662 research outputs found

    Alevis in Germany On the Way to Public Recognition?

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    In the past decade, Alevis in Germany have stressed their distinctness mainly in terms of culture when negotiating with the majority society. Since recently, however, an increased emphasis on religion can be observed, which is not so much due to a regained strength of religiosity. It is rather a response to changed public discourses and an adjustment to the prevailing legal and institutional conditions. In Germany, the issue of immigration has been treated in terms of cultural difference since long ago, the religious identity of the mainly Muslim immigrants having nearly no impact on integration policy. Yet since the end of the 1990s, when attention was drawn to fundamentalist tendencies among the Muslim youth, the religious dimension of immigration has been brought to the fore

    Religiöse Heilung und Heiler in Choresm, Usbekistan

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    The New Garments of Alevism

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    In the past decade, Turkey's official image as a country of Sunni Muslims has been vigorously challenged by the 'coming out' of the Alevis, a large heterodox Islamic minority, which consists of approximately 15 million Turkish- and Kurdish-speaking members. Until that time, due to the official definition of Turkey as an ethnically and religiously homogenous nation, public expressions of deviating collective identities had been banned by law. However, a shift in government policy in the early 1990s enabled the Alevis to come to the fore and to inaugurate an ethno-political movement to achieve official acknowledgement

    19F Electron-nuclear double resonance reveals interaction between redox-active tyrosines across the α/β interface of E. coli ribonucleotide reductase

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    Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, thereby playing a key role in DNA replication and repair. Escherichia coli class Ia RNR is an α2β2 enzyme complex that uses a reversible multistep radical transfer (RT) over 32 Å across its two subunits, α and β, to initiate, using its metallo-cofactor in β2, nucleotide reduction in α2. Each step is proposed to involve a distinct proton-coupled electron-transfer (PCET) process. An unresolved step is the RT involving Y356(β) and Y731(α) across the α/β interface. Using 2,3,5-F3Y122-β2 with 3,5-F2Y731-α2, GDP (substrate) and TTP (allosteric effector), a Y356• intermediate was trapped and its identity was verified by 263 GHz electron paramagnetic resonance (EPR) and 34 GHz pulse electron–electron double resonance spectroscopies. 94 GHz 19F electron-nuclear double resonance spectroscopy allowed measuring the interspin distances between Y356• and the 19F nuclei of 3,5-F2Y731 in this RNR mutant. Similar experiments with the double mutant E52Q/F3Y122-β2 were carried out for comparison to the recently published cryo-EM structure of a holo RNR complex. For both mutant combinations, the distance measurements reveal two conformations of 3,5-F2Y731. Remarkably, one conformation is consistent with 3,5-F2Y731 within the H-bond distance to Y356•, whereas the second one is consistent with the conformation observed in the cryo-EM structure. The observations unexpectedly suggest the possibility of a colinear PCET, in which electron and proton are transferred from the same donor to the same acceptor between Y356 and Y731. The results highlight the important role of state-of-the-art EPR spectroscopy to decipher this mechanism

    Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma

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    Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein expression of DLBCL cell lines. Methods: miR-142 was deleted by CRISPR/Cas9 knockout in cell lines from DLBCL. Results: By proteome analyses, miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in GC-DLBCL lines BJAB and SUDHL4. Various mitochondrial ribosomal proteins were up-regulated in line with their pro-tumorigenic properties, while proteins necessary for MHC-I presentation were down-regulated in accordance with the finding that miR-142 knockout mice have a defective immune response. CFL2, CLIC4, STAU1, and TWF1 are known targets of miR-142, and we could additionally confirm AKT1S1, CCNB1, LIMA1, and TFRC as new targets of miR-142-3p or -5p. Conclusions: Seed-sequence mutants of miR-142 confirmed potential targets and novel targets of miRNAs can be identified in miRNA knockout cell lines. Due to the complex contribution of miRNAs within cellular regulatory networks, in particular when miRNAs highly present in RISC complexes are replaced by other miRNAs, primary effects on gene expression may be covered by secondary layers of regulation

    Individual Radiation Protection Monitoring in the Marshall Islands: Enewetak Atoll (2002-2004)

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    The United States Department of Energy (U.S. DOE) has recently implemented a series of strategic initiatives to address long-term radiological surveillance needs at former U.S. nuclear test sites in the Marshall Islands. The plan is to engage local atoll communities in developing shared responsibilities for implementing radiation protection monitoring programs for resettled and resettling populations in the northern Marshall Islands. Using the pooled resources of the U.S. DOE and local atoll governments, individual radiological surveillance programs have been developed in whole body counting and plutonium urinalysis in order to accurately assess radiation doses resulting from the ingestion and uptake of fallout radionuclides contained in locally grown foods. Permanent whole body counting facilities have been established at three separate locations in the Marshall Islands including Enewetak Island (Figure 1) (Bell et al., 2002). These facilities are operated and maintained by Marshallese technicians with scientists from the Lawrence Livermore National Laboratory (LLNL) providing on-going technical support services. Bioassay samples are collected under controlled conditions and analyzed for plutonium isotopes at the Center for Accelerator Mass Spectrometry at LLNL using state-of-the art measurement technologies. We also conduct an on-going environmental monitoring and characterization program at selected sites in the northern Marshall Islands. The aim of the environmental program is to determine the level and distribution of important fallout radionuclides in soil, water and local foods with a view towards providing more accurate and updated dose assessments, incorporating knowledge of the unique behaviors and exposure pathways of fallout radionuclides in coral atoll ecosystems. These scientific studies have also been essential in helping guide the development of remedial options used in support of island resettlement. Together, the individual and environmental radiological surveillance programs are helping meet the informational needs of the U.S. DOE and the Republic of the Marshall Islands. Our updated environmental assessments provide a strong scientific basis for predicting future change in exposure conditions especially in relation to changes in lifestyle, diet and/or land-use patterns. This information has important implications in addressing questions about existing (and future) radiological conditions on the islands, in determining the cost and estimating the effectiveness of potential remedial measures, and in general policy support considerations. Perhaps most importantly, the recently established individual radiological surveillance programs provide affected atoll communities with an unprecedented level of radiation protection monitoring where, for the first time, local resources are being made available to monitor resettled and resettling populations on a continuous basis. As a hard copy supplement to Marshall Islands Program website (http://eed.llnl.gov/mi/), this document provides an overview of the individual radiation protection monitoring program established for the Enewetak Atoll population group along with a full disclosure of all verified measurement data (2002-2004). Readers are advised that an additional feature of the associated web site is a provision where users are able calculate and track doses delivered to volunteers (de-identified information only) participating in the Marshall Islands Radiological Surveillance Program

    Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

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    The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits
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