Aromastoffprofile und Lagerstabilität technologisch modifizierter Lebensmittel

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Relationship between HDL Cholesterol Efflux Capacity, Calcium Coronary Artery Content, and Antibodies against ApolipoproteinA-1 in Obese and Healthy Subjects

AIMS: To explore the associations between cholesterol efflux capacity (CEC), coronary artery calcium (CAC) score, Framingham risk score (FRS), and antibodies against apolipoproteinA-1 (anti-apoA-1 IgG) in healthy and obese subjects (OS). METHODS AND RESULTS: ABCA1-, ABCG1-, passive diffusion (PD)-CEC and anti-apoA-1 IgG were measured in sera from 34 controls and 35 OS who underwent CAC score determination by chest computed tomography. Anti-apoA-1 IgG ability to modulate CEC and macrophage cholesterol content (MCC) was tested in vitro. Controls and OS displayed similar ABCG1-, ABCA1-, PD-CEC, CAC and FRS scores. Logistic regression analyses indicated that FRS was the only significant predictor of CAC lesion. Overall, anti-apoA-1 IgG were significantly correlated with ABCA1-CEC (r = 0.48, p < 0.0001), PD-CEC (r = -0.33, p = 0.004), and the CAC score (r = 0.37, p = 0.03). ABCA1-CEC was correlated with CAC score (r = 0.47, p = 0.004) and FRS (r = 0.18, p = 0.29), while PD-CEC was inversely associated with the same parameters (CAC: r = -0.46, p = 0.006; FRS: score r = -0.40, p = 0.01). None of these associations was replicated in healthy controls or after excluding anti-apoA-1 IgG seropositive subjects. In vitro, anti-apoA-1 IgG inhibited PD-CEC (p < 0.0001), increased ABCA1-CEC (p < 0.0001), and increased MCC (p < 0.0001). CONCLUSIONS: We report a paradoxical positive association between ABCA1-CEC and the CAC score, with the latter being inversely associated with PD in OS. Corroborating our clinical observations, anti-apoA-1 IgG enhanced ABCA1 while repressing PD-CEC, leading to MCC increase in vitro. These results indicate that anti-apoA-1 IgG have the potential to interfere with CEC and macrophage lipid metabolism, and may underpin paradoxical associations between ABCA1-CEC and cardiovascular risk

Trends in legal and illegal trade of wild birds: a global assessment based on expert knowledge

Wildlife trade is a profitable economic activity. Birds are among the most heavily traded animals worldwide, with numerous species threatened by pet trade. Information on both legal and illegal aspects of trade and consumer demand is difficult to obtain across different countries, particularly given substantial socio-economic and cultural variation. Focusing on consumer demand in each country, we conducted a global survey among 105 international experts on bird conservation to identify expected trends, drivers and market characteristics of legal and illegal wild-caught pet bird trade. Our results suggest that future trends in legal bird trade will be mostly driven by socio-cultural motivations and intentional demand for wild-caught, rather than captive-bred birds. Bird popularity and rarity are the main factors expected to influence the choice of which bird species will be the most traded legally. Percentage of rural population was the main national-level socio-economic predictor for legal bird trade in the future. Demand for future illegal trade is expected to be driven by bird popularity and particular species identity. Experts consider illegal trade to be sustained mainly by consumers from higher socio-economic and educational backgrounds. Human population growth rate was the main national-level socio-economic predictor of illegal trade expected for the future. Legislation enforcement remains a critical issue in wildlife trade. Expanding trade networks and socio-economic changes continue to incorporate new regions into the wildlife trade. Investigating the multidimensional and synergistic determinants of wildlife trade will thus help address potential detrimental impacts bird trade might cause on biodiversity.This research was funded by FEDER Funds through the Operational Competitiveness Factors Program “COMPETE”, and by national funds through the Foundation for Science and Technology (FCT) within the framework of project “PTDC/AAG-GLO/0463/2014-POCI-01-0145-FEDER-016583”. A.N. acknowledges the support of the Darwin Initiative. J.R. acknowledges the support from FCT through Grant ICETA 2017-38 within project “PTDC/AAG-GLO/0463/2014-POCI-01-0145-FEDER-016583”. L.R. and C.C. acknowledge support from the FCT through Grants SFRH/BPD/93079/2013 and SFRH/BPD/84422/2012, respectively

Superior Functional Outcome and Comparable Health-Related Quality of Life after Enhanced Recovery vs. Conventional THA: A Retrospective Matched Pair Analysis

Background: The concept of enhanced recovery after total hip arthroplasty is gaining worldwide interest, as it shortens the length of hospital stay without an increase of complications. The aim of the study was to investigate the functional outcome and health-related quality of life 12 months after cementless total hip arthroplasty with the use of an enhanced recovery concept in comparison to a conventional rehabilitation. Material and Methods: 320 patients were retrospectively analyzed who underwent primary cementless total hip arthroplasty (THA). A total of 123 of the patients received an enhanced recovery program (ERAS) and 197 patients a conventional rehabilitation (Non-ERAS). Twelve months postoperatively, a clinical examination was performed regarding satisfaction, function and pain. Results were evaluated using WOMAC, EQ-5D-5L and EQ-VAS. A 1:1 matching was performed to correct for confounding variables, regarding age, sex and ASA score. Finally, 122 patients (n = 61, in each group) were analyzed and compared. Results: Patients showed a significant improvement of WOMAC total score, subscale pain, subscale stiffness and subscale function from preoperative to the follow up after 12 months in both groups, with significantly superior results for the WOMAC total score for the ERAS group (p = 0.042). EQ-5D and EQ-5D VAS showed a significant improvement from preoperative to 12 months postoperative (p < 0.001) for both groups, while no difference regarding the group-comparison was shown. Conclusion: Health-related quality of life and functional outcome increased to excellent values after total hip arthroplasty with the use of an enhanced recovery concept and a conventional rehabilitation, with a superior WOMAC total score for ERAS and a tendency to better results for health-related quality of life for patients with ERAS within the follow up after 12 months

Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents

Background: Inactivation of the Fanconi anemia (FA) pathway through defects in one of 13 FA genes occurs at low frequency in various solid cancer entities among the general population. As FA pathway inactivation confers a distinct hypersensitivity towards DNA interstrand-crosslinking (ICL)-agents, FA defects represent rational targets for individualized therapeutic strategies. Except for pancreatic cancer, however, the prevalence of FA defects in gastrointestinal (GI) tumors has not yet been systematically explored. Results: A panel of GI cancer cell lines was screened for FA pathway inactivation applying FANCD2 monoubiquitination and FANCD2/RAD51 nuclear focus formation and a newly identified FA pathway-deficient cell line was functionally characterized. The hepatocellular carcinoma (HCC) line HuH-7 was defective in FANCD2 monoubiquitination and FANCD2 nuclear focus formation but proficient in RAD51 focus formation. Gene complementation studies revealed that this proximal FA pathway inactivation was attributable to defective FANCC function in HuH-7 cells. Accordingly, a homozygous inactivating FANCC nonsense mutation (c.553C &gt; T, p.R185X) was identified in HuH-7, resulting in partial transcriptional skipping of exon 6 and leading to the classic cellular FA hypersensitivity phenotype; HuH-7 cells exhibited a strongly reduced proliferation rate and a pronounced G2 cell cycle arrest at distinctly lower concentrations of ICL-agents than a panel of non-isogenic, FA pathway-proficient HCC cell lines. Upon retroviral transduction of HuH-7 cells with FANCC cDNA, FA pathway functions were restored and ICL-hypersensitivity abrogated. Analyses of 18 surgical HCC specimens yielded no further examples for genetic or epigenetic inactivation of FANCC, FANCF, or FANCG in HCC, suggesting a low prevalence of proximal FA pathway inactivation in this tumor type. Conclusions: As the majority of HCC are chemoresistant, assessment of FA pathway function in HCC could identify small subpopulations of patients expected to predictably benefit from individualized treatment protocols using ICL-agents

National mitigation potential from natural climate solutions in the tropics.

Better land stewardship is needed to achieve the Paris Agreement's temperature goal, particularly in the tropics, where greenhouse gas emissions from the destruction of ecosystems are largest, and where the potential for additional land carbon storage is greatest. As countries enhance their nationally determined contributions (NDCs) to the Paris Agreement, confusion persists about the potential contribution of better land stewardship to meeting the Agreement's goal to hold global warming below 2°C. We assess cost-effective tropical country-level potential of natural climate solutions (NCS)-protection, improved management and restoration of ecosystems-to deliver climate mitigation linked with sustainable development goals (SDGs). We identify groups of countries with distinctive NCS portfolios, and we explore factors (governance, financial capacity) influencing the feasibility of unlocking national NCS potential. Cost-effective tropical NCS offers globally significant climate mitigation in the coming decades (6.56 Pg CO2e yr-1 at less than 100 US$ per Mg CO2e). In half of the tropical countries, cost-effective NCS could mitigate over half of national emissions. In more than a quarter of tropical countries, cost-effective NCS potential is greater than national emissions. We identify countries where, with international financing and political will, NCS can cost-effectively deliver the majority of enhanced NDCs while transforming national economies and contributing to SDGs. This article is part of the theme issue 'Climate change and ecosystems: threats, opportunities and solutions'

The Nucleoside Diphosphate Kinase Gene Nme3 Acts as Quantitative Trait Locus Promoting Non-Mendelian Inheritance

The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (>95%) from heterozygous (t/+) males to their offspring. This phenotype is termed transmission ratio distortion (TRD) and is caused by the interaction of the t-complex responder (Tcr) with several quantitative trait loci (QTL), the t-complex distorters (Tcd1 to Tcd4), all located within the t-haplotype region. Current data suggest that the distorters collectively impair motility of all sperm derived from t/+ males; t-sperm is rescued by the responder, whereas +-sperm remains partially dysfunctional. Recently we have identified two distorters as regulators of RHO small G proteins. Here we show that the nucleoside diphosphate kinase gene Nme3 acts as a QTL on TRD. Reduction of the Nme3 dosage by gene targeting of the wild-type allele enhanced the transmission rate of the t-haplotype and phenocopied distorter function. Genetic and biochemical analysis showed that the t-allele of Nme3 harbors a mutation (P89S) that compromises enzymatic activity of the protein and genetically acts as a hypomorph. Transgenic overexpression of the Nme3 t-allele reduced t-haplotype transmission, proving it to be a distorter. We propose that the NME3 protein interacts with RHO signaling cascades to impair sperm motility through hyperactivation of SMOK, the wild-type form of the responder. This deleterious effect of the distorters is counter-balanced by the responder, SMOKTcr, a dominant-negative protein kinase exclusively expressed in t-sperm, thus permitting selfish behaviour and preferential transmission of the t-haplotype. In addition, the previously reported association of NME family members with RHO signaling in somatic cell motility and metastasis, in conjunction with our data involving RHO signaling in sperm motility, suggests a functional conservation between mechanisms for motility control in somatic cells and spermatozoa

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p

Analysis of the RHO-SMOK1 signalling pathway leading to non-Mendalian inheritance in male mice

Der t-Haplotyp der Maus (t), eine variante Form des Mauschromosoms 17, bewirkt in heterozygoten t/+-Männchen eine Verschiebung der Vererbungsrate zu seinen Gunsten. Diese nicht-mendelsche Vererbung ist das Ergebnis eines Signalweges, in dem mehrere Distorter additiv auf die Spermien-Motilitäts-Kinase, SMOK1, wirken und diese in allen Spermienzellen übermäßig stark aktivieren. Diese Hyperaktivierung wird durch die Wirkung des t-Komplex Responders, TCR, nur in den Spermienzellen normalisiert, die auch den Responder-Genlocus tragen. Die Spermien, die zusätzlich zu den Distortern auch unter dem Einfluss des Responders stehen, besitzen somit einen Vorteil, was zu einer höheren Befruchtungswahrscheinlichkeit führt. Wie dieser Vorteil genau erreicht wird, ist nicht bekannt, da bislang keine direkten Interaktionspartner oder Zielmoleküle für SMOK1 beschrieben waren. Mit Hilfe der Hefe-Zwei-Hybrid Methode konnten in dieser Arbeit sowohl Bindungspartner (Preys) für SMOK1 als auch für mehrere Distorter-Proteine identifiziert werden. Weiterführend und basierend auf einer Auswahl wurden fünf dieser Preys (Ammecr1, Akap9, Rhpn1, Spata22, Dnali1) auf ihre mRNA- und Protein-Expression im Hodengewebe und in Spermatozoen untersucht. Durch elektronenmikroskopische Studien, die den genauen Expressionsort der Prey-Proteine zeigen, konnte die Kolokalisation von TCR bzw. SMOK1 und den Preys an subzellulären Strukturen des Spermienschwanzes, wie der Fibrous Sheath und den Outer Dense Fibers, abgeleitet werden. Ein Teil der Hefe-Zwei-Hybrid Interaktionen wurde schließlich in Säugerzellen durch Interaktionsstudien wie der Lumineszenz basierten IP Analyse und der bimolekularen Fluoreszenzkomplementation, sowie der klassischen Pull-Down Untersuchung untermauert. Zusätzlich wurden neue Verknüpfungen beobachtet, die in der Hefe nicht identifiziert wurden. In einer weiteren Analyse konnte eine direkte Bindung von SMOK1 an die GTPasen RAC1 und RHOA aber nicht an CDC42 gezeigt werden. Diese Bindungen lassen vermuten, dass RAC1 und RHOA zum Teil direkt die Aktivität von SMOK1 beeinflussen könnten. Die identifizierten Protein-Protein-Interaktionen wurden abschließend in einem vergrößerten Netzwerk zusammengefasst. Sie zeigen, dass sowohl SMOK1 als auch die Distorter- und RHO-GTPasen über Scaffold-Proteine wie AKAP9 und RHPN1 an flagellären Strukturen gebunden sein können. Die direkten Bindungen von zwei der getesteten GTPasen (RAC1 und RHOA) an SMOK1, konnte die im molekularen Modell dargestellte Distorter-RHO-SMOK1 Verknüpfung erstmals bestätigen. Die Distorter-RHO-Komplexe könnten demzufolge direkten mit SMOK1 in Verbindung stehen. Zudem konnte eine Interaktion von SMOK1 mit einem Bestandteil der inneren Dyneinarme (DNALI1) beobachtet werden, die möglicherweise über einen SMOK1-AMMECR1-Komplex erreicht wird. Die Verbindung zwischen SMOK1 und DNALI1 zeigt zum ersten Mal, dass die Kinase in der Lage sein könnte am Axonem mit der Komponente eines Dyneinkomplexes zu interagieren. Durch eine gezielte Wirkung von SMOK1 am Dyneinbestandteil DNALI1 könnte diese Interaktion die Flagellenbewegung beeinflussen und somit eine gestörte Motilitätsphänotyp verursachen. Die Ergebnisse dieser Arbeit tragen somit dazu bei den Signalweg der nicht-mendelschen Vererbung in der Maus besser zu verstehen.The t-haplotype of the mouse (t), which is a variant form of mouse chromosome 17, causes the preferred transmission of the t allele from heterozygous males (t/+). This non-Mendelian inheritance results from effects on a signalling pathway, where the presence of several distorter genes additively hyperactivate the sperm motility kinase, SMOK1, in the whole sperm population. This hyperactivation is balanced by the t-complex responder, TCR, only in spermatozoa carrying the responder gene. Spermatozoa influenced by the distorters and by the responder have a motility advantage, resulting in a higher probability for fertilization. It is still unclear how this advantage is manifested, as no interaction partners or targets are yet known for SMOK1. New binding partners for SMOK1 and for the distorters were identified in this study using the yeast two-hybrid method. Based on selection criteria, five prey candidate genes (Ammecr1, Akap9, Rhpn1, Spata22, Dnali1) were tested for mRNA and protein expression in testis and spermatozoa, respectively. The co- localization of SMOK1 or TCR with the prey proteins could be deduced within subcellular structures, such as the fibrous sheath and the outer dense fibers of the sperm flagellum, using electron microscopy. The protein-protein interactions identified by yeast two-hybrid were, in part, verified in a mammalian system using a luminescence-based immunoprecipitation analysis and a bimolecular fluorescence complementation assay, as well as classical pull-down studies. In addition, new protein-protein interactions were observed, which were not identified by the yeast two-hybrid analysis. Further studies revealed the direct interaction between SMOK1 and the GTPases RAC1 and RHOA, but not CDC42. This evidence gives rise to the idea that the GTPases RAC1 and RHOA are able to modify SMOK1 activity by binding to it directly. Finally, the identified protein-protein interactions were summarized in an interaction network. The interaction studies showed that SMOK1, as well the distorters and RHO proteins, are bound to flagella via scaffolding proteins like AKAP9 or RHPN1. Furthermore, the direct binding of two GTPases (RAC1 and RHOA) to SMOK1 confirm the link between distorters, RHO-proteins and SMOK1, which is predicted by the molecular model of TRD. The novel interaction of SMOK1 to a component of the inner dynein arms (DNALI1) was additionally observed. This interaction could potentially be generated by a SMOK1-AMMECR1 complex. The specific modification of DNALI1 by SMOK1 could negatively affect the movement of the sperm flagellum, and therefore generate the motility phenotype, leading to non- Mendelian inheritance in males. In summary, the results of these studies clarify our understanding of the signalling pathway leading to non-Mendelian inheritance of the t-haplotype