Biology of a widespread uncultivated archaeon that contributes to carbon fixation in the subsurface

Subsurface microbial life contributes significantly to biogeochemical cycling, yet it remains largely uncharacterized, especially its archaeal members. This 'microbial dark matter' has been explored by recent studies that were, however, mostly based on DNA sequence information only. Here, we use diverse techniques including ultrastuctural analyses to link genomics to biology for the SM1 Euryarchaeon lineage, an uncultivated group of subsurface archaea. Phylogenomic analyses reveal this lineage to belong to a widespread group of archaea that we propose to classify as a new euryarchaeal order ('Candidatus Altiarchaeales'). The representative, double-membraned species 'Candidatus Altiarchaeum hamiconexum' has an autotrophic metabolism that uses a not-yet-reported Factor(420)-free reductive acetyl-CoA pathway, confirmed by stable carbon isotopic measurements of archaeal lipids. Our results indicate that this lineage has evolved specific metabolic and structural features like nano-grappling hooks empowering this widely distributed archaeon to predominate anaerobic groundwater, where it may represent an important carbon dioxide sink

From Expert Discipline to Common Practice: A Vision and Research Agenda for Extending the Reach of Enterprise Modeling

The benefits of enterprise modeling (EM) and its contribution to organizational tasks are largely undisputed in business and information systems engineering. EM as a discipline has been around for several decades but is typically performed by a limited number of people in organizations with an affinity to modeling. What is captured in models is only a fragment of what ought to be captured. Thus, this research note argues that EM is far from its maximum potential. Many people develop some kind of model in their local practice without thinking about it consciously. Exploiting the potential of this “grass roots modeling” could lead to groundbreaking innovations. The aim is to investigate integration of the established practices of modeling with local practices of creating and using model-like artifacts of relevance for the overall organization. The paper develops a vision for extending the reach of EM, identifies research areas contributing to the vision and proposes elements of a future research Agenda

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

n/

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Thematization of Alterity in Christa Wolf\u27s \u3cem\u3eNachdenken über Christa T.\u3c/em\u3e

In this article I will attempt to interpret Christa Wolf\u27s novel Nachdenken über Christa T. (Quest for Christa T.) as a thematization of alterity. This concept will allow me to show thematic as well as structural resemblances between Christa Wolf\u27s novel and other contemporary German fiction. I believe that similar traits could be found in other literatures. The Latin American novel — Cortazar\u27s Rayuela (Hopscotch), for example — and the French nouveau roman seem to be characterized by an alteristic narrative strategy. The principle of alterity, however, is not limited in its function to literature and thereby to literary criticism and the didactics of literature. It seems to be operative in many areas of today\u27s wissenschaften and to underlie certain critical stances in psychology, sociology, and philosophy — particularly in epistemology and hermeneutics — to a lesser degree in the natural sciences

Perspectives on Max Frisch

Max Frisch, with his countryman Friederich Diirrenmatt, shares the place of eminence in contemporary Swiss literature. Indeed, he ranks high among the recent leading writers in the German language. But, although several of his works— novels and plays—have been translated into English, he remains little known in America. In this collection of essays an international group of scholars provides a fresh introduction to this noted author. The three leading essays review Frisch\u27s work in the forms he has used most extensively—drama, narrative fiction, and the personal diary. The remaining nine essays focus on specific works or topics. Among the works examined are I\u27m Not Stiller, A Wilderness of Mirrors, Wilhelm Tell, and the recent Man in the Holocene. Among the topics are Frisch\u27s use of language and images, his treatment of women, and the element of parody. Concluding the volume is the most complete bibliography on Frisch to appear in English to date. Gerhard F. Probst is professor of German at Transylvania University and is also on the faculty of the Technische Universitat (West Berlin). Jay F. Bodine is assistant professor in the department of foreign languages and literatures at Southern Illinois University-Carbondale. May be read with profit by the general public and by Frisch Scholars. —German Quarterlyhttps://uknowledge.uky.edu/upk_german_literature/1003/thumbnail.jp

Fatally invasive actinomycosis masquerading as a tonsillar carcinoma.

BACKGROUND Actinomyces is a bacterial rod found in the normal oral flora. It can gain entry to the submucosa via trivial wounds and ultimately lead to slow growing lesions which may mimic cancerous lesions. METHODS AND RESULTS We present the case of an elderly, immunosuppressed woman who presented with a herald bleed from a tonsillar lesion. Despite initial operative arrest of the hemorrhage, she died of a carotid blowout. At autopsy, no sign of cancer was found, but rather an invasive actinomycosis. CONCLUSION Although actinomycosis of the tonsil is well known and has even been described as mimicking tonsillar cancer, this is, to our knowledge, the first report of a carotid blowout secondary to actinomycosis. © 2014 Wiley Periodicals, Inc. Head Neck 36: E129-E130, 2014

Epithelial cyst in the posterior triangle of the neck: atypical branchial cyst or cystic lymph node metastasis?

We report the case of a 66-year-old man with a cervical neck mass located behind the left sternocleidomastoid muscle. To exclude malignancy, a full workup, including clinical, radiological, and cytological examination, was performed but failed to provide a definitive diagnosis. Histological analysis following excisional biopsy revealed a benign epithelial cyst, consistent with an atypically located branchial cyst. We describe an approach to the management of these neck masses and discuss several theories of the etiology of branchial cysts and how they may come to be abnormally located