LitDB - Keeping Track of Research Papers From Your Institute Made Simple.

BACKGROUND: In science peer-reviewed publications serve as an important indicator of scientific excellence and productivity. Therefore, every scientist and institution must carefully maintain and update records of their scientific publications. However, in most institutions and universities articles are often managed in a redundant file-based and non-central way. Whereas excellent reference management software packages such as Zotero, Endnote or Mendeley exist to manage bibliographies and references when writing scientific articles, we are not aware of any open source database solution keeping track of publication records from large scientific groups, entire institutions and/or universities. RESULTS: We here describe LitDB, a novel open source literature database solution for easy maintenance of publication lists assigned to various topics. In the last 2 years more than 50 users have been using LitDB at our research institute. The LitDB system is accessed via a web browser. Publications can be uploaded through direct exports from reference manager libraries or by entering PubMed IDs. Single users or user groups can track their citation counts, h-index and impact factor statistics and gain insights into the publication records of other users. It offers various visualization functions like coauthor networks and provides ways to organize publications from dedicated projects and user groups. The latter is in particular beneficial to manage publication lists of large research groups and research initiatives through a "crowd-sourcing" effort. CONCLUSIONS: Keeping track of papers authored and published by a research group, institute or university is an important and non-trivial task. By using a centralized web-based platform for publication management such as LitDB the compilation of project- and group-related publication lists becomes easily manageable and it is less likely that papers are forgotten along the way.

Vy-PER: eliminating false positive detection of virus integration events in next generation sequencing data.

Several pathogenic viruses such as hepatitis B and human immunodeficiency viruses may integrate into the host genome. These virus/host integrations are detectable using paired-end next generation sequencing. However, the low number of expected true virus integrations may be difficult to distinguish from the noise of many false positive candidates. Here, we propose a novel filtering approach that increases specificity without compromising sensitivity for virus/host chimera detection. Our detection pipeline termed Vy-PER (Virus integration detection bY Paired End Reads) outperforms existing similar tools in speed and accuracy. We analysed whole genome data from childhood acute lymphoblastic leukemia (ALL), which is characterised by genomic rearrangements and usually associated with radiation exposure. This analysis was motivated by the recently reported virus integrations at genomic rearrangement sites and association with chromosomal instability in liver cancer. However, as expected, our analysis of 20 tumour and matched germline genomes from ALL patients finds no significant evidence for integrations by known viruses. Nevertheless, our method eliminates 12,800 false positives per genome (80× coverage) and only our method detects singleton human-phiX174-chimeras caused by optical errors of the Illumina HiSeq platform. This high accuracy is useful for detecting low virus integration levels as well as non-integrated viruses.

Initial symbiont contact orchestrates host-organ-wide transcriptional changes that prime tissue colonization.

Upon transit to colonization sites, bacteria often experience critical priming that prepares them for subsequent, specific interactions with the host; however, the underlying mechanisms are poorly described. During initiation of the symbiosis between the bacterium Vibrio fischeri and its squid host, which can be observed directly and in real time, approximately five V. fischeri cells aggregate along the mucociliary membranes of a superficial epithelium prior to entering host tissues. Here, we show that these few early host-associated symbionts specifically induce robust changes in host gene expression that are critical to subsequent colonization steps. This exquisitely sensitive response to the host's specific symbiotic partner includes the upregulation of a host endochitinase, whose activity hydrolyzes polymeric chitin in the mucus into chitobiose, thereby priming the symbiont and also producing a chemoattractant gradient that promotes V. fischeri migration into host tissues. Thus, the host responds transcriptionally upon initial symbiont contact, which facilitates subsequent colonization.

RNAi screening identifies mediators of NOD2 signaling: implications for spatial specificity of MDP recognition.

The intracellular nucleotide-binding oligomerization domain-2 (NOD2) receptor detects bacteria-derived muramyl dipeptide (MDP) and activates the transcription factor NF-κB. Here we describe the regulatome of NOD2 signaling using a systematic RNAi screen. Using three consecutive screens, we identified a set of 20 positive NF-κB regulators including the known pathway members RIPK2, RELA, and BIRC4 (XIAP) as well as FRMPD2 (FERM and PDZ domain-containing 2). FRMPD2 interacts with NOD2 via leucine-rich repeats and forms a complex with the membrane-associated protein ERBB2IP. We demonstrate that FRMPD2 spatially assembles the NOD2-signaling complex, hereby restricting NOD2-mediated immune responses to the basolateral compartment of polarized intestinal epithelial cells. We show that genetic truncation of the NOD2 leucine-rich repeat domain, which is associated with Crohn disease, impairs the interaction with FRMPD2, and that intestinal inflammation leads to down-regulation of FRMPD2. These results suggest a structural mechanism for how polarity of epithelial cells acts on intestinal NOD-like receptor signaling to mediate spatial specificity of bacterial recognition and control of immune responses.

Gene expression and physiological changes of different populations of the long-lived bivalve Arctica islandica under low oxygen conditions.

The bivalve Arctica islandica is extremely long lived (>400 years) and can tolerate long periods of hypoxia and anoxia. European populations differ in maximum life spans (MLSP) from 40 years in the Baltic to >400 years around Iceland. Characteristic behavior of A. islandica involves phases of metabolic rate depression (MRD) during which the animals burry into the sediment for several days. During these phases the shell water oxygen concentrations reaches hypoxic to anoxic levels, which possibly support the long life span of some populations. We investigated gene regulation in A. islandica from a long-lived (MLSP 150 years) German Bight population and the short-lived Baltic Sea population, experimentally exposed to different oxygen levels. A new A. islandica transcriptome enabled the identification of genes important during hypoxia/anoxia events and, more generally, gene mining for putative stress response and (anti-) aging genes. Expression changes of a) antioxidant defense: Catalase, Glutathione peroxidase, manganese and copper-zinc Superoxide dismutase; b) oxygen sensing and general stress response: Hypoxia inducible factor alpha, Prolyl hydroxylase and Heat-shock protein 70; and c) anaerobic capacity: Malate dehydrogenase and Octopine dehydrogenase, related transcripts were investigated. Exposed to low oxygen, German Bight individuals suppressed transcription of all investigated genes, whereas Baltic Sea bivalves enhanced gene transcription under anoxic incubation (0 kPa) and, further, decreased these transcription levels again during 6 h of re-oxygenation. Hypoxic and anoxic exposure and subsequent re-oxygenation in Baltic Sea animals did not lead to increased protein oxidation or induction of apoptosis, emphasizing considerable hypoxia/re-oxygenation tolerance in this species. The data suggest that the energy saving effect of MRD may not be an attribute of Baltic Sea A. islandica chronically exposed to high environmental variability (oxygenation, temperature, salinity). Contrary, higher physiological flexibility and stress hardening may predispose these animals to perform a pronounced stress response at the expense of life span.

Genome and low-iron response of an oceanic diatom adapted to chronic iron limitation.

BACKGROUND: Biogeochemical elemental cycling is driven by primary production of biomass via phototrophic phytoplankton growth, with 40% of marine productivity being assigned to diatoms. Phytoplankton growth is widely limited by the availability of iron, an essential component of the photosynthetic apparatus. The oceanic diatom Thalassiosira oceanica shows a remarkable tolerance to low-iron conditions and was chosen as a model for deciphering the cellular response upon shortage of this essential micronutrient. RESULTS: The combined efforts in genomics, transcriptomics and proteomics reveal an unexpected metabolic flexibility in response to iron availability for T. oceanica CCMP1005. The complex response comprises cellular retrenchment as well as remodeling of bioenergetic pathways, where the abundance of iron-rich photosynthetic proteins is lowered, whereas iron-rich mitochondrial proteins are preserved. As a consequence of iron deprivation, the photosynthetic machinery undergoes a remodeling to adjust the light energy utilization with the overall decrease in photosynthetic electron transfer complexes. CONCLUSIONS: Beneficial adaptations to low-iron environments include strategies to lower the cellular iron requirements and to enhance iron uptake. A novel contribution enhancing iron economy of phototrophic growth is observed with the iron-regulated substitution of three metal-containing fructose-bisphosphate aldolases involved in metabolic conversion of carbohydrates for enzymes that do not contain metals. Further, our data identify candidate components of a high-affinity iron-uptake system, with several of the involved genes and domains originating from duplication events. A high genomic plasticity, as seen from the fraction of genes acquired through horizontal gene transfer, provides the platform for these complex adaptations to a low-iron world.

Massively parallel RNA sequencing identifies a complex immune gene repertoire in the lophotrochozoan Mytilus edulis.

The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus.

Core curriculum for the heart rhythm specialist: executive summary.

Heart rhythm (HR) management is rapidly developing as a subspecialty within cardiology, and it is imperative to promote and ensure sufficient and homogeneous training and qualification amongst professionals in Europe. This has led the European Society of Cardiology, through the European Heart Rhythm Association (EHRA), to organize a European Core Curriculum for the HR specialist through the following: definition of the scope of the HR speciality (Syllabus), development of minimum standards and objectives for training in HR management (Curriculum), development of a model to certify HR professionals and teaching units (Accreditation), and development of a Registry for European HR accredited professionals and teaching units and its activity (Registries). The duration of the training period should be of a minimum of 2 years following general cardiology training. During this period, the trainee must develop the required knowledge, practical skills, behaviours, and attitudes to manage HR patients. The trainee must be involved in a minimum number of different procedures and achieve specified levels of competence. The training centre should be integrated within a full-service cardiology department. Assessment of the trainee and the training programmes should include reports by the training programme supervisor and the national society HR organizations, a logbook of procedures, written examinations, and assessment of professionalism. The EHRA presently requires the trainee to pass the EHRA accreditation exams (invasive EP and cardiac pacing and ICDs). Continuous learning and practice are required to maintain standards and practice and because substantial changes may occur in clinical practice or the health-care environment.

Core curriculum for the heart rhythm specialist.

Heart rhythm (HR) management is rapidly developing as a subspecialty within cardiology and it is imperative to promote and ensure sufficient and homogeneous training and qualification among professionals in Europe. This encouraged the European Society of Cardiology, through the European Heart Rhythm Association (EHRA), to organize a European Core Curriculum for the HR specialist through the following: definition of the scope of the HR speciality (Syllabus), development of minimum standards and objectives for training in HR management (Curriculum), development of a model to certify HR professionals and teaching units (Accreditation), and development of a Registry for European HR accredited professionals and teaching units and their activity (Registries). The duration of the training period should be of a minimum of 2 years following general cardiology training. During this period, the trainee must develop the required knowledge, practical skills, behaviours, and attitudes to manage HR patients. The trainee must be involved in a minimum number of different procedures and achieve specified levels of competence. The training centre should be integrated within a full-service cardiology department. Assessment of the trainee and the training programmes should include reports by the training programme supervisor and the national society HR organizations, a logbook of procedures, written examinations, and assessment of professionalism. The EHRA presently requires the trainee to pass the EHRA accreditation exams (invasive EP and cardiac pacing and ICDs). Continuous learning and practice are required to maintain standards and practice because substantial changes may occur in clinical practice or the health-care environment.

STAMP: Extensions to the STADEN sequence analysis package for high throughput interactive microsatellite marker design.

BACKGROUND: Microsatellites (MSs) are DNA markers with high analytical power, which are widely used in population genetics, genetic mapping, and forensic studies. Currently available software solutions for high-throughput MS design (i) have shortcomings in detecting and distinguishing imperfect and perfect MSs, (ii) lack often necessary interactive design steps, and (iii) do not allow for the development of primers for multiplex amplifications. We present a set of new tools implemented as extensions to the STADEN package, which provides the backbone functionality for flexible sequence analysis workflows. The possibility to assemble overlapping reads into unique contigs (provided by the base functionality of the STADEN package) is important to avoid developing redundant markers, a feature missing from most other similar tools. RESULTS: Our extensions to the STADEN package provide the following functionality to facilitate microsatellite (and also minisatellite) marker design: The new modules (i) integrate the state-of-the-art tandem repeat detection and analysis software PHOBOS into workflows, (ii) provide two separate repeat detection steps - with different search criteria - one for masking repetitive regions during assembly of sequencing reads and the other for designing repeat-flanking primers for MS candidate loci, (iii) incorporate the widely used primer design program PRIMER3 into STADEN workflows, enabling the interactive design and visualization of flanking primers for microsatellites, and (iv) provide the functionality to find optimal locus- and primer pair combinations for multiplex primer design. Furthermore, our extensions include a module for storing analysis results in an SQLite database, providing a transparent solution for data access from within as well as from outside of the STADEN Package. CONCLUSION: The STADEN package is enhanced by our modules into a highly flexible, high-throughput, interactive tool for conventional and multiplex microsatellite marker design. It gives the user detailed control over the workflow, enabling flexible combinations of manual and automated analysis steps. The software is available under the OpenBSD License 12. The high efficiency of our automated marker design workflow has been confirmed in three microsatellite development projects.