Quellensicherung im institutionellen Rahmen. Zur Macht und Ohnmacht der Archive bei der Überlieferungsbildung

Im Oktober 2011 war die Vertretung des Landes Schleswig-Holstein beim Bund Gastgeberin der Tagung „Macht und Ohnmacht der Archive“. Kultur- und Archivwissenschaftlerinnen und -wissenschaftler, Archivarinnen und Archivare debattierten über Auftrag und Nutzen, Verantwortung und Leistung der Archive in einer weithin digitalisierten Wissensgesellschaft. Die Archivwissenschaft in Deutschland ist auf die Herausforderung, die durch das von Kulturwissenschaftlerinnen und -wissenschaftlern in der Atmosphäre der Postmoderne geformte Verständnis des Archivs entstanden ist, bislang nicht ausführlich eingegangen. Mit dem hier dokumentierten Symposium wird die überfällige Auseinandersetzung mit diesen Positionen nun begonnen. Die Diskussion wurde dabei betont praxisorientiert und pragmatisch geführt. Die Beiträge verbinden archivwissenschaftliche Überlegungen mit der Präsentation ausgewählter Einzelthemen aus archivarischer Praxis und Archivgeschichte.In October 2011, the Representation of the State of Schleswig-Holstein to the Federal Government hosted the conference “Power and Impotence of the Archives”. Cultural and archival scholars, archivists and academics debated the mission and benefits, responsibility and performance of archives in a widely digitized knowledge society. Archival scholarship in Germany has so far not dealt in detail with the challenge posed by the understanding of the archive in the atmosphere of postmodernity by cultural scholars. With the symposium documented here, the long overdue examination of these positions will now begin. The discussion was conducted in a pragmatic and practice-oriented manner. The contributions combine archival research considerations with the presentation of selected individual topics from archival practice and archive history

Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster

Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer\u27s disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in adult neurons or glia. Overexpression of Ldh in both cell types caused a significant reduction in lifespan whereas Ldh down-regulation resulted in lifespan extension. Moreover, pan-neuronal overexpression of Ldh disrupted circadian locomotor activity rhythms and significantly increased brain neurodegeneration. In contrast, reduction of Ldh in neurons delayed age-dependent neurodegeneration. Thus, our unbiased genetic approach identified Ldh and lactate as potential modulators of aging and longevity in flies

Amyloid Precursor Proteins Are Dynamically Trafficked and Processed during Neuronal Development

Proteolytic processing of the Amyloid Precursor Protein (APP) produces beta-amyloid (Aβ) peptide fragments that accumulate in Alzheimer’s Disease (AD), but APP may also regulate multiple aspects of neuronal development, albeit via mechanisms that are not well understood. APP is a member of a family of transmembrane glycoproteins expressed by all higher organisms, including two mammalian orthologs (APLP1 and APLP2) that have complicated investigations into the specific activities of APP. By comparison, insects express only a single APP-related protein (APP-Like, or APPL) that contains the same protein interaction domains identified in APP. However, unlike its mammalian orthologs, APPL is only expressed by neurons, greatly simplifying an analysis of its functions in vivo. Like APP, APPL is processed by secretases to generate a similar array of extracellular and intracellular cleavage fragments, as well as an Aβ-like fragment that can induce neurotoxic responses in the brain. Exploiting the complementary advantages of two insect models (Drosophila melanogaster and Manduca sexta), we have investigated the regulation of APPL trafficking and processing with respect to different aspects of neuronal development. By comparing the behavior of endogenously expressed APPL with fluorescently tagged versions of APPL and APP, we have shown that some full-length protein is consistently trafficked into the most motile regions of developing neurons both in vitro and in vivo. Concurrently, much of the holoprotein is rapidly processed into N- and C-terminal fragments that undergo bi-directional transport within distinct vesicle populations. Unexpectedly, we also discovered that APPL can be transiently sequestered into an amphisome-like compartment in developing neurons, while manipulations targeting APPL cleavage altered their motile behavior in cultured embryos. These data suggest that multiple mechanisms restrict the bioavailability of the holoprotein to regulate APPL-dependent responses within the nervous system. Lastly, targeted expression of our double-tagged constructs (combined with time-lapse imaging) revealed that APP family proteins are subject to complex patterns of trafficking and processing that vary dramatically between different neuronal subtypes. In combination, our results provide a new perspective on how the regulation of APP family proteins can be modulated to accommodate a variety of cell type-specific responses within the embryonic and adult nervous system

Rice Galaxy: An open resource for plant science

Background: Rice molecular genetics, breeding, genetic diversity, and allied research (such as rice-pathogen interaction) have adopted sequencing technologies and high-density genotyping platforms for genome variation analysis and gene discovery. Germplasm collections representing rice diversity, improved varieties, and elite breeding materials are accessible through rice gene banks for use in research and breeding, with many having genome sequences and high-density genotype data available. Combining phenotypic and genotypic information on these accessions enables genome-wide association analysis, which is driving quantitative trait loci discovery and molecular marker development. Comparative sequence analyses across quantitative trait loci regions facilitate the discovery of novel alleles. Analyses involving DNA sequences and large genotyping matrices for thousands of samples, however, pose a challenge to non−computer savvy rice researchers. Findings: The Rice Galaxy resource has shared datasets that include high-density genotypes from the 3,000 Rice Genomes project and sequences with corresponding annotations from 9 published rice genomes. The Rice Galaxy web server and deployment installer includes tools for designing single-nucleotide polymorphism assays, analyzing genome-wide association studies, population diversity, rice−bacterial pathogen diagnostics, and a suite of published genomic prediction methods. A prototype Rice Galaxy compliant to Open Access, Open Data, and Findable, Accessible, Interoperable, and Reproducible principles is also presented. Conclusions: Rice Galaxy is a freely available resource that empowers the plant research community to perform state-of-the-art analyses and utilize publicly available big datasets for both fundamental and applied science

Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society

BACKGROUND: The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control. METHODS: Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4-6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function). DISCUSSION: Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach

Episodic records of jellyfish ingestion of plastic items reveal a novel pathway for trophic transference of marine litter

Invertebrates represent the most plentiful component of marine biodiversity. To date, only few species have been documented for marine litter intake. Here, we report for the first time the presence of macroplastic debris in a jellyfish species. Such novel target to plastic pollution highlights an under studied vector of marine litter along marine trophic web, raising further concern over the impact on marine wildlife

Usefulness of primary care electronic networks to assess the incidence of chlamydia, diagnosed by general practitioners

Background: Chlamydia is the most common curable sexually transmitted infection (STI) in the Netherlands. The majority of chlamydia diagnoses are made by general practitioners (GPs). Baseline data from primary care will facilitate the future evaluation of the ongoing large population-based screening in the Netherlands. The aim of this study was to assess the usefulness of electronic medical records for monitoring the incidence of chlamydia cases diagnosed in primary care in the Netherlands. Methods. In the electronic records of two regional and two national networks, we identified chlamydia diagnoses by means of ICPC codes (International Classification of Primary Care), laboratory results in free text and the prescription of antibiotics. The year of study was 2007 for the two regional networks and one national network, for the other national network the year of study was 2005. We calculated the incidence of diagnosed chlamydia cases per sex, age group and degree of urbanization. Results: A large diversity was observed in the way chlamydia episodes were coded in the four different GP networks and how easily information concerning chlamydia diagnoses could be extracted. The overall incidence ranged from 103.2/100,000 to 590.2/100,000. Differences were partly related to differences between patient populations. Nevertheless, we observed similar trends in the incidence of chlamydia diagnoses in all networks and findings were in line with earlier reports. Conclusions: Electronic patient records, originally intended for individual patient care in general practice, can be an additional source of data for monitoring chlamydia incidence in primary care and can be of use in assessing the future impact of population-based chlamydia screening programs. To increase the usefulness of data we recommend more efforts to standardize registration by (specific) ICPC code and laboratory results across the existing GP networks

Genetic characterization of Yug Bogdanovac virus

We present pyrosequencing data and phylogenetic analysis for the full genome of Yug Bogdanovac virus (YBV), a member of the Vesicular stomatitis virus serogroup of the Rhabdoviridae isolated from a pool of Phlebotomus perfiliewi sandflies collected in Serbia in 1976. YBV shows very low nucleotide identities to other members of the Vesicular stomatitis virus serogroup and does not contain a reading frame for C′/C proteins

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures

Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified 80 Pf-transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control