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Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level.
Land cover change is a dynamic phenomenon driven by synergetic biophysical and socioeconomic effects. It involves massive transitions from natural to less natural habitats and thereby threatens ecosystems and the services they provide. To retain intact ecosystems and reduce land cover change to a minimum of natural transition processes, a dense network of protected areas has been established across Europe. However, even protected areas and in particular the zones around protected areas have been shown to undergo land cover changes. The aim of our study was to compare land cover changes in protected areas, non-protected areas, and 1 km buffer zones around protected areas and analyse their relationship to climatic and socioeconomic factors across Europe between 2000 and 2012 based on earth observation data. We investigated land cover flows describing major change processes: urbanisation, afforestation, deforestation, intensification of agriculture, extensification of agriculture, and formation of water bodies. Based on boosted regression trees, we modelled correlations between land cover flows and climatic and socioeconomic factors. The results show that land cover changes were most frequent in 1 km buffer zones around protected areas (3.0% of all buffer areas affected). Overall, land cover changes within protected areas were less frequent than outside, although they still amounted to 18,800 km2 (1.5% of all protected areas) from 2000 to 2012. In some parts of Europe, urbanisation and intensification of agriculture still accounted for up to 25% of land cover changes within protected areas. Modelling revealed meaningful relationships between land cover changes and a combination of influencing factors. Demographic factors (accessibility to cities and population density) were most important for coarse-scale patterns of land cover changes, whereas fine-scale patterns were most related to longitude (representing the general east/west economic gradient) and latitude (representing the north/south climatic gradient).
Cocoa Bean Proteins
(2019)
The protein fractions of cocoa have been implicated influencing both the bioactive potential and sensory properties of cocoa and cocoa products. The objective of the present review is to show the impact of different stages of cultivation and processing with regard to the changes induced in the protein fractions. Special focus has been laid on the major seed storage proteins throughout the different stages of processing. The study starts with classical introduction of the extraction and the characterization methods used, while addressing classification approaches of cocoa proteins evolved during the timeline. The changes in protein composition during ripening and maturation of cocoa seeds, together with the possible modifications during the post-harvest processing (fermentation, drying, and roasting), have been documented. Finally, the bioactive potential arising directly or indirectly from cocoa proteins has been elucidated. The “state of the art” suggests that exploration of other potentially bioactive components in cocoa needs to be undertaken, while considering the complexity of reaction products occurring during the roasting phase of the post-harvest processing. Finally, the utilization of partially processed cocoa beans (e.g., fermented, conciliatory thermal treatment) can be recommended, providing a large reservoir of bioactive potentials arising from the protein components that could be instrumented in functionalizing foods.
Cocoa Bean Proteins
(2019)
The protein fractions of cocoa have been implicated influencing both the bioactive potential and sensory properties of cocoa and cocoa products. The objective of the present review is to show the impact of different stages of cultivation and processing with regard to the changes induced in the protein fractions. Special focus has been laid on the major seed storage proteins throughout the different stages of processing. The study starts with classical introduction of the extraction and the characterization methods used, while addressing classification approaches of cocoa proteins evolved during the timeline. The changes in protein composition during ripening and maturation of cocoa seeds, together with the possible modifications during the post-harvest processing (fermentation, drying, and roasting), have been documented. Finally, the bioactive potential arising directly or indirectly from cocoa proteins has been elucidated. The “state of the art” suggests that exploration of other potentially bioactive components in cocoa needs to be undertaken, while considering the complexity of reaction products occurring during the roasting phase of the post-harvest processing. Finally, the utilization of partially processed cocoa beans (e.g., fermented, conciliatory thermal treatment) can be recommended, providing a large reservoir of bioactive potentials arising from the protein components that could be instrumented in functionalizing foods.
Land cover change is a dynamic phenomenon driven by synergetic biophysical and socioeconomic effects. It involves massive transitions from natural to less natural habitats and thereby threatens ecosystems and the services they provide. To retain intact ecosystems and reduce land cover change to a minimum of natural transition processes, a dense network of protected areas has been established across Europe. However, even protected areas and in particular the zones around protected areas have been shown to undergo land cover changes. The aim of our study was to compare land cover changes in protected areas, non-protected areas, and 1 km buffer zones around protected areas and analyse their relationship to climatic and socioeconomic factors across Europe between 2000 and 2012 based on earth observation data. We investigated land cover flows describing major change processes: urbanisation, afforestation, deforestation, intensification of agriculture, extensification of agriculture, and formation of water bodies. Based on boosted regression trees, we modelled correlations between land cover flows and climatic and socioeconomic factors. The results show that land cover changes were most frequent in 1 km buffer zones around protected areas (3.0% of all buffer areas affected). Overall, land cover changes within protected areas were less frequent than outside, although they still amounted to 18,800 km2 (1.5% of all protected areas) from 2000 to 2012. In some parts of Europe, urbanisation and intensification of agriculture still accounted for up to 25% of land cover changes within protected areas. Modelling revealed meaningful relationships between land cover changes and a combination of influencing factors. Demographic factors (accessibility to cities and population density) were most important for coarse-scale patterns of land cover changes, whereas fine-scale patterns were most related to longitude (representing the general east/west economic gradient) and latitude (representing the north/south climatic gradient).
Objectives: The objectives of this study were to determine the interrater reliability (IRR) of assessment of multiple systematic reviews (AMSTAR) 2 for reviews of pharmacological or psychological interventions for the treatment of major depression, to compare it to that of AMSTAR and risk of bias in systematic reviews (ROBIS), and to assess the convergent validity between the appraisal tools. Results: The median kappa values as a measure of IRR indicated a moderate agreement for AMSTAR 2 (median = 0.51), a substantial agreement for AMSTAR (median = 0.62), and a fair agreement for ROBIS (median = 0.27). Validity results showed a positive association for AMSTAR and AMSTAR 2 (r = 0.91) as well as ROBIS and AMSTAR 2 (r = 0.84). For the overall rating, AMSTAR 2 showed a high concordance with ROBIS and a lower concordance with AMSTAR. Conclusion: The IRR of AMSTAR 2 was found to be slightly lower than the IRR of AMSTAR and higher than the IRR of ROBIS. Validity measurements indicate that AMSTAR 2 is closely related to both ROBIS and AMSTAR. (C) 2019 Elsevier Inc. All rights reserved.
BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.
Understanding and quantifying total economic impacts of flood events is essential for flood risk management and adaptation planning. Yet, detailed estimations of joint direct and indirect flood-induced economic impacts are rare. In this study an innovative modeling procedure for the joint assessment of short-term direct and indirect economic flood impacts is introduced. The procedure is applied to 19 economic sectors in eight federal states of Germany after the flood events in 2013. The assessment of the direct economic impacts is object-based and considers uncertainties associated with the hazard, the exposed objects and their vulnerability. The direct economic impacts are then coupled to a supply-side Input-Output-Model to estimate the indirect economic impacts. The procedure provides distributions of direct and indirect economic impacts which capture the associated uncertainties. The distributions of the direct economic impacts in the federal states are plausible when compared to reported values. The ratio between indirect and direct economic impacts shows that the sectors Manufacturing, Financial and Insurance activities suffered the most from indirect economic impacts. These ratios also indicate that indirect economic impacts can be almost as high as direct economic impacts. They differ strongly between the economic sectors indicating that the application of a single factor as a proxy for the indirect impacts of all economic sectors is not appropriate.
Understanding and quantifying total economic impacts of flood events is essential for flood risk management and adaptation planning. Yet, detailed estimations of joint direct and indirect flood-induced economic impacts are rare. In this study an innovative modeling procedure for the joint assessment of short-term direct and indirect economic flood impacts is introduced. The procedure is applied to 19 economic sectors in eight federal states of Germany after the flood events in 2013. The assessment of the direct economic impacts is object-based and considers uncertainties associated with the hazard, the exposed objects and their vulnerability. The direct economic impacts are then coupled to a supply-side Input-Output-Model to estimate the indirect economic impacts. The procedure provides distributions of direct and indirect economic impacts which capture the associated uncertainties. The distributions of the direct economic impacts in the federal states are plausible when compared to reported values. The ratio between indirect and direct economic impacts shows that the sectors Manufacturing, Financial and Insurance activities suffered the most from indirect economic impacts. These ratios also indicate that indirect economic impacts can be almost as high as direct economic impacts. They differ strongly between the economic sectors indicating that the application of a single factor as a proxy for the indirect impacts of all economic sectors is not appropriate.
Background There is evidence that physical exercise training (PET) conducted at the workplace is effective in improving physical fitness and thus health. However, there is no current systematic review available that provides high-level evidence regarding the effects of PET on physical fitness in the workforce. Objectives To quantify sex-, age-, and occupation type-specific effects of PET on physical fitness and to characterize dose-response relationships of PET modalities that could maximize gains in physical fitness in the working population. Data Sources A computerized systematic literature search was conducted in the databases PubMed and Cochrane Library (2000-2019) to identify articles related to PET in workers. Study Eligibility Criteria Only randomized controlled trials with a passive control group were included if they investigated the effects of PET programs in workers and tested at least one fitness measure. Study Appraisal and Synthesis Methods Weighted mean standardised mean differences (SMDwm) were calculated using random effects models. A multivariate random effects meta-regression was computed to explain the influence of key training modalities (e.g., training frequency, session duration, intensity) on the effectiveness of PET on measures of physical fitness. Further, subgroup univariate analyses were computed for each training modality. Additionally, methodological quality of the included studies was rated with the help of the Physiotherapy Evidence Database (PEDro) Scale. Results Overall, 3423 workers aged 30-56 years participated in 17 studies (19 articles) that were eligible for inclusion. Methodological quality of the included studies was moderate with a median PEDro score of 6. Our analyses revealed significant, small-sized effects of PET on cardiorespiratory fitness (CRF), muscular endurance, and muscle power (0.29 <= SMDwm <= 0.48). Medium effects were found for CRF and muscular endurance in younger workers (<= 45 years) (SMDwm = 0.71) and white-collar workers (SMDwm = 0.60), respectively. Multivariate random effects meta-regression for CRF revealed that none of the examined training modalities predicted the effects of PET on CRF (R-2 = 0). Independently computed subgroup analyses showed significant PET effects on CRF when conducted for 9-12 weeks (SMDwm = 0.31) and for 17-20 weeks (SMDwm = 0.74). Conclusions PET effects on physical fitness in healthy workers are moderated by age (CRF) and occupation type (muscular endurance). Further, independently computed subgroup analyses indicated that the training period of the PET programs may play an important role in improving CRF in workers.