ANAC017 coordinates organellar functions and stress responses by reprogramming retrograde signaling

Mitochondria adjust their activities in response to external and internal stimuli to optimize growth via the mitochondrial retrograde response (MRR) signaling pathway. The Arabidopsis (Arabidopsis thaliana) NAC domain transcription factor ANAC017 has previously been identified as a regulator of the MRR. We show here that overexpression of ANAC017 in Arabidopsis leads to growth retardation, altered leaf development with decreased cell size and viability, and early leaf senescence. RNA-seq analyses revealed increased ANAC017 expression leads to higher expression of genes related to mitochondrial stress, cell death/autophagy, and leaf senescence under non-limiting growth conditions, as well as extensive repression of chloroplast function. Gene regulatory network analysis indicated that a complex hierarchy of transcription factors exists downstream of ANAC017. These involve a set of up-regulated ANAC and WRKY transcription factors associated with organellar signaling and senescence. The network also includes a number of ethylene- and gibberellic acid-related transcription factors with established function in stress responses and growth regulation, which down-regulate their target genes. A number of BASIC LEUCINE-ZIPPER MOTIF transcription factors involved in the endoplasmic reticulum unfolded protein response or balancing of energy homeostasis via the SNF1-RELATED PROTEIN KINASE1 were also down-regulated by ANAC017 overexpression. Our results show that the endoplasmic reticulum membrane-tethering of the constitutively expressed ANAC017, and its controlled release, are crucial to fine-tune a fast reactive but potentially harmful signaling cascade. Thus, ANAC017 is a master regulator of cellular responses with mitochondria acting as central sensors

Airborne LiDAR and stereo-photogrammetric characterization of permafrost landscapes and thaw subsidence

Rapid climate change in the northern high latitudes has a strong impact on permafrost stability, apparent as coastal erosion, subsidence, or lake dynamics with potentially severe consequences for local communities and ecology. In a rapidly warming Arctic, the monitoring of these processes is essential to understand and predict permafrost dynamics over the upcoming decades. These landscape dynamics are highly diverse, localized, but widely distributed and require datasets with very high spatial resolution, which are barely achieved by satellite data alone. Repeat observations over several years allow for unprecedented insights into highly critical landscape dynamics and the potential integration with and validation of more coarse resolution satellite data. AWI’s research aircraft (Polar-5 and Polar-6) were equipped with airborne LiDAR (full-waveform, multi-echo) as well with experimental modular sensors such as the DLR-developed multi-spectral optical Modular Airborne Camera System (MACS) with a spatial resolution of few cm, stereo capabilities and a very broad radiometric range. The incoming data stream of acquired laser return point cloud data as well as hundreds of thousands of high-resolution images for individual campaigns poses new challenges of handling and processing large data volumes. Here we present an overview about past and upcoming flight campaigns in Alaska and northwestern Canada. Furthermore, we will show applications of the acquired datasets, such as assessments of subsidence, coastal erosion or infrastructure development

Fludarabine modulates composition and function of the T cell pool in patients with chronic lymphocytic leukaemia

The combination of cytotoxic treatment with strategies for immune activation represents an attractive strategy for tumour therapy. Following reduction of high tumour burden by effective cytotoxic agents, two major immune-stimulating approaches are being pursued. First, innate immunity can be activated by monoclonal antibodies triggering antibody-dependent cellular cytotoxicity. Second, tumour-specific T cell responses can be generated by immunization of patients with peptides derived from tumour antigens and infused in soluble form or loaded onto dendritic cells. The choice of cytotoxic agents for such combinatory regimens is crucial since most substances such as fludarabine are considered immunosuppressive while others such as cyclophosphamide can have immunostimulatory activity. We tested in this study whether fludarabine and/or cyclophosphamide, which represent a very effective treatment regimen for chronic lymphocytic leukaemia, would interfere with a therapeutic strategy of T cell activation. Analysis of peripheral blood samples from patients prior and during fludarabine/cyclophosphamide therapy revealed rapid and sustained reduction of tumour cells but also of CD4+ and CD8+ T cells. This correlated with a significant cytotoxic activity of fludarabine/cyclophosphamide on T cells in vitro. Unexpectedly, T cells surviving fludarabine/cyclophosphamide treatment in vitro had a more mature phenotype, while fludarabine-treated T cells were significantly more responsive to mitogenic stimulation than their untreated counterparts and showed a shift towards TH1 cytokine secretion. In conclusion, fludarabine/cyclophosphamide therapy though inducing significant and relevant T cell depletion seems to generate a micromilieu suitable for subsequent T cell activation

Bone suppression increases the visibility of invasive pulmonary aspergillosis in chest radiographs

Objective: Chest radiographs (CXR) are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA) in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA. Methods: The frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies). The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs) and 132 normal cases (or lungs). For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0-100). The area under the receiver operating characteristics curve (AUC) served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive. Results: The average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01). Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%. Conclusion: The detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity

Metal-Substituted Microporous Aluminophosphates

This chapter aims to present the zeotypes aluminophosphates (AlPOs) as a complementary alternative to zeolites in the isomorphic incorporation of metal ions within all-inorganic microporous frameworks as well as to discuss didactically the catalytic consequences derived from the distinctive features of both frameworks. It does not intend to be a compilation of either all or the most significant publications involving metal-substituted microporous aluminophosphates. Families of AlPOs and zeolites, which include metal ion-substituted variants, are the dominant microporous materials. Both these systems are widely used as catalysts, in particular through aliovalent metal ions substitution. Here, some general description of the synthesis procedures and characterization techniques of the MeAPOs (metal-contained aluminophosphates) is given along with catalytic properties. Next, some illustrative examples of the catalytic possibilities of MeAPOs as catalysts in the transformation of the organic molecules are given. The oxidation of the hardly activated hydrocarbons has probably been the most successful use of AlPOs doped with the divalent transition metal ions Co2+, Mn2+, and Fe2+, whose incorporation in zeolites is disfavoured. The catalytic role of these MeAPOs is rationalized based on the knowledge acquired from a combination of the most advanced characterization techniques. Finally, the importance of the high specificity of the structure-directing agents employed in the preparation of MeAPOs is discussed taking N,N-methyldicyclohexylamine in the synthesis of AFI-structured materials as a driving force. It is shown how such a high specificity could be predicted and how it can open great possibilities in the control of parameters as critical in catalysis as crystal size, inter-and intracrystalline mesoporosity, acidity, redox properties, incorporation of a great variety of heteroatom ions or final environment of the metal site (surrounding it by either P or Al)

Gelingendes Leben - Krise als Chance für Person & Gesellschaft. Band II

• Peter Antes, Rel.wiss. • Petra Bahr, Theol. / Journ. • Matthias Beck Med./JS, AT • Gottfried Biewer, Bildungswiss., AT • Aladin El-Mafaalani, Pol.wiss.• Johannes Eurich, Diak.wiss. • Mario Feigel, Med. CH • Heike Gramkow, Manag.Dir. • Heinrich Greving, Heilpäd. • Udo Hahn, Theol.• Maria-C. Hallwachs, Stud., Beratg. schon betroffen • Walter Hirche, Min. a.D./Präs. Dt. UNESCO • Wolfgang Jantzen †, Soz. • Jochen-C. Kaiser, Hist. • Karl-J. Kemmelmeyer, Präs. Musikrat • Hermes Kick, Med.-Ethik • Waldemar Kippes Redemptorist JN • Ferdinand Klein, SoPäd., SK • Berthold Krüger, bpb • Christian Larsen, Arzt, CH • Ulrich Lilie Präs. Diak.W • Christian Lindmeier, SoPäd., DGfE • Ralf Meister, Bischof • Bertolt Meyer, Org.- u. Wirtschaftspsych, schon betroffen, CH • Peter Neher, Präs. Caritas • Ekkehard Nuissl, Dir. Dt. Inst. EB, DIE • Ulrich Pohl, Vorst. Bethel • Hartmann Römer, Physiker • David Roth, Lt. Hospiz • Hartmut Schlegel SoPäd. • Joachim Schoss, Unternehmer, schon betroffen, CH • Walter Surböck Med., AT• Karl-H. Steinmetz, Trad. Europ. Med., AT • Rudolf Tippelt, Bildg. Forschg. • Inge Wasserberg, Inklu.Beratg. • Walter Thirring †, Phys. CERN, C

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination