Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator

Acknowledgements: The authors thank all German AMD patients for their participation. We also thank Maria Pötsch (Leibniz Institute for Natural Product Reseach and Infection Biology, Jena) for MS analyses. Funding: This research was supported by the German Council “Deutsche Forschungs-Gemeinschaft” SK46, Zi432, LA1206, the “Pro Retina” foundation and the Thuringian Ministry of Science and Education, Germany. HN is a member of the DFG-funded excellence cluster ImmunoSensation (EXC 1023). YL is a doctoral researcher at the International Leibniz Research School (ILRS), part of the Jena school of Microbial Communication (JSMC). Availability of data and materials: Materials are available at [email protected] reviewedPublisher PD

Recent Change—North Sea

This chapter discusses past and ongoing change in the following physical variables within the North Sea: temperature, salinity and stratification; currents and circulation; mean sea level; and extreme sea levels. Also considered are carbon dioxide; pH and nutrients; oxygen; suspended particulate matter and turbidity; coastal erosion, sedimentation and morphology; and sea ice. The distinctive character of the Wadden Sea is addressed, with a particular focus on nutrients and sediments. This chapter covers the past 200 years and focuses on the historical development of evidence (measurements, process understanding and models), the form, duration and accuracy of the evidence available, and what the evidence shows in terms of the state and trends in the respective variables. Much work has focused on detecting long-term change in the North Sea region, either from measurements or with models. Attempts to attribute such changes to, for example, anthropogenic forcing are still missing for the North Sea. Studies are urgently needed to assess consistency between observed changes and current expectations, in order to increase the level of confidence in projections of expected future conditions

Exploration of Long-Chain Vitamin E Metabolites for the Discovery of a Highly Potent, Orally Effective, and Metabolically Stable 5-LOX Inhibitor that Limits Inflammation.

Endogenous long-chain metabolites of vitamin E (LCMs) mediate immune functions by targeting 5-lipoxygenase (5-LOX) and increasing the systemic concentrations of resolvin E3, a specialized proresolving lipid mediator. SAR studies on semisynthesized analogues highlight α-amplexichromanol (27a), which allosterically inhibits 5-LOX, being considerably more potent than endogenous LCMs in human primary immune cells and blood. Other enzymes within lipid mediator biosynthesis were not substantially inhibited, except for microsomal prostaglandin E2 synthase-1. Compound 27a is metabolized by sulfation and β-oxidation in human liver-on-chips and exhibits superior metabolic stability in mice over LCMs. Pharmacokinetic studies show distribution of 27a from plasma to the inflamed peritoneal cavity and lung. In parallel, 5-LOX-derived leukotriene levels decrease, and the inflammatory reaction is suppressed in reconstructed human epidermis, murine peritonitis, and experimental asthma in mice. Our study highlights 27a as an orally active, LCM-inspired drug candidate that limits inflammation with superior potency and metabolic stability to the endogenous lead

Rupture of the atherosclerotic plaque: does a good animal model exist?

By its very nature, rupture of the atherosclerotic plaque is difficult to study directly in humans. A good animal model would help us not only to understand how rupture occurs but also to design and test treatments to prevent it from happening. However, several difficulties surround existing models of plaque rupture, including the need for radical interventions to produce the rupture, lack of direct evidence of rupture per se, and absence of convincing evidence of platelet- and fibrin-rich thrombus at the rupture site. At the present time, attention should therefore focus on the processes of plaque breakdown and thrombus formation in humans, whereas the use of animal models should probably be reserved for studying the function of particular genes and for investigating isolated features of plaques, such as the relationship between cap thickness and plaque stability

The main actors involved in parasitization of Heliothis virescens larva

At the moment of parasitization by another insect, the host Heliothis larva is able to defend itself by the activation of humoral and cellular defenses characterized by unusual reactions of hemocytes in response to external stimuli. Here, we have combined light and electron microscopy, staining reactions, and immunocytochemical characterization to analyze the activation and deactivation of one of the most important immune responses involved in invertebrates defense, i.e., melanin production and deposition. The insect host/parasitoid system is a good model to study these events. The activated granulocytes of the host insect are a major repository of amyloid fibrils forming a lattice in the cell. Subsequently, the exocytosed amyloid lattice constitutes the template for melanin deposition in the hemocel. Furthermore, cross-talk between immune and neuroendocrine systems mediated by hormones, cytokines, and neuromodulators with the activation of stress-sensoring circuits to produce and release molecules such as adrenocorticotropin hormone, alpha melanocyte-stimulating hormone, and neutral endopeptidase occurs. Thus, parasitization promotes massive morphological and physiological modifications in the host insect hemocytes and mimics general stress conditions in which phenomena such as amyloid fibril formation, melanin polymerization, pro-inflammatory cytokine production, and activation of the adrenocorticotropin hormone system occur. These events observed in invertebrates are also reported in the literature for vertebrates, suggesting that this network of mechanisms and responses is maintained throughout evolution

Measurement of the cross-section ratio σψ(2S)/σJ/ψ(1S)\sigma_{\psi(2S )}/\sigma_{J/\psi(1S )} in exclusive photoproduction at HERA

The exclusive photoproduction reactions $\gamma p \to J/\psi(1S) p$ and $\gamma p \to \psi(2S) p$ have been measured at an $ep$ centre-of-mass energy of 318 GeV with the ZEUS detector at HERA using an integrated luminosity of 373 pb$^{-1}$. The measurement was made in the kinematic range $30 < W < 180$ GeV, $Q^2 < 1$ GeV$^2$ and $|t| < 1$ GeV$^2$, where $W$ is the photon--proton centre-of-mass energy, $Q^2$ is the photon virtuality and $t$ is the squared four-momentum transfer at the proton vertex. The decay channels used were $J/\psi(1S) \to \mu^+ \mu^-$, $\psi(2S) \to \mu^+ \mu^-$ and $\psi(2S) \to J/\psi(1S) \pi^+ \pi^-$ with subsequent decay $J/\psi(1S) \to \mu^+ \mu^-$. The ratio of the production cross sections, $R = \sigma_{\psi(2S)} / \sigma_{J/\psi(1S)}$, has been measured as a function of $W$ and $|t|$ and compared to previous data in photoproduction and deep inelastic scattering and with predictions of QCD-inspired models of exclusive vector-meson production, which are in reasonable agreement with the data.Comment: 31 pages, 9 figures. Updated according to comments from journal referee including a new table. Added full collaboration author lis

Search for effective Lorentz and CPT violation using ZEUS data

Lorentz and CPT symmetry in the quark sector of the Standard Model are studied in the context of an effective field theory using ZEUS $e^{\pm} p$ data. Symmetry-violating effects can lead to time-dependent oscillations of otherwise time-independent observables, including scattering cross sections. An analysis using five years of inclusive neutral-current deep inelastic scattering events corresponding to an integrated HERA luminosity of $372\; \text{pb}^{-1}$ at $\sqrt{s} = 318$ Gev has been performed. No evidence for oscillations in sidereal time has been observed within statistical and systematic uncertainties. Constraints, most for the first time, are placed on 42 coefficients parameterising dominant CPT-even dimension-four and CPT-odd dimension-five spin-independent modifications to the propagation and interaction of light quarks.Comment: 36 pages, 12 figures. Additional material included as an ancillary file for this arXiv entr

Search for effective Lorentz and CPT violation using ZEUS data

Lorentz and CPT symmetry in the quark sector of the Standard Model are studied in the context of an effective field theory using ZEUS e±p data. Symmetry-violating effects can lead to time-dependent oscillations of otherwise time-independent observables, including scattering cross sections. An analysis using five years of inclusive neutral-current deep inelastic scattering events corresponding to an integrated HERA luminosity of 372 pb-1 at s=318 GeV has been performed. No evidence for oscillations in sidereal time has been observed within statistical and systematic uncertainties. Constraints, most for the first time, are placed on 42 coefficients parametrizing dominant CPT-even dimension-four and CPT-odd dimension-five spin-independent modifications to the propagation and interaction of light quarks

Burden of non-communicable diseases among adolescents aged 10–24 years in the EU, 1990–2019: a systematic analysis of the Global Burden of Diseases Study 2019

Background: Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. Methods: Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels of the GBD 2019 hierarchy, for which mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were extracted. Estimates, with the 95% uncertainty intervals (UI), were retrieved for EU Member States from 1990 to 2019, three age subgroups (10–14 years, 15–19 years, and 20–24 years), and by sex. Spearman's correlation was conducted between DALY rates for NCDs and the Socio-demographic Index (SDI) of each EU Member State. Findings: In 2019, NCDs accounted for 86·4% (95% uncertainty interval 83·5–88·8) of all YLDs and 38·8% (37·4–39·8) of total deaths in adolescents aged 10–24 years. For NCDs in this age group, neoplasms were the leading causes of both mortality (4·01 [95% uncertainty interval 3·62–4·25] per 100 000 population) and YLLs (281·78 [254·25–298·92] per 100 000 population), whereas mental disorders were the leading cause for YLDs (2039·36 [1432·56–2773·47] per 100 000 population) and DALYs (2040·59 [1433·96–2774·62] per 100 000 population) in all EU Member States, and in all studied age groups. In 2019, among adolescents aged 10–24 years, males had a higher mortality rate per 100 000 population due to NCDs than females (11·66 [11·04–12·28] vs 7·89 [7·53–8·23]), whereas females presented a higher DALY rate per 100 000 population due to NCDs (8003·25 [5812·78–10 701·59] vs 6083·91 [4576·63–7857·92]). From 1990 to 2019, mortality rate due to NCDs in adolescents aged 10–24 years substantially decreased (–40·41% [–43·00 to –37·61), and also the YLL rate considerably decreased (–40·56% [–43·16 to –37·74]), except for mental disorders (which increased by 32·18% [1·67 to 66·49]), whereas the YLD rate increased slightly (1·44% [0·09 to 2·79]). Positive correlations were observed between DALY rates and SDIs for substance use disorders (rs=0·58, p=0·0012) and skin and subcutaneous diseases (rs=0·45, p=0·017), whereas negative correlations were found between DALY rates and SDIs for cardiovascular diseases (rs=–0·46, p=0·015), neoplasms (rs=–0·57, p=0·0015), and sense organ diseases (rs=–0·61, p=0·0005). Interpretation: NCD-related mortality has substantially declined among adolescents in the EU between 1990 and 2019, but the rising trend of YLL attributed to mental disorders and their YLD burden are concerning. Differences by sex, age group, and across EU Member States highlight the importance of preventive interventions and scaling up adolescent-responsive health-care systems, which should prioritise specific needs by sex, age, and location. Funding: Bill &amp; Melinda Gates Foundation

Global mortality from dementia : Application of a new method and results from the Global Burden of Disease Study 2019

Introduction Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. Methods We meta-analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end-stage disease to calculate the total number of deaths that could be attributed to dementia. Results We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41-4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27-2.71]) than men (0.56 million [0.14-1.51]), largely but not entirely due to the higher life expectancy in women (age-standardized female-to-male ratio 1.19 [1.10-1.26]). Due to population aging, there was a large increase in all-age mortality rates from dementia between 1990 and 2019 (100.1% [89.1-117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among individuals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. Discussion Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally.Peer reviewe