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A recent report showed PINK1 transcript levels to be up- or down-regulated by the gain or loss of Ataxin-2 function, respectively, in human blood, in a human neural cell line and in mouse tissues. These observations may have profound implications for the regulation of cell growth and may be medically exploited for the treatment of cancer and neural atrophy...
Body image dissatisfaction is a serious, global problem that negatively affects life satisfaction. Several claims have been made about the possible psychological benefits of naturist activities, but very little empirical research has investigated these benefits or any plausible explanations for them. In three studies—one large-scale, cross-sectional study (n = 849), and 2 prospective studies (n = 24, n = 100) this research developed and applied knowledge about the possible benefits of naturist activities. It was found that more participation in naturist activities predicted greater life satisfaction—a relationship that was mediated by more positive body image, and higher self-esteem (Study 1). Applying these findings, it was found that participation in actual naturist activities led to an increase in life satisfaction, an effect that was also mediated by improvements in body image and self-esteem (Studies 2 and 3). The potential benefits of naturism are discussed, as well as possible future research, and implications for the use of naturist activities.
The important role of fire in regulating vegetation community composition and contributions to emissions of greenhouse gases and aerosols make it a critical component of dynamic global vegetation models and Earth system models. Over 2 decades of development, a wide variety of model structures and mechanisms have been designed and incorporated into global fire models, which have been linked to different vegetation models. However, there has not yet been a systematic examination of how these different strategies contribute to model performance. Here we describe the structure of the first phase of the Fire Model Intercomparison Project (FireMIP), which for the first time seeks to systematically compare a number of models. By combining a standardized set of input data and model experiments with a rigorous comparison of model outputs to each other and to observations, we will improve the understanding of what drives vegetation fire, how it can best be simulated, and what new or improved observational data could allow better constraints on model behavior. In this paper, we introduce the fire models used in the first phase of FireMIP, the simulation protocols applied, and the benchmarking system used to evaluate the models. We have also created supplementary tables that describe, in thorough mathematical detail, the structure of each model.
In this study, we construct a new monthly zonal mean carbon dioxide (CO2) distribution from the upper troposphere to the stratosphere over the 2000–2010 time period. This reconstructed CO2 product is based on a Lagrangian backward trajectory model driven by ERA-Interim reanalysis meteorology and tropospheric CO2 measurements. Comparisons of our CO2 product to extratropical in situ measurements from aircraft transects and balloon profiles show remarkably good agreement. The main features of the CO2 distribution include (1) relatively large mixing ratios in the tropical stratosphere; (2) seasonal variability in the extratropics, with relatively high mixing ratios in the summer and autumn hemisphere in the 15–20 km altitude layer; and (3) decreasing mixing ratios with increasing altitude from the upper troposphere to the middle stratosphere ( ∼ 35 km). These features are consistent with expected variability due to the transport of long-lived trace gases by the stratospheric Brewer–Dobson circulation. The method used here to construct this CO2 product is unique from other modelling efforts and should be useful for model and satellite validation in the upper troposphere and stratosphere as a prior for inversion modelling and to analyse features of stratosphere–troposphere exchange as well as the stratospheric circulation and its variability.
The fractional release factor (FRF) gives information on the amount of a halocarbon that is released at some point into the stratosphere from its source form to the inorganic form, which can harm the ozone layer through catalytic reactions. The quantity is of major importance because it directly affects the calculation of the ozone depletion potential (ODP). In this context time-independent values are needed which, in particular, should be independent of the trends in the tropospheric mixing ratios (tropospheric trends) of the respective halogenated trace gases. For a given atmospheric situation, such FRF values would represent a molecular property.
We analysed the temporal evolution of FRF from ECHAM/MESSy Atmospheric Chemistry (EMAC) model simulations for several halocarbons and nitrous oxide between 1965 and 2011 on different mean age levels and found that the widely used formulation of FRF yields highly time-dependent values. We show that this is caused by the way that the tropospheric trend is handled in the widely used calculation method of FRF.
Taking into account chemical loss in the calculation of stratospheric mixing ratios reduces the time dependence in FRFs. Therefore we implemented a loss term in the formulation of the FRF and applied the parameterization of a mean arrival time to our data set.
We find that the time dependence in the FRF can almost be compensated for by applying a new trend correction in the calculation of the FRF. We suggest that this new method should be used to calculate time-independent FRFs, which can then be used e.g. for the calculation of ODP.
Background: Women’s participation in medicine and the need for gender equality in healthcare are increasingly recognised, yet little attention is paid to leadership and management positions in large publicly funded academic health centres. This study illustrates such a need, taking the case of four large European centres: Charité – Universitätsmedizin Berlin (Germany), Karolinska Institutet (Sweden), Medizinische Universität Wien (Austria), and Oxford Academic Health Science Centre (United Kingdom).
Case:The percentage of female medical students and doctors in all four countries is now well within the 40–60% gender balance zone. Women are less well represented among specialists and remain significantly under-represented among senior doctors and full professors. All four centres have made progress in closing the gender leadership gap on boards and other top-level decision-making bodies, but a gender leadership gap remains relevant. The level of achieved gender balance varies significantly between the centres and largely mirrors country-specific welfare state models, with more equal gender relations in Sweden than in the other countries. Notably, there are also similar trends across countries and centres: gender inequality is stronger within academic enterprises than within hospital enterprises and stronger in middle management than at the top level. These novel findings reveal fissures in the ‘glass ceiling’ effects at top-level management, while the barriers for women shift to middle-level management and remain strong in academic positions. The uneven shifts in the leadership gap are highly relevant and have policy implications.
Conclusion: Setting gender balance objectives exclusively for top-level decision-making bodies may not effectively promote a wider goal of gender equality. Academic health centres should pay greater attention to gender equality as an issue of organisational performance and good leadership at all levels of management, with particular attention to academic enterprises and newly created management structures. Developing comprehensive gender-sensitive health workforce monitoring systems and comparing progress across academic health centres in Europe could help to identify the gender leadership gap and utilise health human resources more effectively.
The hallmark of classical Hodgkin lymphoma (cHL) is the presence of giant, mostly multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Whereas it has recently been shown that giant HRS cells evolve from small Hodgkin cells by incomplete cytokinesis and re-fusion of tethered sister cells, it remains unsolved why this phenomenon particularly takes place in this lymphoma and what the differences between these cell types of variable sizes are. The aim of the present study was to characterize microdissected small and giant HRS cells by gene expression profiling and to assess differences of clonal growth behavior as well as susceptibility toward cytotoxic intervention between these different cell types to provide more insight into their distinct cellular potential. Applying stringent filter criteria, only two differentially expressed genes between small and giant HRS cells, SHFM1 and LDHB, were identified. With looser filter criteria, 13 genes were identified to be differentially overexpressed in small compared to giant HRS cells. These were mainly related to energy metabolism and protein synthesis, further suggesting that small Hodgkin cells resemble the proliferative compartment of cHL. SHFM1, which is known to be involved in the generation of giant cells, was downregulated in giant RS cells at the RNA level. However, reduced mRNA levels of SHFM1, LDHB and HSPA8 did not translate into decreased protein levels in giant HRS cells. In cell culture experiments it was observed that the fraction of small and big HRS cells was adjusted to the basic level several days after enrichment of these populations via cell sorting, indicating that small and big HRS cells can reconstitute the full spectrum of cells usually observed in the culture. However, assessment of clonal growth of HRS cells indicated a significantly reduced potential of big HRS cells to form single cell colonies. Taken together, our findings pinpoint to strong similarities but also some differences between small and big HRS cells.
Der Erzählforscher Johannes Merkel hat unlängst (2015) einen bemerkenswerten Überblick zur Gesamttradition des mündlichen Erzählens vorgelegt. Die folgenden Überlegungen, von einer Teilbesprechung dieser Neuerscheinung ausgehend, zielen grundsätzlich auf eine kritische Überprüfung von verschiedenen in der bisherigen Forschung für selbstverständlich gehaltenen Basisfaktoren (insbesondere den theoretischen Ansätzen von Nilsson und Parry). Dabei geht es zunächst einmal um jene allgemein vorausgesetzte vorgriechische Phase von oral poetry, auf die sich auch Merkel im 3. Kapitel unter dem Titel ‚Das singende Gedächtnis: Epenvortrag in Mittelasien und auf dem Balkan‘ bezog (105-148). Die neuere Forschung tendiert bekanntlich dazu, es habe eine längere oral poetry in den sog. "dunklen Jahrhunderten" zwischen 1200 und 850 v. Chr. noch vor Ausbildung der frühgriechischen Kultur gegeben; so z.B. der englische Althistoriker Robin Lane Fox (2008/11): "Ilias und Odyssee sind im Wesentlichen Werke der Mündlichkeit, die letzten in einem langen 'Zeitalter der Mündlichkeit'…". Eng damit verbunden waren Martin P. Nilssons Hypothese "The Mycenaen Origin of Greek Mythology" (1932) und der von Milman Parry seit 1928 konstituierte, von seinem Schüler Arthur B. Lord weiter entwickelte Ansatz, dass für frühgriechische Epen eine Vergleichbarkeit mit neueren Phasen mündlicher Epik z.B. auf dem Balkan gegeben sei. Merkels jüngste Ausführungen verstärken meine früheren Bedenken gegen dieses Gesamtkonzept.
In den Jahren 1886 und 1887 fanden sich in Avenches (Schweiz, Kanton Waadt), der ehemaligen römischen Colonia Pia Flavia Constans Emerita Helvetiorum Foederata, mehrere Fragmente einer Grabinschrift aus Marmor, die schon häufiger das Interesse der Forschung geweckt haben, da auf der Grabplatte anscheinend eine kaiserliche Gouvernante, eine educatrix Augusti nostri, genannt wird...
The paper assesses current rising reparations claims for the Maafa/ Maangamizi (‘African holocaust,’ comprising transatlantic slavery, colonialism and neo-colonialism) from two angles. First, it explores the connectivity of reparations and global justice, peace and security. Second, it discusses how the claim is justified in international law. The concept of reparations in international law is also explored, revealing that reparations cannot be limited to financial compensation due to the nature of the damage and international law prescriptions. Comprehensive reparations based in international law require the removal of structures built on centuries of illegal acts and aggression, in the forms of transatlantic slavery, colonialism and neo-colonialism. Reparations must also lead to the restitution of sovereignty to African and indigenous peoples globally. They are indispensable to halt the destruction of the earth as human habitat, caused by the violent European cultural, political, socio-economic system known as apitalism that is rooted in transatlantic slavery.
From reparations for slavery to international racial justice: a critical republican perspective
(2017)
This paper focuses on demands for reparations for colonial slavery and their public reception in France. It argues that this bottom-up, context-sensitive approach to theorising reparations enables us to formulate a critical republican theory of international racial justice. It contrasts the critical republican perspective on reparations with a nation-state centred approach in which reparations activists are accused of threatening the French republic’s sense of homogeneity and unity, thus undermining the national narrative on the French identity. It also rejects the liberal egalitarian perspective, which itself rejects reparations in favour of focusing on present disadvantages. In so doing, this paper illustrates how the notion of non-domination offers a superior way of conceptualising global racial injustices compared to more traditional distributive outlooks.
If Third World women form ‘the bedrock of a certain kind of global exploitation of labour,’ as Chandra Mohanty argues, how can our theoretical definitions of exploitation account for this? This paper argues that liberal theories of exploitation are insufficiently structural and that Marxian accounts are structural but are insufficiently intersectional. What we need is a structural and intersectional definition of exploitation in order to correctly identify global structural exploitation. Drawing on feminist, critical race/post-colonial and post-Fordist critiques of the Marxist definition and the intersectional accounts of Maria Mies and Iris Marion Young, this paper offers the following definition of structural exploitation: structural exploitation refers to the forced transfer of the productive powers of groups positioned as socially inferior to the advantage of groups positioned as socially superior. Global structural exploitation is a form of global injustice because it is a form of oppression.
Many theories of global distributive justice are based on the assumption that all humans hold common ownership of the earth. As the earth is finite and our actions interconnect, we need a system of justice that regulates the potential appropriation of the common earth to ensure fairness. According to these theories, imposing limits and distributive obligations on private and public property arrangements may be the best mechanism for governing common ownership. We present a critique of the assumption that this issue can be solved within the private–public property regime, arguing that the boundaries of this regime should not be taken for granted and that the growing literature on the democratic commons movement suggests how this can be accomplished. We consider that, if the earth is defined as a common, the private– public property paradigm must be open to questioning, and democratic commoners’ activities should be considered.
All cosmopolitan approaches to global distributive justice are premised on the idea that humans are the primary units of moral concern. In this paper, I argue that neither relational nor non-relational cosmopolitans can unquestioningly assume the moral primacy of humans. Furthermore, I argue that, by their own lights, cosmopolitans must extend the scope of justice to most, if not all, nonhuman animals. To demonstrate that cosmopolitans cannot simply ‘add nonhuman animals and stir,’ I examine the cosmopolitan position developed by Martha Nussbaum in Frontiers of Justice. I argue that while Nussbaum explicitly includes nonhuman animals within the scope of justice, her account is marked by an unjustifiable anthropocentric bias. I ultimately conclude that we must radically reconceptualise the primary unit of cosmopolitan moral concern to encompass most, if not all, sentient animals.
Excessive neutrophil activation accompanied by delayed apoptotic cell death in inflammatory conditions causes progressive damage of cells and tissues, leading to life-threatening multiple organ dysfunction syndrome. Previous work suggested that circulating serum factors during inflammation are critically involved in the suppression of neutrophil cell death although the identity of these antiapoptotic mediators remained elusive. In this study, we identified the acute phase protein α-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced apoptosis in human neutrophils through a mechanism implicating caspases-independent pathways. We show here that serum levels of AAT, potentially in part released by stimulated neutrophils, are markedly elevated in major trauma patients suffering from systemic inflammatory response syndrome (SIRS). Notably, AAT depletion from serum increased sensitivity of human neutrophils for STS-induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis resistance by preventing PKC/Akt inactivation and subsequent proteasomal degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered antiapoptotic pathways in neutrophils. In summary, these results establish a novel pivotal role of circulating AAT in mediating survival by antagonizing the proapoptotic action of the PKC inhibitor STS and should be considered for AAT augmentation therapies in future.
Natural killer (NK) cells are a promising tool for the use in adoptive immunotherapy, since they efficiently recognize and kill tumor cells. In this context, ex vivo cultivation is an attractive option to increase NK cells in numbers and to improve their antitumor potential prior to clinical applications. Consequently, various strategies to generate NK cells for adoptive immunotherapy have been developed. Here, we give an overview of different NK cell cultivation approaches and their impact on shaping the NK cell antitumor activity. So far, the cytokines interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 are used to culture and expand NK cells. The selection of the respective cytokine combination is an important factor that directly affects NK cell maturation, proliferation, survival, distribution of NK cell subpopulations, activation, and function in terms of cytokine production and cytotoxic potential. Importantly, cytokines can upregulate the expression of certain activating receptors on NK cells, thereby increasing their responsiveness against tumor cells that express the corresponding ligands. Apart from using cytokines, cocultivation with autologous accessory non-NK cells or addition of growth-inactivated feeder cells are approaches for NK cell cultivation with pronounced effects on NK cell activation and expansion. Furthermore, ex vivo cultivation was reported to prime NK cells for the killing of tumor cells that were previously resistant to NK cell attack. In general, NK cells become frequently dysfunctional in cancer patients, for instance, by downregulation of NK cell activating receptors, disabling them in their antitumor response. In such scenario, ex vivo cultivation can be helpful to arm NK cells with enhanced antitumor properties to overcome immunosuppression. In this review, we summarize the current knowledge on NK cell modulation by different ex vivo cultivation strategies focused on increasing NK cytotoxicity for clinical application in malignant diseases. Moreover, we critically discuss the technical and regulatory aspects and challenges underlying NK cell based therapeutic approaches in the clinics.
Background and Purpose: This review aims to provide a comprehensive overview of the literature and elucidate open questions for future clinical trials concerning diagnostics and treatment modalities for cervical cancer of unknown primary (CUP).
Methods: A literature search for head and neck CUP was performed with focus on diagnostics and therapies as well as molecular markers.
Results: High level evidence on CUP is limited. However, it seems that a consensus exists regarding the optimal diagnostic procedures. The correct implementation of biomarkers for patient stratification and treatment remains unclear. An even greater dispute dominates about the ideal treatment with publications ranging from sole surgery to surgery with postoperative bilateral radiotherapy with inclusion of the mucosa and concomitant chemotherapy.
Conclusions: Cervical CUP represents a very heterogeneous malignant disease. On this account many aspects concerning treatment optimization remain unclear, despite a considerable number of publications in the past. Future research in form of prospective randomized trials is needed in order to better define patient stratification criteria and enable tailored treatment.
We explored the characteristics and motivations of people who, having obtained their genetic or genomic data from Direct-To-Consumer genetic testing (DTC-GT) companies, voluntarily decide to share them on the publicly accessible web platform openSNP. The study is the first attempt to describe open data sharing activities undertaken by individuals without institutional oversight. In the paper we provide a detailed overview of the distribution of the demographic characteristics and motivations of people engaged in genetic or genomic open data sharing. The geographical distribution of the respondents showed the USA as dominant. There was no significant gender divide, the age distribution was broad, educational background varied and respondents with and without children were equally represented. Health, even though prominent, was not the respondents’ primary or only motivation to be tested. As to their motivations to openly share their data, 86.05% indicated wanting to learn about themselves as relevant, followed by contributing to the advancement of medical research (80.30%), improving the predictability of genetic testing (76.02%) and considering it fun to explore genotype and phenotype data (75.51%). Whereas most respondents were well aware of the privacy risks of their involvement in open genetic data sharing and considered the possibility of direct, personal repercussions troubling, they estimated the risk of this happening to be negligible. Our findings highlight the diversity of DTC-GT consumers who decide to openly share their data. Instead of focusing exclusively on health-related aspects of genetic testing and data sharing, our study emphasizes the importance of taking into account benefits and risks that stretch beyond the health spectrum. Our results thus lend further support to the call for a broader and multi-faceted conceptualization of genomic utility.