Incorporation of Multiple Sources into IT - and Data Protection Concepts: Lessons Learned from the FARKOR Project

The IT- and data protection concept of the FAmiliäres Risiko für das KOloRektale Karzinom (FARKOR) project will be presented. FARKOR is a risk adapted screening-project in Bavaria, Germany focusing on young adults with familial colorectal cancer (CRC). For each participant, data from different sources have to be integrated: Treatment records centrally administered by the resident doctors association (KVB), data from health insurance companies (HIC), and patient reported lifestyle data. Patient privacy rights must be observed. Record Linkage is performed by a central independent trust center. Data are decrypted, integrated and analyzed in a secure part of the scientific evaluation center with no connection to the internet (SECSP). The presented concept guarantees participants privacy through different identifiers, separation of responsibilities, data pseudonymization, public-private key encryption of medical data and encrypted data transfer

Drug-induced eRF1 degradation promotes readthrough and reveals a new branch of ribosome quality control.

Suppression of premature termination codons (PTCs) by translational readthrough is a promising strategy to treat a wide variety of severe genetic diseases caused by nonsense mutations. Here, we present two potent readthrough promoters-NVS1.1 and NVS2.1-that restore substantial levels of functional full-length CFTR and IDUA proteins in disease models for cystic fibrosis and Hurler syndrome, respectively. In contrast to other readthrough promoters that affect stop codon decoding, the NVS compounds stimulate PTC suppression by triggering rapid proteasomal degradation of the translation termination factor eRF1. Our results show that this occurs by trapping eRF1 in the terminating ribosome, causing ribosome stalls and subsequent ribosome collisions, and activating a branch of the ribosome-associated quality control network, which involves the translational stress sensor GCN1 and the catalytic activity of the E3 ubiquitin ligases RNF14 and RNF25

Analysis of differences and commonalities in wildlife hunting across the Africa-Europe South-North gradient

Hunting and its impacts on wildlife are typically studied regionally, with a particular focus on the Global South. Hunting can, however, also undermine rewilding efforts or threaten wildlife in the Global North. Little is known about how hunting manifests under varying socioeconomic and ecological contexts across the Global South and North. Herein, we examined differences and commonalities in hunting characteristics across an exemplary Global South-North gradient approximated by the Human Development Index (HDI) using face-to-face interviews with 114 protected area (PA) managers in 25 African and European countries. Generally, we observed that hunting ranges from the illegal, economically motivated, and unsustainable hunting of herbivores in the South to the legal, socially and ecologically motivated hunting of ungulates within parks and the illegal hunting of mainly predators outside parks in the North. Commonalities across this Africa-Europe South-North gradient included increased conflict-related killings in human-dominated landscapes and decreased illegal hunting with beneficial community conditions, such as mutual trust resulting from community involvement in PA management. Nevertheless, local conditions cannot outweigh the strong effect of the HDI on unsustainable hunting. Our findings highlight regional challenges that require collaborative, integrative efforts in wildlife conservation across actors, while identified commonalities may outline universal mechanisms for achieving this goal.publishedVersio

The Arabidopsis cytochrome P450 CYP86A1 encodes a fatty acid ω-hydroxylase involved in suberin monomer biosynthesis

The lipophilic biopolyester suberin forms important boundaries to protect the plant from its surrounding environment or to separate different tissues within the plant. In roots, suberin can be found in the cell walls of the endodermis and the hypodermis or periderm. Apoplastic barriers composed of suberin accomplish the challenge to restrict water and nutrient loss and prevent the invasion of pathogens. Despite the physiological importance of suberin and the knowledge of the suberin composition of many plants, very little is known about its biosynthesis and the genes involved. Here, a detailed analysis of the Arabidopsis aliphatic suberin in roots at different developmental stages is presented. This study demonstrates some variability in suberin amount and composition along the root axis and indicates the importance of ω-hydroxylation for suberin biosynthesis. Using reverse genetics, the cytochrome P450 fatty acid ω-hydroxylase CYP86A1 (At5g58860) has been identified as a key enzyme for aliphatic root suberin biosynthesis in Arabidopsis. The corresponding horst mutants show a substantial reduction in ω-hydroxyacids with a chain length <C20, demonstrating that CYP86A1 functions as a hydroxylase of root suberized tissue. Detailed expression studies revealed a strong root specificity and a localized expression in the root endodermis. Transgenic expression of CYP86A1 fused to GFP distributed CYP86A1 to the endoplasmic reticulum, indicating that suberin monomer biosynthesis takes place in this sub-cellular compartment before intermediates are exported in the apoplast

Characterisation and expression of calpain family members in relation to nutritional status, diet composition and flesh texture in gilthead sea bream (Sparus aurata).

Calpains are non-lysosomal calcium-activated neutral proteases involved in a wide range of cellular processes including muscle proteolysis linked to post-mortem flesh softening. The aims of this study were (a) to characterise several members of the calpain system in gilthead sea bream and (b) to examine their expression in relation to nutritional status and muscle tenderisation. We identified the complete open reading frame of gilthead sea bream calpains1-3, sacapn1, sacapn2, sacapn3, and two paralogs of the calpain small subunit1, sacapns1a and sacapns1b. Proteins showed 63-90% sequence identity compared with sequences from mammals and other teleost fishes, and the characteristic domain structure of vertebrate calpains. Transcripts of sacapn1, sacapn2, sacapns1a and sacapns1b had a wide tissue distribution, whereas sacapn3 was almost exclusively detected in skeletal muscle. Next, we assessed transcript expression in skeletal muscle following alteration of nutritional status by (a) fasting and re-feeding or (b) feeding four experimental diets with different carbohydrate-to-protein ratios. Fasting significantly reduced plasma glucose and increased free fatty acids and triglycerides, together with a significant increase in sacapns1b expression. Following 7 days of re-feeding, plasma parameters returned to fed values and sacapn1, sacapn2, sacapns1a and sacapns1b expression was significantly reduced. Furthermore, an increase in dietary carbohydrate content (11 to 39%) diminished growth but increased muscle texture, which showed a significant correlation with decreased sacapn1 and sacapns1a expression, whilst the other calpains remained unaffected. This study has demonstrated that calpain expression is modulated by nutritional status and diet composition in gilthead sea bream, and that the expression of several calpain members is correlated with muscle texture, indicating their potential use as molecular markers for flesh quality in aquaculture production

Clientside Pseudonymization with Trusted Third-Party Using Modern Web Technology

There is a demand for a pseudonymization service by a Trusted Third Party (TTP), that features clientside pseudonymization. We propose a system using modern web technology, which requires no installation but can handle data preprocessing and pseudonymization safely on the client

Student and preceptor perceptions of primary health care clinical placements during pre-service education: Qualitative results from a quasi-experimental study

As a practice discipline, nursing education has a mandate to collaborate with all clinical settings, including primary health care (PHC), to prepare nursing students to function effectively in different settings upon deployment. Prior to 2011, nursing and midwifery students received minimal exposure to PHC settings in Lesotho. In 2010, the Maternal and Child Health Integrated Program began working with nurses' training institutions to support PHC clinical placements. Between April 2013 and June 2014, a multi-methods study was conducted to describe the effect of PHC placements on students and preceptors. The study employed qualitative methods, namely seven focus group discussions (FGDs), held with 69 students and preceptors. Data analysis followed the principles of grounded theory. Students, nurse educators and preceptors perceived PHC clinical placements as appropriate settings for acquisition of a variety of country relevant clinical experiences for nurses and midwives in Lesotho. Students expressed their likelihood to accept deployment at PHC settings post-graduation. Preceptors indicated that PHC clinical placements re-enforced the importance of continuing education for practicing clinicians. The placements supported an increase in competence and confidence of nursing and midwifery students, which will likely aid their transition into the workforce and perhaps increase the likelihood for the young professionals to accept deployment to these areas post-graduation. Given the disease burden in Lesotho and that majority of Basotho people access healthcare at the PHC level, every effort should be taken to ensure that nursing and midwifery students get adequate exposure to health care provision at these facilities

Genome comparison of the epiphytic bacteria <it>Erwinia billingiae </it>and <it>E. tasmaniensis </it>with the pear pathogen <it>E. pyrifoliae</it>

<p>Abstract</p> <p>Background</p> <p>The genus <it>Erwinia </it>includes plant-associated pathogenic and non-pathogenic <it>Enterobacteria</it>. Important pathogens such as <it>Erwinia amylovora</it>, the causative agent of fire blight and <it>E. pyrifoliae </it>causing bacterial shoot blight of pear in Asia belong to this genus. The species <it>E. tasmaniensis </it>and <it>E. billingiae </it>are epiphytic bacteria and may represent antagonists for biocontrol of fire blight. The presence of genes that are putatively involved in virulence in <it>E. amylovora </it>and <it>E. pyrifoliae </it>is of special interest for these species in consequence.</p> <p>Results</p> <p>Here we provide the complete genome sequences of the pathogenic <it>E. pyrifoliae </it>strain Ep1/96 with a size of 4.1 Mb and of the non-pathogenic species <it>E. billingiae </it>strain Eb661 with a size of 5.4 Mb, <it>de novo </it>determined by conventional Sanger sequencing and next generation sequencing techniques. Genome comparison reveals large inversions resulting from homologous recombination events. Furthermore, comparison of deduced proteins highlights a relation of <it>E. billingiae </it>strain Eb661 to <it>E. tasmaniensis </it>strain Et1/99 and a distance to <it>E. pyrifoliae </it>for the overall gene content as well as for the presence of encoded proteins representing virulence factors for the pathogenic species. Pathogenicity of <it>E. pyrifoliae </it>is supposed to have evolved by accumulation of potential virulence factors. <it>E. pyrifoliae </it>carries factors for type III secretion and cell invasion. Other genes described as virulence factors for <it>E. amylovora </it>are involved in the production of exopolysaccharides, the utilization of plant metabolites such as sorbitol and sucrose. Some virulence-associated genes of the pathogenic species are present in <it>E. tasmaniensis </it>but mostly absent in <it>E. billingiae</it>.</p> <p>Conclusion</p> <p>The data of the genome analyses correspond to the pathogenic lifestyle of <it>E. pyrifoliae </it>and underlines the epiphytic localization of <it>E. tasmaniensis </it>and <it>E. billingiae </it>as a saprophyte<it/>.</p

Differentiation and visualization of diverse cellular phenotypic responses in primary high-content screening

High throughput screening based on sub-cellular imaging has become a powerful tool in lead discovery. Through the generation of high quality images not only the specific target signal can be analyzed but also phenotypic changes of the whole cell are recorded. Yet analysis strategies for the exploration of high content screening results in a manner that is independent on predefined control phenotypes are largely missing. The approach presented here is based on a modeling technique, self-organizing maps (SOMs), which utilizes multi-parametric results by grouping treatments that create similar morphological effects. As a new way to visualize the results each node is represented with an image highlighting the representative cell phenotype. The approach has the potential to identify both expected hits as well as novel cell phenotypes. Moreover, different compound chemotypes, which cause the same phenotypic effects, are identified facilitating “scaffold hopping”