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Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. Here, we report that in human cells programmed stop codon readthrough is used to generate peroxisomal isoforms of cytosolic enzymes. We could show for NAD-dependent lactate dehydrogenase B (LDHB) and NAD-dependent malate dehydrogenase 1 (MDH1) that translational readthrough results in C-terminally extended protein variants containing a peroxisomal targeting signal 1 (PTS1). Efficient readthrough occurs at a short sequence motif consisting of a UGA termination codon followed by the dinucleotide CU. Leaky termination at this stop codon context was observed in fungi and mammals. Comparative genome analysis allowed us to identify further readthrough-derived peroxisomal isoforms of metabolic enzymes in diverse model organisms. Overall, our study highlights that a defined stop codon context can trigger efficient ribosomal readthrough to generate dually targeted protein isoforms. We speculate that beyond peroxisomal targeting stop codon readthrough may have also other important biological functions, which remain to be elucidated.
Ähnlich wie in anderen Krieg führenden Ländern war gerade die großstädtische Bevölkerung von Kriegseuphorie und einer spontanen Bereitschaft getragen, sich in den Dienst des Kriegs zu stellen. Das bald auch im Krieg florierende Unterhaltungstheater der meisten europäischen Metropolen zeigte geradezu mustergültig diese patriotisch-affirmative Tendenz. Doch in einem Land wie Portugal, in dem wenige Jahre zuvor durch eine vom städtischen liberalen Bürgertum getragene Revolution eine laizistische Republik nach französischem Vorbild installiert wurde, die noch einigermaßen instabil war, folgte die Unterhaltungskultur nicht dieser Art von patriotischer Gleichschaltung sondern bewahrte sich durchaus – besonders im Genre der Revue – satirische und kritische Eigenheiten.
Carniella brignolii Thaler & Steinberger, 1988 was first described based on a male from Austria and still belongs to the rare, scarcely studied species. Based on material from Germany and Switzerland the hitherto unknown female now can be assigned and presented. In this context a new synonymy is also proposed: The cave-dwelling, troglomorphic C. mihaili (Georgescu, 1989) from Romania, originally established as new genus Marianana, is synonymised with C. brignolii.
The three-dimensional quantification of small scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe and TACTS/ESMVal aircraft campaigns. The focus of this work is on the so-called dynamics mode data characterized by a medium spectral and a very high spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3 and CFC-12) and their spatial resolution are discussed. During ESSenCe, high resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in-situ data indicate a good agreement between the data sets. During TACTS/ESMVal a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere has been performed. This filament could be reconstructed with an unprecedented spatial resolution of better than 500 m vertically and 20 km × 20 km horizontally.
The debate about the Sustainable Development Goals (SDGs), which are to replace the Millennium Development Goals (MDGs) when they expire in 2015, is moving very quickly. Weighing in on this debate, we argue that if the SDGs are to be as effective as they can realistically be, concrete responsibilities must be assigned to specific competent actors, measurement methods involved in development targets must not be allowed to be changed midway, and the tracking of progress must be left to independent experts. New development goals should aim for inequality reduction, a more comprehensive view of poverty, and, most importantly, systemic reforms of global institutions. The world will not make decent progress against poverty until the most powerful agents accept real action commitments, not only in the marginal area of development assistance, but in all their policy and institutional design decisions, at both the domestic and especially the supranational level. We end with eight examples of institutional reform goals – ranging from deterring trade barriers to mitigating the effects of lost corporate tax revenues on poor populations – that should be included in the new list.
Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-α mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol.
Reaction times to previously ignored information are often delayed, a phenomenon referred to as negative priming (NP). Rothermund et al. (2005) proposed that NP is caused by the retrieval of incidental stimulus-response associations when consecutive displays share visual features but require different responses. In two experiments we examined whether the features (color, shape) that reappear in consecutive displays, or their level of processing (early-perceptual, late-semantic) moderate the likelihood that stimulus-response associations are retrieved. Using a perceptual matching task (Experiment 1), NP occurred independently of whether responses were repeated or switched. Only when implementing a semantic-matching task (Experiment 2), negative priming was determined by response-repetition as predicted by response-retrieval theory. The results can be explained in terms of a task-dependent temporal discrimination process (Milliken et al., 1998): Response-relevant features are encoded more strongly and/or are more likely to be retrieved than irrelevant features.
Response to Kriticos et al.
(2014)
Intensive land use is a driving force for biodiversity decline in many ecosystems. In semi-natural grasslands, land-use activities such as mowing, grazing and fertilization affect the diversity of plants and arthropods, but the combined effects of different drivers and the chain of effects are largely unknown. In this study we used structural equation modelling to analyse how the arthropod communities in managed grasslands respond to land use and whether these responses are mediated through changes in resource diversity or resource quantity (biomass). Plants were considered resources for herbivores which themselves were considered resources for predators. Plant and arthropod (herbivores and predators) communities were sampled on 141 meadows, pastures and mown pastures within three regions in Germany in 2008 and 2009. Increasing land-use intensity generally increased plant biomass and decreased plant diversity, mainly through increasing fertilization. Herbivore diversity decreased together with plant diversity but showed no response to changes in plant biomass. Hence, land-use effects on herbivore diversity were mediated through resource diversity rather than quantity. Land-use effects on predator diversity were mediated by both herbivore diversity (resource diversity) and herbivore quantity (herbivore biomass), but indirect effects through resource quantity were stronger. Our findings highlight the importance of assessing both direct and indirect effects of land-use intensity and mode on different trophic levels. In addition to the overall effects, there were subtle differences between the different regions, pointing to the importance of regional land-use specificities. Our study underlines the commonly observed strong effect of grassland land use on biodiversity. It also highlights that mechanistic approaches help us to understand how different land-use modes affect biodiversity.
Background. Depression is the most common type of mental disorder in Germany. It is associated with a high level of suffering for individuals and imposes a significant burden on society. The aim of this study was to estimate the depression related costs in Germany taking a societal perspective.
Materials and Methods. Data were collected from the primary care monitoring for depressive patients trial (PRoMPT) of patients with major depressive disorder who were treated in a primary care setting. Resource utilisation and days of sick leave were observed and analysed over a 1-year period.
Results. Average depression related costs of €3813 were calculated. Significant differences in total costs due to sex were demonstrated. Male patients had considerable higher total costs than female patients, whereas single cost categories did not differ significantly. Further, differences in costs according to severity of disease and age were observed. The economic burden to society was estimated at €15.6 billion per year.
Conclusion. The study results show that depression poses a significant economic burden to society. There is a high potential for prevention, treatment, and patient management innovations to identify and treat patients at an early stage.
Channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) is a light-activated cation channel, which is a promising optogenetic tool. We show by resonance Raman spectroscopy and retinal extraction followed by high pressure liquid chromatography (HPLC) that the isomeric ratio of all-trans to 13-cis of solubilized channelrhodopsin-1 is with 70:30 identical to channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2). Critical frequency shifts in the retinal vibrations are identified in the Raman spectrum upon transition to the open (conductive P2(380)) state. Fourier transform infrared spectroscopy (FTIR) spectra indicate different structures of the open states in the two channelrhodopsins as reflected by the amide I bands and the protonation pattern of acidic amino acids.
Inhibitors of the mammalian target of rapamycin (mTOR) have improved the treatment of renal cell carcinoma (RCC). However, chronic drug exposure may trigger resistance, limiting the utility of these agents. The metastatic behavior of RCC cells, susceptible (RCC(par)) or resistant (RCC(res)) to the mTOR inhibitor temsirolimus, was investigated. Adhesion to vascular endothelium or immobilized collagen and fibronectin was quantified. Chemotactic motility was evaluated with a modified Boyden chamber assay. Integrin α and β subtype receptors were analyzed by flow cytometry and Western blot analysis. The physiological relevance of the integrins was then determined by blocking studies and small interfering RNA knockdown. Adhesion to endothelial cells and to fibronectin (not to collagen) and chemotaxis were enhanced in RCC(res) compared to RCC(par). RCC(res) detached from fibronectin and motile activity further increased under retreatment with low-dosed temsirolimus. α5 integrin was diminished inside the cell and at the cell surface, whereas the β3 subtype was reduced intracellularly but elevated at the plasma membrane. In RCC(par), blocking α5 surface receptors enhanced RCC-collagen but reduced RCC-fibronectin interaction, whereas the opposite was true for RCC(res). Chemotaxis of RCC(par) but not of RCC(res) was strongly diminished by the α5 antibody. Blocking β3 significantly lowered chemotaxis with stronger effects on RCC(res), compared to RCC(par). Importantly, β3 knockdown reduced chemotaxis of RCC(par) but upregulated the motile behavior of RCC(res). Temsirolimus resistance is characterized by quantitative alterations of integrin α5 and β3 expression, coupled to functional changes of the integrin molecules, and forces a switch from RCC adhesion to RCC migration.
The highly conserved eukaryotic process of macroautophagy (autophagy) is a non-specific bulk-degradation program critical for maintaining proper cellular homeostasis, and for clearing aged and damaged organelles. This decision is inextricably dependent upon prevailing metabolic demands and energy requirements of the cell. Soluble monomeric decorin functions as a natural tumor repressor that antagonizes a variety of receptor tyrosine kinases. Recently, we discovered that decorin induces endothelial cell autophagy, downstream of VEGFR2. This process was wholly dependent upon Peg3, a decorin-inducible genomically imprinted tumor suppressor gene. However, the signaling cascades responsible have remained elusive. In this report we discovered that Vps34, a class III phosphoinositide kinase, is an upstream kinase required for Peg3 induction. Moreover, decorin triggered differential formation of Vps34/Beclin 1 complexes with concomitant dissolution of inhibitive Bcl-2/Beclin 1 complexes. Further, decorin inhibited anti-autophagic signaling via suppression of Akt/mTOR/p70S6K activity with the concurrent activation of pro-autophagic AMPK-mediated signaling cascades. Mechanistically, AMPK is downstream of VEGFR2 and inhibition of AMPK signaling abrogated decorin-evoked autophagy. Collectively, these findings hint at the complexity of the underlying molecular relays necessary for decorin-evoked endothelial cell autophagy and reveal important therapeutic targets for augmenting autophagy and combatting tumor angiogenesis.
Der Wald wird häufig als ein natürliches Landschaftselement wahrgenommen, das im Gegensatz zu anderen, anthropogen begründeten Flächennutzungsarten über sehr lange Zeiträume besteht. Im Ergebnis einer seit Jahrhunderten andauernden Landnutzungsgeschichte hat sich aber auch der Wald in Mitteleuropa in seinem strukturellen Aufbau stark gewandelt. Anhand historischer und aktueller Forsteinrichtungswerke sowie weiterer historischer topographischer Karten wurden diese Veränderungen für die vergangenen zwei Jahrhunderte am Beispiel der Nationalparkregion Sächsische Schweiz flächengenau untersucht. Die wesentlichen Ziele der Studie bestanden darin, die Eignung der historischen Kartenwerke zur Forsteinrichtung für eine digitale Aufbereitung zu prüfen und den aus dieser Datenbasis ableitbaren Erkenntnisgewinn zu den strukturellen Veränderungen in den Wäldern zu ermitteln. Die Erkenntnisse wurden mit Ergebnissen zu räumlichen Veränderungen der Waldbedeckung in der Sächsischen Schweiz verknüpft. Die Ergebnisse zeigen, dass auf der erstellten Datengrundlage räumlich-statistische Analysen zur Waldentwicklung möglich sind, insbesondere quantitative aber auch qualitative Aussagen zu den strukturellen Veränderungen sowie zum Wandel der Nutzungsstrukturen. Analysen auf Basis von historischen topographischen Karten zeigen, dass der Waldanteil von 1780 bis heute von 60 % auf 56 % nur wenig abnahm. Deutlich werden jedoch örtlich großflächige Abnahmen an den Rändern der Rodungsinseln sowie eine Abnahme kleinerer Waldflächen des Offenlandes. Dem gegenüber stehen Zunahmen durch die Aufforstung offener Bereiche innerhalb großer geschlossener Waldbereiche. Aus dem Vergleich der berechneten Flächenanteile einzelner Altersklassen und Baumartengruppen aus den Forsteinrichtungskarten waren Entwicklungen wie die Zunahme der Altbestände im Bereich des Nationalparks Sächsische Schweiz oder die Abnahme der Weißtannenbestände in der Nationalparkregion quantitativ erfassbar. Für Erkenntnisse zu den Veränderungen in der Baumartenzusammensetzung wurden flächengenaue Analysen durchgeführt, die es beispielsweise ermöglichen, die Entwicklung der gegenwärtig sehr geringen Verbreitung der Weißtanne zu rekonstruieren. Es sind auf dieser Grundlage genaue Aussagen möglich, welche Baumarten an die Stelle der historischen Vorkommen der Weißtanne getreten sind. Die Ergebnisse belegen, dass die Intensivierung der Forstwirtschaft zu Beginn des letzten Jahrhunderts zu wenig standortgerechten Wäldern geführt hat. Mittlerweile zeigt sich eine deutliche Annäherung der Baumarten- und Alterszusammensetzung an einen naturnäheren Zustand. Ein wesentlicher Wert solcher Untersuchungen liegt darin, dass die Zielformulierungen für Waldflächen anhand der generierten Informationen überprüft und die Pflege- und Entwicklungsplanung der Wälder unterstützt werden können.
This dataset represents a registry of species that are not native but recorded to live in the wild of at least one of the four countries that comprise the Two Seas Area, i.e. Great Britain, France, Belgium and the Netherlands. For each of the 6,661 species, subspecies and hybrids listed, we provide detailed information on its status in each country, taxonomic affiliation and environment inhabited. The data were collected by review of 36 web- and print-based sources over an eight-month period. Further systematic scanning of three of the most relevant scientific journals, i.e. Neobiota, Aquatic Invasions and BioInvasions Records, recovered 19 additional relevant publications from which information was included in the registry. As a result, the registry will serve as a basis for developing effective, cross-boundary strategies to manage and control non-native species, which can have severe ecological and economic impacts. The registry can further be used as a general reference for both scientists and practitioners, as well as a tool to assess reliability and comprehensiveness of other well-known databases such as the DAISIE portal.
U radu su prikazani refleksi praslavenskih naglasnih tipova imenica a-deklinacije u mjesnom govoru Dolnje i Gorenje Mraševo, koji pripada skupini dolenjskih narječja slovenskoga jezika. Opisan je i naglasni sustav navedenoga govora s naglaskom na nizu oblika u kojima se pojavljuje postpraslavenski novi cirkumfleks. Povijesnojezična analiza naglasnih tipova imenica a-deklinacije donosi neke važne spoznaje za naglasni sustav slovenskoga jezika. U govoru dolazi do analognoga podudaranja samoglasnika praslavenskoga naglasnog tipa a, s imenicama praslavenskoga naglasnog tipa b i to refleksa imenica s praslavenskim dugim samoglasnikom u jedinom/zadnjem slogu osnove, što je posljedica prenošenja naglaska na dužinu. Novost predstavlja analogija u instrumentalu množine. Kod nekih je imenica praslavenskoga naglasnog tipa c očuvano povlačenje cirkumfleksa na dužinu uz proklitike (mr. na glàːvo, na nùːge). Došlo je također i do podudaranja imenica praslavenskoga naglasnog tipa b, koje imaju u jedinom/zadnjem slogu osnove praslavenski kratki samoglasnik ili poluglas, s imenicama praslavenskoga naglasnog tipa c, koje imaju u jedinom/zadnjem slogu osnove praslavenski kratki samoglasnik ili poluglas.
Introduction: Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated.
Methods: Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively.
Results: MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability.
Conclusions: These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.
Highly promising preclinical data obtained in cultured cells and in nude mice bearing xenografts contrast with the rather modest clinical efficacy of Polo-like kinase 1 (Plk1) inhibitors. In the present study, we investigated if Plk1 might be a suitable target in hepatocellular carcinoma (HCC) and if a genetically engineered mouse tumor model that well reflects the tumor cell and micro-environmental features of naturally occurring cancers might be suitable to study anti-Plk1 therapy. Analysis of Plk1 expression in human HCC samples confirmed that HCC express much higher Plk1 levels than the adjacent normal liver tissue. Inhibition of Plk1 by an adenovirus encoding for a short hairpin RNA against Plk1 or by the small-molecule inhibitor BI 2536 reduced the viability of HCC cell lines and inhibited HCC xenograft progression in nude mice. Treatment of transforming growth factor (TGF) α/c-myc bitransgenic mice with BI 2536 during hepatocarcinogenesis reduced the number of dysplastic foci and of Ki-67-positive cells within the foci, indicating diminished tumorigenesis. In contrast, BI 2536 had no significant effect on HCC progression in the transgenic mouse HCC model as revealed by magnetic resonance imaging. Measurement of BI 2536 by mass spectrometry revealed considerably lower BI 2536 levels in HCC compared with the adjacent normal liver tissue. In conclusion, low intratumoral levels are a novel mechanism of resistance to the Plk1 inhibitor BI 2536. Plk1 inhibitors achieving sufficient intratumoral levels are highly promising in HCC treatment.
U ovome se radu nastoji prikazati položaj nekih promjenljivih i nepromjenljivih nenaglasnica u kajkavskome književnom jeziku i u suvremenim kajkavskim govorima u odnosu na kajkavsku gramatičku normu. Istraživanje nenaglašenih rečeničnih sastavnica u kajkavskome narječju temelji se na rezultatima ankete provedene u svibnju i lipnju 2012. godine na Učiteljskome fakultetu u Zagrebu, Odsjeku u Čakovcu te, prema dijalektološkim kriterijima, na odabranim starijim ispitanicima.
The structure of the title compound, C8H16N4, which consists of four fused seven-membered rings, has been redetermined at 173 K. This redetermination corrects the orientation of two H atoms, which were located at unrealistic positions in the original room-temperature study [Murray-Rust (1974[Murray-Rust, P. (1974). J. Chem. Soc. Perkin Trans. 2, pp. 1136-1141.]). J. Chem. Soc. Perkin Trans. 2, pp. 1136–1141]. The complete molecule is generated by -42m symmetry, with one quarter of a molecule [one N atom (site symmetry m), two C atoms (one with site symmetry m and the other with site symmetry 2) and two H atoms] in the asymmetric unit. No directional interactions beyond van der Waals contacts are apparent in the crystal structure.
Na tragu učenja praške funkcionalne (aktualne) rečenične perspektive o osnovnom i aktualiziranom redu riječi razmatrat će se redoslijed sastavnica u složenim strukturama (subordiniranima i koordiniranima). U prvome redu zanimat će nas poredak surečenica (klauza) u sastavu zavisnosložene rečenice. Postavlja se naime pitanje čime sve može biti uvjetovana anteponiranost zavisne surečenice (tzv. inverzija), i to u različitim tipovima tekstova odnosno komunikacijskim situacijama (npr. u akademskom/ znanstvenom i/ili predavačkom diskursu, potom u privatnim razgovorima itd.). U tu svrhu pozornost ćemo obratiti na primjere poput ovih: Kao što je naslovom najavljeno, bavit ćemo se složenim rečenicama.; Kako bismo ubrzali objavljivanje zbornika, želja nam je što prije skupiti radove.; Kao što je prethodno rečeno, nastava počinje u listopadu.; Ako ne prekineš s glupostima, odlazim!; Dok ne ispraviš jedinice, ništa od izlazaka! i sl. Što se pak nezavisnosloženih rečenica tiče, ponajprije ćemo se suočiti s pitanjem utvrđivanja primarnog redoslijeda sastavnica (Sjedim i razmišljam. ili Razmišljam i sjedim.), da bismo potom pokušali utvrditi moguće razloge remećenja toga redoslijeda (npr. Umro – brao trešnje i pao sa stabla. prema Popeo se, brao trešnje, pao sa stabla, umro.). Naposljetku budući da pristajemo uz gledište da se već složena rečenica može smatrati činjenicom teksta (J. Silić), ali i zbog toga što se aktualizirani red riječi/komponenata ostvaruje upravo u (kon)tekstualno uključenoj rečenici, u svjetlu ćemo novije lingvistike teksta (R. de Beaugrande i W. Dressler) o redoslijedu komponenata promišljati kao o kohezivnom sredstvu.
Red riječi u smješnicama
(2014)
U radu se promatra i analizira red riječi u rečenici u hrvatskim anonimnim komedijama u prozi nastalim u 17. stoljeću na dubrovačkom području. Rezultati se analize uspoređuju s redom riječi potvrđenim u onodobnom književnom jeziku. Sinkronijskom su prikazu pridružene i usporedbe s rezultatima istraživanja Laznibata o dubrovačkim arhivskim spisima 17. i 18. stoljeća i I. Lovrić Jović o dubrovačkim oporukama iz istog tog razdoblja, dok je dijakronijski pregled napravljen usporedbom s Rešetarovim istraživanjima jezika Ranjinina zbornika i Držićeva jezika, s istraživanjem frančezarija 18. stoljeća I. Lovrić Jović te s Budmanijevim istraživanjem devetnaestostoljetnoga dubrovačkoga govora. Posebna se pozornost posvećuje poretku zanaglasnica, koji je, kao što je bilo očekivano, uglavnom stariji pa zamjenička zanaglasnica prethodi glagolskoj, no ovisno o smješnici, potvrđena su i brojna odstupanja.
Iako je riječ o srodnim jezicima sa slobodnim redom riječi, hrvatski i poljski standardni jezik razlikuju se u obveznom redu riječi, između ostalog i u pozicioniranju klitika; hrvatski pokazuje tendenciju slijediti tzv. Wackernagelovo pravilo, dok u poljskom jeziku po tom pitanju vlada puno veća sloboda. U ovom radu iznosim rezultate analize pogrešaka u redu riječi u hrvatskom jeziku koje su u pisanim radovima činili studenti kroatistike s dvaju sveučilišta u Poljskoj. Pretpostavka temeljena na teoriji usvajanja stranog jezika bila je da su pogreške rezultat negativnog prijenosa iz materinskog jezika. No tijekom analize pojavila se potreba za daljnjim i detaljnijim istraživanjem (iako je indikativna, analiza pogrešaka daje tek djelomičan uvid u problematiku) kojim bi se preciznije ustanovili razlozi negativnog prijenosa. Na samom kraju navodim pedagoške implikacije ovog i potencijalnih budućih istraživanja navedene problematike.
U radu se račlanjuje odnos reda riječi i negacije u hrvatskome crkvenoslavenskome jeziku. Prvi se vid toga odnosa tiče položaja niječnih izraza ne, ni i bez. U zadanome korpusu oni stoje ispred, odnosno lijevo od jezične jedinice koju niječu. Jedinica ispred koje se niječni izraz nalazi nije nužno glagol, pa ni finitni glagolski oblik. Položaj niječnih izraza povezan je i s razlikom, odnosno s utvrđivanjem razlike između sastavničke negacije, kao negacije nepredikatne sastavnice, i rečenične negacije, negacije predikata. Konačno, o redu riječi ovisi hoće li se ili neće provesti niječno slaganje. U hrvatskome je crkvenoslavenskome jeziku provođenje niječnoga slaganja djelomično (ne i proizvoljno), a ovisi o tome na kojemu se mjestu u rečenici nalazi niječna zamjenica ili prilog.
Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage.
Emotional competence has an important influence on development in school. We hypothesized that reading and discussing children’s books with emotional content increases children’s emotional competence. To examine this assumption, we developed a literature-based intervention, named READING and FEELING, and tested it on 104 second and third graders in their after-school care center. Children who attended the same care center but did not participate in the emotion-centered literary program formed the control group (n = 104). Our goal was to promote emotional competence and to evaluate the effectiveness of the READING and FEELING program. Emotional competence variables were measured prior to the intervention and 9 weeks later, at the end of the program. Results revealed significant improvements in the emotional vocabulary, explicit emotional knowledge, and recognition of masked feelings. Regarding the treatment effect for detecting masked feelings, we found that boys benefited significantly more than girls. These findings underscore the assumption that children’s literature is an appropriate vehicle to support the development of emotional competence in middle childhood.
U radu se analizira obradba računalnih naziva u Novome rječniku stranih riječi Bratoljuba Klaića i Školske knjige. Analizira se ustroj rječničkoga članka natuknica koje nose terminološku odrednicu INFORM. te se analiziraju pojedini elementi rječničkoga članka (natuknica, morfološko-naglasni blok, definicija, odrednice). Leksikografska se obradba računalnih naziva uspoređuje s obradbom u postojećim englesko-hrvatskim informatičkim rječnicima (Kiš, Panian), ali i s obradbom u općim rječnicima hrvatskoga jezika (HER, Školski rječnik hrvatskoga jezika).
Baveći se (kao recenzentica) djelom Bratoljuba Klaića Naglasni sustav standardnoga hrvatskog jezika, Klaićev me način bilježenja naglasaka podsjetio i na nešto starije gramatike hrvatskoga jezika i na bilježenje naglasaka u tim gramatikama, pa se tim uspoređivanjem vrlo lako uočava razlika između pisanja naglasaka „nekad i sad”, premda to „nekad” i nije bilo tako davno. Kako su u hrvatskoj kroatistici akcentološka djela rijetka, prilika je da se na skupu posvećenu između ostaloga i akcentologu Bratoljubu Klaiću progovori nešto više o razlikama u bilježenju hrvatskih naglasaka u Klaićevo vrijeme (prije pedesetak godina) i u vrijeme bliže današnjemu, jer su te razlike od vremena pisanja Klaićeva djela do danas očite. U svojem izlaganju osvrnula sam se na poteškoće u novijem bilježenju hrvatskih standardnih naglasaka, poglavito na slogovima s dugim refleksom staroga glasa jata,te o razlozima koji su do njih doveli. Usredotočila sam se poglavito na Klaićevo i današnje pisanje naglasaka na nekadašnjoj tzv. dugoj (dvosložnoj) zamjeni jata – koliko god to neki lingvisti tretirali kao dvoglasnik ie, ipak se riječi kao snijeg, brijeg i sl. mogu rastaviti na slogove, dakle ipak su posrijedi dva sloga, a ne jedan – jer upravo u tome i jesu razlike između Klaićeva bilježenja naglasaka i onih današnjih u standardološkim djelima.
U prilogu je riječ o raspoređivanju suznačnih riječi, i to zamjenica i priloga (upitnih i odnosnih), čestica i veznika, u rečenicama ili surečenicama. To su riječi koje služe za povezivanje surečenica u sastavu nezavisnosloženih i zavisnosloženih rečenica (konjunktori i subjunktori) ili za povezivanje rečenica na razini teksta (konektori), za izražavanje raznolikih modalnih značenja, za označavanje upitnosti, za isticanje, za poticanje, za nijekanje i sl. Takve se riječi dijele u dvije skupine s obzirom na to mogu li funkcionirati i kao članovi rečeničnoga ustrojstva (zamjeničke riječi) ili ne mogu (ostala vezna sredstva i čestice). Riječi iz ove druge skupine mogle bi se (bar sa sintaktičkoga stajališta) nazvati suznačnima u užem smislu. Osobita će se pozornost posvetiti raspoređivanju suznačnih riječi ili spojeva koji, čiji, i, ni, niti, a, ali, ili, što, samo što, da, zar, zar da, kao da. Bit će također riječi i o raspoređivanju suznačnih (zamjeničkih) riječi u situacijama u kojima te riječi dolaze u funkcijama koje međusobno kolidiraju, npr. u funkciji subjunktora i u funkciji nesročnoga atributa, npr. To su pravila primjena kojih zahtijeva punu koncentraciju. odnosno To su pravila kojih primjena zahtijeva punu koncentraciju.
Species' geographical distributions are tracking latitudinal and elevational surface temperature gradients under global climate change. To evaluate the opportunities to track these gradients across space, we provide a first baseline assessment of the steepness of these gradients for the world's terrestrial birds. Within the breeding ranges of 9,014 bird species, we characterized the spatial gradients in temperature along latitude and elevation for all and a subset of bird species, respectively. We summarized these temperature gradients globally for threatened and non-threatened species and determined how their steepness varied based on species' geography (range size, shape, and orientation) and projected changes in temperature under climate change. Elevational temperature gradients were steepest for species in Africa, western North and South America, and central Asia and shallowest in Australasia, insular IndoMalaya, and the Neotropical lowlands. Latitudinal temperature gradients were steepest for extratropical species, especially in the Northern Hemisphere. Threatened species had shallower elevational gradients whereas latitudinal gradients differed little between threatened and non-threatened species. The strength of elevational gradients was positively correlated with projected changes in temperature. For latitudinal gradients, this relationship only held for extratropical species. The strength of latitudinal gradients was better predicted by species' geography, but primarily for extratropical species. Our findings suggest threatened species are associated with shallower elevational temperature gradients, whereas steep latitudinal gradients are most prevalent outside the tropics where fewer bird species occur year-round. Future modeling and mitigation efforts would benefit from the development of finer grain distributional data to ascertain how these gradients are structured within species' ranges, how and why these gradients vary among species, and the capacity of species to utilize these gradients under climate change.
Background: Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection.
Methods: Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period.
Results: A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [−6.0 %, 19.8 %] does not include the lower noninferiority margin (−10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups.
Conclusion: The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.
The success of invasive species has been explained by two contrasting but non-exclusive views: (i) intrinsic factors make some species inherently good invaders; (ii) species become invasive as a result of extrinsic ecological and genetic influences such as release from natural enemies, hybridization or other novel ecological and evolutionary interactions. These viewpoints are rarely distinguished but hinge on distinct mechanisms leading to different management scenarios. To improve tests of these hypotheses of invasion success we introduce a simple mathematical framework to quantify the invasiveness of species along two axes: (i) interspecific differences in performance among native and introduced species within a region, and (ii) intraspecific differences between populations of a species in its native and introduced ranges. Applying these equations to a sample dataset of occurrences of 1,416 plant species across Europe, Argentina, and South Africa, we found that many species are common in their native range but become rare following introduction; only a few introduced species become more common. Biogeographical factors limiting spread (e.g. biotic resistance, time of invasion) therefore appear more common than those promoting invasion (e.g. enemy release). Invasiveness, as measured by occurrence data, is better explained by inter-specific variation in invasion potential than biogeographical changes in performance. We discuss how applying these comparisons to more detailed performance data would improve hypothesis testing in invasion biology and potentially lead to more efficient management strategies.
Background: Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess – among other domains – daily functioning from a patient’s perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness. The objective of this study was, therefore, to determine the cross-sectional and longitudinal relationships between HRQoL, physical activity and fitness in patients with CF.
Methods: Baseline (n = 76) and 6-month follow-up data (n = 70) from patients with CF (age ≥12 years, FEV1 ≥35%) were analysed. Patients participated in two multi-centre exercise intervention studies with identical assessment methodology. Outcome variables included HRQoL (German revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition, pulmonary function, physical activity, short-term muscle power, and aerobic fitness by peak oxygen uptake and aerobic power.
Results: Peak oxygen uptake was positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46). Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were positively related to 4 scales each, and reported physical activity to 1 scale (r = 0.29). Changes in HRQoL-scores were directly and significantly related to changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34), and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates of HRQoL such as FEV1 or body mass index correlated positively with fewer scales (all 0.24 < r < 0.55).
Conclusions: HRQoL was associated with physical fitness, especially aerobic fitness, and to a lesser extent with reported physical activity. These findings underline the importance of physical fitness for HRQoL in CF and provide an additional rationale for exercise testing in this population.
Trial registration: ClinicalTrials.gov, NCT00231686
This note offers reflections on qualified market access (QMA) - the practice of linking trade agreements to values such as human rights, labour standards, or environmental protection. This idea has been suggested by political theorists as a way of fulfilling our duties to the global poor and of making the global economic system more just, and it has influenced a number of concrete policies, such as European Union (EU) trade policies. Yet, in order to assess its merits tout court, different perspectives and disciplines need to be brought together, such as international law, economics, political science, and philosophy. It is also worth reflecting on existing practices, such as those of the EU. This note summarises some insights about QMA by drawing such research together and considers the areas in which further research is needed, whilst reflecting also on the merits of interdisciplinary exchanges on such topics.
In den römischen Grabinschriften CIL XIII 8356 und 8267b aus Köln muss entgegen der gängigen Meinung der Forschung der Buchstabe Q jeweils als q(uondam) gelesen werden, nicht als Q(uinti filia), <o(bitus)> oder <Θ>. Die Wendung wurde oftmals mit einem Q wiedergegeben und manchmal zwischen dem Gentiliz und dem Cognomen platziert. Nördlich der Alpen findet sich quondam vor allem in Pannonien.
Micky Maus, Superman, Asterix, Popeye - zahlreiche Figuren aus Comics haben ein Eigenleben entwickelt und sich als Marke etabliert. Die Figuren halten die Fortsetzungsgeschichten zusammen und stellen entsprechend einen Wiedererkennungswert dar. Vor diesem Hintergrund ist es bemerkenswert, dass sich die inzwischen doch einigermaßen etablierte Comic-Forschung der Betrachtung der Figuren nur am Rande gewidmet hat. Das gilt erst recht für jene Sonderform des Comics, die im Folgenden in den Fokus gerückt werden soll: die Graphic Novel.
Das Thema des Monologs ist das Schreiben und Sprechen als
"närrische Sache". Ich beginne meine Lektüre, indem ich den Begriff wörtlich nehme: Ein Narr ist, in der Psychologie der Zeit, jemand, der an Melancholie leidet, dessen Verstand bzw. Vernunft jedoch nicht vollständig, sondern nur teilweise angegriffen ist. [...] Die Diagnose der Narrheit gilt auch [...] für denjenigen, der sich in Novalis' Augen der Sprache zuwendet. Auch er wird zum Narren oder Partialwahnsinnigen, der sowohl vernünftig als auch ganz und gar unvernünftig sprechen kann. Die Krankheit liegt aber, und das stellt eine Differenz gegenüber der Psychologie der Zeit dar, nicht im Sprechenden, zumindest nicht in ihm allein, sondern in der Sprache. Sie selbst ist es, welche die "närrische Sache" ausmacht.
Prämissen für die Vermittlung interkultureller Kompetenzen im studienbegleitenden DaF-Unterricht
(2014)
Language teaching alone is not sufficient in order to communicate successfully in the foreign language. Even with the acquisition of one’s native language, one does not learn just vocabulary, grammar, reading, writing, speaking and listening. Apart from all that one learns how to identify and to practice cultural patterns. Here, the learning and teaching process is accompanied by another component: intercultural communication and the acquisition of intercultural competences. These teach the lerner to understand first and foremost their own cultural background in order for them to be able to change perspective and look at and understand the cultural background of the target language. Teaching must be centered on the learner, and the foreign language is not taught „in general“, but with regard to the learners’ culture of origin.
Bei der Lorbeerkirsche handelt es sich um eine giftige Pflanze, deren toxische Wirkung durchaus nicht zu unterschätzen ist. Das Pflanzenporträt der Lorbeerkirsche dazu beitragen, die Art richtig ansprechen zu können, um mögliche Vergiftungen zu vermeiden. Darüber hinaus wird im Folgenden darüber informiert, welche positive Wirkung das beliebte Hecken- und Sichtschutzgehölz hat, wo die Art ursprünglich wächst und dass sie mittlerweile in milden Gebieten in Deutschland auch außerhalb der Gärten und Parks wild wachsend angetroffen werden kann.
Background: There is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).
Methods and findings: Eighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.
Conclusions: Proteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.
Background: Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients.
Methods: The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators. Survival analyses were calculated for all patients receiving adjuvant chemotherapy in relation to expression of all makers above.
Results: Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination.
Conclusions: The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/− irinotecan in stage II/III colorectal cancer.
Protein signatures of oxidative stress response in a patient specific cell line model for autism
(2014)
Background: Known genetic variants can account for 10% to 20% of all cases with autism spectrum disorders (ASD). Overlapping cellular pathomechanisms common to neurons of the central nervous system (CNS) and in tissues of peripheral organs, such as immune dysregulation, oxidative stress and dysfunctions in mitochondrial and protein synthesis metabolism, were suggested to support the wide spectrum of ASD on unifying disease phenotype. Here, we studied in patient-derived lymphoblastoid cell lines (LCLs) how an ASD-specific mutation in ribosomal protein RPL10 (RPL10[H213Q]) generates a distinct protein signature. We compared the RPL10[H213Q] expression pattern to expression patterns derived from unrelated ASD patients without RPL10[H213Q] mutation. In addition, a yeast rpl10 deficiency model served in a proof-of-principle study to test for alterations in protein patterns in response to oxidative stress.
Methods: Protein extracts of LCLs from patients, relatives and controls, as well as diploid yeast cells hemizygous for rpl10, were subjected to two-dimensional gel electrophoresis and differentially regulated spots were identified by mass spectrometry. Subsequently, Gene Ontology database (GO)-term enrichment and network analysis was performed to map the identified proteins into cellular pathways.
Results: The protein signature generated by RPL10[H213Q] is a functionally related subset of the ASD-specific protein signature, sharing redox-sensitive elements in energy-, protein- and redox-metabolism. In yeast, rpl10 deficiency generates a specific protein signature, harboring components of pathways identified in both the RPL10[H213Q] subjects' and the ASD patients' set. Importantly, the rpl10 deficiency signature is a subset of the signature resulting from response of wild-type yeast to oxidative stress.
Conclusions: Redox-sensitive protein signatures mapping into cellular pathways with pathophysiology in ASD have been identified in both LCLs carrying the ASD-specific mutation RPL10[H213Q] and LCLs from ASD patients without this mutation. At pathway levels, this redox-sensitive protein signature has also been identified in a yeast rpl10 deficiency and an oxidative stress model. These observations point to a common molecular pathomechanism in ASD, characterized in our study by dysregulation of redox balance. Importantly, this can be triggered by the known ASD-RPL10[H213Q] mutation or by yet unknown mutations of the ASD cohort that act upstream of RPL10 in differential expression of redox-sensitive proteins.
Aim. To compare the efficacy, safety, and patient’s perception of two prostaglandin E2 application methods for induction of labour.
Method. Above 36th weeks of gestation, all women, who were admitted to hospital for induction of labour, were prospectively randomised to intravaginal 1 mg or intracervical 0.5 mg irrespective of cervical Bishop score. The main outcome variables were induction-to-delivery interval, number of foetal blood samples, PDA rate, rate of oxytocin augmentation, rate of vaginal delivery, and patient’s perception using semantic differential questionnaire.
Results. Thirty-nine patients were enrolled in this study. There was no statistical significant difference between the two groups in regard to perceptions of induction. The median induction delivery time using intravaginal versus intracervical administration was 29.9 versus 12.8 hours, respectively (). No statistically difference between the groups was detected in regard to parity, gestation age, cervical Bishop score, number of foetal blood samples, PDA rate, rate of oxytocin augmentation, and mode of birth.
Summary. Irrespective of the cervical Bishop Score, intracervical gel had a shorter induction delivery time without impingement on the women’s perception of induction.
Proslov
(2014)
Background: The aim of this study was to compare outcome of patients with previous cardiac surgery undergoing transapical aortic valve implantation (Redo-TAVI) to those undergoing classic aortic valve replacement (Redo-AVR) by using propensity analysis.
Methods: From January 2005 through May 2012, 52 high-risk patients underwent Redo-TAVI using a pericardial xenograft fixed within a stainless steel, balloon-expandable stent (Edwards SAPIEN™). During the same period of time 167 patients underwent classic Redo-AVR. Logistic regression analysis was used to identify covariates among 11 baseline patient variables including the type of initial surgery. Using the significant regression coefficients, each patient’s propensity score was calculated, allowing selectively matched subgroups of 40 patients each. Initial surgery included coronary artery bypass grafting in 30 patients, aortic valve replacement in 7 patients and mitral valve reconstruction in 3 patients in each group. Follow-up was 4 ± 2 years and was 100% complete.
Results: Postoperative chest tube drainage (163 ± 214 vs. 562 ± 332 ml/24 h, p = 0.02) and incidence of early permanent neurologic deficit (0 vs. 13%, p = 0.04) was lower in patients with Redo-TAVI and there was a trend towards improved 30-day survival (p = 0.06). Also we detected a decreased ventilation time (p = 0.04) and lower transfusion rate of allogenic blood products (p ≤ 0.05) in the Redo-TAVI group. At late follow up differences regarding incidence of major adverse events, including death and permanent neurologic deficits (25% vs. 43%, p = 0.01) statistically supported early postoperative findings.
Conclusion: The encouraging results regarding early and long-term outcomes following TAVI in patients with previous cardiac surgery show, that this evolving approach may be particularly beneficial in this patient cohort.
Epigenetic silencing of tumour suppressor genes has been observed in various cancers. Looking at hepatocellular carcinoma (HCC) specific protein silencing was previously demonstrated to be associated with the Hepatitis C virus (HCV). However, the proposed HCV dependent promoter methylation of DNA mismatch repair (MMR) genes and thereby enhanced progression of hepatocarcinogenesis has been the subject of controversial discussion. We investigated promoter methylation pattern of the MMR genes MLH1, MSH2 and PMS2 as well as the cyclin-dependent kinase inhibitor 2A gene (p16) in 61 well characterized patients with HCCs associated with HCV, Hepatitis B virus infection or alcoholic liver disease. DNA was isolated from formalin-fixed, paraffin-embedded tumour and non-tumour adjacent tissue and analysed by methylation-specific PCR. Moreover, microsatellite analysis was performed in tissues showing methylation in MMR gene promoters. Our data demonstrated that promoter methylation of MLH1, MSH2, PMS2 and p16 is present among all considered HCCs. Hereby, promoter silencing was detectable more frequently in advanced-stage HCCs than in low-stage ones. However, there was no significant correlation between aberrant DNA methylation of MMR genes or p16 and HCV infection in related HCC specimens. In summary, we show that promoter methylation of essential MMR genes and p16 is detectable in HCCs most dominantly in pT3 stage tumour cases. Since loss of MMR proteins was previously described to be not only responsible for tumour development but also for chemotherapy resistance, the knowledge of mechanisms jointly responsible for HCC progression might enable significant improvement of individual HCC therapy in the future.