Low-level Circulation of Enterovirus D68–Associated Acute Respiratory Infections, Germany, 2014

We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August–October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions

Cathelicidins have direct antiviral activity against respiratory syncytial virus in vitro and protective function in vivo in mice and humans.

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection in infants, causing significant morbidity and mortality. No vaccine or specific, effective treatment is currently available. A more complete understanding of the key components of effective host response to RSV and novel preventative and therapeutic interventions are urgently required. Cathelicidins are host defense peptides, expressed in the inflamed lung, with key microbicidal and modulatory roles in innate host defense against infection. In this article, we demonstrate that the human cathelicidin LL-37 mediates an antiviral effect on RSV by inducing direct damage to the viral envelope, disrupting viral particles and decreasing virus binding to, and infection of, human epithelial cells in vitro. In addition, exogenously applied LL-37 is protective against RSV-mediated disease in vivo, in a murine model of pulmonary RSV infection, demonstrating maximal efficacy when applied concomitantly with virus. Furthermore, endogenous murine cathelicidin, induced by infection, has a fundamental role in protection against disease in vivo postinfection with RSV. Finally, higher nasal levels of LL-37 are associated with protection in a healthy human adult RSV infection model. These data lead us to propose that cathelicidins are a key, nonredundant component of host defense against pulmonary infection with RSV, functioning as a first point of contact antiviral shield and having additional later-phase roles in minimizing the severity of disease outcome. Consequently, cathelicidins represent an inducible target for preventative strategies against RSV infection and may inform the design of novel therapeutic analogs for use in established infection

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

Hautkrebsprävention bei Kindern und Jugendlichen nach einer Organtransplantation: Eine Mixed-Methods-Studie

Das Hautkrebsrisiko korreliert stark mit Faktoren wie der kumulativen UV-Lichtexposition und dem individuellen Hauttyp. Weniger bekannt ist, dass auch eine Organtransplantation aufgrund der benötigten immunsuppressiven Therapie zu einem erhöhten Risiko führt, im späteren Lebensverlauf an einem Hautkrebs zu erkranken. Gerade Kinder und Jugendliche, die bereits in jungen Jahren eine Transplantation erhalten sind stark gefährdet. Das Erkrankungsrisiko kann durch die Verringerung der kumulativen UV-Lichtexposition deutlich reduziert werden. Wichtig ist, das Bewusstsein der Kinder und Jugendlichen und deren Eltern zu erhöhen, um im Alltag ein angemessenes Sonnenschutzverhalten zu erzielen. Oftmals werden einfache Sonnenschutzmaßnahmen jedoch nicht adäquat umgesetzt. Als vielversprechende Ansätze in der Krebsprävention können m- und e-Health-gestützte Interventionen gesehen werden. Allerdings haben bislang nur wenige Studien die Wirkung solcher Ansätze in der Hautkrebsprävention von Kindern und Jugendlichen nach einer Organtransplantation untersucht. Auch ist bislang wenig über die individuellen Bedürfnisse von Familien mit organtransplantierten Kindern und Jugendliche bekannt. Denn auch die alltäglichen Herausforderungen in den Familien müssen Berücksichtigung finden, nur so kann es angemessenes Sonnenschutzverhalten im Alltag übernommen werden. In dieser Dissertation werden in einem Mixed-Methods-Ansatz zwei verschiedene Fragestellungen untersucht. Mit Hilfe einer randomisierten Vergleichsstudie wurde der Frage nachgegangen, ob eine Mehrebenen-Intervention in Form von einer persönlichen Sonnenschutzschulung mit anschließendem SMS-Versand von UV-Indexabhängigen Sonnenschutzempfehlungen einen stärkeren Effekt auf den beabsichtigten Wissenszuwachs und die Verhaltensänderung der teilnehmenden Kinder und Jugendlichen hat als eine Online-Schulung ohne anschließenden SMS-Versand. Zusätzlich wurden halbstrukturierte Leitfadeninterviews mit den Eltern geführt, um die Frage nach dem Umgang und dem Bewusstsein der Eltern zum Thema Sonnenschutz zu ergründen. Folgende Themenbereiche standen hierbei im Fokus: Einstellung zum Thema Sonne und Sonnenschutz, Sonnenschutzverhalten, Risikoabwägung und Verhaltensänderung, Aufklärung sowie Wünsche und Bedürfnisse

Low-level Circulation of Enterovirus D68–Associated Acute Respiratory Infections, Germany, 2014

We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August–October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions

Randomised controlled trial to evaluate the influence of mHealth and eHealth skin cancer prevention education among young organ transplant recipients: the HIPPOlino intervention study

OBJECTIVES: To determine whether a multicomponent sun protection intervention programme (mHealth) for young organ transplant recipients (OTR) leads to a higher increase of preventive knowledge and behavioural change than an e-learning education programme (eHealth). DESIGN: Randomised controlled trial with one preintervention baseline survey and three follow-up surveys after 6 weeks, 6 and 12 months. Comparison of two different intervention schedules with a control group (CG). SETTING: Multicomponent sun protection trainings in Germany, the Netherlands and Austria between June 2013 and September 2015. PARTICIPANTS: Participants 137 OTRs (5–22 years of age, 61 females/76 males) participated in the study. INTERVENTIONS: (A) Intervention group 1 (IG1): personal training with subsequent forwarding of individual ultraviolet index-dependent sun protection recommendations via short message service (SMS); (B) intervention group 2 (IG2): e-learning training without SMS; (C) CG: regular information letters, online training after 1 year. OUTCOME MEASURES: Key questions were used to form a knowledge and a behavioural score. Behavioural strategies and knowledge were quantified through self-administered questionnaires. RESULTS: Analyses 6 weeks after the intervention showed a higher knowledge increase in both IG compared with the CG (IG1 to CG: OR 12.64, 95% CI 4.20 to 38.20; IG2 to CG: OR 2.59, 95% CI 0.95 to 7.04). Sun protection behaviour improved slightly but not significantly in both IG (IG1 to CG: OR 2.56, 95% CI 0.93 to 7.00; IG2 to CG: OR 1.22, 95% CI 0.45 to 3.32). One year after the intervention, no behavioural changes were observed in either IG compared with the CG. IG1 but not IG2 still scored significantly higher in sun protection knowledge than the CG 1 year after intervention (IG1 to CG: OR 4.46, 95% CI 1.48 to 13.43; IG2 to CG: OR 1.41, 95% CI 0.51 to 3.93). CONCLUSIONS: This multicomponent sun protection programme provides a promising strategy to increase sun protection knowledge and possibly also protective behaviour in young OTR. TRIAL REGISTRATION NUMBER: DRKS0001139

L25 functions as a conserved ribosomal docking site shared by nascent chain-associated complex and signal-recognition particle

The nascent chain-associated complex (NAC) is a dimeric protein complex of archaea and eukarya that interacts with ribosomes and translating polypeptide chains. We show that, in yeast, NAC and the signal-recognition particle (SRP) share the universally conserved ribosomal protein L25 as a docking site, which is in close proximity to the ribosomal exit tunnel. The amino-terminal segment of β-NAC was found to be required for L25 binding. Purified NAC can prevent protein aggregation in vitro and thus shows certain properties of a molecular chaperone. Interestingly, the α-subunit of NAC interacts with the 54 kDa subunit of SRP. Consistent with a regulatory role of NAC in protein translocation into the endoplasmic reticulum (ER), we find that deletion of NAC results in an induction of the ER stress-response pathway. These results identify L25 as a conserved interaction platform for specific cytosolic factors that guide nascent polypeptides to their proper cellular destination