Functional relevance of novel p300-mediated lysine 314 and 315 acetylation of RelA/p65

Nuclear factor kappaB (NF-κB) plays an important role in the transcriptional regulation of genes involved in immunity and cell survival. We show here in vitro and in vivo acetylation of RelA/p65 by p300 on lysine 314 and 315, two novel acetylation sites. Additionally, we confirmed the acetylation on lysine 310 shown previously. Genetic complementation of RelA/p65−/− cells with wild type and non-acetylatable mutants of RelA/p65 (K314R and K315R) revealed that neither shuttling, DNA binding nor the induction of anti-apoptotic genes by tumor necrosis factor α was affected by acetylation on these residues. Microarray analysis of these cells treated with TNFα identified specific sets of genes differently regulated by wild type or acetylation-deficient mutants of RelA/p65. Specific genes were either stimulated or repressed by the acetylation-deficient mutants when compared to RelA/p65 wild type. These results support the hypothesis that site-specific p300-mediated acetylation of RelA/p65 regulates the specificity of NF-κB dependent gene expression

Inflammation-associated Cell Cycle–independent Block of Apoptosis by Survivin in Terminally Differentiated Neutrophils

Survivin has received great attention due to its expression in many human tumors and its potential as a therapeutic target in cancer. Survivin expression has been described to be cell cycle–dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells. In agreement with this current view, we found that survivin expression was high in immature neutrophils, which proliferate during differentiation. In contrast with immature cells, mature neutrophils contained only little or no survivin protein. Strikingly, these cells reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF) or granulocyte CSF stimulation in vitro and under inflammatory conditions in vivo. Moreover, survivin-deficient mature neutrophils were unable to increase their lifespan after survival factor exposure. Together, our findings demonstrate the following: (a) overexpression of survivin occurs in primary, even terminally differentiated cells and is not restricted to proliferating cells; and (b) survivin acts as an inhibitor of apoptosis protein in a cell cycle–independent manner. Therefore, survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells. These data provide new insights into the regulation and function of survivin and have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases and cancer

Seniors, and their food handlers and caregivers, need food safety and nutrition education

Seniors are at greater risk than other adults for foodborne illness, poor nutrition and high rates of nutrition- and lifestyle-related chronic diseases. They also represent a major underserved segment of the UC Cooperative Extension client population. The Make Food Safe for Seniors (MFSFS) initiative assessed food safety and nutrition education needs of fixed-income seniors and food handlers and caregivers serving seniors in 10 California counties. Baseline survey results found unsafe practices by over 50% of the participants in six areas - and by over 65% of participants in three of those areas. After one food safety training, a post-test showed an average knowledge gain of 18.1%; seniors had gained the least knowledge, food handlers had gained some knowledge, and caregivers had gained the most. The unsafe food handling practices of a majority of the study group, as well as poor food behaviors, suggested areas in which education could reinforce or improve food safety, healthy eating and disease prevention practices of seniors, caregivers and food handlers serving seniors

Complete Genome Sequence of Francisella tularensis Subspecies holarctica FTNF002-00

Francisella tularensis subspecies holarctica FTNF002-00 strain was originally obtained from the first known clinical case of bacteremic F. tularensis pneumonia in Southern Europe isolated from an immunocompetent individual. The FTNF002-00 complete genome contains the RD23 deletion and represents a type strain for a clonal population from the first epidemic tularemia outbreak in Spain between 1997–1998. Here, we present the complete sequence analysis of the FTNF002-00 genome. The complete genome sequence of FTNF002-00 revealed several large as well as small genomic differences with respect to two other published complete genome sequences of F. tularensis subsp. holarctica strains, LVS and OSU18. The FTNF002-00 genome shares >99.9% sequence similarity with LVS and OSU18, and is also ∼5 MB smaller by comparison. The overall organization of the FTNF002-00 genome is remarkably identical to those of LVS and OSU18, except for a single 3.9 kb inversion in FTNF002-00. Twelve regions of difference ranging from 0.1–1.5 kb and forty-two small insertions and deletions were identified in a comparative analysis of FTNF002-00, LVS, and OSU18 genomes. Two small deletions appear to inactivate two genes in FTNF002-00 causing them to become pseudogenes; the intact genes encode a protein of unknown function and a drug:H+ antiporter. In addition, we identified ninety-nine proteins in FTNF002-00 containing amino acid mutations compared to LVS and OSU18. Several non-conserved amino acid replacements were identified, one of which occurs in the virulence-associated intracellular growth locus subunit D protein. Many of these changes in FTNF002-00 are likely the consequence of direct selection that increases the fitness of this subsp. holarctica clone within its endemic population. Our complete genome sequence analyses lay the foundation for experimental testing of these possibilities

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

Remote sensing applications for deformation monitoring and process analyses of landslides in alpine environment

Hochalpine Regionen reagieren mit Gletscher- und Permafrostrückgang besonders sensibel auf die Erderwärmung. Inwieweit sich klimatische Veränderungen auf die Stabilität von glazialen und periglazialen Hängen und Felsflanken auswirken, ist aufgrund des komplexen Prozessverhaltens von Massenbewegungen schwer abzuschätzen. Ziel der Doktorarbeit ist die Ableitung des Prozessverhaltens von hochalpinen Massenbewegungen aus Bild- und Laserscandaten. Bestehende und neue Methoden werden angewendet und weiterentwickelt um erstens das Bewegungsverhalten von Massenbewegungen der letzten Jahrzehnte zu rekonstruieren und um zweitens die zukünftige Entwicklung von Massenbewegungen zu überwachen. Im Rahmen dieser Arbeit wurden die hochalpinen tiefgründigen Felsgleitungen Bliggspitze und Marzell, sowie ein Blockgletscher im Finstertal untersucht. Die drei Massenbewegungen unterscheiden sich in ihrer Topographie und im Prozessverhalten. Die hier vorgestellten Arbeitsabläufe und Methoden sind auch auf andere Massenbewegungen übertragbar. Im ersten Schritt werden Bild- und Laserscandaten aus nationalen Archiven, Landesarchiven und örtlichen Archiven gesammelt. Für das Monitoring rezenter Bewegungen wurden tragbare Sensoren (terrestrisches Laserscanning und Drohnen-Photogrammetrie), die im hochalpinen Raum ohne das Vorhandensein von Infrastruktur (Wege und Elektrizität) anwendbar sind, verwendet. Die Daten aus den Monitoring-Kampagnen und Archiven wurden aufbereitet und als geo-referenzierte Punktwolke bzw. als Orthofoto in einem gemeinsamen Koordinatensystem zusammengeführt. Für die Untersuchung der Massenbewegungen wurden unterschiedliche Analyseverfahren angewendet. Ein in dieser Arbeit entwickeltes robustes 3D-Distanzmessverfahren auf Basis der Punktwolke wurde für Prozesse mit völliger Zerstörung der Oberfläche (z.B. Felsstürze) genutzt. Für die Untersuchung von Prozessen, bei denen sich die Oberfläche im Ganzen verlagert hat (z.B. Felsgleitung), wurden Verfahren der Bildkorrelation und des Bruchkantentrackings verwendet. Die Verschiebungen und Distanzveränderungen wurden in Karten dargestellt und zusammen mit geologisch-geomorphologischen Informationen aus Geländebegehungen und Geländefotos im Hinblick auf das Prozessverhalten der Massenbewegung interpretiert. Die Interpretation umfasst erstens die Identifikation von unterschiedlichen Prozessen (z.B. Felsgleitungen, Schuttstrome, Blockgletscher, Felsstürze und Steinschlag), zweitens die Abgrenzung von Schollen (Felsgleitung) bzw. Zonen (Blockgletscher) und die Analyse von deren Geometrie und Kinematik sowie drittens die Identifikation von verschieden Bewegungstypen wie z.B. Rotationsgleitungen oder Kippbewegungen. Diese Informationen dienten zur Entwicklung eines geologischen Modells der Massenbewegung. Mit Hilfe der Deformations- und Prozessanalysen konnte gezeigt werden, dass beide Felsgleitungen aus unterschiedlichen Schollen mit unterschiedlichem räumlichen und zeitlichen Bewegungsverhalten bestehen. Bei der Massenbewegung Marzell wurde das Bewegungsverhalten der Felsgleitung und der Gletscherrückgang seit den 1950er rekonstruiert. Eine Korrelation zwischen Gletscherrückgang und erhöhter Aktivität der Massenbewegung ist deutlich erkennbar. Die Aktivität des Blockgletschers Finstertal wurde seit den 1970er rekonstruiert. Seit Ende des letzten Jahrtausends ist eine deutliche Beschleunigung der Blockgletscherbewegung erkennbar. Die Methoden und Arbeitsläufe, die in dieser Studie entwickelt wurden sind ein wesentlicher Beitrag zur Abschätzung des Gefahrenpotentials der Massenbewegung für Infrastruktur, zur Entwicklung von Sicherheitsmaßnahmen sowie zur Erforschung der potentiellen Auslöser von Massenbewegung.In high mountain environment, changing boundary conditions from climate change such as melting glaciers and permafrost retreat influence the stability of alpine soil and rock slopes. Slope deformation processes are complex and a sound understanding is a prerequisite to investigate the impact of changing climatic conditions and to predict the future behaviour as well as to develop safety measures. The thesis aims to exploit all information about landslide deformation behaviour and landslide processes from imagery and laser scanning data which are required to understand past and present landslide evolution. Already existing and new deformation analyses methods are applied, improved and developed with the aim to i) analyse the retrospective landslide development over a longer time period and ii) to analyse the current landslide behaviour by appropriate and ongoing monitoring methods. Laser scanning and imagery data are well suited for this task because the data is available in national, federal and local archives of most Alpine countries and the sensors are applicable for the monitoring campaigns in rough mountain environment with no direct access to infrastructure. In the frame of this study, two active high alpine deep-seated compound rock slides and an active rock glacier were investigated. The three study sites are located in the Eastern Alps, Austria, and differ in their topography as well as process characteristics. For process and deformation analyses, the data from airborne and imaging campaigns was collected and field campaigns with terrestrial laser scanning and UAV were performed. The data from different sources were pre-processed to a geo-referenced point cloud, respectively to a geo-referenced ortho-image and then compiled into a common coordinate reference system. Slope deformation processes with a destruction of the surface, e.g. due to rock fall, were analysed by means of a robust 3D distance measurement approach for point cloud data. Slope processes with en-block displacements (e.g. slides) were analysed by applying an image correlation and breakline tracking technique. The derived distance change and displacement maps, together with information from field surveys and terrestrial photographs, were used for interpretation. This includes i) the identification of different landslide processes (i.e. rock and soil slide displacements, rock fall, rock avalanches, rock glacier creep, debris slides etc.), ii) the delineation of different slabs (rock slide) or zones (rock glacier) and analyses of their activity, geometry and kinematics and iii) the interpretation of the failure mechanism (e.g. toppling or rotational sliding behaviour). The extracted information was used to develop a geological model of the slope deformation. The analyses show that both rock slides are composed of different slabs with different spatial and temporal deformation behaviour. For the ice contacted rock slide, the glacier retreat was reconstructed since the 1950s based on imagery, laser scanning data and historic topographic maps. The results show a correlation between glacier retreat and rock slide activity. The rock glacier deformation behaviour was reconstructed since the 1970s and showed an increase in creep velocity since the end of the last century. The results derived with the methods and workflows developed in this thesis focusing on the kinematics and the geometry of the landslides could serve as input to study the impact of permafrost degradation and glacier retreat on landslides (e.g. by numerical modelling). The results are further an essential contribution to assess the risk in the context of infrastructure, to design safety measures, and to predict the future deformation development.by Christine FeyKumulative Dissertation aus sechs ArtikelnZusammenfassung in deutscher SpracheUniversity of Innsbruck, Dissertation, 2018OeBB(VLID)250896

TLS based snow covered area maps of the Weisssee snow research site (Kaunertal, Austria)

The data set comprises an inter- and intra-annual timeseries of ten high-resolution (0.5 x 0.5 m) binary snow covered area (SCA) maps derived from TLS scans at the Weisssee Snow Research Site in Austria between March 2017 and November 2019. TLS based digital elevation models and difference (snow depth) grids can be downloaded as a separate dataset (Fey et al., 2018; https://doi.org/10.1594/PANGAEA.896843). The binary classification of snow-covered and snow-free areas is based on intensity and snow depth. An intensity threshold of 3000 was defined based on histogram analysis in patchy snowpack conditions. Snow-covered areas were delineated according to TLS based snow depth information. Snow-depth related classifications were based on a threshold value representing the precision of the TLS acquisition represented by the standard deviation of snow-free surfaces (see Fey et al., 2019). The resulting classification was validated with fully snow covered scenes. For the scene of 2017-05-07 two available TLS scans, one with a Riegl VZ-4000 and another with a Riegl VZ-6000 scanner, were combined into one snow covered area map. This was done due to the fact that the VZ-4000 data is better suited for snow cover discrimination based on intensity data, while not providing data on wet snow surfaces in larger distance where the VZ-6000 scanner still provides snow depth observations. The overall coverage of the scan area is identical to the one of the DGM dataset. The SCA dataset comprises three classes: snow-free (0), snow-covered (1) and NoData (-99999). No data areas are caused by obstacles in the field-of-view of the laserscanner. The SCA data can be used for validating remote sensing products including fractional snow coverage from e.g. Landsat and Sentinel-2 as done in the related literature

TLS snow distribution maps of the Weisssee snow research site (Kaunertal, Austria)

The data set comprises the inter- and intra-annual snow depth distribution recorded by TLS scans at Weisssee snow research site in Austria between November 2014 and May 2018. The data set comprises 23 snow-on digital elevation models (DEM), one snow-off DEM, and the difference raster calculated between a snow-off and snow-on scans. The relative accuracy of the TLS scans was determined by measuring the distance between snow-free planes from the snow-on and snow-off scans and shows mean values smaller than 0.03 m and standard deviations ranging between 0.02 and 0.1 m. The reliability of the snow depths derived from TLS was further assessed by comparing snow depths from snow probing, GNSS measurements, and continuous snow depth measurements from the weather station. Comparison of the different measurement methods shows average deviations of less than 0.1 m. The data can be used for analysing snow distributions, or for assessing the representativeness of conventional snow depth sensors. Other use cases include assessing other in-situ sensors like Cosmic-Ray-Neutron Sensors, or space-borne snow-covered area products. More details are described in an article submitted to the Water Resources Research Special Issue: Advances in remote sensing, measurement, and simulation of seasonal snow