients with IBD were included if they previously had been switched from originator infliximab to the biosimilar CT-P13 and had a follow-up time of at least 52 weeks after the initial switch. The reasons for reverse switching were categorized into worsening gastrointestinal symptoms, adverse effects, or loss of response to CT-P13. Drug persistence was analyzed through survival analyses. RESULTS: A total of 758 patients with IBD were identified. Reverse switching was observed in 75 patients (9.9%). Patients with reverse switching were predominantly female (70.7%). Gastrointestinal symptoms (25.5%) and dermatological symptoms (21.8%) were the most commonly reported reasons for reverse switching. In 9 patients (12.0%), loss of response to CT-P13 was the reason for reverse switching. Improvement of reported symptoms was seen in 73.3% of patients after reverse switching and 7 out of 9 patients (77.8%) with loss of response regained response. Infliximab persistence was equal between patients who were reverse-switched and those who were maintained on CT-P13. CONCLUSIONS: Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13

Contingent self-importance among pathological narcissists: Evidence from an implicit task

Pathological narcissists are thought to hold unstable, contingent views of their self-importance. They harbor grandiose fantasies about the self, but are vulnerable and hypersensitive as well. The present study (N = 84) sought to provide evidence for this important set of clinical ideas. Following a manipulation priming dominant versus submissive self-views, a task developed to assess implicit self-importance of an interpersonal type was administered. As hypothesized, the manipulation and levels of pathological narcissism interacted to predict implicit self-importance. Implicit self-importance scores were unaffected by the priming manipulation at low levels of pathological narcissism, but were strongly affected at high levels of pathological narcissism. These results support clinical intuitions concerning pathological narcissism